Researcher Profile and Settings

Master

Affiliation (Master)

• Faculty of Medicine　Specialized Medicine　Reconstructive Surgery and Rehabilitation Medicine

Affiliation (Master)

• Faculty of Medicine　Specialized Medicine　Reconstructive Surgery and Rehabilitation Medicine

researchmap

Profile and Settings

Degree

• medical doctor

Profile and Settings

• Name (Japanese)

  Iwasaki

• Name (Kana)

  Norimasa

• Name

  200901045611701200

Achievement

Research Interests

• Orthopaedic Surgery   Sports medicine   Tissue engineering   Biomaterial   

Research Areas

• Life sciences / Orthopedics
• Life sciences / Sports science
• Life sciences / Biomaterials
• Life sciences / Biomedical engineering
• Life sciences / Immunology

Research Experience

• 2012/10 - Today 北海道大学大学院医学研究院機能再生医学分野整形外科学教室教授
• 2010/04 - 2012/09 北海道大学大学院医学研究科機能再生医学講座整形外科学分野准教授
• 2004/02 - 2010/03 北海道大学病院整形外科講師
• 2000/01 - 2004/01 北海道大学大学院医学研究科運動器再建医学分野助手
• 1994/04 - 1995/08 米国Johns Hopkins大学整形外科留学
• 1988/04 Hokkaido University

Education

• 1994/04 - 1998/03  北海道大学大学院
•        - 1988/04  Hokkaido University  Graduate School, Division of Medicine
• 1982/04 - 1988/03  Asahikawa Medical University  School of Medicine  Medical Course

Awards

• 2022/02 北海道 北海道科学技術賞
  
• 2018 北海道大学大学院医学研究院・大学院医学院・医学部医学科 優秀研究賞
  
• 2006 日本手外科学会 Traveling Fellow
  
• 2003 北海道整形災害外科学会 学術奨励賞
  

Published Papers

• Higher association of articular surface destruction with rheumatoid forefoot deformity arising from dislocation of the metatarsophalangeal joints in the lateral column.

  Yuki Suzuki, Tomohiro Onodera, Koji Iwasaki, Masatake Matsuoka, Masanari Hamasaki, Eiji Kondo, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2024/08/14 

  BACKGROUND: To evaluate the relationship between the pattern and severity of metatarsophalangeal (MTP) joint dislocation in the lesser toes and severity of joint destruction in rheumatoid forefoot deformities. METHODS: Participants comprised of 13 patients (16 feet) who underwent resection arthroplasty of the metatarsal head of the lesser toes for rheumatoid arthritis of the MTP joints. Correlations between preoperative radiographic findings and histological grades second to fifth metatarsal heads taken intraoperatively were analyzed. RESULTS: In 62 metatarsal heads, complete dislocation of the MTP joint in the lesser toes significantly resulted in severe joint destruction compared to mild or moderate dislocation (P < 0.05). The proportion of severe cartilage damage in MTP joints with complete dislocation was 100 % in the 5th MTP joint, 83.3 % in the 4th MTP joint, and 58.3 % in the 2nd and 3rd MTP joints. Moreover, complete dislocation of the MTP joints in the lateral column showed the most severe joint destruction compared to that in the medial column (P = 0.03). CONCLUSION: Complete dislocation of the MTP joint in the lateral column is related to joint destruction in rheumatoid forefoot deformities.
• Amputation surgery associated with shortened survival in patients with localized extremity bone sarcoma.

  Nayuhito Yanagisawa, Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Masanari Hamasaki, Taku Ebata, Yoshiaki Hosokawa, Eiji Kondo, Norimasa Iwasaki

  Journal of orthopaedics 54 124 - 130 2024/08 

  BACKGROUND: This study assesses survival rates among patients with localized extremity bone sarcoma who have undergone amputation, pinpointing subpopulations that are disproportionately affected by amputation-related survival disparities. METHODS: Examination of data was conducted using the Surveillance, Epidemiology, and End Results (SEER) program, analyzing records of 3765 patients diagnosed with localized extremity bone sarcoma between 2000 and 2019. Of these, 857 received amputations (Amputation cohort), and 2908 underwent limb-sparing surgeries. Propensity score matching, considering demographic and clinical features, was utilized to ensure a fair comparison. RESULTS: Following propensity score matching, the study focused on 1714 cases. The Amputation cohort was observed to have significantly poorer survival rates (Cancer-Specific Survival [CSS]: Hazard Ratio [HR] = 1.28, 95% Confidence Interval [CI]: 1.05-1.55; Overall Survival [OS]: HR = 1.37, 95% CI: 1.15-1.63). Subsequent subgroup analysis indicated that individuals with tumors exceeding 8 cm in size or those located in the lower limbs were notably at a higher risk of shortened survival (for tumors >8 cm - CSS: HR = 1.32, 95% CI: 1.02-1.71; OS: HR = 1.39, 95% CI: 1.09-1.76; for lower limb tumors - CSS: HR = 1.25, 95% CI: 1.01-1.54; OS: HR = 1.33, 95% CI: 1.11-1.61). CONCLUSIONS: Our findings demonstrate that patients diagnosed with localized extremity bone sarcoma undergoing amputation exhibit lower survival rates, especially in cases involving tumors of greater size or those situated in the lower limbs. In patient groups where amputation is inevitable, careful follow-up is required after surgical intervention.
• Depletion of b-series ganglioside prevents limb length discrepancy after growth plate injury.

  Yoshiaki Hosokawa, Masatake Matsuoka, Yuko Sakai, Ryuichi Fukuda, Keizumi Matsugasaki, Kentaro Homan, Jun-Ichi Furukawa, Tomohiro Onodera, Norimasa Iwasaki

  BMC musculoskeletal disorders 25 (1) 565 - 565 2024/07/20 

  INTRODUCTION: Growth plate damage in long bones often results in progressive skeletal growth imbalance and deformity, leading to significant physical problems. Gangliosides, key glycosphingolipids in cartilage, are notably abundant in articular cartilage and regulate chondrocyte homeostasis. This suggests their significant roles in regulating growth plate cartilage repair. METHODS: Chondrocytes from 3 to 5 day-old C57BL/6 mice underwent glycoblotting and mass spectrometry. Based on the results of the glycoblotting analysis, we employed GD3 synthase knockout mice (GD3-/-), which lack b-series gangliosides. In 3-week-old mice, physeal injuries were induced in the left tibiae, with right tibiae sham operated. Tibiae were analyzed at 5 weeks postoperatively for length and micro-CT for growth plate height and bone volume at injury sites. Tibial shortening ratio and bone mineral density were measured by micro-CT. RESULTS: Glycoblotting analysis indicated that b-series gangliosides were the most prevalent in physeal chondrocytes among ganglioside series. At 3 weeks, GD3-/- exhibited reduced tibial shortening (14.7 ± 0.2 mm) compared to WT (15.0 ± 0.1 mm, P = 0.03). By 5 weeks, the tibial lengths in GD3-/- (16.0 ± 0.4 mm) closely aligned with sham-operated lengths (P = 0.70). Micro-CT showed delayed physeal bridge formation in GD3-/-, with bone volume measuring 168.9 ± 5.8 HU at 3 weeks (WT: 180.2 ± 3.2 HU, P = 0.09), but normalizing by 5 weeks. CONCLUSION: This study highlights that GD3 synthase knockout mice inhibit physeal bridge formation after growth plate injury, proposing a new non-invasive approach for treating skeletal growth disorders.
• Radiation therapy improves survival in elderly patients with localized extremity soft tissue sarcoma.

  Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Masanari Hamasaki, Taku Ebata, Yoshiaki Hosokawa, Ryuichi Fukuda, Eiji Kondo, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2024/07/15 

  BACKGROUND: This study aims to evaluate the efficacy of radiation therapy in enhancing survival outcomes among elderly patients diagnosed with localized extremity soft tissue sarcomas (STSs). Furthermore, it seeks to explore whether the survival benefits conferred by radiation therapy differ according to tumor characteristics and treatment modalities. METHODS: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database to identify patients aged 80 years and older diagnosed with localized extremity STSs. The study assessed 1498 eligible patients, analyzing cancer-specific survival (CSS) and overall survival (OS) through Kaplan-Meier survival analysis and Cox proportional hazards modeling. Propensity score matching was employed to adjust for potential confounders. RESULTS: Among the analyzed patients, 773 patients underwent radiation therapy (Radiation group), while 725 patients either did not receive radiation therapy or it was unknown if they had (No-Radiation group). The 5-year OS rate was 40% in the radiation group compared to 38% in the no-radiation group. After propensity score matching, radiation therapy was associated with a significant improvement in OS (P = 0.005, HR = 0.8, 95% CI 0.7-0.9). Subgroup analyses indicated that patients undergoing primary tumor resection benefited most from radiation therapy in terms of OS. CONCLUSION: Radiation therapy is associated with improved overall survival in elderly patients with localized extremity STSs. These findings suggest that radiation therapy should be considered as a key component of the treatment strategy for this patient population, taking into account individual patient characteristics and comorbidities.
• Effect of the Sauvé–Kapandji method on the wrist contact surface for distal radial ulnar joint disorders

  Tomoaki Suzuki, Daisuke Momma, Nozomu Inoue, Eiji Kondo, Yuichiro Matsui, Norimasa Iwasaki

  BMC Musculoskeletal Disorders 25 (1) 2024/07/11 

  Abstract Background The Sauvé–Kapandji (S-K) method is a surgical procedure performed for chronic deformities of the distal radial ulnar joint (DRUJ). Changes to the joint contact surface from pre- to postoperatively under physiological in vivo conditions have not yet been determined for this useful treatment. The aim of the present study was therefore to compare the articular contact area of the wrist joint between before and after the S-K method for DRUJ disorders. Methods The SK method was performed for 15 patients with DRUJ osteoarthritis and ulnar impaction syndrome. We calculated the Mayo Wrist Score as the patient’s clinical findings and created 3-dimensional bone models of cases in which the S-K method was performed and calculated the contact area and shift in the center of the contact area using customized software. Results The Mean modified Mayo Wrist Score improved significantly from 60.3 preoperatively to 80.3 postoperatively (P < 0.01). Scaphoid contact area to the radius increased significantly from 112.6 ± 37.0 mm² preoperatively to 127.5 ± 27.8 mm² postoperatively (P = 0.03). Lunate contact area to radius-ulna was 121.3 ± 43.3 mm² preoperatively and 112.5 ± 37.6 mm² postoperatively, but this decrease was not significant (P = 0.38). Contact area ratio of scaphoid to lunate increased significantly from 1.01 ± 0.4 preoperatively to 1.20 ± 0.3 postoperatively (P = 0.02). Postoperative translations of the center of the scaphoid and lunate contact areas were decomposed into ulnar and proximal directions. Ulnar and proximal translation distances of the scaphoid contact area were 0.8 ± 1.7 mm and 0.4 ± 0.6 mm, respectively, and those of the lunate contact area were 1.1 ± 1.7 mm and 0.4 ± 1.1 mm, respectively. This study revealed changes in wrist contact area and center of the contact area before and after the S-K method. Conclusion These results may accurately indicate changes in wrist joint contact area from pre- to postoperatively using the S-K method for patients with DRUJ disorder. Evaluation of changes in contact area due to bone surface modeling of the wrist joint using 3DCT images may be useful in considering surgical methods.
• Deep learning-based detection of lumbar spinal canal stenosis using convolutional neural networks.

  Hisataka Suzuki, Terufumi Kokabu, Katsuhisa Yamada, Yoko Ishikawa, Akito Yabu, Yasushi Yanagihashi, Takahiko Hyakumachi, Hiroyuki Tachi, Tomohiro Shimizu, Tsutomu Endo, Takashi Ohnishi, Daisuke Ukeba, Ken Nagahama, Masahiko Takahata, Hideki Sudo, Norimasa Iwasaki

  The spine journal : official journal of the North American Spine Society 2024/06/22 

  BACKGROUND CONTEXT: Lumbar spinal canal stenosis (LSCS) is the most common spinal degenerative disorder in elderly people and usually first seen by primary care physicians or orthopedic surgeons who are not spine surgery specialists. Magnetic resonance imaging (MRI) is useful in the diagnosis of LSCS, but the equipment is often not available or difficult to read. LSCS patients with progressive neurologic deficits have difficulty with recovery if surgical treatment is delayed. So, early diagnosis and determination of appropriate surgical indications are crucial in the treatment of LSCS. Convolutional neural networks (CNNs), a type of deep learning, offers significant advantages for image recognition and classification, and work well with radiographs, which can be easily taken at any facility. PURPOSE: Our purpose was to develop an algorithm to diagnose the presence or absence of LSCS requiring surgery from plain radiographs using CNNs. STUDY DESIGN: Retrospective analysis of consecutive, nonrandomized series of patients at a single institution. PATIENT SAMPLE: Data of 150 patients who underwent surgery for LSCS, including degenerative spondylolisthesis, at a single institution from January 2022 to August 2022, were collected. Additionally, 25 patients who underwent surgery at 2 other hospitals were included for extra external validation. OUTCOME MEASURES: In annotation 1, the area under the curve (AUC) computed from the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated. In annotation 2, correlation coefficients were used. METHODS: Four intervertebral levels from L1/2 to L4/5 were extracted as region of interest from lateral plain lumbar spine radiographs totaling 600 images were obtained. Based on the date of surgery, 500 images derived from the first 125 cases were used for internal validation, and 100 images from the subsequent 25 cases used for external validation. Additionally, 100 images from other hospitals were used for extra external validation. In annotation 1, binary classification of operative and nonoperative levels was used, and in annotation 2, the spinal canal area measured on axial MRI was labeled as the output layer. For internal validation, the 500 images were divided into each 5 dataset on per-patient basis and 5-fold cross-validation was performed. Five trained models were registered in the external validation prediction performance. Grad-CAM was used to visualize area with the high features extracted by CNNs. RESULTS: In internal validation, the AUC and accuracy for annotation 1 ranged between 0.85-0.89 and 79-83%, respectively, and the correlation coefficients for annotation 2 ranged between 0.53 and 0.64 (all p<.01). In external validation, the AUC and accuracy for annotation 1 were 0.90 and 82%, respectively, and the correlation coefficient for annotation 2 was 0.69, using 5 trained CNN models. In the extra external validation, the AUC and accuracy for annotation 1 were 0.89 and 84%, respectively, and the correlation coefficient for annotation 2 was 0.56. Grad-CAM showed high feature density in the intervertebral joints and posterior intervertebral discs. CONCLUSIONS: This technology automatically detects LSCS from plain lumbar spine radiographs, making it possible for medical facilities without MRI or nonspecialists to diagnose LSCS, suggesting the possibility of eliminating delays in the diagnosis and treatment of LSCS that require early treatment.
• Paradoxical Change in Subchondral Bone Density in the Medial Compartment of the Proximal Tibial Articular Surface After High Tibial Osteotomy: A Detailed Subchondral Bone Density Analysis.

  Yuki Fujie, Koji Iwasaki, Masanari Hamasaki, Yuki Suzuki, Masatake Matsuoka, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki

  The American journal of sports medicine 3635465241256100 - 3635465241256100 2024/06/20 

  BACKGROUND: High tibial osteotomy (HTO) aims to realign the varus knee to alleviate stress in the medial compartment. However, detailed information on the impact of HTO on stress distribution across the tibiofemoral joint surface still needs to be completely elucidated. PURPOSE/HYPOTHESIS: The present study aimed to analyze the subchondral bone density distribution to validate the alignment threshold causing paradoxical changes. We hypothesized that there would be a paradoxical stress change in the medial compartment beyond a specific threshold for lower limb realignment after HTO. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective clinical study of 32 knees from 30 patients who underwent medial opening-wedge HTO between 2015 and 2019 was conducted at Hokkaido University Hospital. The subchondral bone density across the tibiofemoral joint was analyzed using computed tomography-osteoabsorptiometry before and after HTO. The high-density area (HDA) within the medial and lateral compartments and their subregions, which were quartered in the coronal plane, was specifically examined. RESULTS: The hip-knee-ankle angle, medial proximal tibial angle (MPTA), joint line obliquity (JLO), and joint line convergence angle significantly changed after HTO (P < .01). The HDA of the medial compartment to the total HDA ratio decreased from 83% to 77%. Paradoxically, the HDA in the most central subregion of the medial compartment increased from 24% to 30%. There were significant differences between MPTA and JLO in patients with and without paradoxical changes in the HDA. MPTA and JLO cutoff values causing paradoxical changes in the HDA were 94° and 4°, respectively. CONCLUSION: There was a paradoxical stress increase in the M4 region at the medial compartment associated with the MPTA and JLO beyond specific thresholds. Therefore, surgical planning should be cautiously performed to prevent overcorrection, which can lead to adverse stress distribution changes.
• Ossification of the posterior longitudinal ligament is linked to heterotopic ossification of the ankle/foot tendons.

  Tsutomu Endo, Masahiko Takahata, Yoshinao Koike, Ryo Fujita, Daisuke Yoneoka, Masahiro Kanayama, Ken Kadoya, Tomoka Hasegawa, Mohamad Alaa Terkawi, Katsuhisa Yamada, Hideki Sudo, Taku Ebata, Misaki Ishii, Norimasa Iwasaki

  Journal of bone and mineral metabolism 2024/06/08 

  INTRODUCTION: Systemic osteogenesis has been speculated to be involved in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL). Our purpose was to compare the radiologic prevalence and severity of heterotopic ossification in foot tendons of Japanese patients with OPLL and to determine their association with systemic heterotopic ossification. MATERIALS AND METHODS: Clinical and radiographic data of 114 patients with OPLL were collected from 2020 to 2022. Control data were extracted from a medical database of 362 patients with ankle radiographs. Achilles and plantar tendon ossification were classified as grades 0-4, and the presence of osteophytes at five sites in the foot/ankle joint was assessed by radiography. Factors associated with the presence and severity of each ossification were evaluated by multivariable logistic regression and linear regression analysis. RESULTS: The prevalence of Achilles and plantar tendon ossification (grade ≥ 2) was 4.0-5.5 times higher in patients with OPLL (40-56%) than in the controls (10-11%). The presence of Achilles tendon ossification was associated with OPLL, age, and coexisting plantar tendon ossification, and was most strongly associated with OPLL (standardized regression coefficient, 0.79; 95% confidence interval, 1.34-2.38). The severity of Achilles and plantar tendon ossification was associated with the severity of ossification of the entire spinal ligament. CONCLUSIONS: The strong association of foot tendon ossification with OPLL suggests that patients with OPLL have a systemic osteogenesis background. These findings will provide a basis for exploring new treatment strategies for OPLL, including control of metabolic abnormalities.
• Bone Marrow Aspirate Concentrate Combined with Ultra-Purified Alginate Bioresorbable Gel Enhances Intervertebral Disc Repair in a Canine Model: A Preclinical Proof-of-Concept Study.

  Daisuke Ukeba, Yoko Ishikawa, Katsuhisa Yamada, Takashi Ohnishi, Hiroyuki Tachi, Khin Khin Tha, Norimasa Iwasaki, Hideki Sudo

  Cells 13 (11) 2024/06/05 

  Although discectomy is commonly performed for lumbar intervertebral disc (IVD) herniation, the capacity for tissue repair after surgery is limited, resulting in residual lower back pain, recurrence of IVD herniation, and progression of IVD degeneration. Cell-based therapies, as one-step procedures, are desirable for enhancing IVD repair. This study aimed to investigate the therapeutic efficacy of a combination of newly developed ultra-purified alginate (UPAL) gel and bone marrow aspirate concentrate (BMAC) implantation for IVD repair after discectomy. Prior to an in vivo study, the cell concentration abilities of three commercially available preparation kits for creating the BMAC were compared by measuring the number of bone marrow mesenchymal stem cells harvested from the bone marrow of rabbits. Subsequently, canine-derived BMAC was tested in a canine model using a kit which had the highest concentration rate. At 24 weeks after implantation, we evaluated the changes in the magnetic resonance imaging (MRI) signals as well as histological degeneration grade and immunohistochemical analysis results for type II and type I collagen-positive cells in the treated IVDs. In all quantitative evaluations, such as MRI and histological and immunohistochemical analyses of IVD degeneration, BMAC-UPAL implantation significantly suppressed the progression of IVD degeneration compared to discectomy and UPAL alone. This preclinical proof-of-concept study demonstrated the potential efficacy of BMAC-UPAL gel as a therapeutic strategy for implementation after discectomy, which was superior to UPAL and discectomy alone in terms of tissue repair and regenerative potential.
• Elucidation of the association between additional distal femoral resection and extension angle improvement following the actual surgical steps with the Robot-TKA system.

  Ryosuke Hishimura, Koji Iwasaki, Yuki Suzuki, Masatake Matsuoka, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki

  The Knee 49 36 - 44 2024/06/04 

  BACKGROUND: This study investigates the association between additional distal femoral resection and improved flexion contracture in total knee arthroplasty (TKA) with a robot-assisted system. Flexion contracture is a common issue in patients with knee osteoarthritis, which causes postoperative complications and functional limitations. This study aims to evaluate the effectiveness of additional bone resection in flexion contracture correction and knee extension angle improvement after the actual surgical steps. METHODS: The study included 11 patients who underwent posterior-stabilized (PS)-type TKA with a robot-assisted system. The surgical technique consisted of precise bone resection and range of motion evaluation using a navigation system. A precut technique was used to facilitate posterior access and remove osteophytes that cause the contracture. The amount of additional distal femoral resection was determined based on the thickness of the insert trial required for achieving full extension. RESULTS: The flexion contracture correction angle and the amount of additional distal femoral resection demonstrated a linear relationship. An average of 2.0° with the standard error (SE) of 0.6° improvement in flexion contracture was observed per 1.0 mm of additional bone resection. The postoperative evaluation demonstrated a significant improvement in knee extension angle, thereby reducing the contracture degree. CONCLUSION: This study was the first to perform the additional distal femoral resection on the living knee, which closely replicates the actual surgical steps. The current study revealed that an additional 1.0 mm of distal femoral resection in PS-type TKA improves knee extension angle by 2.0° (SE 0.6°) within an additional resection range of 1.0 mm to 3.3 mm.
• Analysis of foot-originating malignant bone tumors: Epidemiology, characteristics, and survival outcomes.

  Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Masanari Hamasaki, Taku Ebata, Yoshiaki Hosokawa, Ryuichi Fukuda, Eiji Kondo, Norimasa Iwasaki

  Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons 2024/05/29 

  BACKGROUND: The study examines the characteristics and outcomes of foot-originating malignant bone tumors via Surveillance Epidemiology and End Results (SEER) database analysis. METHODS: A retrospective review of 14,695 malignant bone tumor cases from 2000 to 2019 was conducted. RESULTS: Of the eligible cases, 147 (2.3 %) were foot-origin tumors, typically smaller and more commonly treated with surgery than those in other locations. These tumors were more frequently treated with surgical resection, with a higher proportion undergoing amputation. In contrast, foot-origin tumors were less often managed with chemotherapy and radiation. Foot-origin tumors exhibited higher survival rates compared to non-foot-origin tumors as shown in univariate analysis, although multivariate analysis did not reflect significant differences. CONCLUSION: Foot-originating malignant bone tumors tend to be smaller and are frequently surgically treated, correlating with favorable survival outcomes. These findings point to early detection as a potential factor in the improved survival rates, not necessarily the tumor's origin.
• A patient and public involvement study to explore patient perspectives on the efficacy of treatments for pain and numbness derived from ossification of posterior longitudinal ligament of the spine.

  Masahiko Takahata, Yasuko Masuda, Tsutomu Endo, Yoshinao Koike, Masashi Yamazaki, Hiroshi Taneichi, Masayuki Miyagi, Hiroshi Takahashi, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2024/05/28 

  BACKGROUND: Chronic pain and numbness are common complaints in patients with ossification of the posterior longitudinal ligament of the spine (OPLL). However, it is unclear whether the current treatments are effective in patients with OPLL in terms of improving pain and numbness. METHODS: A cross-sectional survey of patients with OPLL was conducted to determine patient satisfaction with surgery and drug therapy for pain and numbness, and its association with health-related quality of life. The survey was conducted by a patient association and its members, and anonymized data were analyzed by physicians. Comparisons between groups were made using T-tests or Kruskal-Wallis and Steel-Dwass tests, chi-square tests, and Fisher's exact tests. RESULTS: Data from 121 patients with OPLL (age 69 ± 11 years, 69 males; 43 females; and 7 unknown) who completed a mailed questionnaire were analyzed. Of the 93 patients with a history of surgery for OPLL, 24% and 18% reported much improvement in pain and numbness, respectively. After surgery, 42% and 48% reported some improvement, and 34% and 34% reported no improvement, respectively. Patients whose numbness did not improve with surgery had a significantly poorer health-related quality of life than those who did. Of the 78 patients who received medication, only 2% reported "much improvement," 64% reported "some improvement," and 31% reported "no improvement at all." Compared to patients with OPLL only in the cervical spine, those with diffuse-type OPLL showed poorer improvement in numbness after surgery and poorer quality of life. CONCLUSIONS: The majority of patients with OPLL belonging to the association were unsatisfied with surgery and pharmacotherapy in terms of pain and numbness improvement, indicating that there is an unmet medical need for more effective treatment for chronic pain and numbness in patients with OPLL.
• Itaconate reduces proliferation and migration of fibroblast-like synoviocytes and ameliorates arthritis models.

  Maria Tada, Yuki Kudo, Michihito Kono, Masatoshi Kanda, Shuhei Takeyama, Kodai Sakiyama, Hotaka Ishizu, Tomohiro Shimizu, Tsutomu Endo, Ryo Hisada, Yuichiro Fujieda, Masaru Kato, Olga Amengual, Norimasa Iwasaki, Tatsuya Atsumi

  Clinical immunology (Orlando, Fla.) 264 110255 - 110255 2024/05/18 

  Fibroblast-like synoviocytes (FLS) play critical roles in rheumatoid arthritis (RA). Itaconate (ITA), an endogenous metabolite derived from the tricarboxylic acid (TCA) cycle, has attracted attention because of its anti-inflammatory, antiviral, and antimicrobial effects. This study evaluated the effect of ITA on FLS and its potential to treat RA. ITA significantly decreased FLS proliferation and migration in vitro, as well as mitochondrial oxidative phosphorylation and glycolysis measured by an extracellular flux analyzer. ITA accumulates metabolites including succinate and citrate in the TCA cycle. In rats with type II collagen-induced arthritis (CIA), intra-articular injection of ITA reduced arthritis and bone erosion. Irg1-deficient mice lacking the ability to produce ITA had more severe arthritis than control mice in the collagen antibody-induced arthritis. ITA ameliorated CIA by inhibiting FLS proliferation and migration. Thus, ITA may be a novel therapeutic agent for RA.
• DAP12/TREM2 signalはRANKL中和抗体中止後の過剰な骨吸収に影響を及ぼす

  石津 帆高, 清水 智弘, 長谷川 智香, 網塚 憲生, 岩崎 倫政

  日本骨形態計測学会雑誌 日本骨形態計測学会 34 (1) 117 - 117 0917-4648 2024/05
• DXAにおいて影響を及ぼし得る体内アーチファクトに対するREMSの有用性検討

  石津 帆高, 清水 智弘, 北原 圭太, 高山 寛己, 宮本 守孝, 岩崎 倫政

  日本骨形態計測学会雑誌 日本骨形態計測学会 34 (1) 129 - 129 0917-4648 2024/05
• Effect of urgent surgery within 8 hours compared to surgery between 8 and 24 hours on perioperative complications and neurological prognosis in patients older than 70 years with cervical spinal cord injury: a propensity score-matched analysis.

  Tomoaki Shimizu, Kota Suda, Satoko Matsumoto Harmon, Miki Komatsu, Masahiro Ota, Hiroki Ushirozako, Kento Inomata, Akio Minami, Katsuhisa Yamada, Tsutomu Endo, Masahiko Takahata, Norimasa Iwasaki, Hiroshi Takahashi, Masao Koda, Masashi Yamazaki

  Journal of neurosurgery. Spine 40 (5) 642 - 652 2024/05/01 

  OBJECTIVE: This study aimed to investigate the effect of surgery within 8 hours on perioperative complications and neurological prognosis in older patients with cervical spinal cord injury by using a propensity score-matched analysis. METHODS: The authors included 87 consecutive patients older than 70 years who had cervical spinal cord injury and who had undergone posterior decompression and fusion surgery within 24 hours of injury. The patients were divided into two groups based on the time from injury to surgery: surgery within 8 hours (group 8 hours) and between 8 and 24 hours (group 8-24 hours). Following the preliminary study, the authors established a 1:1 matched model using propensity scores to adjust for baseline characteristics and neurological status on admission. Perioperative complication rates and neurological outcomes at discharge were compared between the two groups. RESULTS: Preliminary analysis of 87 prematched patients (39 in group 8 hours and 48 in group 8-24 hours) revealed that the motor index score (MIS) on admission was lower for lower extremities (12.3 ± 15.5 vs 20.0 ± 18.6, respectively; p = 0.048), and total extremities (26.7 ± 27.1 vs 40.2 ± 30.6, respectively; p = 0.035) in group 8 hours. In terms of perioperative complications, group 8 hours had significantly higher rates of cardiopulmonary dysfunction (46.2% vs 25.0%, respectively; p = 0.039). MIS improvement (the difference in scores between admission and discharge) was greater in group 8 hours for lower extremities (15.8 ± 12.6 vs 9.0 ± 10.5, respectively; p = 0.009) and total extremities (29.4 ± 21.7 vs 18.7 ± 17.7, respectively; p = 0.016). Using a 1:1 propensity score-matched analysis, 29 patient pairs from group 8 hours and group 8-24 hours were selected. There were no significant differences in baseline characteristics, neurological status on admission, and perioperative complications between the two groups, including cardiopulmonary dysfunction. Even after matching, MIS improvement was significantly greater in group 8 hours for upper extremities (13.0 ± 10.9 vs 7.8 ± 8.3, respectively; p = 0.045), lower extremities (14.8 ± 12.7 vs 8.3 ± 11.0, respectively; p = 0.044) and total extremities (27.8 ± 21.0 vs 16.0 ± 17.5, respectively; p = 0.026). CONCLUSIONS: Results of the comparison after matching demonstrated that urgent surgery within 8 hours did not increase the perioperative complication rate and significantly improved the MIS, suggesting that surgery within 8 hours may be efficient, even in older patients.
• Glycosphingolipids in Osteoarthritis and Cartilage-Regeneration Therapy: Mechanisms and Therapeutic Prospects Based on a Narrative Review of the Literature.

  Kentaro Homan, Tomohiro Onodera, Masatake Matsuoka, Norimasa Iwasaki

  International journal of molecular sciences 25 (9) 2024/04/30 

  Glycosphingolipids (GSLs), a subtype of glycolipids containing sphingosine, are critical components of vertebrate plasma membranes, playing a pivotal role in cellular signaling and interactions. In human articular cartilage in osteoarthritis (OA), GSL expression is known notably to decrease. This review focuses on the roles of gangliosides, a specific type of GSL, in cartilage degeneration and regeneration, emphasizing their regulatory function in signal transduction. The expression of gangliosides, whether endogenous or augmented exogenously, is regulated at the enzymatic level, targeting specific glycosyltransferases. This regulation has significant implications for the composition of cell-surface gangliosides and their impact on signal transduction in chondrocytes and progenitor cells. Different levels of ganglioside expression can influence signaling pathways in various ways, potentially affecting cell properties, including malignancy. Moreover, gene manipulations against gangliosides have been shown to regulate cartilage metabolisms and chondrocyte differentiation in vivo and in vitro. This review highlights the potential of targeting gangliosides in the development of therapeutic strategies for osteoarthritis and cartilage injury and addresses promising directions for future research and treatment.
• The alterations in nerve growth factor concentration in plasma and synovial fluid before and after total knee arthroplasty.

  Tomohiro Onodera, Koji Iwasaki, Masatake Matsuoka, Yasuhide Morioka, Shinji Matsubara, Eiji Kondo, Norimasa Iwasaki

  Scientific reports 14 (1) 8943 - 8943 2024/04/18 

  Total knee arthroplasty (TKA) is an effective procedure for pain relief; however, the emergence of postsurgical pain remains a concern. In this study, we investigated the production of nerve growth factor (NGF) and mediators that affect NGF production and their function in the synovial fluid and plasma after TKA. This study included 19 patients (20 knees) who had rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and knee osteoarthritis (OA) who underwent TKA, categorized into OA and non-OA groups. The levels of NGF, inflammatory cytokines, and lipid mediators were analyzed before and after surgery. The intraoperative synovial fluid NGF concentration was more than seven times higher in the non-OA group than in the OA group. The intra-articular NGF levels increased significantly by more than threefold postoperatively in the OA group but not in the non-OA group. Moreover, the levels of inflammatory cytokines and lipid mediators were increased in the synovial fluid of both groups. The intra-articular cytokines or NGF concentrations positively correlated with postoperative pain. Targeted NGF control has the potential to alleviate postsurgical pain in TKA, especially in patients with OA, emphasizing the importance of understanding NGF dynamics under different knee conditions.
• Clinical outcomes of perforator-based propeller flaps versus free flaps in soft tissue reconstruction for lower leg and foot trauma: a retrospective single-centre comparative study.

  Mitsutoshi Ota, Makoto Motomiya, Naoya Watanabe, Kohei Shimoda, Norimasa Iwasaki

  BMC musculoskeletal disorders 25 (1) 297 - 297 2024/04/16 

  BACKGROUND: The efficacy and safety of perforator-based propeller flaps (PPF) versus free flaps (FF) in traumatic lower leg and foot reconstructions are debated. PPFs are perceived as simpler due to advantages like avoiding microsurgery, but concerns about complications, such as flap congestion and necrosis, persist. This study aimed to compare outcomes of PPF and FF in trauma-related distal lower extremity soft tissue reconstruction. METHODS: We retrospectively studied 38 flaps in 33 patients who underwent lower leg and foot soft tissue reconstruction due to trauma at our hospital from 2015 until 2022. Flap-related outcomes and complications were compared between the PPF group (18 flaps in 15 patients) and the FF group (20 flaps in 18 patients). These included complete and partial flap necrosis, venous congestion, delayed osteomyelitis, and the coverage failure rate, defined as the need for secondary flaps due to flap necrosis. RESULTS: The coverage failure rate was 22% in the PPF group and 5% in the FF group, with complete necrosis observed in 11% of the PPF group and 5% of the FF group, and partial necrosis in 39% of the PPF group and 10% of the FF group, indicating no significant difference between the two groups. However, venous congestion was significantly higher in 72% of the PPF group compared to 10% of the FF group. Four PPFs and one FF required FF reconstruction due to implant/fracture exposure from necrosis. Additionally, four PPFs developed delayed osteomyelitis post-healing, requiring reconstruction using free vascularized bone graft in three out of four cases. CONCLUSIONS: Flap necrosis in traumatic lower-leg defects can lead to reconstructive failure, exposing implants or fractures and potentially causing catastrophic outcomes like osteomyelitis, jeopardizing limb salvage. Surgeons should be cautious about deeming PPFs as straightforward and microsurgery-free procedures, given the increased complication rates compared to FFs in traumatic reconstruction. DATA ACCESS STATEMENT: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
• Author Correction: Effect of longer femoral head on leg length, offset, and range of motion in total hip arthroplasty: a simulation study.

  Tomohiro Shimizu, Takuji Miyazaki, Shunichi Yokota, Hotaka Ishizu, Daisuke Takahashi, Norimasa Iwasaki

  Scientific reports 14 (1) 8481 - 8481 2024/04/11
• Osteoporosis, Osteoarthritis, and Subchondral Insufficiency Fracture: Recent Insights.

  Shunichi Yokota, Hotaka Ishizu, Takuji Miyazaki, Daisuke Takahashi, Norimasa Iwasaki, Tomohiro Shimizu

  Biomedicines 12 (4) 2024/04/11 

  The increased incidence of osteoarthritis (OA), particularly knee and hip OA, and osteoporosis (OP), owing to population aging, have escalated the medical expense burden. Osteoarthritis is more prevalent in older women, and the involvement of subchondral bone fragility spotlights its association with OP. Notably, subchondral insufficiency fracture (SIF) may represent a more pronounced condition of OA pathophysiology. This review summarizes the relationship between OA and OP, incorporating recent insights into SIF. Progressive SIF leads to joint collapse and secondary OA and is associated with OP. Furthermore, the thinning and fragility of subchondral bone in early-stage OA suggest that SIF may be a subtype of OA (osteoporosis-related OA, OPOA) characterized by significant subchondral bone damage. The high bone mineral density observed in OA may be overestimated due to osteophytes and sclerosis and can potentially contribute to OPOA. The incidence of OPOA is expected to increase along with population aging. Therefore, prioritizing OP screening, early interventions for patients with early-stage OA, and fracture prevention measures such as rehabilitation, fracture liaison services, nutritional management, and medication guidance are essential.
• Clinical Outcomes of Total Wrist Arthroplasty in Patients With Rheumatoid Arthritis: Minimum 10-Year Follow-Up Study.

  Yuichiro Matsui, Akio Minami, Makoto Kondo, Jyunichi Ishikawa, Makoto Motomiya, Daisuke Kawamura, Norimasa Iwasaki

  The Journal of hand surgery 2024/04/09 

  PURPOSE: We developed a semiconstrained total wrist prosthesis that was used in a series of patients with rheumatoid arthritis. We previously reported favorable clinical outcomes for up to 5 years after surgery; however, the longer-term outcomes remain unclear. The objective of this study was to evaluate the clinical outcomes of this wrist prosthesis for the treatment of severe wrist rheumatoid arthritis during a minimum 10 years of follow-up. METHODS: From 2010 through 2012, total wrist arthroplasty using the semiconstrained total wrist arthroplasty device was performed in 20 wrists in 20 patients with rheumatoid arthritis (five men and 15 women). The mean patient age was 64 years (range, 50-84 years). Preoperative radiographs showed Larsen grade IV changes in 16 wrists and grade V changes in four wrists. Patients were evaluated clinically and radiologically before surgery, 5 years after surgery, and 10 years or more after surgery. Evaluated parameters were the visual analog scale for pain, range of motion, Figgie score, and Disabilities of the Arm, Shoulder, and Hand score. RESULTS: The minimum 10-year follow-up clinical results (mean, 11.3 years) were available for all 14 surviving patients (three men and 11 women). Significant improvements in the mean visual analog scale for pain, Figgie score, and Disabilities of the Arm, Shoulder, and Hand score, compared with those before surgery, were maintained from 5 years after surgery to the final follow-up. The mean wrist flexion angle tended to slightly decrease at 5 years after surgery compared with that before surgery but remained similar from 5 years after surgery to the final follow-up. The increase in the mean wrist extension angle, compared with that before surgery, was maintained from 5 years after surgery to the final follow-up. Radiographic evaluation had already revealed implant loosening in five of the 19 wrists at 5 years after surgery, but there were no new cases of component loosening identified at the final follow-up. CONCLUSIONS: Total wrist arthroplasty using the semiconstrained arthroplasty system achieves favorable clinical outcomes with no serious complications requiring revision for 10 years after surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
• Surgical Resection of Primary Tumor for Bone Metastatic Breast Cancer Patients at Initial Presentation.

  Nayu Kitsuya, Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Yuki Suzuki, Masanari Hamasaki, Eiji Kondo, Norimasa Iwasaki

  Anticancer research 44 (4) 1591 - 1601 2024/04 

  BACKGROUND/AIM: The purpose of this study was to investigate whether primary tumor resection in patients with bone metastatic breast cancer has an impact on survival using the Surveillance, Epidemiology, and End Results database, considering subtype classification. PATIENTS AND METHODS: We included all female patients with bone metastatic breast cancer at initial presentation between 2010 and 2016 with known hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) statuses. Cases showing unknown cause of death or unknown HR/HER2 status were excluded. Survival analysis was performed using Cox proportional hazards modeling to calculate hazard ratios (HZR). RESULTS: Of the 13,450 patients included in this study, 2,073 patients were HR+/HER2+, 8,597 patients were HR+/HER2-, 797 patients were HR-/HER2+, and 1,182 patients were HR-/HER2- (triple-negative). Five-year overall survival (OS) rate was 34.5% in HR+/HER2+, 26.0% in HR+/HER2-, 29.2% in HR-/HER2+ and 8.0% in triple-negative. Triple-negative patients showed the worsen OS [HR+/HER2+: HZR=2.1, 95% confidence interval (CI)=1.9-2.3; HR+/HER2-: HZR= 2.4, 95%CI=2.2-2.6; HR-/HER2+: HZR=1.5, 95%CI=1.3-1.6]. After excluding patients who died within six months, primary tumor resection prolonged survival in each subtype classification except HR-/HER2+. CONCLUSION: Patients with triple-negative bone metastatic breast cancer showed unfavorable survival. Primary tumor resection prolonged survival in each subtype except for HR-/HER2+.
• Bone Density Distribution Pattern in the Lateral Wall of the Femoral Intercondylar Notch: Implications for the Direct Insertion of the Femoral ACL Attachment.

  Yutaro Sugawara, Koji Iwasaki, Yuki Suzuki, Ryosuke Hishimura, Shinji Matsubara, Masatake Matsuoka, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki

  Orthopaedic journal of sports medicine 12 (4) 23259671241236807 - 23259671241236807 2024/04 

  BACKGROUND: The ideal position of the femoral bone tunnel in the anterior cruciate ligament (ACL) is controversial. The functional importance of the ACL fiber varies depending on where it is attached to the femur. Functionally important fibers can cause high mechanical stress on the bone, and the Wolff law predicts that bone mineral density will increase at high mechanical stress sites. PURPOSE/HYPOTHESIS: The purpose of this study was to use computed tomography imaging to determine the distribution pattern of bone density in the lateral intercondylar wall. It was hypothesized that the high-density area (HDA) of the lateral intercondylar wall would reflect the functional insertion of the ACL as reported in previous anatomic studies. STUDY DESIGN: Descriptive epidemiology study. METHODS: Data from 39 knees without ACL injuries were retrospectively collected. The HDA of the lateral intercondylar wall was defined as the region containing the top 10% of the radiodensity values. The shape of the HDA was approximated as an ellipse, and the quadrant method was used to determine the center of the ellipse. The association between the ratio of the minor axis to the major axis of the ellipse and background characteristics was investigated. RESULTS: According to the quadrant method, the center of the HDA ellipse was 33.6% in the deep-shallow direction and 23.4% in the high-low direction. The center of the ellipse was comparable to the anatomic center of the ACL footprint, as previously reported. The ratio of the minor axis to the major axis of the ellipse was 0.58 (95% CI, 0.54-0.62). There was a significant negative correlation between the ratio of the minor axis to the major axis of the HDA ellipse and the posterior tibial slope (r = -0.38, P = .02). CONCLUSION: The center of the HDA ellipse was found to be similar to the anatomic center of the ACL footprint. Considering the mechanical stress responses in bone, the HDA of the lateral intercondylar wall has the potential to represent the ACL insertion, especially functional insertion.
• Articular cartilage corefucosylation regulates tissue resilience in osteoarthritis.

  Kentaro Homan, Tomohiro Onodera, Hisatoshi Hanamatsu, Jun-Ichi Furukawa, Daisuke Momma, Masatake Matsuoka, Norimasa Iwasaki

  eLife 12 2024/03/11 

  This study aimed to investigate the glycan structural changes that occur before histological degeneration in osteoarthritis (OA) and to determine the mechanism by which these glycan conformational changes affect cartilage degeneration. An OA model was established in rabbits using mannosidase injection, which reduced high-mannose type N-glycans and led to cartilage degeneration. Further analysis of glycome in human OA cartilage identified specific corefucosylated N-glycan expression patterns. Inhibition of N-glycan corefucosylation in mice resulted in unrecoverable cartilage degeneration, while cartilage-specific blocking of corefucosylation led to accelerated development of aging-associated and instability-induced OA models. We conclude that α1,6 fucosyltransferase is required postnatally to prevent preosteoarthritic deterioration of articular cartilage. These findings provide a novel definition of early OA and identify glyco-phenotypes of OA cartilage, which may distinguish individuals at higher risk of progression.
• 大腿骨近位部骨折患者における重症骨粗鬆症の有病率 3年間322症例の解析から

  浅野 毅, 芝山 浩樹, 有田 皓介, 伊藤 華奈子, 泉 泰純, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (2) S105 - S105 0021-5325 2024/03
• 偏心性寛骨臼回転骨切り術の膝関節への荷重負荷に与える影響

  小川 裕生, 清水 智弘, 横田 隼一, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (2) S170 - S170 0021-5325 2024/03
• 大腿骨転子間彎曲内反骨切り術(CVO)後の骨頭圧潰に対するテリパラチド投与の有効性

  横田 隼一, 清水 智弘, 石津 帆高, 菅原 悠太郎, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (2) S217 - S217 0021-5325 2024/03
• 臼蓋骨欠損に対して塊状骨移植併用KT plateとIBG併用metal meshを用いた人工股関節再置換術の術後成績の比較検討

  石津 帆高, 清水 智弘, 笹沢 史生, 金山 雅弘, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (2) S357 - S357 0021-5325 2024/03
• 大動脈弁狭窄症を有する大腿骨近位部骨折の周術期合併症の検討

  石田 健太, 下段 俊, 久田 雄一郎, 沼口 京介, 高橋 練也, 佐藤 知哉, 梅本 貴央, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (2) S362 - S362 0021-5325 2024/03
• DXA法と比較した超音波骨密度測定装置EchoSシステムの有用性検討

  石津 帆高, 清水 智弘, 北原 圭太, 高山 寛己, 宮本 守孝, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (3) S835 - S835 0021-5325 2024/03
• DAP12/TREM2シグナルはRANKL中和抗体中止後の過剰な骨吸収に影響を及ぼす

  石津 帆高, 清水 智弘, 山本 知真也, 長谷川 智香, 網塚 憲生, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (3) S840 - S840 0021-5325 2024/03
• 当院における発育性股関節形成不全検診時のアンケート調査と装具療法の関連

  小川 拓也, 清水 智弘, 大上 哲郎, 横田 隼一, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (3) S931 - S931 0021-5325 2024/03
• 発育性股関節形成不全(DDH)ハイリスク児の歩行開始後のDDH罹患率

  大橋 佑介, 清水 智弘, 小川 拓也, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (3) S932 - S932 0021-5325 2024/03
• リーメンビューゲル治療後に補正手術を要した症例の検討

  小川 拓也, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (3) S933 - S933 0021-5325 2024/03
• THAにおいて,脚長差とoffsetが臨床成績に与える影響

  姜 博文, 宮崎 拓自, 清水 智弘, 高橋 要, 金山 雅弘, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (3) S1012 - S1012 0021-5325 2024/03
• 重症骨粗鬆症を背景に持つ大腿骨近位部骨折患者の二次骨折,死亡リスク 多施設共同前向き研究

  石津 帆高, 清水 智弘, 有田 皓介, 佐藤 恒明, 高橋 練也, 楠 兼一, 下段 俊, 浅野 毅, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (3) S1317 - S1317 0021-5325 2024/03
• 大腿骨近位部骨折リエゾンサービスにおける真の骨粗鬆症治療継続率と継続率向上の可能性の検証

  下段 俊, 梅本 貴央, 久田 雄一郎, 沼口 京介, 高橋 練也, 石田 健太, 佐藤 知哉, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (3) S1363 - S1363 0021-5325 2024/03
• 遠隔転移を有する原発性悪性骨腫瘍において原発巣切除は生存を改善するか? 米国SEERデータベースを用いた研究

  福田 龍一, 松岡 正剛, 小野寺 智洋, 岩崎 浩司, 江畑 拓, 濱崎 雅成, 近藤 英司, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (2) S94 - S94 0021-5325 2024/03
• 内側型変形性膝関節症および膝蓋大腿関節症に対する組み合わせ式二顆置換術(BiKA)の術後10年成績

  馬場 力哉, 大越 康充, 前田 龍智, 岩館 茜, 岩崎 浩司, 小野寺 智洋, 近藤 英司, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (2) S168 - S168 0021-5325 2024/03
• 農業従事者における変形性膝関節症に対する手術加療の短期成績 膝周囲骨切り術と人工膝関節全置換術の比較

  上徳 善太, 横山 慎, 小林 悠人, 下田 康平, 福井 隆史, 太田 光俊, 本宮 真, 安井 啓悟, 小野寺 智洋, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (2) S190 - S190 0021-5325 2024/03
• 足部に発生した原発性悪性骨腫瘍の生存解析 SEER databaseを用いた研究

  松岡 正剛, 小野寺 智洋, 岩崎 浩司, 濱崎 雅成, 江畑 拓, 近藤 英司, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (2) S277 - S277 0021-5325 2024/03
• 脛骨関節面の骨密度分布に半月板逸脱と下肢アライメントが与える影響

  佐藤 知哉, 岩崎 浩司, 濱崎 雅成, 鈴木 裕貴, 松岡 正剛, 小野寺 智洋, 近藤 英司, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (2) S399 - S399 0021-5325 2024/03
• 80歳以上高齢者に発生した四肢発生軟部肉腫における放射線照射

  松岡 正剛, 小野寺 智洋, 岩崎 浩司, 濱崎 雅成, 江畑 拓, 近藤 英司, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (2) S415 - S415 0021-5325 2024/03
• 女性乳がんサブタイプ分類が骨転移症例における生存へ与える影響 米国SEERデータベースを用いた研究

  松岡 正剛, 木津谷 菜悠, 小野寺 智洋, 横田 勲, 岩崎 浩司, 濱崎 雅成, 江畑 拓, 近藤 英司, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (2) S417 - S417 0021-5325 2024/03
• コラーゲン膜を用いた自家培養軟骨移植の臨床成績 骨膜被覆との比較

  甲斐原 拓真, 近藤 英司, 濱崎 雅成, 江畑 拓, 原 健人, 岩崎 浩司, 松岡 正剛, 小野寺 智洋, 門間 太輔, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 98 (2) S448 - S448 0021-5325 2024/03
• 外反膝に対して行った内側閉鎖式大腿骨遠位内反骨切り術の成績と膝蓋大腿関節のバイオメカニクスに与える影響

  濱崎 雅成, 松岡 正剛, 岩崎 浩司, 鈴木 裕貴, 小野寺 智洋, 岩崎 倫政, 近藤 英司, 井上 雅之, 八木 知徳, 安田 和則

  日本関節病学会誌 (一社)日本関節病学会 43 (1) 63 - 71 1883-2873 2024/03
• The Influence of Patello-Femoral Overstuffing After Modular Unlinked Bicompartmental Knee Arthroplasty (BiKA) for Medial Tibio-Femoral and Patello-Femoral Osteoarthritis of the Knee.

  Rikiya Baba, Yasumitsu Ohkoshi, Tatsunori Maeda, Ko Suzuki, Akane Iwadate, Koji Iwasaki, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki

  The Journal of arthroplasty 39 (3) 638 - 644 2024/03 

  BACKGROUND: The factors affecting results after bicompartmental knee arthroplasty (BiKA) have not been fully elucidated. This major ligament-preserving procedure may be more susceptible to overstuffing of the patello-femoral (PF) joint than the major ligament-sacrificing total knee arthroplasty. Currently, we investigated the effect of PF overstuffing after BiKA on its clinical outcome. METHODS: There were 71 patients (74 knees) who underwent modular unlinked BiKA at our clinic who had a follow-up of 5 to 9 years. Final follow-up results were assessed by evaluating knee range of motion, the 2011 Knee Society Score (2011KSS), Japanese Knee Osteoarthritis Measure, and radiological findings. The degree of postoperative PF overstuffing was evaluated by computed tomography and magnetic resonance images for 55 knees, and the correlation between the degree of overstuffing and postoperative clinical results were examined. RESULTS: Overall clinical results improved significantly after surgery without any revision cases. The X-ray measurements showed the improved coronal alignments and the appropriate implant installation angles. Higher degree of postoperative PF overstuffing caused by insufficient amount of osteotomy on the anterior surface of the femur correlated with worse postoperative total 2011KSS at 2 years after surgery (Spearman's rank correlation coefficient (rs) = -0.387, P = .004), as opposed to no correlation at the time of the final follow-up (Spearman's rank correlation coefficient = 0.068, P = .623). CONCLUSION: Modular unlinked BiKA provided patients with a high level of satisfaction and functional improvement over 5 to 9 years postoperatively. However, because PF overstuffing affects initial patient satisfaction, the amount of osteotomy should be determined carefully during the surgery.
• Simultaneous medial closing wedge distal femoral varus osteotomy and double-bundle anterior cruciate ligament reconstruction in the symptomatic femoral valgus deformity: A case report.

  Masatake Matsuoka, Eiji Kondo, Koji Iwasaki, Tomohiro Onodera, Ryuichi Nakamura, Hiroshi Nakayama, Takenori Akiyama, Daisuke Momma, Norimasa Iwasaki

  Joint diseases and related surgery 35 (2) 422 - 432 2024/02/13 

  Distal femoral varus osteotomy (DFVO) is a widely recognized surgical procedure used to address valgus malalignment in patients with knee joint disorders. However, it still remains unclear whether anterior cruciate ligament (ACL) reconstruction can be performed in a single procedure along with DFVO. Herein, we present a 73-year-old female patient who developed lateral osteoarthritis of the knee with valgus alignment due to chronic ACL deficiency following a twisting injury during skiing. She was physiologically very active, and strongly demanded to return to sports. We performed a combined procedure involving a medial closing wedge DFVO using an anatomical locking plate, along with double-bundle ACL reconstruction. The postoperative radiograph confirmed successful correction of knee alignment, specifically achieving varus alignment with precise conformance of the anatomical plate to the medial contour of the distal femur following the osteotomy. The patient resumed her previous sports activities without experiencing knee pain. The operated knee demonstrated restored anterior stability, as indicated by negative Lachman test results, and regained full range of motion. Both the Knee Injury and Osteoarthritis Outcome Score and the 2011 Knee Society score demonstrated continuous postoperative improvements over the three-year follow-up period, indicating positive functional outcomes and joint preservation. To the best of our knowledge, this is the first case of medial closing wedge DFVO with anatomic double-bundle ACL reconstruction in the symptomatic femoral valgus deformity with chronic ACL deficiency in the literature.
• Zinc improves Denosumab and eldecalcitol efficacy for bone mineral density in patients with hypozincemia.

  Hotaka Ishizu, Tomohiro Shimizu, Yusuke Ohashi, Kenichi Kusunoki, Masahiro Kanayama, Norimasa Iwasaki, Fumihiro Oha

  Journal of bone and mineral metabolism 42 (2) 233 - 241 2024/02/07 

  INTRODUCTION: We aimed to investigate the effects of zinc deficiency and zinc medication in osteoporosis patients undergoing denosumab (DMAb). MATERIALS AND METHODS: This retrospective study was conducted at a single hospital. The participants were female osteoporosis patients visiting between April 2019 and April 2020. All patients were treated with DMAb and eldecalcitol and recommended zinc-rich food. Based on zinc medication and serum zinc levels at the 12th month of dietary guidance, patients were categorized into the following four groups: hypozincemia with zinc medication, latent zinc deficiency with zinc medication, without zinc medication, and control without zinc medication. Longitudinal serum zinc concentrations, bone mineral density (BMD), and occurrence of fractures were measured. We investigated the factors influencing no response to DMAb and eldecalcitol treatment. RESULTS: Among the 145 patients followed up for 24 months, dietary guidance did not change the serum zinc concentration; however, zinc medication significantly increased these levels. The hypozincemia group did not show a significant BMD increase in the lumbar spine and femoral neck after DMAb and eldecalcitol treatment during dietary guidance; however, zinc medication increased these to the same levels as the other groups. In multivariate analyses, hypozincemia and thyroid disease were identified as the factors affecting no response. While 28.2% of patients with latent zinc deficiency without zinc medication suffered fractures, no fractures occurred in hypozincemia patients with zinc medication. CONCLUSION: Hypozincemia may reduce the efficacy of DMAb and eldecalcitol in increasing BMD and fracture prevention.
• Secondary fracture and mortality risk with very high fracture risk osteoporosis and proximal femoral fracture.

  Hotaka Ishizu, Tomohiro Shimizu, Kosuke Arita, Komei Sato, Renya Takahashi, Kenichi Kusunoki, Shun Shimodan, Tsuyoshi Asano, Norimasa Iwasaki

  Journal of bone and mineral metabolism 42 (2) 196 - 206 2024/02/03 

  INTRODUCTION: We aimed to investigate secondary fracture and mortality rates, and risk factors in patients with proximal femoral fractures. MATERIALS AND METHODS: We conducted a multicenter prospective cohort study on female patients with proximal femoral fractures who underwent surgical treatment between April 2020 and March 2021. Postoperative follow-ups were performed at 6-, 12-, 18-, and 24-month intervals to determine the secondary fracture and mortality rates, and the risk factors and its influence were examined. RESULTS: Of the 279 registered patients, 144 patients (51.6%) were diagnosed with very high fracture risk osteoporosis. The postoperative osteoporosis rate exceeded 96%; however, osteoanabolic agents were used sparingly. The risk factor of both secondary fracture and mortality was very high fracture risk osteoporosis, and secondary fractures within 12 months were markedly occurred. Secondary fracture rates increased as the number of matched very high fracture risk osteoporosis criteria increased. Notably, secondary fractures and mortality were recorded in 21.4% and 23.5% of the patients who met all criteria, respectively. CONCLUSION: Over half of the female patients with proximal femoral fractures had very high fracture risk osteoporosis. Although, very high fracture risk osteoporosis demonstrated a notably increased risk of secondary fractures, particularly at 12 months post-surgery, the use of osteoanabolic agents was substantially low. Collectively, our findings highlight the need to consider the risk of very high fracture risk osteoporosis, expand the use of medications to include osteoanabolic agents, and reconsider the current healthcare approach for proximal femoral fractures.
• Effect of longer femoral head on leg length, offset, and range of motion in total hip arthroplasty: a simulation study.

  Tomohiro Shimizu, Takuji Miyazaki, Shunichi Yokota, Hotaka Ishizu, Daisuke Takahashi, Norimasa Iwasaki

  Scientific reports 14 (1) 1829 - 1829 2024/01/21 

  In this study, we investigated the relationship between head length, leg length, offset, and dislocation resistance using range of motion (ROM) simulations based on computed tomography data to examine if a longer femoral head reduces the risk of dislocation. The femoral components were set to eliminate leg length differences with a + 0 mm head, and variations for + 4-, + 7-, and + 8-mm heads were analyzed. Offset and ROM were assessed when longer heads were used, with the leg length adjusted to be similar to that of the contralateral side. While internal rotation at flexion and external rotation at extension increased with + 4-mm longer heads, the + 7- and + 8-mm heads did not increase dislocation resistance. When adjusting for leg length, the longer heads showed no significant differences in offset and ROM. Enhancing dislocation resistance by solely increasing the offset with a longer head, while simultaneously adjusting the depth of stem insertion, may be a beneficial intraoperative technique. Although a + 4-mm longer head possibly increases ROM without impingement, heads extended by + 7 or + 8 mm may not exhibit the same advantage. Therefore, surgeons should consider this technique based on the implant design.
• Methylprednisolone pulse-enhanced neutrophil extracellular trap formation in mice with imiquimod-induced lupus-like disease, resulting in ischaemia of the femoral head cartilage.

  Hodaka Ogawa, Shunichi Yokota, Yumeka Hosoi, Ayano Shindo, Naho Ogawa, Ryodai Yamamura, Tomohiro Shimizu, Issei Nakade, Suishin Arai, Mai Taniguchi, Yuka Nishibata, Sakiko Masuda, Daigo Nakazawa, Utano Tomaru, Norimasa Iwasaki, Akihiro Ishizu

  Lupus science & medicine 10 (2) 2023/12/28 

  OBJECTIVES: Methylprednisolone (mPSL) pulse therapy is an essential option for patients with active systemic lupus erythematosus, but there is a risk of adverse events related to microcirculation disorders, including idiopathic osteonecrosis of the femoral head (ONFH). Recent studies have revealed that excessive neutrophil extracellular traps (NETs) are involved in microcirculation disorders. This study aimed to demonstrate that mPSL pulse could induce NETs in lupus mice and identify the factors contributing to this induction. METHODS: Six mice with imiquimod (IMQ)-induced lupus-like disease and six normal mice were intraperitoneally injected with mPSL on days 39 to 41, and five mice with IMQ-induced lupus-like disease and six normal mice were injected with phosphate-buffered saline. Pathological examinations were conducted to evaluate the ischaemic state of the femoral head and tissue infiltration of NET-forming neutrophils. Proteome analysis was performed to extract plasma proteins specifically elevated in mPSL-administered mice with IMQ-induced lupus-like disease, and their effects on NET formation were assessed in vitro. RESULTS: Mice with IMQ-induced lupus-like disease that received mPSL pulse demonstrated ischaemia of the femoral head cartilage with tissue infiltration of NET-forming neutrophils. Proteome analysis suggested that prenylcysteine oxidase 1 (PCYOX1) played a role in this phenomenon. The reaction of PCYOX1-containing very low-density lipoproteins (VLDL) with its substrate farnesylcysteine (FC) induced NETs in vitro. The combined addition of IMQ and mPSL synergistically enhanced VLDL-plus-FC-induced NET formation. CONCLUSION: PCYOX1 and related factors are worthy of attention to understand the underlying mechanisms and create novel therapeutic strategies for mPSL-mediated microcirculation disorders, including ONFH.
• Radiofrequency Echographic Multispectrometry (REMS) can Overcome the Effects of Structural Internal Artifacts and Evaluate Bone Fragility Accurately.

  Hotaka Ishizu, Tomohiro Shimizu, Yuki Sakamoto, Fumi Toyama, Keita Kitahara, Hiroki Takayama, Moritaka Miyamoto, Norimasa Iwasaki

  Calcified tissue international 114 (3) 246 - 254 2023/12/21 

  PURPOSE: This study measured bone mineral density (BMD) in a Japanese population using the novel non-ionizing system using radiofrequency echographic multispectrometry (REMS) and compared the results with those obtained using traditional dual-energy X-ray absorptiometry (DXA). We aimed to identify any discrepancies between measurements obtained using these instruments and identify the influencing factors. METHODS: This cross-sectional study examined patients with osteoporosis treated at a single center from April to August 2023. We examined BMD assessment by DXA and REMS in lumbar spine and proximal femur. Patients were categorized into two groups: those with discrepancies between lumbar spine BMD measured by DXA and REMS, and those without. Semiquantitative evaluation of vertebral fractures and abdominal aortic calcification scoring were also performed and compared between the two groups, along with various patient characteristics. RESULTS: A total of 70 patients (88.6% female; mean age 78.39 ± 9.50 years) undergoing osteoporosis treatment were included in the study. A significant difference was noted between DXA and REMS measurement of BMD and T-scores, with REMS recording consistently lower values. The discrepancy group exhibited a higher incidence of multiple vertebral fractures and increased vascular calcification than the non-discrepancy group. Multivariate analysis indicated that diabetes mellitus, severe vertebral fractures, and increased abdominal aortic calcification scores were significantly associated with discrepancies in lumbar spine T-scores. CONCLUSION: This study suggests that REMS may offer a more accurate measurement of BMD, overcoming the overestimation of BMD by DXA owing to factors such as vertebral deformities, abdominal aortic calcification, and diabetes mellitus.
• 変形性膝関節症の重症度別外的膝関節モーメント成分の寄与率変化の検討

  鈴木 裕貴, 小野寺 智洋, 岩崎 倫政, 大越 康充, 前田 龍智, 川上 健作, 清水 健太, 千田 周也, 浮城 健吾, 岩崎 浩司, 鈴木 昭二, 近藤 英司

  日本関節病学会誌 (一社)日本関節病学会 42 (4) 340 - 346 1883-2873 2023/12 

  目的:内側型変形性膝関節症(KOA:knee osteoarthritis)の運動力学的特徴に関しては,いまだ解明されていない部分が多い。本研究の目的は,重症度別モーメント寄与率の特徴を明らかにすることである。方法:当院で歩行解析を実施し得たKOA症例77例93膝(北大KOA重症度分類;Stage II:19例22膝,Stage III:26例30膝,Stage IV:17例24膝,Stage V:15例19膝)を対象としてStageごとに群分けした。全症例に対し,膝関節可動域,歩行速度,単純X線所見を評価した。また,ポイントクラスター法に準じた光学式モーションキャプチャー技術と逆動力学計算により,床反力ピーク時における外的膝関節モーメントの総量(TJM:total joint moment)とそれに対する各モーメントの寄与率を求めた。結果:歩行速度と膝屈曲可動域はKOAの重症例ほど有意に小さかった(P<0.05)。KOA重症例では,femorotibial angleは大きく,TJMは大きく,TJM第一ピーク時における各モーメント寄与率は,内反モーメント(KAM:knee adduction moment)の割合が有意に大きく,屈曲モーメント(KFM:knee flexion moment)の割合が有意に小さかった。考察:KOAの重症例においては,高度の膝内反変形による長いレバーアームがKAMの寄与率が大きい要因と考えられた。また,膝屈曲可動域とKFMの寄与率が低いことから,大腿四頭筋力と膝関節機能の不良が示唆された。(著者抄録)
• A simple free flap strategy using end-to-side anastomosis to the main vessels in injured extremity.

  Makoto Motomiya, Naoya Watanabe, Mitsutoshi Ota, Kohei Shimoda, Daisuke Kawamura, Norimasa Iwasaki

  JPRAS open 38 48 - 59 2023/12 

  BACKGROUND: During free flap surgery, the surgeon sometimes encounters problems with anastomosis such as intractable arterial spasms or vessel size discrepancy in venous anastomoses. End-to-side (ETS) anastomosis has the advantages of limited chance of vessel spasm and easy handling by adjusting for vessel size discrepancy. We introduced the arterial and venous end-to-side anastomosis (AV-ETS) strategy, which is based on the ETS anastomosis to the main artery and accompanying veins, to avoid intraoperative anastomotic problems when creating a free flap. The aim of this study was to compare flap outcomes and intraoperative anastomotic problems before and after introduction of the AV-ETS strategy in extremity free flap surgery. MATERIALS AND METHODS: We retrospectively examined 72 consecutive extremity free flaps. Before introducing the AV-ETS strategy, we used the conventional strategy in which the recipient artery was selected according to the number of the remaining main artery and the anastomosis technique was flexibly changed, although the end-to-end (ETE) technique was used in most cases. RESULTS: The conventional group had 18 flaps and the AV-ETS group had 54 flaps. The rate of flap survival did not differ between these groups, and there were no cases of flap failure after the introduction of the AV-ETS strategy. The AV-ETS group had significantly fewer flaps that required a change in preoperative planning for the recipient artery or anastomotic site of the artery. CONCLUSIONS: The AV-ETS strategy may facilitate reliable preoperative planning and the performance of stable free flap surgery without requiring a flexible response during surgery.
• Epidemic Preventive Management during the Coronavirus Disease 2019 Pandemic Is a Risk Factor for Delirium after Spinal Cord Injury Surgery.

  Hiroki Ushirozako, Kota Suda, Satoko Matsumoto Harmon, Miki Komatsu, Masahiro Ota, Tomoaki Shimizu, Akio Minami, Masahiko Takahata, Norimasa Iwasaki, Yukihiro Matsuyama

  Spine surgery and related research 7 (6) 474 - 481 2023/11/27 

  INTRODUCTION: Epidemic preventive management during the coronavirus disease 2019 (COVID-19) pandemic may have negatively impacted perioperative outcomes in patients with traumatic spinal cord injury (SCI). However, little is known about the relationship between epidemic preventive management and delirium after traumatic SCI. Here, we clarified the predictors of delirium after SCI surgery. METHODS: We retrospectively analyzed 231 patients (mean age, 66 years) who underwent SCI surgery between 2017 and 2021. Patients were categorized into the delirium and non-delirium groups. Preoperative characteristics and laboratory data related to the occurrence of delirium were assessed. During the study period, we continued early surgical intervention. However, early rehabilitation intervention was not performed in the hospital rehabilitation room from May 2020 due to epidemic preventive management, which involved performing rehabilitation on the bed for 8 days postoperatively. RESULTS: Postoperatively, 33 (14.3%) patients experienced delirium. Univariate analysis showed that age (p<0.01), presence of a psychiatric disorder (p<0.05), dementia (p<0.05), serum albumin (p<0.05) and hemoglobin (p<0.01) levels, American Society of Anesthesiologists classification score (p<0.05), and treatment during the COVID-19 pandemic (p<0.01) differed significantly in the delirium and non-delirium groups. Multivariate logistic regression analysis showed that an age ≥73 years (odds ratio [OR], 15.78; 95% confidence interval [CI], 4.54-54.80; p<0.01), treatment during the COVID-19 pandemic (OR, 3.85; 95% CI, 1.61-9.22; p<0.01), and psychiatric disorder (OR, 29.38; 95% CI, 5.63-153.43; p<0.01) were associated with delirium. CONCLUSIONS: Our comprehensive preventive management during the COVID-19 pandemic was identified as one of the risk factors for delirium after SCI surgery. Patients with preventive management should be cautioned regarding the risk of delirium.
• Valgus instability and related factors beyond 2 years following unlinked total elbow arthroplasty.

  Yuki Matsui, Makoto Kondo, Yasuhiko Nishio, Sadatoshi Kato, Norimasa Iwasaki

  Journal of shoulder and elbow surgery 33 (3) 544 - 549 2023/11/26 

  HYPOTHESIS AND BACKGROUND: Total elbow arthroplasty (TEA), categorized into linked and unlinked types, is commonly reported treatment for rheumatoid arthritis of the elbow. Although unlinked TEA preserves bone, it may result in instability. This study aimed to assess the outcomes of unlinked TEA in rheumatoid arthritis of the elbow beyond two years and to identify factors correlating with postoperative valgus instability of unlinked TEA. METHODS: This study included patients who underwent TEA for rheumatoid arthritis of the elbow at our department between August 2009 and January 2017, with a follow-up period exceeding two years. Elbow joint range of motion (ROM) and clinical scores were evaluated preoperatively and at the final follow-up. Factors contributing to valgus instability, such as the Larsen grade, sex, age, side, preoperative ROM, postoperative ROM, implant placement, preoperative carrying angle, and the use of biological disease-modifying antirheumatic drugs (bDMARDs), were also assessed. RESULTS: This study encompassed 26 elbows from 23 patients, with a mean patient age at surgery of 64.8 years and a mean follow-up duration of 92.4 months. Significant improvements were observed in the ROM (extension: from -31° preoperatively to -21° postoperatively [p = 0.02], flexion: from 116°-137° [p < 0.001]), Japanese Orthopaedic Association-Japan Elbow Society Elbow Function Score (from 45.9-86.3 points [p < 0.001]), and Mayo Elbow Performance Score (from 43.6-91.7 points [p < 0.001]). At the last follow-up, two elbows exhibited radiolucent lines around the humeral stem, whereas seven had valgus instability. Factors correlated with valgus instability included total arc at the final follow-up, preoperative carrying angle, and the use of bDMARDs. DISCUSSION AND CONCLUSION: Unlinked TEA demonstrated favorable midterm outcomes for rheumatoid arthritis of the elbow, albeit with occasional valgus instability. Surgeons should consider preoperative carrying angle and bDMARD use, and exercise caution regarding intraoperative extensions.
• Assessing knee joint biomechanics and trunk posture according to medial osteoarthritis severity.

  Yuki Suzuki, Yasumitsu Ohkoshi, Kensaku Kawakami, Kenta Shimizu, Shuya Chida, Kengo Ukishiro, Tomohiro Onodera, Koji Iwasaki, Tatsunori Maeda, Sho'ji Suzuki, Eiji Kondo, Norimasa Iwasaki

  Scientific reports 13 (1) 19186 - 19186 2023/11/06 

  During progression of knee osteoarthritis (OA), gait biomechanics changes three-dimensionally; however, its characteristics and trunk posture according to OA severity remain unknown. The present study investigated three-dimensional knee joint biomechanics and trunk posture according to knee OA severity. Overall, 75 patients (93 knees) with medial knee OA [Kellgren-Lawrence grade ≥ 2, grade 2: 20 patients with 24 knees (mean 60.0 years old); grade 3: 25 with 28 knees (mean 62.0 years old); grade 4: 30 with 41 knees (mean 67.9 years old)] and 14 healthy controls (23 knees, mean 63.6 years old) underwent gait analysis using an optical motion capture system and point cluster technique. In grade 2 knee OA, the relative contribution of the knee adduction moment (KAM) increased significantly (P < 0.05), and that of the knee flexion moment decreased (P < 0.05) prior to significant progression of varus knee deformity. Grade 3 knee OA showed significant exacerbation of varus knee deformity (P < 0.01) and KAM increase (P < 0.001). The maximum knee extension angle decreased (P < 0.05) and trunk flexion increased during gait in grade 4 knee OA (P < 0.001). Our study clarified the kinematics and kinetics of medial knee OA with trunk flexion according to severity. Kinetic conversion occurred in grade 2 knees prior to progression of varus deformities, knee flexion contractures, and sagittal imbalance during gait in patients with severe knee OA.
• 【変形性関節症の病態に迫る-疾患修飾による治療を展望して-】変形性関節症発症機序の解明に向けた軟骨変性制御機構における糖鎖機能解析

  松岡 正剛, 小野寺 智洋, 岩崎 倫政

  整形・災害外科 金原出版(株) 66 (12) 1459 - 1463 0387-4095 2023/11 

  ＜文献概要＞変形性関節症において,関節軟骨の病態進行と関連してN型糖鎖の変化が生じ,関節軟骨の恒常性維持において糖脂質が重要な役割を果たすことも報告されている。特にガングリオシドと呼ばれる糖脂質のサブグループが関節軟骨に豊富に存在していることが明らかにされている。さらに,関節軟骨修復過程の研究においても糖脂質の重要性が示されており,一部の糖脂質の欠損により関節軟骨の修復が促進されることが報告されている。これらの研究結果から,糖鎖修飾や糖脂質の制御が変形性関節症の治療標的となる可能性があることが示唆されている。
• 遺伝性低リン血症性くる病患者に対するブロスマブ投与による下肢アライメント改善効果の検討

  坂井 裕子, 小野寺 智洋, 松岡 正剛, 中村 明枝, 岩崎 倫政

  日本小児整形外科学会雑誌 (一社)日本小児整形外科学会 32 (3) S111 - S111 0917-6950 2023/11
• ソルター手術は進化しているのか?(骨切り法、固定材料、矯正損失防止などの工夫) Angulated Innominate Osteotomy(AIO)の3次元的解析と固定法評価

  高橋 大介, 小川 拓也, 高橋 練也, 清水 智弘, 岩崎 倫政

  日本小児整形外科学会雑誌 (一社)日本小児整形外科学会 32 (3) S36 - S36 0917-6950 2023/11
• リーメンビューゲル治療後に補正手術を要した症例の検討

  小川 拓也, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本小児整形外科学会雑誌 (一社)日本小児整形外科学会 32 (3) S62 - S62 0917-6950 2023/11
• 発育性股関節形成不全(DDH)ハイリスク児の歩行開始後のDDH罹患率 前向き研究調査

  大橋 佑介, 清水 智弘, 小川 拓也, 高橋 大介, 岩崎 倫政

  日本小児整形外科学会雑誌 (一社)日本小児整形外科学会 32 (3) S121 - S121 0917-6950 2023/11
• 当院における発育性股関節形成不全検診時のアンケート調査と装具療法の関連

  小川 拓也, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本小児整形外科学会雑誌 (一社)日本小児整形外科学会 32 (3) S121 - S121 0917-6950 2023/11
• Unique skin findings in a case of the A3 pulley trigger finger due to an osteochondroma

  Takuya Yabumoto, Takeshi Endo, Ryo Itoga, Daisuke Kawamura, Yuichiro Matsui, Norimasa Iwasaki

  Joint Diseases and Related Surgery 35 (1) 249 - 253 2687-4784 2023/10/31 

  Trigger finger is usually caused by stenosing tenosynovitis and hypertrophy of the retinacular sheath, and the most common site of tendon triggering is the A1 pulley. Although the A3 pulley trigger finger has been described in a few cases caused by hypertrophy of the retinacular sheath and ganglion, associated skin findings have not been reported to date. Herein, we report a rare case of the A3 pulley trigger finger due to osteochondroma with unique skin findings in a 50-year-old woman. In this case, we observed a V-shaped skin depression on the palmar side of the proximal interphalangeal joint of the right middle finger during finger locking. Additionally, we observed bilateral linear skin depressions on the sides of the proximal phalange. These findings might be caused by the traction force on the A3 pulley, connected to the skin via the Grayson and Cleland ligaments, which are fibrous tissues that connect the skin and tendon sheath.
• Joint instability in patients with borderline developmental dysplasia of the hip.

  Fumiya Kizawa, Daisuke Suzuki, Satoshi Nagoya, Arata Kanaizumi, Tomohiro Shimizu, Tohru Irie, Daisuke Takahashi, Norimasa Iwasaki

  Clinical biomechanics (Bristol, Avon) 111 106136 - 106136 2023/10/30 

  BACKGROUND: The treatment strategy for developmental dysplasia of the hip is determined based on the lateral center-edge angle. Nonetheless, an evaluation of joint instability may be important in determining the treatment strategy. This study classified the displacement patterns of the femoral head center during hip abduction. METHODS: Ten patients with borderline developmental dysplasia of the hip, 10 patients with developmental dysplasia of the hip, and 10 patients with normal hips were analyzed. Image matching was performed using X-ray images of hip abduction with a three-dimensional hip model. The displacement of the femoral head center and its trajectory length were measured. A cluster analysis was conducted to classify the displacement pattern of the femoral head center, and trajectory lengths were compared. FINDINGS: Displacement was classified into three patterns: medialization, hinge abduction, and centering. Patients with borderline developmental hip dysplasia exhibited all three patterns. Almost all patients with developmental dysplasia of the hip showed medialization and hinge abduction, whereas all normal patients had the centering type. The mean trajectory length indices for the medialization and hinge abduction types were significantly longer than those for the centering type (P = 0.01 and P = 0.016, respectively). INTERPRETATION: Borderline developmental dysplasia of the hip is a heterogeneous condition characterized by varying hip instability levels. Our findings suggest that uniform evaluation based on the lateral center-edge angle is inappropriate and that joint instability must be evaluated in each patient with borderline developmental dysplasia of the hip.
• Arthrodesis of the interphalangeal joints of the hand by two-dimensional intraosseous wiring.

  Tomoaki Suzuki, Daisuke Kawamura, Yuichiro Matsui, Norimasa Iwasaki

  BMC musculoskeletal disorders 24 (1) 843 - 843 2023/10/25 

  BACKGROUND: Numerous techniques for arthrodesis have been described to fix interphalangeal (IP) joints, and the fixation method should be considered on a case-by-case basis. This study aimed to investigate the availability of IP joint arthrodesis of the hand, using a two-dimensional intraosseous wiring (two-DIOW) method. METHODS: A total of 43 joints (19 thumb IP joints, 9 proximal finger interphalangeal (PIP) joints and 15 distal interphalangeal (DIP) joints in 29 patients with a mean age of 66 years (range, 24-85 y) were retrospectively analyzed. All operations were performed with two-DIOW method. We evaluated the bone union rate, correction loss, presence of any surgical complications, and oral steroid use in cases of joint fixation using the two-DIOW method. RESULTS: Of these 43 digits, 42 achieved bone union (97.7%). Non-union was seen in a thumb IP joint of mutilans rheumatoid arthritis. Mean correction loss of deviation was 1.0°, and flexion or extension angulation was 1.6° in the direction of extension. Surgical complications included mild nail deformity in 2 digits and wire irritation necessitating wire removal in 2 digits. Oral steroids were used for 18 of the 43 digits, including 2 digits complicated by nail deformities. There was no infection and skin necrosis in all digits with or without steroid use. CONCLUSIONS: The two-DIOW method appears to offer an effective method of IP joint fixation, but caution should be exercised in digits of severe joint destruction and in the treatment of wire knot.
• Arthrodesis of the interphalangeal joints of the hand by two-dimensional intraosseous wiring

  Tomoaki Suzuki, Daisuke Kawamura, Yuichiro Matsui, Norimasa Iwasaki

  BMC Musculoskeletal Disorders 24 (1) 385 - 385 2023/10/25 

  Abstract Background Numerous techniques for arthrodesis have been described to fix interphalangeal (IP) joints, and the fixation method should be considered on a case-by-case basis. This study aimed to investigate the availability of IP joint arthrodesis of the hand, using a two-dimensional intraosseous wiring (two-DIOW) method. Methods A total of 43 joints (19 thumb IP joints, 9 proximal finger interphalangeal (PIP) joints and 15 distal interphalangeal (DIP) joints in 29 patients with a mean age of 66 years (range, 24–85 y) were retrospectively analyzed. All operations were performed with two-DIOW method. We evaluated the bone union rate, correction loss, presence of any surgical complications, and oral steroid use in cases of joint fixation using the two-DIOW method. Results Of these 43 digits, 42 achieved bone union (97.7%). Non-union was seen in a thumb IP joint of mutilans rheumatoid arthritis. Mean correction loss of deviation was 1.0°, and flexion or extension angulation was 1.6° in the direction of extension. Surgical complications included mild nail deformity in 2 digits and wire irritation necessitating wire removal in 2 digits. Oral steroids were used for 18 of the 43 digits, including 2 digits complicated by nail deformities. There was no infection and skin necrosis in all digits with or without steroid use. Conclusions The two-DIOW method appears to offer an effective method of IP joint fixation, but caution should be exercised in digits of severe joint destruction and in the treatment of wire knot.
• Chronic shoulder injury related to vaccine administration following coronavirus disease 2019 vaccination: a case report.

  Masahiro Miyano, Yukinori Tsukuda, Shigeto Hiratsuka, Masanari Hamasaki, Norimasa Iwasaki

  Journal of medical case reports 17 (1) 456 - 456 2023/10/17 

  BACKGROUND: Shoulder injury related to vaccine administration, defined as shoulder pain and limited range of motion occurring after administration in the upper arm, has been previously reported. The symptom resolved completely after treatment with oral nonsteroidal anti-inflammatory drugs or an intraarticular steroid injection, however there have been few reports of long-term symptoms following coronavirus disease 2019 vaccination. This case report describes a healthy, middle-aged, healthcare worker who developed post-vaccination subacromial-subdeltoid bursitis that lasted for more than 6 months after Pfizer-BioNTech coronavirus disease 2019 vaccination. CASE PRESENTATION: A 55-year-old Japanese woman with no significant medical history was vaccinated in the standard site, with the needle direction perpendicular to the skin. Within a few hours after the second vaccination, severe shoulder pain and limited range of motion appeared. Although shoulder range of motion improved, her shoulder pain did not improved for several months, and she consulted an orthopedic doctor 5 months later. Radiographs of her left shoulder did not provide helpful diagnostic information. High intensity in the subacromial-subdeltoid space was seen on short TI inversion recovery of magnetic resonance imaging, showing subacromial-subdeltoid bursitis. She was diagnosed with a shoulder injury related to vaccine administration. The patient was started on an oral anti-inflammatory drug, and the left subacromial space was injected with 2.5 mg of betamethasone with 3 ml of 1% lidocaine without epinephrine every 2 weeks. One month after starting this treatment, since her shoulder pain had not improved, the oral anti-inflammatory drug was switched to tramadol hydrochloride acetaminophen. However, 3 months after switching medication, the shoulder pain continued, and she worked so as to have minimal impact on her shoulder. CONCLUSION: A case of subacromial-subdeltoid bursitis following a second dose of the Pfizer-BioNTech coronavirus disease 2019 vaccine that lasted many months is reported. Injection technique is a modifiable risk factor, the adverse effects of which could potentially be mitigated with appropriate and relevant training of healthcare providers. To prevent this type of case, the appropriate landmark, needle length, and direction should be confirmed.
• 広範な膝軟骨損傷に対するアテロコラーゲンを用いた自家培養軟骨移植術後の活動レベルの変化

  甲斐原 拓真, 近藤 英司, 小野寺 智洋, 門間 太輔, 岩崎 倫政

  日本臨床スポーツ医学会誌 (一社)日本臨床スポーツ医学会 31 (4) S300 - S300 1346-4159 2023/10
• An international study to explore the feasibility of collecting standardised outcome data for Complex Regional Pain Syndrome: recommendations for an international clinical research registry.

  Sharon Grieve, Florian Brunner, Danylo F Cabral, Robyn Connett, Hitoshi Hirata, Norimasa Iwasaki, Yasunobu Nakagawa, Afrin Sagir, Gudson Sousa, Jean-Jacques Vatine, Nicole Vaughan-Spickers, Jijun Xu, Lisa Buckle, Candida McCabe

  British journal of pain 17 (5) 468 - 478 2023/10 

  INTRODUCTION: Complex Regional Pain Syndrome (CRPS) is a persistent pain condition with low prevalence. Multi-centre collaborative research is needed to attain sufficient sample sizes for meaningful studies. This international observational study: (1) tested the feasibility and acceptability of collecting outcome data using an agreed core measurement set (2) tested and refined an electronic data management system to collect and manage the data. METHODS: Adults with CRPS, meeting the Budapest diagnostic clinical criteria, were recruited to the study from 7 international research centres. After informed consent, a questionnaire comprising the core set outcome measures was completed: on paper at baseline (T1), and at 3 or 6 months (T2) using a paper or e-version. Participants and clinicians provided feedback on the data collection process. Clinicians completed the CRPS severity score at T1 and optionally, at T2. Ethical approval was obtained at each international centre. RESULTS: Ninety-eight adults were recruited (female n=66; mean age 46.6 years, range 19-89), of whom 32% chose to receive the T2 questionnaire in an electronic format. Fifty-five participants completed both T1 and T2. Eighteen participants and nine clinicians provided feedback on their data collection experience. CONCLUSION: This study confirmed the questionnaire core outcome data are feasible and practicable to collect in clinical practice. The electronic data management system provided a robust means of collecting and managing the data across an international population. The findings have informed the final data collection tools and processes which will comprise the first international, clinical research registry and data bank for CRPS.
• Effect of Patient Age on Clinical and Radiological Outcomes After Medial Open-Wedge High Tibial Osteotomy: A Comparative Study With 344 Knees.

  Koji Yabuuchi, Eiji Kondo, Takuma Kaibara, Jun Onodera, Koji Iwasaki, Masatake Matsuoka, Tomohiro Onodera, Norimasa Iwasaki, Tomonori Yagi, Kazunori Yasuda

  Orthopaedic journal of sports medicine 11 (10) 23259671231200227 - 23259671231200227 2023/10 

  BACKGROUND: There exists some controversy regarding whether patient age is a predictive factor for outcomes after high tibial osteotomy (HTO). PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate whether patient age affects clinical and radiological outcomes after medial open-wedge HTO (OWHTO) in a large population with a wider age range than previous studies. It was hypothesized that there would be no differences in outcomes when compared across age-groups. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective comparative study was conducted using 344 patients (303 knees) who underwent OWHTO from 2009 to 2018. These patients were divided into 3 groups based on age at the time of surgery: ≥55 years (group Y: 76 knees in 57 patients), 56 to 64 years (group M: 129 knees in 120 patients), and ≤65 years (group O: 139 knees in 126 patients). Clinical and radiological evaluations were performed immediately before surgery and at the final follow-up period, at a mean of 5.1 years (range, 3-11 years). Comparisons among the 3 groups were conducted with 1-way analysis of variance for continuous variables. When a significant result was obtained, a post hoc test with Bonferroni correction was conducted for multiple comparisons. RESULTS: In clinical evaluations, there were no significant differences among the 3 groups either preoperatively or postoperatively concerning the Japanese Orthopaedic Association score, the Lysholm score, or the Knee injury and Osteoarthritis Outcome Score (KOOS), with the exception of the preoperative KOOS Symptoms subscale, which was significantly higher in group Y versus group O (48.9 ± 18.7 vs 58.7 ± 15.4, respectively; P = .011). The Tegner activity score was significantly different among the groups, both preoperatively and postoperatively (P < .001 for both). There was no significant difference in the occurrence of complications or the survival rate at final follow-up among the 3 groups. CONCLUSION: The study findings suggest that patient age does not affect clinical and radiological outcomes after OWHTO.
• Initial patient demographics affecting return to original work after traumatic hand injury in a rural area in Japan: A retrospective single-center study

  Kazuhiro Yamamoto, Makoto Motomiya, Kota Ono, Yuichiro Matsui, Keigo Yasui, Norimasa Iwasaki

  Journal of Orthopaedic Science 0949-2658 2023/10 

  BACKGROUND: Time off work after traumatic hand injury not only affects individuals but also has socioeconomic repercussions, becoming a serious problem from the viewpoint of labor shortages. In depopulated rural areas, the impact of labor shortages due to time off work is more serious than in urban areas; however, few studies have examined return to original work in rural areas. The purpose of this study was to investigate the patient demographics at the time of hand injury that affect return to original work in a rural area of Japan. METHODS: We retrospectively examined 246 patients with traumatic hand and/or forearm injuries who were working at the time of injury, and who underwent surgical operations and postoperative rehabilitation in a level II hospital in a rural agricultural area. We examined patients' initial demographic data, including gender, age, occupation (white or blue collar), employment status (self-employed, full-time, or part-time workers), complications other than hand injury, workers' compensation, dominant hand injury, and injury severity as determined using the modified Hand Injury Severity Score. Multivariate logistic regression analysis examined the association between initial patient demographics and return to original work within 150 days after injury. RESULTS: In total, 186 patients (76 %) were able to return to original work within 150 days. A multivariate logistic regression analysis showed that three explanatory variables (i.e., severity of injury, complications other than hand injury, and female gender) significantly compromised return to original work. CONCLUSIONS: In the treatment of traumatic hand injury, intensive support should be provided for return to original work for patients who are expected to have difficulty returning to work quickly. In addition, labor shortages can be mitigated by sharing information with the workplace about patients' prospects of return to original work.
• Median neuropathy after multiple punctures of the forearm for catheterization: A case report.

  Tomoaki Suzuki, Yuichiro Matsui, Daisuke Momma, Takeshi Endo, Norimasa Iwasaki

  World journal of clinical cases 11 (25) 5941 - 5946 2023/09/06 

  BACKGROUND: Neuropathy may occur at some sites after catheterization for close examination of cardiac disease. Although the radial artery is considered a relatively uncom-plicated site for catheterization, the radial artery and median nerve are in relatively close proximity, with the risk of median nerve injury depending on the angle of puncture. The purpose of this study was to report the outcomes of surgery performed for conservative therapy-resistant median neuropathy following forearm catheterization. CASE SUMMARY: A 50-year-old woman experienced palsy from the right thumb to the radial side of the ring finger after catheterization from the radial artery of the right forearm. Paresthesia developed at the same site and a positive tinel-like sign was seen for the median nerve area at the high level of the puncture site. Nerve conduction study showed reduced compound muscle action potentials and loss of sensory nerve action potentials. Symptoms did not improve despite pharmacotherapy and the patient gradually developed flexion restrictions of the index and middle fingers. Median nerve injury and associated flexor tendon adhesion was diagnosed, and the patient was referred for surgery at 3 mo after injury. When the same area was opened, no injury to the median nerve epithelium was obvious, but the area of the positive tinel-like sign was highly adherent to surrounding tissue and to the flexor digitorum superficialis of the index and middle fingers. The surgery was terminated with adequate adhesion release. Rehabilitation was initiated postoperatively, improving neurological symptoms and range of motion of the fingers. Six months after surgery, the patient returned to daily activities without discomfort. CONCLUSION: This case provides the appropriate diagnosis and treatment for a suspected peripheral nerve injury.
• Development of Notch-Free, Pre-Bent Rod Applicable for Posterior Corrective Surgery of Thoracolumbar/Lumbar Adolescent Idiopathic Scoliosis.

  Yoko Ishikawa, Satoshi Kanai, Katsuro Ura, Terufumi Kokabu, Katsuhisa Yamada, Yuichiro Abe, Hiroyuki Tachi, Hisataka Suzuki, Takashi Ohnishi, Tsutomu Endo, Daisuke Ukeba, Masahiko Takahata, Norimasa Iwasaki, Hideki Sudo

  Journal of clinical medicine 12 (17) 2023/09/04 

  Adolescent idiopathic scoliosis (AIS), the most common pediatric musculoskeletal disorder, causes a three-dimensional spine deformity. Lenke type 5 AIS is defined as a structural thoracolumbar/lumbar curve with nonstructural thoracic curves. Although a rod curvature will affect clinical outcomes, intraoperative contouring of the straight rod depends on the surgeon's knowledge and experience. This study aimed to determine the optimum rod geometries to provide a pre-bent rod system for posterior spinal surgery in patients with Lenke type 5 AIS. These pre-bent rods will be beneficial for achieving proper postoperative outcomes without rod contouring based on surgeon experience. We investigated 20 rod geometries traced in posterior spinal reconstruction in patients with Lenke type 5 AIS. The differences between the center point clouds in each cluster were evaluated using the iterative closest point (ICP) method with modification. Before the evaluation using the ICP method, the point clouds were divided into four clusters based on the rod length using a hierarchical cluster analysis. Because the differences in the values derived from the ICP method were <5 mm for each length-based cluster, four representative rod shapes were generated from the length-based clusters. We identified four optimized rod shapes that will reduce operation time, leading to a decreased patient and surgeon burden.
• The Impact of Diffuse Idiopathic Skeletal Hyperostosis on Nutritional Status, Neurological Outcome, and Perioperative Complications in Patients with Cervical Spinal Cord Injury.

  Tomoaki Shimizu, Kota Suda, Satoko Matsumoto Harmon, Miki Komatsu, Masahiro Ota, Hiroki Ushirozako, Akio Minami, Masahiko Takahata, Norimasa Iwasaki, Hiroshi Takahashi, Masashi Yamazaki

  Journal of clinical medicine 12 (17) 2023/09/01 

  This retrospective study aimed to investigate the characteristics of patients with cervical spinal cord injuries (CSCI) with diffuse idiopathic skeletal hyperostosis (DISH). We included 153 consecutive patients with CSCI who underwent posterior decompression and fusion surgery. The patients were divided into two groups based on the presence of DISH. Patient characteristics, neurological status on admission, nutritional status, perioperative laboratory variables, complications, neurological outcomes at discharge, and medical costs were compared between the groups. The DISH group (n = 24) had significantly older patients (72.1 vs. 65.9, p = 0.036), more patients with low-impact trauma (62.5% vs. 34.1%, p = 0.009), and a lower preoperative prognostic nutritional index on admission (39.8 vs. 42.5, p = 0.014) than the non-DISH group (n =129). Patients with DISH had significantly higher rates of ventilator management (16.7% vs. 3.1%, p = 0.022) and pneumonia (29.2% vs. 8.5%, p = 0.010). There was no significant difference in medical costs and neurological outcomes on discharge. Patients with CSCI and DISH were older, had poor nutritional status, and were prone to postoperative respiratory complications, while no differences were found between the neurological outcomes of patients with CSCI with and without DISH.
• 骨折リスクの高い骨粗鬆症の脊柱矢状断アライメント異常の検証

  有田 皓介, 清水 智弘, 石津 帆高, 岩崎 倫政

  日本骨粗鬆症学会雑誌 (一社)日本骨粗鬆症学会 9 (Suppl.1) 370 - 370 2189-8383 2023/09
• 大腿骨近位部骨折患者における重症骨粗鬆症の割合

  山崎 秀, 下段 俊, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本骨粗鬆症学会雑誌 (一社)日本骨粗鬆症学会 9 (Suppl.1) 448 - 448 2189-8383 2023/09
• 薬剤誘発性FGF23関連低リン血症性骨軟化症に伴う両側大腿骨頭軟骨下脆弱性骨折の1例

  奥村 眞子, 清水 智弘, 石津 帆高, 横田 隼一, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本骨粗鬆症学会雑誌 (一社)日本骨粗鬆症学会 9 (Suppl.1) 468 - 468 2189-8383 2023/09
• A Review: Methodologies to Promote the Differentiation of Mesenchymal Stem Cells for the Regeneration of Intervertebral Disc Cells Following Intervertebral Disc Degeneration.

  Takashi Ohnishi, Kentaro Homan, Akira Fukushima, Daisuke Ukeba, Norimasa Iwasaki, Hideki Sudo

  Cells 12 (17) 2023/08/28 

  Intervertebral disc (IVD) degeneration (IDD), a highly prevalent pathological condition worldwide, is widely associated with back pain. Treatments available compensate for the impaired function of the degenerated IVD but typically have incomplete resolutions because of their adverse complications. Therefore, fundamental regenerative treatments need exploration. Mesenchymal stem cell (MSC) therapy has been recognized as a mainstream research objective by the World Health Organization and was consequently studied by various research groups. Implanted MSCs exert anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects and promote extracellular component production, as well as differentiation into IVD cells themselves. Hence, the ultimate goal of MSC therapy is to recover IVD cells and consequently regenerate the extracellular matrix of degenerated IVDs. Notably, in addition to MSC implantation, healthy nucleus pulposus (NP) cells (NPCs) have been implanted to regenerate NP, which is currently undergoing clinical trials. NPC-derived exosomes have been investigated for their ability to differentiate MSCs from NPC-like phenotypes. A stable and economical source of IVD cells may include allogeneic MSCs from the cell bank for differentiation into IVD cells. Therefore, multiple alternative therapeutic options should be considered if a refined protocol for the differentiation of MSCs into IVD cells is established. In this study, we comprehensively reviewed the molecules, scaffolds, and environmental factors that facilitate the differentiation of MSCs into IVD cells for regenerative therapies for IDD.
• ラット坐骨神経を使用した慢性絞扼性神経障害の新規モデル開発

  山本 康弘, 角家 健, 内藤 聖人, 石島 旨章, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1757 - S1757 0021-5325 2023/08
• 四肢原発悪性骨腫瘍症例における患肢温存術と切断術の比較 米国SEERデータベースを用いた研究

  柳澤 那由他, 松岡 正剛, 小野寺 智洋, 岩崎 浩司, 鈴木 裕貴, 濱崎 雅成, 近藤 英司, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1887 - S1887 0021-5325 2023/08
• 診断時遠隔転移を有する四肢発生原発性悪性骨腫瘍の原発巣切除が生存に与える影響 米国SEERデータベースを用いた研究

  福田 龍一, 松岡 正剛, 小野寺 智洋, 岩崎 浩司, 鈴木 裕貴, 濱崎 雅成, 近藤 英司, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1888 - S1888 0021-5325 2023/08
• 腰椎後方除圧術における棘上棘間靱帯・棘突起温存は,術後の二次性椎間板変性の進行を抑制する

  大西 貴士, 中下 並人, 山田 勝久, 須藤 英毅, 岩崎 倫政

  東日本整形災害外科学会雑誌 東日本整形災害外科学会 35 (3) 292 - 292 1342-7784 2023/08
• AI技術により作成した3D腰神経MRI像を用いたL5/Sレベルの全内視鏡下椎間板ヘルニア摘出術シミュレーションの有用性

  山田 勝久, 長濱 賢, 安倍 雄一郎, 日向寺 義則, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 高畑 雅彦, 須藤 英毅, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1698 - S1698 0021-5325 2023/08
• 三次元デプスセンサーと人工知能を用いた側彎角の自動予測 着衣の有無による精度検証

  石川 蓉子, 小甲 晃史, 山田 勝久, 安倍 雄一郎, 舘 弘之, 鈴木 久崇, 大西 貴士, 遠藤 努, 岩崎 倫政, 須藤 英毅

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1914 - S1914 0021-5325 2023/08
• アテロコラーゲンを用いた自家培養軟骨移植後に軟骨下骨嚢胞を生じた1例

  甲斐原 拓真, 近藤 英司, 濱崎 雅成, 鈴木 裕貴, 岩崎 浩司, 松岡 正剛, 小野寺 智洋, 種井 善一, 田中 伸哉, 岩崎 倫政

  東日本整形災害外科学会雑誌 東日本整形災害外科学会 35 (3) 361 - 361 1342-7784 2023/08
• 薬剤誘発性FGF23関連低リン血症性骨軟化症に伴う両側大腿骨頭軟骨下脆弱性骨折の1例

  奥村 眞子, 清水 智弘, 石津 帆高, 横田 隼一, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  東日本整形災害外科学会雑誌 東日本整形災害外科学会 35 (3) 254 - 254 1342-7784 2023/08
• 骨折リスクの高い骨粗鬆症の脊柱矢状断アライメント異常の検証

  有田 皓介, 清水 智弘, 石津 帆高, 岩崎 倫政, 浅野 毅

  東日本整形災害外科学会雑誌 東日本整形災害外科学会 35 (3) 282 - 282 1342-7784 2023/08
• 炎症性軟骨細胞は骨細胞のパイロトーシスを誘導する

  小川 裕生, 徳廣 泰貴, 江畑 拓, 北原 圭太, 塩田 惇喜, 西田 善郎, 清水 智弘, 遠藤 努, 高橋 大介, 照川 アラー, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1573 - S1573 0021-5325 2023/08
• 炎症収束型好中球由来細胞外小胞による軟骨細胞抗異化作用についての検討

  北原 圭太, 江畑 拓, 照川 アラー, 清水 智弘, 遠藤 努, 浅野 毅, 高橋 大介, 角家 健, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1667 - S1667 0021-5325 2023/08
• RANKL中和抗体中止後の骨吸収過剰亢進におけるメカニズム解明アプローチ

  石津 帆高, 清水 智弘, 長谷川 智香, 網塚 憲生, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1739 - S1739 0021-5325 2023/08
• Ferroptosisを標的としたポリエチレン摩耗粉による炎症性骨吸収抑制効果

  小川 拓也, 横田 隼一, 徳廣 泰貴, 照川 アラー, 照川 ヘンド, 西田 善郎, 塩田 惇喜, 北原 圭太, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1831 - S1831 0021-5325 2023/08
• 閉経後骨粗鬆症モデルマウスを用いた新規骨マクロファージ由来分子タンパクの生体内治療効果

  塩田 惇喜, 照川 アラー, 高橋 大介, 清水 智弘, 横田 隼一, 北原 圭太, 西田 善郎, 徳廣 泰貴, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1872 - S1872 0021-5325 2023/08
• 細胞老化に着目した骨マクロファージの骨代謝調節機能の検討

  西田 善郎, 松前 元, 横田 隼一, 照川 ヘンド, 清水 智弘, 高橋 大介, 遠藤 努, 照川 アラー, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1873 - S1873 0021-5325 2023/08
• 破骨細胞分化阻害剤としての骨マクロファージ由来神経ペプチド様タンパク質の同定

  徳廣 泰貴, 塩田 惇喜, 西田 善郎, 北原 圭太, 清水 智弘, 遠藤 努, 高橋 大介, 照川 アラー, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1878 - S1878 0021-5325 2023/08
• Metastatic acetabular classification Type 4の寛骨臼周囲転移性骨腫瘍に対し再建術を行った1例

  楠 兼一, 浅野 毅, 清水 智弘, 大橋 佑介, 高橋 大介, 岩崎 倫政

  Hip Joint 日本股関節学会 49 (1) 134 - 139 0389-3634 2023/08 

  71歳男。術前のCT検査で左寛骨臼の「ドーム」「内壁」「前柱」「後柱」すべてに病変(転移)を認め、Metastatic acetabular classification Type 4に分類されたが、後柱は骨接合可能であったため、Type 3相当にグレードダウンした状態で寛骨臼の再建とTHAを行うことができた。手術方法は、Kocher-Langenbeck approachで展開し、先ず骨頭の脱臼・骨切りを行い、後柱の骨折部を確認し、後柱後方と臼蓋縁をクランプで圧迫把持し整復した状態でストレートプレートを用いて後柱を固定し、不安定性は消失した。次に臼蓋上方を鋭匙で新鮮化し、臼蓋内上方の骨欠損部に同種骨頭1/6を塊状骨として充填し、KTプレートで補強を行った後にセメントカップを固定した。大腿骨側にはExeterセミロングステムを使用した。術後1週から1/2荷重を開始、2週から全荷重を開始し、術後1ヵ月で独歩可能となったが、その後、全身状態の悪化から離床時間が短くなり、術後7ヵ月で死亡した。
• セメントレス人工股関節の中心性脱臼に至ったadverse reactions to metal debrisによる偽腫瘍の1例

  横山 慎, 清水 智弘, 高橋 大介, 浅野 毅, 石津 帆高, 宮崎 拓自, 岩崎 倫政

  Hip Joint 日本股関節学会 49 (2) 599 - 603 0389-3634 2023/08 

  症例は84歳で、左股関節痛を主訴とした。30年前に両側人工股関節全置換術、10年前に右側人工股関節再置換術の既往があった。単純CTで中心性脱臼とオステオライシスによる嚢胞を認め、造影CTでは股関節腹側にリング状に造影された腫瘤性病変を認め、MRI Gd造影のT1強調画像では低～等信号であった。血液検査ではチタン濃度が1332ng/mLであった。インプラント破損による中心性脱臼、偽腫瘍、寛骨臼骨欠損と診断し、impaction grafting法による再置換術を施行した。術中所見としてメタルヘッドが筋膜直下にあり、大腿骨前方に偽腫瘍を認め、メタルヘッドはメタルカップを貫通し、メタルカップとポリエチレンライナーに大きな摩耗を認めた。偽腫瘍はメタローシスと診断され、病理組織学的所見では密なリンパ球の凝集と黒色の金属粒子を認めた。再置換術後1年経過してHarris hip scoreは手術時の16点から93点に改善し、血清チタン濃度は690ng/mLまで低下した。
• 人工股関節全置換術後に生じた腸恥滑液包炎による大腿動静脈圧迫を呈した1例

  村上 相登, 浅野 毅, 菅原 悠太郎, 高橋 大介, 清水 智弘, 岩崎 倫政

  Hip Joint 日本股関節学会 49 (2) 772 - 776 0389-3634 2023/08 

  症例は84歳女性で、右変形性股関節症に対する人工股関節全置換術後2年より右下肢腫脹・疼痛が出現し、前医で腸恥滑液包炎と診断され、手術目的に当科紹介となった。術前MRIでは腸恥滑液包炎・血腫による大腿動静脈圧迫を呈し、単純X線よりカップ突出によるインピンジメントが原因と考え、カップ再置換術を施行した。術後6ヵ月の時点で腸恥滑液包は消失し、その後は症状の出現なく、良好に経過している。
• Single-step ultra-purified alginate gel implantation in patients with knee chondral defects.

  Tomohiro Onodera, Daisuke Momma, Masatake Matsuoka, Eiji Kondo, Koji Suzuki, Masayuki Inoue, Masaki Higano, Norimasa Iwasaki

  The bone & joint journal 105-B (8) 880 - 887 2023/08/01 

  AIMS: Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury. METHODS: A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm2) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations. RESULTS: No obvious adverse events related to UPAL gel implantation were observed. Self-assessed clinical scores, including pain, symptoms, activities of daily living, sports activity, and quality of life, were improved significantly at three years after surgery. Defect filling was confirmed using second-look arthroscopy at 72 weeks. Significantly improved MRI scores were observed from 12 to 144 weeks postoperatively. Histological examination of biopsy specimens obtained at 72 weeks after implantation revealed an extracellular matrix rich in glycosaminoglycan and type II collagen in the reparative tissue. Histological assessment yielded a mean overall International Cartilage Regeneration & Joint Preservation Society II score of 69.1 points (SD 10.4; 50 to 80). CONCLUSION: This study provides evidence supporting the safety of acellular UPAL gel implantation in facilitating cartilage repair. Despite being a single-arm study, it demonstrated the efficacy of UPAL gel implantation, suggesting it is an easy-to-use, one-step method of cartilage tissue repair circumventing the need to harvest donor cells.
• AI技術により作成した3D腰神経MRI像を用いたL5/Sレベルの全内視鏡下椎間板ヘルニア摘出術シミュレーションの有用性

  山田 勝久, 長濱 賢, 安倍 雄一郎, 日向寺 義則, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 高畑 雅彦, 須藤 英毅, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1698 - S1698 0021-5325 2023/08
• 骨髄由来間葉系細胞移植による再生医療を背景とした椎間板再生に有効な核酸ターゲットの探索

  大西 貴士, 宝満 健太郎, 須藤 英毅, 山田 勝久, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1858 - S1858 0021-5325 2023/08
• 三次元デプスセンサーと人工知能を用いた側彎角の自動予測 着衣の有無による精度検証

  石川 蓉子, 小甲 晃史, 山田 勝久, 安倍 雄一郎, 舘 弘之, 鈴木 久崇, 大西 貴士, 遠藤 努, 岩崎 倫政, 須藤 英毅

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (8) S1914 - S1914 0021-5325 2023/08
• 腰椎後方除圧術における棘上棘間靱帯・棘突起温存は,術後の二次性椎間板変性の進行を抑制する

  大西 貴士, 中下 並人, 山田 勝久, 須藤 英毅, 岩崎 倫政

  東日本整形災害外科学会雑誌 東日本整形災害外科学会 35 (3) 292 - 292 1342-7784 2023/08
• アテロコラーゲンを用いた自家培養軟骨移植後に軟骨下骨嚢胞を生じた1例

  甲斐原 拓真, 近藤 英司, 濱崎 雅成, 鈴木 裕貴, 岩崎 浩司, 松岡 正剛, 小野寺 智洋, 種井 善一, 田中 伸哉, 岩崎 倫政

  東日本整形災害外科学会雑誌 東日本整形災害外科学会 35 (3) 361 - 361 1342-7784 2023/08
• Incidence and Risk Factors for Pneumonia in the Chronic Phase of Cervical Spinal Cord Injury with Complete Motor Paralysis.

  Chikara Ushiku, Kota Suda, Takehiro Michikawa, Satoko Matsumoto Harmon, Miki Komatsu, Osahiko Tsuji, Masahiko Takahata, Mitsuru Saito, Norimasa Iwasaki, Akio Minami

  Spine surgery and related research 7 (4) 333 - 340 2023/07/27 

  INTRODUCTION: Pneumonia is one of the leading causes of acute- and chronic-phase mortality in patients with cervical spinal cord injury (CSCI) with quadriplegia. The risk factors for chronic-phase pneumonia recurrence in CSCI are still unknown. This study aimed to investigate the incidence of pneumonia in the chronic phase after injury and to identify its risk factors. METHODS: This retrospective clinical observational study included patients with CSCI with American Spinal Injury Association Impairment Scale grades of A or B admitted to our center within 72 h of CSCI injury who started treatment and were available for follow-up for at least 90 days. The patients were assessed for incidences of pneumonia and its associations with clinical characteristics, including risk factors at the time of injury. Patients in whom pneumonia developed within 30 days postadmission and those after 30 days of hospitalization were comparatively examined using univariate and multivariate analyses. RESULTS: Pneumonia occurred in 36% of the 69 enrolled patients throughout the study period and in 20% of all patients after 30 days of hospitalization. Multivariate analysis of risk factors for pneumonia showed that atelectasis (adjusted OR [aOR], 95% confidence interval [CI]: 4.9, 1.2-20.0), enteral feeding (aOR [95% CI]: 13.3 [3.0-58.9]), mechanical ventilation (aOR [95% CI]: 4.0 [1.0-15.0]), and tracheotomy (aOR [95% CI]: 14.6 [2.3-94.6]) within 30 days of admission were significantly associated with the occurrence of pneumonia even after 30 days of hospitalization. CONCLUSIONS: The risk factors for developing pneumonia in the chronic phase were atelectasis, enteral feeding, mechanical ventilation, and tracheotomy within 30 days of hospitalization. This study suggests that treatment of atelectasis, long-term respiratory muscle rehabilitation, and training to improve swallowing function are essential to prevent the recurrence of pneumonia after 30 days of hospitalization.
• Validation of parameters recommended for secondary screening for developmental dysplasia of the hip in Japan.

  Tomohiro Shimizu, Daisuke Takahashi, Hisataka Suzuki, Hirokazu Shimizu, Takuya Ogawa, Shunichi Yokota, Hotaka Ishizu, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2023/07/12 

  BACKGROUND: Based on the Japanese Pediatric Orthopaedic Association's guidelines, secondary screening and imaging including ultrasonography and radiography, are recommended in infants with limited hip abduction (<70°) or in those with multiple risk factors including the following: asymmetrical skin creases, a family history of developmental dysplasia of the hip, female sex, and pelvic position at delivery. However, there is still little information regarding the usefulness of this guideline. The objective of this study was to investigate the association between the risk factors and developmental dysplasia of the hip diagnosed using ultrasound and radiography. METHODS: A total of 356 infants (67 boys and 289 girls) underwent secondary ultrasonographic and radiological screening for developmental dysplasia of the hip in our hospital. Risk factors were documented from their medical records. The recommended item score, which we defined as an integrated value of the recommended item, was calculated for each patient. The limitation of hip abduction alone was a criterion for secondary screening; therefore, we defined the scores as follows: the limitation of hip abduction scored 2 points and other recommended scores were assigned 1 point. If the recommended item score was 2 points or more, we classified the infants as high-risk. RESULTS: A total of 280 of 356 infants were included in the high-risk group, which showed a higher ratio of cases with abnormal imaging findings than the low-risk group. According to the multivariate logistic regression analyses among the recommended items, being female, skin asymmetry, and limb limitation were identified as independent risk factors for imaging abnormality and the need for Pavlik harness treatment. CONCLUSIONS: The recommended items for secondary screening based on the Japanese Pediatric Orthopaedic Association's guidelines could be useful for screening infants in need of treatment.
• High whole-body bone mineral density in ossification of the posterior longitudinal ligament.

  Ryo Fujita, Tsutomu Endo, Masahiko Takahata, Yoshinao Koike, Daisuke Yoneoka, Ryota Suzuki, Masaru Tanaka, Katsuhisa Yamada, Hideki Sudo, Tomoka Hasegawa, Mohamad Alaa Terkawi, Ken Kadoya, Norimasa Iwasaki

  The spine journal : official journal of the North American Spine Society 23 (10) 1461 - 1470 2023/07/10 

  BACKGROUND CONTEXT: Recent studies suggest that ossification of the posterior longitudinal ligament (OPLL) is exacerbated by systemic metabolic disturbances, including obesity. However, although an increase in bone mineral density (BMD) measured at the lumbar spine has been reported in patients with OPLL, no studies have investigated the systemic BMD of patients with OPLL in detail. PURPOSE: We investigated whether patients with OPLL develop increased whole-body BMD. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with symptomatic OPLL (OPLL [+]; n=99). Control data (OPLL [-]; n=226) without spinal ligament ossification were collected from patients who underwent spinal decompression, spinal fusion, or hip replacement surgery. OUTCOME MEASURES: Demographic data, including age, body mass index (BMI), comorbidities, history of treatment for osteoporosis, and history of vertebral and nonvertebral fractures, was obtained from all participants. In addition, whole-body BMD, including the lumbar spine, thoracic spine, femoral neck, skull, ribs, entire upper extremity, entire lower extremity, and pelvis, were measured in all participants using whole-body dual-energy X-ray absorptiometry. METHODS: Patient data were collected from 2018 to 2022. All participants were categorized based on sex, age (middle-aged [<70 years] and older adults [≥70 years]), and OPLL type (localized OPLL [OPLL only in the cervical spine], diffuse OPLL [OPLL in regions including the thoracic spine]), and OPLL [-]) and each parameter was compared. The factors associated with whole-body BMD were evaluated via multivariable linear regression analysis. RESULTS: Compared with the OPLL (-) group, the OPLL (+) group of older women had significantly higher BMD in all body parts (p<.01), and the OPLL (+) group of older men had significantly higher BMD in all body parts except the ribs, forearm, and skull (p<.01). The factors associated with increased BMD of both the femoral neck (load-bearing bone) and skull (nonload-bearing bone) were age, BMI, and coexisting diffuse OPLL in women and BMI and coexisting localized OPLL in men. CONCLUSIONS: Patients with OPLL have increased whole-body BMD regardless of sex, indicating that it is not simply due to load-bearing from obesity. These findings suggested that OPLL is associated with a systemic pathology.
• Complications Associated with Preventive Management to Reduce the Risk of COVID-19 Spread After Surgery for Spinal Cord Injury.

  Hiroki Ushirozako, Kota Suda, Satoko Matsumoto Harmon, Miki Komatsu, Masahiro Ota, Tomoaki Shimizu, Akio Minami, Masahiko Takahata, Norimasa Iwasaki, Yukihiro Matsuyama

  The Journal of bone and joint surgery. American volume 105 (13) 1001 - 1011 2023/07/05 

  BACKGROUND: Preventive management to reduce the risk of coronavirus disease-2019 (COVID-19) spread led to delays in active rehabilitation, which may have negatively impacted the outcomes of patients with traumatic spinal cord injury (SCI). Therefore, the aim of this study was to clarify the influence of preventive management on the rate of perioperative complications after surgical treatment for SCI. METHODS: This single-center retrospective study examined the cases of 175 patients who had SCI surgery between 2017 and 2021. We could not continue early rehabilitation interventions starting on April 30, 2020, because of our preventive management to reduce the risk of COVID-19 spread. Using a propensity score-matched model, we adjusted for age, sex, American Spinal Injury Association impairment scale score at admission, and risk factors for perioperative complications described in previous studies. Perioperative complication rates were compared between the COVID-19 pandemic and prepandemic groups. RESULTS: Of the 175 patients, 48 (the pandemic group) received preventive management. The preliminary analysis revealed significant differences between the unmatched pandemic and prepandemic groups with respect to age (75.0 versus 71.2 years, respectively; p = 0.024) and intraoperative estimated blood loss (152 versus 227 mL; p = 0.013). The pandemic group showed significant delays in visiting the rehabilitation room compared with the prepandemic group (10 versus 4 days from hospital admission; p < 0.001). There were significant differences between the pandemic and prepandemic groups with respect to the rates of pneumonia (31% versus 16%; p = 0.022), cardiopulmonary dysfunction (38% versus 18%; p = 0.007), and delirium (33% versus 13%; p = 0.003). With a propensity score-matched analysis (C-statistic = 0.90), 30 patients in the pandemic group and 60 patients in the prepandemic group were automatically selected. There were significant differences between the matched pandemic and prepandemic groups with respect to the rates of cardiopulmonary dysfunction (47% versus 23%; p = 0.024) and deep venous thrombosis (60% versus 35%; p = 0.028). CONCLUSIONS: Even with early surgical intervention, late mobilization and delays in active rehabilitation during the COVID-19 pandemic increased perioperative complications after SCI surgery. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.
• Bone metastatic cancer of unknown primary at initial presentation.

  Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Yuki Suzuki, Hamasaki Masanari, Eiji Kondo, Norimasa Iwasaki

  Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 26 (2) 461 - 467 2023/07/03 

  INTRODUCTION: Cancer of unknown primary (CUP) is a challenging malignancy. The purpose of this study was to investigate the clinical characteristics and prognosis of bone metastatic CUP using the population-based Surveillance, Epidemiology, and End Results (SEER) database. METHODS: From the SEER database, we identified 1908 patients with bone metastatic CUP at initial presentation between 2010 and 2018. Histology was subdivided following International Classification of Diseases for Oncology codes as Adenocarcinoma, Squamous cell, Neuroendocrine, or Carcinoma not otherwise specified (NOS). Cox proportional hazard modeling was applied using factors of age, sex, ethnicity, histological subtype, and therapeutic intervention. RESULTS: Among the 1908 patients, histology was Neuroendocrine in 240 patients, Squamous cell in 201 patients, Adenocarcinoma in 810 patients and NOS in 657 patients. In each subtype, patients tended to be predominantly male and white. Chemotherapy was introduced for 28% of patients and radiation for 34% in the entire cohort. Survival in patients with bone metastatic CUP was unfavorable, with a median survival of 2 months. Among the histological subtypes, Adenocarcinoma showed shorter survival than the other groups. In addition, treatment interventions such as chemotherapy and radiation therapy prolonged survival, particularly for Squamous cell, Adenocarcinoma and NOS, but not for Neuroendocrine. DISCUSSION: Bone metastatic CUP showed extremely poor prognosis, but treatment interventions such as chemotherapy and radiation generally offered survival benefits. Further randomized clinical research is needed to confirm the present results.
• RANKL中和抗体中止後の骨吸収過剰亢進におけるメカニズム解明アプローチ

  石津 帆高, 清水 智弘, 長谷川 智香, 網塚 憲生, 岩崎 倫政

  日本骨代謝学会学術集会プログラム抄録集 (一社)日本骨代謝学会 41回 141 - 141 1349-0761 2023/07
• 腰椎後方除圧術における棘上棘間靱帯・棘突起温存は、術後の二次性椎間板変性の進行を抑制する

  大西 貴士, 中下 並人, 楫野 知道, 久田 雄一郎, 山田 勝久, 須藤 英毅, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 42 (3) 189 - 189 1883-2873 2023/06
• 薬剤誘発性FGF23関連低リン血症性骨軟化症に伴う両側大腿骨頭軟骨下脆弱性骨折の1例

  奥村 眞子, 清水 智弘, 石津 帆高, 横田 隼一, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 42 (3) 129 - 129 1883-2873 2023/06
• 臼蓋骨欠損に対してKerboull-type plateとMetal meshを用いた人工股関節再置換術の術後成績の比較検討

  石津 帆高, 清水 智弘, 笹沢 史生, 高橋 大介, 金山 雅弘, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 42 (3) 183 - 183 1883-2873 2023/06
• 人工股関節全置換術におけるヘッド延長の脚長、オフセット、可動域に与える影響

  宮崎 拓自, 清水 智弘, 小川 拓也, 高橋 大介, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 42 (3) 187 - 187 1883-2873 2023/06
• 大腿骨寛骨臼インピンジメントと発育性股関節形成不全の股関節応力分布に与える影響の比較

  小川 裕生, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 42 (3) 187 - 187 1883-2873 2023/06
• SLEモデルマウスに対するステロイドパルス治療の大腿骨頭血流に与える影響の検証

  横田 隼一, 清水 智弘, 高橋 大介, 岩崎 倫政, 石津 明洋

  日本関節病学会誌 (一社)日本関節病学会 42 (3) 256 - 256 1883-2873 2023/06
• 腰椎後方除圧術における棘上棘間靱帯・棘突起温存は、術後の二次性椎間板変性の進行を抑制する

  大西 貴士, 中下 並人, 楫野 知道, 久田 雄一郎, 山田 勝久, 須藤 英毅, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 42 (3) 189 - 189 1883-2873 2023/06
• コロナ禍で始まった大腿骨近位部骨折リエゾンサービス1年後の骨粗鬆症加療状況

  下段 俊, 清水 智弘, 梅本 貴央, 百貫 亮太, 高橋 大介, 岩崎 倫政

  骨折 (一社)日本骨折治療学会 45 (Suppl.) S283 - S283 0287-2285 2023/06
• Computer model of IL-6-dependent rheumatoid arthritis in F759 mice

  Reiji Yamamoto, Satoshi Yamada, Toru Atsumi, Kaoru Murakami, Ari Hashimoto, Seiichiro Naito, Yuki Tanaka, Izuru Ohki, Yuta Shinohara, Norimasa Iwasaki, Akihiko Yoshimura, Jing-Jing Jiang, Daisuke Kamimura, Shintaro Hojyo, Shimpei I Kubota, Shigeru Hashimoto, Masaaki Murakami

  International Immunology 35 (9) 403 - 421 2023/05/25 

  Abstract The interleukin-6 (IL-6) amplifier, which describes the simultaneous activation of signal transducer and activator of transcription 3 (STAT3) and NF-κb nuclear factor kappa B (NF-κB), in synovial fibroblasts causes the infiltration of immune cells into the joints of F759 mice. The result is a disease that resembles human rheumatoid arthritis. However, the kinetics and regulatory mechanisms of how augmented transcriptional activation by STAT3 and NF-κB leads to F759 arthritis is unknown. We here show that the STAT3-NF-κB complex is present in the cytoplasm and nucleus and accumulates around NF-κB binding sites of the IL-6 promoter region and established a computer model that shows IL-6 and IL-17 (interleukin 17) signaling promotes the formation of the STAT3-NF-κB complex followed by its binding on promoter regions of NF-κB target genes to accelerate inflammatory responses, including the production of IL-6, epiregulin, and C-C motif chemokine ligand 2 (CCL2), phenotypes consistent with in vitro experiments. The binding also promoted cell growth in the synovium and the recruitment of T helper 17 (Th17) cells and macrophages in the joints. Anti-IL-6 blocking antibody treatment inhibited inflammatory responses even at the late phase, but anti-IL-17 and anti-TNFα antibodies did not. However, anti-IL-17 antibody at the early phase showed inhibitory effects, suggesting that the IL-6 amplifier is dependent on IL-6 and IL-17 stimulation at the early phase, but only on IL-6 at the late phase. These findings demonstrate the molecular mechanism of F759 arthritis can be recapitulated in silico and identify a possible therapeutic strategy for IL-6 amplifier-dependent chronic inflammatory diseases.
• Dyslipidemia as a novel risk for the development of symptomatic ossification of the posterior longitudinal ligament.

  Shotaro Fukada, Tsutomu Endo, Masahiko Takahata, Masahiro Kanayama, Yoshinao Koike, Ryo Fujita, Ryota Suzuki, Toshifumi Murakami, Tomoka Hasegawa, Mohamad Alaa Terkawi, Tomoyuki Hashimoto, Kastuhisa Yamada, Hideki Sudo, Ken Kadoya, Norimasa Iwasaki

  The spine journal : official journal of the North American Spine Society 23 (9) 1287 - 1295 2023/05/07 

  BACKGROUND CONTEXT: Obesity and visceral fat have been implicated as potential factors in the pathogenesis of the ossification of the posterior longitudinal ligament (OPLL); the details of the factors involved in OPLL remain unclear. PURPOSE: We aimed to determine the association between dyslipidemia and symptomatic OPLL. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with OPLL (n=92) who underwent whole-spine computed tomography scanning. Control data (n=246) without any spinal ligament ossification were collected from 627 Japanese participants who underwent physical examination. OUTCOME MEASURES: Baseline information and lipid parameters, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from fasting blood samples were collected to assess the comorbidity of dyslipidemia. METHODS: Patient data were collected from 2020 to 2022. Patients with dyslipidemia were defined as those who were taking medication for dyslipidemia and who met one of the following criteria: TG ≥150 mg/dL, LDL-C ≥140 mg/dL, and/or HDL-C <40 mg/dL. The factors associated with OPLL development were evaluated using multivariate logistic regression analysis. RESULTS: The comorbidity of dyslipidemia in the OPLL group was more than twice that in the control group (71.7% and 35.4%, respectively). The mean body mass index (BMI) of the OPLL group was significantly higher than that of the control group (27.2 kg/m2 and 23.0 kg/m2). Multivariate logistic regression analysis revealed that dyslipidemia was associated with the development of OPLL (regression coefficient, 0.80; 95% confidence interval, 0.11-1.50). Additional risk factors included age, BMI, and diabetes mellitus. CONCLUSIONS: We demonstrated a novel association between dyslipidemia and symptomatic OPLL development using serum data. This suggests that visceral fat obesity or abnormal lipid metabolism are associated with the mechanisms of onset and exacerbation of OPLL as well as focal mechanical irritation due to being overweight.
• Bilateral Humeral Retrotorsion Angle Measured Using an Ultrasound-Assisted Technique in Asian Baseball Players.

  Shota Ike, Daisuke Momma, Kyosuke Numaguchi, Yuki Matsui, Masashi Yokota, Jun Oohinata, Eiji Kondo, Norimasa Iwasaki

  Orthopaedic journal of sports medicine 11 (5) 23259671231166927 - 23259671231166927 2023/05 

  BACKGROUND: Repetitive pitching is thought to restrict the physiological derotation process of the humeral head. Some studies have reported that side-to-side differences in the humeral retrotorsion angle (ΔHRA) occur between the ages of 9 and 11 years in baseball players. However, it remains unclear whether the ΔHRA in Asian baseball players depends on pitching skill or competitive level. PURPOSE: To evaluate the ΔHRA in Asian collegiate and professional baseball players and to determine the effects of pitching activity on the physiological derotation process of the humeral head. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: We evaluated 128 shoulders in 64 Asian baseball players who were stratified into 4 groups as follows: 13 professional pitchers; 9 professional fielders; 8 collegiate pitchers; and 34 collegiate fielders. The throwing and nonthrowing side HRA was assessed using an ultrasound-assisted technique, and the ΔHRA was compared among the 4 groups. In addition, Pearson correlation analysis was used to assess the relationship between ΔHRA and glenohumeral range of motion, baseball starting age, and fastball velocity in pitchers. RESULTS: The HRA was significantly greater in the throwing arm than in the nonthrowing arm in each group, with no significant differences among the groups. There was no correlation between ΔHRA and range of motion or fastball velocity. There was a significant negative correlation between baseball starting age and ΔHRA in professional fielders (r = -0.633; P = .036). CONCLUSION: The findings of the present study provide evidence that in Asian baseball players, the HRA was significantly greater in the throwing arm than in the nonthrowing arm. There were no clear associations between HRA and pitching ability or competitive level.
• Evaluation of Surgical Indications for Full Endoscopic Discectomy at Lumbosacral Disc Levels Using Three-Dimensional Magnetic Resonance/Computed Tomography Fusion Images Created with Artificial Intelligence.

  Katsuhisa Yamada, Ken Nagahama, Yuichiro Abe, Yoshinori Hyugaji, Daisuke Ukeba, Tsutomu Endo, Takashi Ohnishi, Katsuro Ura, Hideki Sudo, Norimasa Iwasaki, Masahiko Takahata

  Medicina (Kaunas, Lithuania) 59 (5) 2023/04/28 

  Background and Objectives: Although full endoscopic lumbar discectomy with the transforaminal approach (FED-TF) is a minimally invasive spinal surgery for lumbar disc herniation, the lumbosacral levels present anatomical challenges when performing FED-TF surgery due to the presence of the iliac bone. Materials and Methods: In this study, we simulated whether FED-TF surgery could be safely performed on a total of 52 consecutive cases with L5-S1 or L5-L6 disc herniation using fused three-dimensional (3D) images of the lumbar nerve root on magnetic resonance imaging (MRI) created with artificial intelligence and of the lumbosacral spine and iliac on computed tomography (CT) images. Results: Thirteen of the fifty-two cases were deemed operable according to simulated FED-TF surgery without foraminoplasty using the 3D MRI/CT fusion images. All 13 cases underwent FED-TF surgery without neurological complications, and their clinical symptoms significantly improved. Conclusions: Three-dimensional simulation may allow for the assessment from multiple angles of the endoscope entry and path, as well as the insertion angle. FED-TF surgery simulation using 3D MRI/CT fusion images could be useful in determining the indications for full endoscopic surgery for lumbosacral disc herniation.
• Symptomatic bilateral complete discoid medial menisci of the knee in a child: A case report.

  Yuki Suzuki, Eiji Kondo, Takuma Kaibara, Masatake Matsuoka, Ryosuke Hishimura, Koji Iwasaki, Tomohiro Onodera, Daisuke Momma, Shinya Tanaka, Norimasa Iwasaki

  Joint diseases and related surgery 34 (2) 455 - 462 2023/04/26 

  Bilateral complete discoid medial menisci are extremely rare congenital anatomic variants of the knee. Currently, arthroscopic partial meniscectomy with or without peripheral suture repair is performed for symptomatic discoid meniscus. However, most of the outcomes are short-term. In this article, we present a pediatric case of symptomatic bilateral complete discoid medial menisci and highlight the effectiveness of arthroscopic partial meniscectomy with or without peripheral suture on symptomatic complete discoid medial menisci based on 60-month excellent clinical and functional results.
• Anatomical and Simulation Studies Based on Three-Dimensional-Computed Tomography Image Reconstruction of Femoral Offset.

  Tomohiro Shimizu, Daisuke Takahashi, Hotaka Ishizu, Shunichi Yokota, Yoshihiro Hasebe, Keita Uetsuki, Norimasa Iwasaki

  Diagnostics (Basel, Switzerland) 13 (8) 2023/04/16 

  Although the hip joint morphology varies by race, few studies have investigated the associations between two-dimensional (2D) and three-dimensional (3D) morphologies. This study aimed to use computed tomography simulation data and radiographic (2D) data to clarify the 3D length of offset, 3D changes in the hip center of rotation, and femoral offset as well as investigate the anatomical parameters associated with the 3D length and changes. Sixty-six Japanese patients with a normal femoral head shape on the contralateral side were selected. In addition to radiographic femoral, acetabular, and global offsets, 3D femoral and cup offsets were investigated using commercial software. Our findings revealed that the mean 3D femoral and cup offsets were 40.0 mm and 45.5 mm, respectively; both were distributed around the mean values. The difference between the 3D femoral and cup offsets (i.e., 5 mm) was associated with the 2D acetabular offset. The 3D femoral offset was associated with the body length. In conclusion, these findings can be applied to the design of better ethnic-specific stem designs and can help physicians achieve more accurate preoperative diagnoses.
• Secondary fracture rates and risk factors 1 year after a proximal femoral fracture under FLS.

  Hotaka Ishizu, Tomohiro Shimizu, Shu Yamazaki, Yusuke Ohashi, Komei Sato, Shun Shimodan, Norimasa Iwasaki

  Journal of bone and mineral metabolism 41 (4) 1 - 8 2023/04/10 

  INTRODUCTION: We aimed to investigate the secondary fracture rates and risk factors in patients with proximal femoral fractures using fracture liaison service (FLS) during the coronavirus disease (COVID)-19 pandemic. MATERIALS AND METHODS: In this multi-center prospective cohort study, patients with proximal femoral fractures who were treated surgically at three hospitals from April 2020 to March 2021 were included. Follow-up examinations at 6 and 12 months postoperatively were conducted to investigate the clinical data and ascertain whether osteoporosis treatment could be continued. RESULTS: A total of 316 patients with proximal femoral fractures were registered. During the follow-up period, 17 patients died and 67 patients could not visit the hospitals owing to the COVID-19 pandemic. In total, 172 patients who could be followed-up 12 months postoperatively were examined using dual-energy X-ray absorptiometry during hospitalization; underwent postoperative osteoporosis treatment, mainly with bisphosphonates (89.5%); and were administered medications continuously. Secondary fractures occurred within 1 year in 14 patients (8.1%). Multivariate analysis showed that patients who used sleeping pills and had a lower functional independence measure had an increased risk for developing secondary fractures. CONCLUSION: During the COVID-19 pandemic, secondary fractures can be prevented if the patients can be followed and osteoporosis treatment can be continued. Conversely, despite adequate osteoporosis drug examination and treatment, a certain number of secondary fractures still occurred. The finding that postoperative osteoporosis therapy using routine medications and rehabilitation is associated with secondary fractures may support the importance of establishing clinical standards consisting of a multidisciplinary collaboration for FLS.
• Comparison of the Efficacy of Zoledronate Acid or Denosumab After Switching from Romosozumab in Japanese Postmenopausal Patients.

  Tetsuro Oue, Tomohiro Shimizu, Tsuyoshi Asano, Shun Shimodan, Hotaka Ishizu, Kosuke Arita, Norimasa Iwasaki

  Calcified tissue international 112 (6) 683 - 690 2023/04/10 

  We aimed to compare the efficacy of switching from romosozumab (RMAb) to denosumab (DMAb) or zoledronic acid (Zol) with respect to changes in bone mineral density (BMD) and bone metabolism. We also aimed to determine predictors of changes in BMD among patients who received sequential therapy from RMAb. One hundred patients who received RMAb therapy were recruited for this study. A total 49 patients received bisphosphonate (BP) pre-treatment and 51 received active vitamin D3 analog pre-treatment or no treatment. Forty-two patients were switched to Zol (BP-RMAb-Zol; 20 and RMAb-Zol; 22), and 58 patients were switched to DMAb (BP-RMAb-DMAb; 29 and RMAb-DMAb; 29). Longitudinal changes in bone metabolic markers (P1NP and TRACP-5b) and BMD were also evaluated. In the BP-RMAb-Zol group, TRACP-5b increased after administration of Zol, and the mean BMD of the lumbar spine (LS) was significantly lower than those in the BP-RMAb-DMAb, RMAb-Zol and RMAb-DMAb groups at 24 months. The % changes in BMD of the LS after 24 months were associated with TRACP-5b values at baseline and at 12 months in patients who received Zol therapy, and with TRACP-5b value at baseline in patients who received DMAb therapy. The DMAb follow-on regimen could be considered more effective than Zol as a sequential agent for the enhancement of BMD after RMAb in patients with BP pretreatment. TRACP-5b, especially the baseline value, may predict the efficacy of sequential therapy from RMAb, as well as previous treatments.
• 3次元デプスセンサーと人工知能を用いた側彎角の自動予測 着衣の有無による精度検証

  石川 蓉子, 小甲 晃史, 山田 勝久, 舘 弘之, 鈴木 久崇, 大西 貴士, 安倍 雄一郎, 岩崎 倫政, 須藤 英毅

  Journal of Spine Research (一社)日本脊椎脊髄病学会 14 (3) 136 - 136 1884-7137 2023/04
• AIにて自動作成した3D腰椎神経根画像を用いた全内視鏡下経椎間孔アプローチ手術における安全域の形態解析 進入角度・腰椎高位別解析

  山田 勝久, 長濱 賢, 安倍 雄一郎, 日向寺 義則, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 高畑 雅彦, 須藤 英毅, 岩崎 倫政

  Journal of Spine Research (一社)日本脊椎脊髄病学会 14 (3) 205 - 205 1884-7137 2023/04
• AI技術を用いて作成した3次元腰神経画像によるL5/Sレベルの全内視鏡下椎間板ヘルニア摘出術(FED)の手術適応可否の評価

  山田 勝久, 長濱 賢, 安倍 雄一郎, 日向寺 義則, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 高畑 雅彦, 須藤 英毅, 岩崎 倫政

  Journal of Spine Research (一社)日本脊椎脊髄病学会 14 (3) 308 - 308 1884-7137 2023/04
• Lenke 5特発性側彎症における最下位固定椎の側方変位がL4傾斜と冠状面バランスに与える影響 術式別解析

  山田 勝久, 須藤 英毅, 安倍 雄一郎, 小甲 晃史, 舘 弘之, 遠藤 努, 大西 貴士, 高畑 雅彦, 岩崎 倫政

  Journal of Spine Research (一社)日本脊椎脊髄病学会 14 (3) 401 - 401 1884-7137 2023/04
• 腰椎後方除圧術における棘上棘間靱帯・棘突起温存は,術後の二次性椎間板変性の進行を抑制する

  大西 貴士, 中下 並人, 楫野 知道, 久田 雄一郎, 山田 勝久, 須藤 英毅, 岩崎 倫政

  Journal of Spine Research (一社)日本脊椎脊髄病学会 14 (3) 442 - 442 1884-7137 2023/04
• Peripheral nerve-derived fibroblasts promote neurite outgrowth in adult dorsal root ganglion neurons more effectively than skin-derived fibroblasts.

  Masato Hara, Ken Kadoya, Takeshi Endo, Norimasa Iwasaki

  Experimental physiology 108 (4) 621 - 635 2023/04 

  NEW FINDINGS: What is the central question of this study? Although fibroblasts are involved in the regenerative process associated with peripheral nerve injury, detailed information regarding their characteristics is largely lacking. What is the main finding and its importance? Nerve-derived fibroblasts have a greater neurite-promoting effect than skin-derived fibroblasts, and epineurium-derived fibroblasts can promote neurite outgrowth more effectively than parenchyma-derived fibroblasts. The epineurium-derived fibroblasts and parenchyma-derived fibroblasts have distinctly different molecular profiles, including genes of soluble factors to promote axonal growth. Fibroblasts are molecularly and functionally different depending on their localization in nerve tissue, and epineurium-derived fibroblasts might be involved in axon regeneration after peripheral nerve injury more than previously thought. ABSTRACT: Although fibroblasts (Fb) are components of a peripheral nerve involved in the regenerative process associated with peripheral nerve injury, detailed information regarding their characteristics is largely lacking. The objective of the present study was to investigate the capacity of Fb derived from peripheral nerves to stimulate the outgrowth of neurites from adult dorsal root ganglion neurons and to clarify their molecular characteristics. Fibroblasts were prepared from the epineurium and parenchyma of rat sciatic nerves and skin. The Fb derived from epineurium showed the greatest effect on neurite outgrowth, followed by the Fb derived from parenchyma, indicating that Fb derived from nerves promote neurite outgrowth more effectively than skin-derived Fb. Although both soluble and cell-surface factors contributed evenly to the neurite-promoting effect of nerve-derived Fb, in crush and transection injury models, Fb were not closely associated with regenerating axons, indicating that only soluble factors from Fb are available to regenerating axons. A transcriptome analysis revealed that the molecular profiles of these Fb were distinctly different and that the gene expression profiles of soluble factors that promote axonal growth are unique to each Fb. These findings indicate that Fb are molecularly and functionally different depending on their localization in nerve tissue and that Fb derived from epineurium might be involved more than was previously thought in axon regeneration after peripheral nerve injury.
• Effects of Preserving Anatomically Positioned and Adequate Remnant ACL Tissue in Double-Bundle ACL Reconstruction.

  Dai Sato, Masayuki Inoue, Yasuhiko Kasahara, Hiroki Hamano, Ryota Suzuki, Eiji Kondo, Norimasa Iwasaki

  Orthopaedic journal of sports medicine 11 (4) 23259671231162389 - 23259671231162389 2023/04 

  BACKGROUND: The advantages of remnant tissue preservation in anterior cruciate ligament (ACL) reconstruction (ACLR) remain controversial. HYPOTHESIS: It was hypothesized that a large amount of remnant tissue, especially if anatomically positioned, would improve patient-reported outcomes and second-look graft appearance after preserved double-bundle ACLR (DB-ACLR). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective study included 89 consecutive patients who underwent unilateral remnant-preserving DB-ACLR using 2 hamstring tendon autografts. The authors categorized the arthroscopic findings into 3 groups according to the location and volume of the ACL remnant tissue in the femoral notch: (1) anatomical attachment (group AA; n = 34); (2) nonanatomical attachment (group NA; n = 33); and (3) no remnant (group NR; n = 22). Based on second-look arthroscopy, the reconstructed graft was graded as excellent, fair, or poor. Patient-reported outcomes were evaluated at 2 years after surgery using the Knee injury and Osteoarthritis Outcome Score (KOOS) and the Japanese Anterior Cruciate Ligament Questionnaire-25 (JACL-25). RESULTS: The AA and NA groups had a significantly shorter time from injury to surgery compared with the NR group (P = .0165). Considering the second-look arthroscopic findings, the authors found a significant difference in synovial coverage of the grafts between the 3 groups (P = .0018). There were no significant differences in the overall KOOS and JACL-25 score among the 3 groups; however, the KOOS-Sport and Recreation and KOOS-Quality of Life subscale scores were significantly higher in the AA group compared with the NA and NR groups (P = .0014 and .0039, respectively). The JACL-25 score for middle- to high-speed flexion and extension was significantly better in the AA group versus the NR group (P = .0261). CONCLUSION: This study showed that preserving anatomically positioned and adequate remnant tissue during DB-ACLR improved second-look graft appearance and KOOS-Sport and Recreation and KOOS-Quality of Life scores.
• Simultaneous and sialic acid linkage-specific N- and O-linked glycan analysis by ester-to-amide derivatization.

  Hisatoshi Hanamatsu, Yoshiaki Miura, Takashi Nishikaze, Ikuko Yokota, Kentaro Homan, Tomohiro Onodera, Yoshihiro Hayakawa, Norimasa Iwasaki, Jun-Ichi Furukawa

  Glycoconjugate journal 40 (2) 259 - 267 2023/04 

  Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. Most O-glycans are modified with sialic acid residues at the non-reducing termini through various linkages. In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans was performed, and the resulting sialylated glycan isomers were discriminated by mass spectrometry. In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. This novel glycomic approach will facilitate detailed characterization of biologically relevant sialylated N- and O-glycans on glycoproteins.
• Clinical outcomes of short-segment lumbar fusion in patients older than 85 years with a minimum 2-year follow-up.

  Takeru Tsujimoto, Ryo Itoga, Masahiro Kanayama, Fumihiro Oha, Yukitoshi Shimamura, Masaru Tanaka, Yuichi Hasegawa, Syotaro Fukada, Tomoyuki Hashimoto, Masahiko Takahata, Norimasa Iwasaki

  Journal of neurosurgery. Spine 39 (1) 1 - 7 2023/03/24 

  OBJECTIVE: Although the number of elderly patients requiring lumbar fusion for lumbar degenerative disorders has increased over time, the postoperative outcomes of lumbar fusion in very elderly patients (> 85 years) remains unknown. This study aimed to evaluate the comprehensive outcomes of lumbar fusion in elderly patients older than 85 years with mid-term follow-up. METHODS: The authors retrospectively researched patients older than 85 years who underwent single- or double-level posterior lumbar interbody fusion or transforaminal lumbar interbody fusion from 2012 to 2019. Twenty-nine patients who had at least 2 years of follow-up were included in this study. The average age was 86.4 years, and the average follow-up period was 42.2 months. Each patient was matched with 60- to 75-year-old controls. The Oswestry Disability Index (ODI) score; Roland-Morris Disability Questionnaire (RMDQ) score; Japanese Orthopaedic Association (JOA) score; JOA recovery rate; and low-back pain (LBP), leg pain, and leg numbness visual analog scale (VAS) scores were obtained. The spinopelvic parameters were measured using lateral standing radiographs of the whole spine. RESULTS: Although there were no significant differences in the ODI, RMDQ, JOA recovery rate, and leg pain and leg numbness VAS scores at 2 years postoperatively between the very elderly and control groups, the VAS LBP score was significantly lower in the very elderly group than in the control group. Preoperative and postoperative sagittal vertical axes were significantly higher and sacral slopes were significantly lower in the very elderly group than in the control group. The incidences of postoperative delirium and new lumbar vertebral fracture were significantly higher in the very elderly group (17.2%) than in the control group (4.6%). CONCLUSIONS: This study showed that lumbar fusion could be performed in patients older than 85 years with satisfactory postoperative outcomes at the 2-year follow-up. In contrast, progressive spinopelvic sagittal imbalance, the incidence of lumbar vertebral fracture up to the final follow-up, and postoperative delirium were greater in the very elderly group than in the control group.
• Supratentorial multifocal gliomas associated with Ollier disease harboring IDH1 R132H mutation: A case report.

  Hiroshi Ikeda, Shigeru Yamaguchi, Yukitomo Ishi, Kento Wakabayashi, Ai Shimizu, Hiromi Kanno-Okada, Takeshi Endo, Mitsutoshi Ota, Michinari Okamoto, Hiroaki Motegi, Norimasa Iwasaki, Miki Fujimura

  Neuropathology : official journal of the Japanese Society of Neuropathology 43 (5) 413 - 420 2023/03/20 

  Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.
• Macrophage‐derived extracellular vesicles trigger non‐canonical pyroptosis in chondrocytes leading to cartilage catabolism in osteoarthritis

  Taku Ebata, Mohamad Alaa Terkawi, Keita Kitahara, Syunichi Yokota, Junki Shiota, Yoshio Nishida, Gen Matsumae, Hend Alhasan, Masanari Hamasaki, Kazutoshi Hontani, Tomohiro Shimizu, Daisuke Takahashi, Tsutomu Endo, Tomohiro Onodera, Ken Kadoya, Norimasa Iwasaki

  Arthritis & Rheumatology 75 (8) 1358 - 1369 2023/03/16 

  OBJECTIVES: The severity of osteoarthritis and cartilage degeneration are highly correlated with the development of synovitis, which is mediated by the activity of inflammatory macrophages. A better understanding of intercellular communication between inflammatory macrophages and chondrocytes should aid in the discovery of novel therapeutic targets. Here, we explored the pathological role of inflammatory macrophage extracellular vesicles in cartilage degeneration. METHODS: Macrophages were stimulated by treatment with bacterial lipopolysaccharides to mimic the state of inflammatory macrophages and the resulting extracellular vesicles were harvested for chondrocyte stimulation in vitro and intraarticular injection in a mouse model. The stimulated chondrocytes were further subjected to RNA-seq analysis and other functional assays. The action of caspase-11 was disrupted in vitro using a specific siRNA or wedelolactone, and in experimental OA-murine models by the intraarticular injection of wedelolactone. RESULTS: Stimulated chondrocytes exhibited a significant elevation in the expression of chondrocyte catabolic factors. Consistent with these results, RNA-seq analyses of stimulated chondrocytes indicated that upregulated genes are mainly categorized into apoptotic process and TNF-signaling pathway which suggests the induction of apoptotic process. Moreover, these chondrocytes exhibited a significant elevation in the expression of pyroptosis-related molecules that were correlated with the expression of chondrocyte catabolic factors. The disruption of caspase-11 significantly alleviated pyroptotic and catabolic processes in stimulated chondrocytes and the pathological changes in collagenase-and joint instability-induced OA models. CONCLUSIONS: Our results provide a new insight into the pathological mechanisms of OA and suggest that non-canonical pyroptosis in chondrocytes represents an attractive therapeutic target for future treatment.
• Amputation surgery associated with shortened survival in patients with localized soft tissue sarcoma.

  Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Masanari Hamasaki, Akira Iwata, Eiji Kondo, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 29 (2) 637 - 645 2023/03/15 

  BACKGROUND: The objectives of this study were to clarify whether localized extremity soft tissue sarcoma (STS) patients who underwent amputation surgery experienced worsened survival and to identify those patients for whom amputation surgery worsened survival. METHODS: Using the Surveillance, Epidemiology, and End Results database, we identified 8897 patients with localized extremity STS between 1983 and 2016. Of these 6431 patients, 733 patients underwent amputation surgery (Amputation group), and 5698 underwent limb-sparing surgery (Limb-sparing group). RESULTS: After adjusting for patient background by propensity score matching, a total of 1346 patients were included. Patients in the Amputation group showed worsened survival (cancer-specific survival (CSS): hazard ratio (HR) = 1.42, 95% confidence interval (CI) 1.15-1.75, overall survival (OS): HR = 1.41, 95%CI 1.20-1.65). In subclass analysis, patients with high-grade STS, spindle cell sarcoma and liposarcoma in the Amputation group showed shortened survival (high-grade-CSS: HR = 1.44, 95%CI 1.16-1.77, OS: HR = 1.38, 95%CI 1.18-1.62; spindle cell sarcoma-CSS: HR = 4.75, 95%CI 1.56-14.4, OS: HR = 2.32, 95%CI 1.45-3.70; liposarcoma-CSS: HR = 2.91, 95%CI 1.54-5.50, OS: HR = 2.32, 95%CI 1.45-3.70). CONCLUSIONS: Survival was shortened in localized extremity STS patients who received amputation surgery.
• 大腿骨顆間外側壁における骨密度分布 前十字靱帯の大腿骨付着部に関する考察

  菅原 悠太郎, 岩崎 浩司, 遠藤 香織, 菱村 亮介, 松原 新史, 松岡 正剛, 門間 太輔, 小野寺 智洋, 近藤 英司, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (2) S193 - S193 0021-5325 2023/03
• 慢性絞扼性神経障害の新規動物モデル開発と病態解明

  山本 康弘, 角家 健, 内藤 聖人, 石島 旨章, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (2) S316 - S316 0021-5325 2023/03
• 遠隔転移を有する軟部肉腫症例において原発巣切除は生存を延長する SEERデータベースを用いた研究

  松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 松原 新史, 菱村 亮介, 近藤 英司, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 64 (2) 49 - 58 1343-3873 2023/03 

  【目的】本研究の目的は,遠隔転移を有する四肢発生軟部肉腫(Soft tissue sarcoma:STS)症例について,原発巣切除が生存を延長するか否かを明らかにし,さらに原発巣切除を考慮すべき患者群を明らかにすることである.【方法】SEERデータベースを用いて,1983年から2016年の間に初診時に遠隔転移を有する四肢発生STS1453例を抽出した.そのうち原発巣切除を施行された患者は898名,されなかった症例は555名であった.傾向スコアマッチングにより患者背景を調整後,804名を解析対象とし切除群では生存が延長した(Cancer specific survival(CSS):Hazard ratio[HR]=0.59,95% confidence interval[CI]0.50-0.71;Overall survival[OS]:HR=0.60,95% CI 0.60-0.71).サブクラス解析では,病理学的高悪性度腫瘍や未分化多形肉腫,平滑筋肉腫,滑膜肉腫症例において,原発巣切除は生存を改善した(高悪性度;CSS:HR=0.57,95% CI 0.45-0.72,OS:HR=0.58,95% CI 0.48-0.71,未分化多形肉腫;CSS:HR=0.60,95% CI 0.42-0.84,OS:HR=0.61,95% CI 0.46-0.82,平滑筋肉腫;CSS:HR=0.50,95% CI 0.33-0.75,OS HR=0.50,95% CI 0.35-0.72,滑膜肉腫;CSS:HR=0.46,95% CI 0.31-0.68,OS:HR=0.43,95% CI 0.30-0.62).【結語】本研究は,遠隔転移を有する四肢発生STS症例において原発巣切除術が生存を延長することを示した.今後,本研究結果を追試するための前向き臨床試験が必要である.(著者抄録)
• 三次元デプスセンサーと人工知能を用いた側彎角の自動予測 着衣の有無による精度検証

  石川 蓉子, 小甲 晃史, 山田 勝久, 舘 弘之, 鈴木 久崇, 大西 貴士, 安倍 雄一郎, 岩崎 倫政, 須藤 英毅

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (3) S905 - S905 0021-5325 2023/03
• ステロイド関連特発性大腿骨頭壊死症における多発骨壊死の関連因子

  菅原 悠太郎, 清水 智弘, 横田 隼一, 石津 帆高, 宮崎 拓自, 小川 拓也, 高橋 大介, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 42 (1) 30 - 33 1883-2873 2023/03 

  目的:特発性大腿骨頭壊死症患者(ONFH)が股関節以外に骨壊死を引き起こす多発骨壊死は,3関節以上と定義した際には約3%とこれまで報告されてきた。一方で,無症候性壊死を検出感度の高い全身MRIを用いた先行研究では,ONFH患者の約25%に多発骨壊死が発生し全例ステロイド関連ONFHであった。そこで本研究は,ステロイド関連ONFH症例を対象として,多発骨壊死の関連性を調査することを目的とした。方法:対象は当院における定点モニタリング対象となったONFH症例328名のうち,特発性ONFH 9名,アルコール関連ONFH 75名およびデータ詳細不明の16名を除外したステロイド関連ONFH 228名(男性108名,女性120名)である。基礎疾患,ステロイド投与最大量,ステロイドパルス療法,アルコール,喫煙,股関節以外の関節の骨壊死発生を調査した。結果:多発骨壊死は228名中59名(男性24名,女性35名)に生じていた。多発骨壊死症を生じたONFH症例は,若年,両側ONFH症例,ステロイド高用量,ステロイドパルス症例,喫煙,全身性エリテマトーデス症例の傾向があった。多変量解析を行ったところ,ステロイドパルス(オッズ比3.0倍,P=0.008)が多発骨壊死の独立した関連因子であった。考察・結論:ONFH発生に関してステロイド投与量やステロイドパルスが関連することと同様に,多発骨壊死とステロイドパルスは関連したことから多発骨壊死発生もステロイド感受性が関連することが示唆された。多発性骨壊死発生のメカニズムはわかっていないが,ステロイド関連ONFHが発生した際には,多発骨壊死のスクリーニングを行うことを考慮する必要があると考えられた。(著者抄録)
• 抗RANKL抗体とゾレドロン酸がマウス化膿性骨髄炎モデルに与える効果の違い

  小林 英之, 藤田 諒, 平塚 重人, 清水 智弘, 佐藤 大, 濱野 博基, 岩崎 倫政, 高畑 雅彦

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 64 (2) 39 - 48 1343-3873 2023/03 

  骨髄炎は強い疼痛と機能障害を伴う進行性の炎症性骨破壊を特徴とする.骨粗鬆症治療薬であるZoledronic acid(ZA)と抗Receptor activator of nuclear factor-kB ligand(RANKL)抗体は強力な破骨細胞抑制効果により,炎症性骨破壊の抑制が期待できるが,骨髄炎に対する効果と安全性は確立されていない.本研究では,遺伝子組み換え発光黄色ブドウ球菌をマウス大腿骨に植菌した骨髄炎モデルマウスを作成し,ZAと抗RANKL抗体を投与した.縦断的に感染の指標となる黄色ブドウ球菌の発光量とマイクロCTによる骨破壊を観察した結果,ZA投与群では感染の自然治癒が遅延していた.一方骨破壊はZAと抗RANKL抗体は有意に骨破壊を抑制した.組織学的評価では,ZA投与で破骨細胞数が著明に減少し,骨壊死範囲が有意に大きくなっているのに対し,抗RANKL抗体投与では壊死骨周囲でRANKL非依存的に誘導されたと考えられる破骨細胞が多く見られ,壊死骨増加を来さなかった.抗RANKL抗体は感染巣となる壊死骨の除去を妨げず,骨保護効果を発揮することが期待できると考えられた.(著者抄録)
• 人工関節置換術後無菌性緩みの局所骨溶解におけるチミジンホスホリラーゼの機能解析

  松前 元, 清水 智弘, 田 園, 高橋 大介, 江畑 拓, 照川 ヘンド, 横田 隼一, 角家 健, 照川 アラー, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 64 (2) 59 - 72 1343-3873 2023/03 

  マクロファージは,炎症と病的骨吸収を惹起することで人工関節後の無菌性緩みに関与する.本研究の目的は,無菌性緩み発症におけるマクロファージ由来因子の同定とその機能解析である.まず,ポリエチレン摩耗粉とマクロファージを共培養し,RNAシークエンス解析を行った.この結果,破骨細胞分化に関与する12個の因子を同定した.この中で,チミジンホスホリラーゼ(TYMP)が最も破骨細胞を誘導した.無菌性緩み症例の血清と滑膜からTYMPが同定できた.動物実験では,TYMPは炎症細胞,破骨細胞の誘導に加え,骨吸収域を増加させた.TYMPの破骨細胞誘導機序を検証するためRNAシークエンス解析を行ったところ,Srcチロシンキナーゼの一種であるFYNが有意に上昇した.そこでFYNの抑制剤であるサラカチニブをモデルマウスに投与したところ,摩耗粉による骨吸収域が有意に低下した.以上の結果から,TYMPは人工関節無菌性緩みにおける有用な治療ターゲットとなり得ることが示唆された.(著者抄録)
• 北海道における女性整形外科医の働き方 女性整形外科医の経験と北海道大学における女性整形外科医師の働き方

  後藤 佳子, 大泉 尚美, 清水 智弘, 門間 太輔, 近藤 英司, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 64 (2) 74 - 81 1343-3873 2023/03
• RA,RA周辺疾患の骨代謝動態および微細構造とインプラント手術 ステロイド長期使用患者における脊椎固定術のインプラントフェイラーとその対策

  高畑 雅彦, 山田 勝久, 遠藤 努, 大西 貴士, 筌場 大介, 須藤 英毅, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (2) S140 - S140 0021-5325 2023/03
• 成育基本法の拡充に則した側彎症検診のあり方 3Dスキャナーと人工知能による側彎症検診 検診の確実な実施に向けた課題への取り組み

  須藤 英毅, 石川 蓉子, 小甲 晃史, 山田 勝久, 舘 弘之, 鈴木 久崇, 大西 貴士, 安倍 雄一郎, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (2) S349 - S349 0021-5325 2023/03
• AI技術を用いて作成した三次元腰神経画像によるL5/Sレベルの全内視鏡下椎間板ヘルニア摘出術(FED)の手術適応可否の評価

  山田 勝久, 長濱 賢, 安倍 雄一郎, 日向寺 義則, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 須藤 英毅, 高畑 雅彦, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (2) S427 - S427 0021-5325 2023/03
• SLEモデルマウスへのステロイドパルスは好中球細胞外トラップを誘導する

  小川 帆貴, 横田 隼一, 清水 智弘, 西端 友香, 益田 紗季子, 外丸 詩野, 岩崎 倫政, 石津 明洋

  日本リウマチ学会総会・学術集会プログラム・抄録集 (一社)日本リウマチ学会 67回 886 - 886 2023/03
• リーメンビューゲル治療前に水平牽引を行うことで脱臼整復率は改善する

  小川 拓也, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (2) S52 - S52 0021-5325 2023/03
• Angulated innominate osteotomyにおける術中三次元矯正と術後1年単純X線との関連

  小川 拓也, 高橋 大介, 清水 智弘, 宮崎 拓自, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (2) S52 - S52 0021-5325 2023/03
• 大腿骨近位部骨折後のリエゾンサービスにおける二次骨折発生とリスク因子 COVID-19状況下の前向き研究

  佐藤 恒明, 清水 智弘, 石津 帆高, 山崎 秀, 大橋 佑介, 下段 俊, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (2) S126 - S126 0021-5325 2023/03
• ステロイド関連特発性大腿骨頭壊死症における多発骨壊死の関連因子

  菅原 悠太郎, 清水 智弘, 横田 隼一, 石津 帆高, 宮崎 拓自, 小川 拓也, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (2) S158 - S158 0021-5325 2023/03
• ロモソズマブの逐次療法におけるゾレドロン酸とデノスマブの比較

  大上 哲郎, 清水 智弘, 浅野 毅, 下段 俊, 石津 帆高, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (2) S202 - S202 0021-5325 2023/03
• 発育性股関節形成不全の二次検診受診時期による装具治療の有無の検討

  小川 拓也, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (2) S224 - S224 0021-5325 2023/03
• コロナ禍で始まった大腿骨近位部骨折リエゾンサービス1年後の骨粗鬆症加療状況

  下段 俊, 清水 智弘, 梅本 貴央, 百貫 亮太, 竹内 博紀, 小川 裕生, 池 翔太, 福島 瑛, 佐藤 知哉, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (2) S238 - S238 0021-5325 2023/03
• 人工股関節全置換術後1年における筋量および筋力の変化 筋量DXAを用いた筋量測定

  七條 俊希, 千田 伸一, 樋口 陽子, 相馬 栄大, 武田 恵李, 大井 雅人, 高橋 要, 大羽 文博, 田中 将, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (2) S406 - S406 0021-5325 2023/03
• 日本人におけるTHAの適切なオフセットの検証

  高橋 大介, 清水 智弘, 宮崎 拓自, 小川 拓也, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (3) S735 - S735 0021-5325 2023/03
• 人工股関節全置換術におけるヘッド延長の脚長,オフセット,可動域に与える影響 A computer simulation study

  宮崎 拓自, 清水 智弘, 小川 拓也, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (3) S735 - S735 0021-5325 2023/03
• アネキシンA1(AnxA1)の炎症性骨吸収抑制効果の検討 人工関節術後無菌性緩みの治療薬開発にむけて

  西田 善郎, 照川 ヘンド, 江畑 拓, 清水 智弘, 横田 隼一, 遠藤 努, 高橋 大介, 照川 アラー, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (3) S953 - S953 0021-5325 2023/03
• Covid-19流行下における大腿骨近位部骨折治療 full-PPE装備での手術治療の特徴

  浅野 毅, 菅原 悠太郎, 佐藤 恒明, 松岡 知樹, 芝山 浩樹, 山賀 慎太郎, 高橋 大介, 清水 智弘, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (3) S1052 - S1052 0021-5325 2023/03
• VLIANステムでTHA術後ステム周囲骨折は予防できるか 多施設共同研究の結果から

  高橋 大介, 清水 智弘, 宮崎 拓自, 浅野 毅, 下段 俊, 高橋 要, 福井 隆史, 大浦 久典, 片山 直行, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (3) S1075 - S1075 0021-5325 2023/03
• 大腿骨近位部骨折における重症骨粗鬆症患者の割合

  山崎 秀, 下段 俊, 楠 兼一, 中條 誠也, 鈴木 瞭太, 百貫 亮太, 梅本 貴央, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (3) S1170 - S1170 0021-5325 2023/03
• 骨折リスクの高い重症骨粗鬆症患者の脊柱矢状面アライメント異常の検証

  有田 皓介, 清水 智弘, 石津 帆高, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (3) S1179 - S1179 0021-5325 2023/03
• ステロイド関連特発性大腿骨頭壊死症における多発骨壊死の関連因子

  菅原 悠太郎, 清水 智弘, 横田 隼一, 石津 帆高, 宮崎 拓自, 小川 拓也, 高橋 大介, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 42 (1) 30 - 33 1883-2873 2023/03 

  目的:特発性大腿骨頭壊死症患者(ONFH)が股関節以外に骨壊死を引き起こす多発骨壊死は,3関節以上と定義した際には約3%とこれまで報告されてきた。一方で,無症候性壊死を検出感度の高い全身MRIを用いた先行研究では,ONFH患者の約25%に多発骨壊死が発生し全例ステロイド関連ONFHであった。そこで本研究は,ステロイド関連ONFH症例を対象として,多発骨壊死の関連性を調査することを目的とした。方法:対象は当院における定点モニタリング対象となったONFH症例328名のうち,特発性ONFH 9名,アルコール関連ONFH 75名およびデータ詳細不明の16名を除外したステロイド関連ONFH 228名(男性108名,女性120名)である。基礎疾患,ステロイド投与最大量,ステロイドパルス療法,アルコール,喫煙,股関節以外の関節の骨壊死発生を調査した。結果:多発骨壊死は228名中59名(男性24名,女性35名)に生じていた。多発骨壊死症を生じたONFH症例は,若年,両側ONFH症例,ステロイド高用量,ステロイドパルス症例,喫煙,全身性エリテマトーデス症例の傾向があった。多変量解析を行ったところ,ステロイドパルス(オッズ比3.0倍,P=0.008)が多発骨壊死の独立した関連因子であった。考察・結論:ONFH発生に関してステロイド投与量やステロイドパルスが関連することと同様に,多発骨壊死とステロイドパルスは関連したことから多発骨壊死発生もステロイド感受性が関連することが示唆された。多発性骨壊死発生のメカニズムはわかっていないが,ステロイド関連ONFHが発生した際には,多発骨壊死のスクリーニングを行うことを考慮する必要があると考えられた。(著者抄録)
• 変形性膝関節症患者における下腿加速度と膝関節の荷重分布との関係 ウェアラブルセンサーを用いて

  佐橋 健人, 岩崎 浩司, 安倍 雄一郎, 渡邊 謙太郎, 千徳 風真, 千葉 健, 小野寺 智洋, 近藤 英司, 岩崎 倫政, 遠山 晴一

  日本整形外科学会雑誌 (公社)日本整形外科学会 97 (3) S864 - S864 0021-5325 2023/03
• Usefulness of Intraoperative Arthrography for Postaxial Polysyndactyly of the Foot.

  Yuko Sakai, Daisuke Kawamura, Takeshi Endo, Norimasa Iwasaki

  Journal of pediatric orthopedics 43 (3) e244-e248  2023/03/01 

  BACKGROUND: Surgery for polydactyly of the foot aims to achieve good cosmesis and improve shoe fitting. An accurate understanding of toe morphology will help to minimize the skin incision or optimize the surgical plan before incision. However, it is difficult to determine the shape of the articular surface using radiographs of children with immature bone. We performed arthrography during surgery for postaxial polydactyly of the foot to assess the cartilaginous structures. The purpose of this study was to investigate the usefulness of arthrography in postaxial polydactyly of the foot. METHODS: We included 36 digits of 31 patients (16 males and 15 females), including 5 bilateral cases. The age at surgery ranged from 9 to 75 months (mean, 20 mo). Intraoperative arthrography was performed and all radiographs and arthrograms were reviewed and classified by 3 observers using the Watanabe classification. The absolute percentage agreement between the observers was calculated. The senior author assigned the arthrograms as the reference. The types determined by the other 2 observers using radiographs and arthrograms were compared with the reference. RESULTS: Full agreement occurred in 66.7% of the radiographs and in 75% of arthrograms. The mean kappa coefficient was 0.58, indicating fair agreement, between the reference and the radiologic assessment, while it was 0.81, indicating excellent or almost perfect agreement, in the evaluation using arthrograms. CONCLUSIONS: Intraoperative arthrography is an easy and reliable diagnostic method that can be used to determine the detailed articular shape. LEVEL OF EVIDENCE: Level III.
• Higher Association of Pelvis-Knee-Ankle Angle Compared With Hip-Knee-Ankle Angle With Knee Adduction Moment and Patient-Reported Outcomes After High Tibial Osteotomy.

  Koji Iwasaki, Yasumitsu Ohkoshi, Yoshiaki Hosokawa, Shuya Chida, Kengo Ukishiro, Kensaku Kawakami, Sho'ji Suzuki, Tatsunori Maeda, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki

  The American journal of sports medicine 51 (4) 977 - 984 2023/03 

  BACKGROUND: High tibial osteotomy (HTO) reduces the load distribution of the medial compartment by modifying leg alignment. Knee adduction moment (KAM), a surrogate measure of dynamic loading in the knee joint, decreases after HTO. However, leg alignment does not fully account for KAM. PURPOSE: To assess the association between the pelvis-knee-ankle angle (PKA), a novel radiographic parameter reflecting leg alignment and pelvic width, and KAM and patient-reported outcomes after HTO. STUDY DESIGN: Cross sectional study; Level of evidence, 3. METHODS: PKA is the angle between the line from the midpoint of the anterior superior iliac spine to the center of the knee joint and the mechanical axis of the tibia. In this study, 54 patients with medial compartment knee osteoarthritis and varus alignment who underwent 3-dimensional gait analysis preoperatively and 2 years after medial open-wedge HTO were evaluated. The primary outcomes were hip-knee-ankle angle (HKA), PKA, KAM peaks, and Knee Society Score (KSS). Single and multivariate regression analysis including PKA and KAM peaks as well as other demographic and radiologic factors was performed. RESULTS: HKA was weakly correlated with the first peak KAM (r = -0.33; P < .01) and second peak KAM (r = -0.27; P = .01) before HTO, but not significantly correlated after HTO. PKA was moderately correlated with the first peak KAM (r = 0.45; P < .01) and second peak KAM (r = 0.45; P < .01) before HTO and with the first peak KAM (r = 0.51; P < .01) and second peak KAM (r = 0.56; P < .01) after HTO. Multivariate linear regression revealed that postoperative PKA was still associated with the KAM peaks after HTO. Only postoperative PKA was correlated with the KSS satisfaction subscale (r = -0.30; P = .03). CONCLUSION: Although HKA was not correlated with KAM peaks after HTO, PKA was significantly correlated with KAM peaks in patients with varus knee osteoarthritis after HTO.
• Patterns of Vertebral Bone Marrow Edema in the Normal Healing Process of Lumbar Interbody Fusion: Baseline Data for Diagnosis of Pathological Events.

  Yuichi Hasegawa, Masahiro Kanayama, Fumihiro Oha, Yukitoshi Shimamura, Takeru Tsujimoto, Tomoyuki Hashimoto, Norimasa Iwasaki

  Spine 48 (5) 358 - 363 2023/03/01 

  STUDY DESIGN: Retrospective investigation using a prospectively collected database. OBJECTIVE: To examine the appearance and characteristics of vertebral bone marrow edema (BME) in the normal healing of lumbar interbody fusion. SUMMARY OF BACKGROUND DATA: Although BME in pathological spinal conditions has been well-documented, the patterns and characteristics of BME in the normal healing process of spinal fusion remains unexplored. MATERIALS AND METHODS: We reviewed imaging from 225 patients with normal healing following posterior lumbar interbody fusion or transforaminal lumbar interbody fusion. BME was identified on magnetic resonance imaging at the third postoperative week and categorized with respect to its appearance, including assessment of area and extension within the relevant vertebrae. RESULTS: Three hundred eighty-nine of the 450 instrumented vertebrae (86.4%) displayed evidence BME. All instances of BME were associated with the area of contact with the endplate. The average extent of BME was 32.7±1.0%. BME within normal healing following interbody fusion could be categorized into four types: no edema (13.6%), anterior corner (36.6%), around-the-cage focal (48.0%), and diffuse (1.8%). Anterior corner BME was significantly associated with instances of single cage placement than in dual cages (42.6% vs. 24.7%, P =0.0002). Single cages had a significantly higher rate of BME than dual cages (92.0% vs. 75.3%, P <0.0001). The extent of BME was significantly greater in the single cage cohort (36.9% vs. 24.2% in dual cages, P <0.0001). CONCLUSIONS: This serves as the first study demonstrating the patterns of BME associated with normal healing following lumbar interbody fusion procedures. Anterior corner BME and around-the-cage focal BME were the most common patterns encountered, with diffuse BME a relatively rare pattern. These findings might contribute to the better differentiation of postoperative pathological events from normal healing following lumbar interbody fusion. LEVEL OF EVIDENCE: 4.
• Comparison of re-revision rate and radiological outcomes between Kerboull-type plate and metal mesh with impaction bone grafting for revision total hip arthroplasty.

  Hotaka Ishizu, Tomohiro Shimizu, Fumio Sasazawa, Daisuke Takahashi, Mohamad Alaa Terkawi, Kaname Takahashi, Yusuke Ohashi, Masahiro Kanayama, Norimasa Iwasaki

  BMC musculoskeletal disorders 24 (1) 134 - 134 2023/02/20 

  BACKGROUND: This study compared the re-revision rate and radiographic outcomes of revision total hip arthroplasty (THA) using a Kerboull-type acetabular reinforcement device (KT plate) with bulk structural allograft and metal mesh with impaction bone grafting (IBG). METHODS: Ninety-one hips of 81 patients underwent revision THA for American Academy of Orthopedic Surgeons (AAOS) classification type III defects from 2008 to 2018. Of these, seven hips of five patients and 15 hips of 13 patients were excluded due to insufficient follow-up information (< 24 months) and large bone defects with a vertical defect height ≥ 60 mm, respectively. The current study compared the survival and radiographic parameters of 45 hips of 41 patients using a KT plate (KT group) and 24 hips of 24 patients using a metal mesh with IBG (mesh group). RESULTS: Eleven hips (24.4%) in the KT group and 1 hip (4.2%) in the mesh group exhibited radiological failure. Moreover, 8 hips in the KT group (17.0%) required a re-revision THA, while none of the patients in the mesh group required a re-revision. The survival rate with radiographic failure as the endpoint in the mesh group was significantly higher than that in the KT group (100% vs 86.7% at 1-year and 95.8% vs 80.0% at 5-years, respectively; p = 0.032). On multivariable analysis evaluating factors associated with radiographic failure, there were no significant associations with any radiographic measurement. Of the 11 hips with radiographic failure, 1 (11.1%), 3 (12.5%), and 7 (58.3%) hips were of Kawanabe classification stages 2, 3, and 4, respectively. CONCLUSIONS: The findings of this study suggest that revision THA using KT plates with bulk structure allografts could provide poorer clinical outcomes than revision THA using a metal mesh with IBG. Although revision THA using KT plates with bulk structural allografts could set the true hip center, there is no association between a high hip center and clinical outcomes. The relationship between the position of the KT plate and the host bone might be considered more carefully.
• Influence of Lateral Translation of Lowest Instrumented Vertebra on L4 Tilt and Coronal Balance for Thoracolumbar and Lumbar Curves in Adolescent Idiopathic Scoliosis

  Katsuhisa Yamada, Hideki Sudo, Yuichiro Abe, Terufumi Kokabu, Hiroyuki Tachi, Tsutomu Endo, Takashi Ohnishi, Daisuke Ukeba, Katsuro Ura, Masahiko Takahata, Norimasa Iwasaki

  Journal of Clinical Medicine 12 (4) 1389 - 1389 2023/02/09 

  This study aimed to evaluate the lowest instrumented vertebra translation (LIV-T) in the surgical treatment of thoracolumbar/lumbar adolescent idiopathic scoliosis and to analyze the radiographic parameters in relation to LIV-T and L4 tilt and global coronal balance. A total of 62 patients underwent posterior spinal fusion (PSF, n = 32) or anterior spinal fusion (ASF, n = 30) and were followed up for a minimum of 2 years. The mean preoperative LIV-T was significantly larger in the ASF group than the PSF (p < 0.01), while the final LIV-T was equivalent. LIV-T at the final follow-up was significantly correlated with L4 tilt and the global coronal balance (r = 0.69, p < 0.01, r = 0.38, p < 0.01, respectively). Receiver-operating characteristic analysis for good outcomes, with L4 tilt <8° and coronal balance <15 mm at the final follow-up, calculated the cutoff value of the final LIV-T as 12 mm. The cutoff value of preoperative LIV-T that would result in the LIV-T of ≤12 mm at the final follow-up was 32 mm in PSF, although no significant cutoff value was calculated in ASF. ASF can centralize the LIV better than PSF with a shorter segment fusion, and could be useful in obtaining a good curve correction and global balance without fixation to L4 in cases with large preoperative LIV-T.
• Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model

  Hisataka Suzuki, Katsuro Ura, Daisuke Ukeba, Takashi Suyama, Norimasa Iwasaki, Masatoki Watanabe, Yumi Matsuzaki, Katsuhisa Yamada, Hideki Sudo

  Cells 12 (3) 505 - 505 2023/02/03 

  Intervertebral disc (IVD) degeneration is a major cause of low back pain. However, treatments directly approaching the etiology of IVD degeneration and discogenic pain are not yet established. We previously demonstrated that intradiscal implantation of cell-free bioresorbable ultra-purified alginate (UPAL) gel promotes tissue repair and reduces discogenic pain, and a combination of ultra-purified, Good Manufacturing Practice (GMP)-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs), and the UPAL gel increasingly enhanced IVD regeneration in animal models. This study investigated the therapeutic efficacy of injecting a mixture of REC and UPAL non-gelling solution for discogenic pain and IVD regeneration in a rat caudal nucleus pulposus punch model. REC and UPAL mixture and UPAL alone suppressed not only the expression of TNF-α, IL-6, and TrkA (p < 0.01, respectively), but also IVD degeneration and nociceptive behavior compared to punching alone (p < 0.01, respectively). Furthermore, REC and UPAL mixture suppressed these expression levels and nociceptive behavior compared to UPAL alone (p < 0.01, respectively). These results suggest that this minimally invasive treatment strategy with a single injection may be applied to treat discogenic pain and as a regenerative therapy.
• Protocol for treating lumbar spinal canal stenosis with a combination of ultrapurified, allogenic bone marrow-derived mesenchymal stem cells and in situ-forming gel: a multicentre, prospective, double-blind randomised controlled trial.

  Hideki Sudo, Takashi Miyakoshi, Yudai Watanabe, Yoichi M Ito, Kaoru Kahata, Khin Khin Tha, Nozomi Yokota, Hiroe Kato, Tomoko Terada, Norimasa Iwasaki, Teruyo Arato, Norihiro Sato, Toshiyuki Isoe

  BMJ open 13 (2) e065476  2023/02/02 

  INTRODUCTION: In patients with combined lumbar spinal canal stenosis (LSCS), a herniated intervertebral disc (IVD) that compresses the dura mater and nerve roots is surgically treated with discectomy after laminoplasty. However, defects in the IVD after discectomy may lead to inadequate tissue healing and predispose patients to the development of IVD degeneration. Ultrapurified stem cells (rapidly expanding clones (RECs)), combined with an in situ-forming bioresorbable gel (dMD-001), have been developed to fill IVD defects and prevent IVD degeneration after discectomy. We aim to investigate the safety and efficacy of a new treatment method in which a combination of REC and dMD-001 is implanted into the IVD of patients with combined LSCS. METHODS AND ANALYSIS: This is a multicentre, prospective, double-blind randomised controlled trial. Forty-five participants aged 20-75 years diagnosed with combined LSCS will be assessed for eligibility. After performing laminoplasty and discectomy, participants will be randomised 1:1:1 into the combination of REC and dMD-001 (REC-dMD-001) group, the dMD-001 group or the laminoplasty and discectomy alone (control) group. The primary outcomes of the trial will be the safety and effectiveness of the procedure. The effectiveness will be assessed using visual analogue scale scores of back pain and leg pain as well as MRI-based estimations of morphological and compositional quality of the IVD tissue. Secondary outcomes will include self-assessed clinical scores and other MRI-based estimations of compositional quality of the IVD tissue. All evaluations will be performed at baseline and at 1, 4, 12, 24 and 48 weeks after surgery. ETHICS AND DISSEMINATION: This study was approved by the ethics committees of the institutions involved. We plan to conduct dissemination of the outcome data by presenting our data at national and international conferences, as well as through formal publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCT2013210076.
• Arthroscopic superior capsular reconstruction combined with pectoralis minor transfer for irreparable anterosuperior rotator cuff tear: a case report.

  Yukinori Tsukuda, Atsushi Urita, Masahiro Miyano, Hiroshi Taneichi, Norimasa Iwasaki

  JSES reviews, reports, and techniques 3 (1) 101 - 106 2023/02
• Dupuytren's contracture-associated SNPs increase SFRP4 expression in nonimmune cells including fibroblasts to enhance inflammation development.

  Hiroaki Kida, Jing-Jing Jiang, Yuichiro Matsui, Ikuko Takahashi, Rie Hasebe, Daisuke Kawamura, Takeshi Endo, Hiroki Shibayama, Makoto Kondoh, Yasuhiko Nishio, Kinya Nishida, Yoshihiro Matsuno, Tsukasa Oikawa, Shimpei Kubota, Shintaro Hojyo, Norimasa Iwasaki, Shigeru Hashimoto, Yuki Tanaka, Masaaki Murakami

  International immunology 35 (7) 303 - 312 2023/01/31 

  Dupuytren's contracture (DC) is an inflammatory fibrosis characterized by fibroproliferative disorders of the palmar aponeurosis, for which there is no effective treatment. Although several genome-wide association studies have identified risk alleles associated with DC, the functional linkage between these alleles and the pathogenesis remains elusive. We here focused on two SNPs associated with DC, rs16879765 and rs17171229, in secreted frizzled related protein 4 (SFRP4). We investigated the association of SRFP4 with the IL-6 amplifier, which amplifies the production of IL-6, growth factors, and chemokines in non-immune cells and aggravates inflammatory diseases via NF-κB enhancement. Knockdown of SFRP4 suppressed activation of the IL-6 amplifier in vitro and in vivo, whereas the overexpression of SFRP4 induced the activation of NF-κB-mediated transcription activity. Mechanistically, SFRP4 induced NF-κB activation by directly binding to molecules of the ubiquitination SFC complex, such as IkBα and βTrCP, followed by IkBα degradation. Furthermore, SFRP4 expression was significantly increased in fibroblasts derived from DC patients bearing the risk alleles. Consistently, fibroblasts with the risk alleles enhanced activation of the IL-6 amplifier. These findings indicate that the IL-6 amplifier is involved in the pathogenesis of DC, particularly in patients harboring the SFRP4 risk alleles. Therefore, SFRP4 is a potential therapeutic target for various inflammatory diseases and disorders, including DC.
• Characteristics of the Patients with Poor Clinical Outcomes After Symptomatic Postoperative Lumbar Epidural Hematoma.

  Takeru Tsujimoto, Masahiro Kanayama, Fumihiro Oha, Yukitoshi Shimamura, Masaru Tanaka, Yuichi Hasegawa, Syotaro Fukada, Tomoyuki Hashimoto, Masahiko Takahata, Norimasa Iwasaki

  World neurosurgery 172 e364-e371  2023/01/12 

  OBJECTIVE: Symptomatic postoperative lumbar epidural hematoma (PLEH) may lead to poor outcomes even after evacuation. This study aimed to verify the short-term clinical outcomes after the evacuation of PLEH and to clarify the characteristics of the patients with poor postoperative outcomes. METHODS: Twenty-five patients (average age; 70.4 years) underwent PLEH evacuation after lumbar spine surgery. The mean follow-up period was 12.0 (range 3-37) months. Pre and postoperative Japanese Orthopedic Association scores and visual analog scale (VAS) of low back pain (LBP), leg pain, and leg numbness were retrospectively collected. The dural sac cross-sectional area at the most compressed level was measured on magnetic resonance imaging. The patients were classified into 2 groups: poor outcome group (P group) had less than 50% of Japanese Orthopedic Associationrecovery rate and good group (G group) with 50% or more recovery rate. RESULTS: The rate of delayed evacuation (over 24 hours of onset) was significantly higher in P group than in G group (P = 0.027). There was no significant difference in dural sac cross-sectional areabetween the 2 groups (P = 0.438). VAS of LBP, leg pain, and leg numbness in G group significantly improved postoperatively. Although VAS of LBP and leg pain in P group significantly improved postoperatively, there was no significant difference between the pre and postoperative VAS of leg numbness. CONCLUSIONS: Delayed evacuation of PLEH can lead to poor postoperative outcomes after lumbar spine surgery. Moreover, patients with poor outcomes remained with postoperative leg numbness. Early evacuation of symptomatic PLEH is key to avoid poor outcomes and persistent leg numbness.
• Lumbar ossification of the ligamentum flavum reflects a strong ossification tendency of the entire spinal ligament.

  Kazuha Nakabachi, Tsutomu Endo, Masahiko Takahata, Ryo Fujita, Yoshinao Koike, Ryota Suzuki, Yuichi Hasegawa, Toshifumi Murakami, Katsuhisa Yamada, Hideki Sudo, Mohamad Alaa Terkawi, Ken Kadoya, Norimasa Iwasaki

  Scientific reports 13 (1) 638 - 638 2023/01/12 

  Patients with ossification of the ligamentum flavum (OLF) in the lumbar spine may be at high risk of developing concomitant ossification of the entire spinal ligament, but the etiology remains unclear. We investigated the propensity for spinal ligament ossification in asymptomatic subjects with lumbar OLF using the data of 595 Japanese individuals receiving medical check-ups, including computed tomography (CT) scanning. The severity of OLF (total number of intervertebral segments with OLF) of the entire spine on CT was quantified using an OLF index. Subjects with OLF were grouped according to this index: localized OLF (n = 138), intermediate OLF (n = 70), and extensive OLF (n = 31). The proportion of subjects with lumbar OLF increased with increasing OLF index (localized 13.7%, intermediate 41.4%, and extensive 70.9%). Multiple regression analysis found that lumbar OLF index was associated with thoracic OLF index, and co-existence of ossification of the posterior longitudinal ligament (OPLL) of the thoracic and lumbar spine. This study showed that subjects with more multilevel lumbar OLF were more likely to develop multilevel thoracic OLF and to have coexisting OPLL. Patients with lumbar OLF may be a distinctive subgroup with a strong tendency to ossification of the entire spinal ligament.
• Atelocollagen-associated autologous chondrocyte implantation for the repair of large cartilage defects of the knee: Results at three to seven years.

  Takuma Kaibara, Eiji Kondo, Masatake Matsuoka, Koji Iwasaki, Tomohiro Onodera, Keita Sakamoto, Yoshitaka Oda, Zen-Ichi Tanei, Daisuke Momma, Shinya Tanaka, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 29 (1) 207 - 216 2023/01/09 

  BACKGROUND: Recently, various types of engineered autologous chondrocyte implantation (ACI) have been developed. Atelocollagen-associated ACI (A-ACI) is the only ACI procedure covered by Japanese Health Insurance since 2013. The indications of the A-ACI are traumatic cartilage defects and osteochondral dissecans (OCD) for knee joints. PURPOSE: To evaluate midterm clinical results after A-ACI for the treatment for full-thickness cartilage defects of the knee. METHODS: Thirteen consecutive patients who underwent A-ACI between 2014 and 2018 had been prospectively enrolled in this study. There were 11 men and 2 women with a mean age of 34 years at the time of surgery. The causes of the cartilage defect were trauma in 10 knees and OCD in 3 knees. The total number of lesions was 15, which were comprised of the medial femoral condyle in 5 knees, the lateral femoral condyle in 5 knees, and the femoral trochlea in 5 knees. The mean size of the lesion was 5.3 cm2. Each knee was clinically and radiologically evaluated preoperatively and postoperatively. RESULTS: The mean Lysholm score improved significantly from 74.0 points to 94.0 points (p = 0.008) and each subscale in Knee injury and Osteoarthritis Outcome Score improved significantly (p < 0.001) at the mean final follow-up period of 51 months (range, 36-84 months). The magnetic resonance observation of cartilage repair tissue 2.0 score at the mean follow-up of 38 months was significantly higher than that at 2 months postoperatively (p = 0.014). According to the International Cartilage Repair Society (ICRS) grading scale, 3 knees were graded as normal, 3 knees as nearly normal, and 1 knee as severely abnormal in second-look arthroscopic evaluation at a mean of 22 months (range, 8-41 months) after A-ACI. CONCLUSION: The present study showed a significant subjective and objective clinical improvement in the A-ACI for large cartilage defects of the knee at a mean follow-up of 51 months (range, 36-84 months).
• Prediction of Cobb Angle Using Deep Learning Algorithm with Three-Dimensional Depth Sensor Considering the Influence of Garment in Idiopathic Scoliosis

  Yoko Ishikawa, Terufumi Kokabu, Katsuhisa Yamada, Yuichiro Abe, Hiroyuki Tachi, Hisataka Suzuki, Takashi Ohnishi, Tsutomu Endo, Daisuke Ukeba, Katsuro Ura, Masahiko Takahata, Norimasa Iwasaki, Hideki Sudo

  Journal of Clinical Medicine 12 (2) 499 - 499 2023/01/07 

  Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Early detection of deformity and timely intervention, such as brace treatment, can help inhibit progressive changes. A three-dimensional (3D) depth-sensor imaging system with a convolutional neural network was previously developed to predict the Cobb angle. The purpose of the present study was to (1) evaluate the performance of the deep learning algorithm (DLA) in predicting the Cobb angle and (2) assess the predictive ability depending on the presence or absence of clothing in a prospective analysis. We included 100 subjects with suspected AIS. The correlation coefficient between the actual and predicted Cobb angles was 0.87, and the mean absolute error and root mean square error were 4.7° and 6.0°, respectively, for Adam’s forward bending without underwear. There were no significant differences in the correlation coefficients between the groups with and without underwear in the forward-bending posture. The performance of the DLA with a 3D depth sensor was validated using an independent external validation dataset. Because the psychological burden of children and adolescents on naked body imaging is an unignorable problem, scoliosis examination with underwear is a valuable alternative in clinics or schools.
• The Novel Ulnar Nerve Coverage Method Which Has the Potential to Prevent the Postoperative Ulnar Neuropathy after Plate Fixation of Distal Humerus Fractures: Three Case Reports.

  Hiroki Shibayama, Shintaro Yamaga, Yutaro Sugawara, Tsuyoshi Asano, Norimasa Iwasaki

  Case reports in orthopedics 2023 5008141 - 5008141 2023 

  INTRODUCTION: Postoperative ulnar neuropathy is still an unresolved complication in patients undergoing plate fixation of distal humerus fractures. We hypothesized that decreased blood flow to the ulnar nerve due to intraoperative procedures is an important factor in the development of postoperative ulnar neuropathy. We herein report three cases of distal humerus fractures in which the soft tissues surrounding the ulnar nerve were preserved as much as possible and finally not transferred anteriorly. Case Presentation. A 76-year-old woman, 82-year-old woman, and 34-year-old woman underwent plate fixation for distal humerus fractures. None of the patients developed postoperative ulnar neuropathy, and there were no complaints of numbness after postoperative day 1. Nerve conduction studies were performed after 3 months postoperatively and revealed that the motor nerve conduction velocities and compound motor nerve action potentials of the ulnar nerve in two of the three patients were higher than those of the noninjured side. In one of the three patients, these values were slightly lower than those of the noninjured side. All three patients achieved bony union after several months postoperatively. CONCLUSIONS: We obtained good outcomes with the ulnar nerve coverage method for preventing postoperative ulnar neuropathy in patients with distal humerus fractures. Preservation of blood flow to the ulnar nerve was considered important, and anatomical repositioning of the ulnar nerve after plate fixation has the potential to prevent adhesion between the ulnar nerve and the plate.
• 後縦靱帯骨化症患者は全身的な骨形成の亢進が示唆される アキレス腱と足底腱の骨化解析

  遠藤 努, 小池 良直, 山田 勝久, 大西 貴士, 筌場 大介, 岩崎 倫政, 高畑 雅彦, 金山 雅弘

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 14 - 14 1343-3873 2023
• AI技術により作成した3D腰神経MRI像を用いたL5/Sレベルの全内視鏡下椎間板ヘルニア摘出術シミュレーションの有用性

  山田 勝久, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 高畑 雅彦, 岩崎 倫政, 長濱 賢, 安倍 雄一郎, 須藤 英毅

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 15 - 15 1343-3873 2023
• 腰椎後方除圧術における棘上棘間靱帯・棘突起温存は、術後の二次性椎間板変性の進行を抑制する

  大西 貴士, 山田 勝久, 岩崎 倫政, 中下 並人, 楫野 知道, 久田 雄一郎, 須藤 英毅

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 15 - 15 1343-3873 2023
• 3次元デプスセンサーと人工知能を用いた側彎角の自動予測 着衣の有無による精度検証

  石川 蓉子, 小甲 晃史, 山田 勝久, 舘 弘之, 鈴木 久崇, 大西 貴士, 岩崎 倫政, 須藤 英毅, 安倍 雄一郎

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 16 - 16 1343-3873 2023
• 治療に苦慮した慢性再発性多発性骨髄炎(CRMO)を背景とした環軸椎回旋位固定の一例

  石田 健太, 遠藤 努, 高畑 雅彦, 須藤 英毅, 山田 勝久, 大西 貴士, 筌場 大介, 浦 勝郎, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 18 - 18 1343-3873 2023
• 遅発性麻痺を生じた高齢者の頸椎脱臼骨折の一例

  白井 良樹, 浦 勝郎, 山田 勝久, 筌場 大介, 大西 貴士, 遠藤 努, 高畑 雅彦, 岩崎 倫政, 須藤 英毅

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 21 - 21 1343-3873 2023
• 炎症性軟骨細胞は骨細胞のパイロトーシスを誘導する

  小川 裕生, 徳廣 泰貴, 江畑 拓, 北原 圭太, 塩田 惇喜, 西田 善郎, 清水 智弘, 遠藤 努, 高橋 大介, 照川 アラー, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 3 - 3 1343-3873 2023
• 細胞老化に着目した骨マクロファージの骨代謝調節機能の検討

  西田 善郎, 松前 元, 横田 隼一, 照川 ヘンド, 清水 智弘, 高橋 大介, 遠藤 努, 照川 アラー, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 5 - 5 1343-3873 2023
• 大腿骨近位部骨折後のリエゾンサービスにおける二次骨折発生とリスク因子 Covid 19状況下の前向き研究

  石津 帆高, 清水 智弘, 佐藤 恒明, 大橋 佑介, 山崎 秀, 岩崎 倫政, 下段 俊

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 42 - 42 1343-3873 2023
• 大腿骨近位部骨折患者における重症骨粗鬆症の割合

  山崎 秀, 下段 俊, 梅本 貴央, 山崎 秀, 清水 智弘, 岩崎 倫政, 高橋 大介

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 42 - 42 1343-3873 2023
• 骨マクロファージ由来神経ペプチド様タンパク質は破骨細胞分化を阻害する

  徳廣 泰貴, 塩田 惇喜, 北原 圭太, 西田 善郎, 清水 智弘, 遠藤 努, 高橋 大介, 照川 アラー, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 43 - 43 1343-3873 2023
• RANKL中和抗体中止後の骨吸収過剰亢進におけるメカニズム解明アプローチ

  石津 帆高, 清水 智弘, 岩崎 倫政, 長谷川 智香, 網塚 憲生

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 44 - 44 1343-3873 2023
• ロモソズマブの逐次療法におけるゾレドロン酸とデノスマブの比較

  大上 哲郎, 清水 智弘, 石津 穂高, 岩崎 倫政, 浅野 毅, 下段 俊

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 44 - 44 1343-3873 2023
• 新規骨マクロファージ由来分子タンパクの生体内治療効果

  塩田 惇喜, 照川 アラー, 高橋 大介, 清水 智弘, 横田 隼一, 北原 圭太, 西田 善郎, 徳廣 泰貴, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 65 - 65 1343-3873 2023
• 炎症収束型好中球由来細胞外小胞による軟骨細胞における抗異化作用の検討

  北原 圭太, 江畑 拓, 横田 隼一, 塩田 惇喜, 西田 善郎, 徳廣 泰貴, 清水 智弘, 浅野 毅, 高橋 大介, 角家 健, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 66 - 66 1343-3873 2023
• 骨折リスクの高い骨粗鬆症の脊柱矢状断アライメント異常の検証

  有田 皓介, 清水 智弘, 石津 帆高, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 72 - 72 1343-3873 2023
• Polished cement stemにおけるhead延長が脚長、オフセット、可動域に与える影響A computer simulation study

  宮崎 拓自, 清水 智弘, 小川 拓也, 高橋 大介, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 87 - 87 1343-3873 2023
• 不安定型大腿骨転子部骨折に対し前方アプローチで一期的人工骨頭置換を行った症例の検討

  加藤 琢磨, 放生 憲博, 清水 智弘, 高橋 大介, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 90 - 90 1343-3873 2023
• コロナ禍で始めた大腿骨近位部骨折リエゾンサービスにおける骨粗鬆症治療継続状況と中断例の検討

  下段 俊, 梅本 貴央, 久田 雄一郎, 沼口 京介, 高橋 錬也, 石田 健太, 佐藤 知哉, 清水 智弘, 高橋 大介, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 92 - 92 1343-3873 2023
• Ferroptosisを標的としたポリエチレン摩耗粉による炎症性骨吸収抑制効果

  小川 拓也, 横田 隼一, 徳廣 泰貴, 照川 アラー, 照川, 西田 善郎, 塩田 惇喜, 北原 圭太, 清水 智弘, 高橋 大介, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 93 - 93 1343-3873 2023
• ステロイド関連特発性大腿骨頭壊死症における多発骨壊死の関連因子

  菅原 悠太郎, 清水 智弘, 横田 隼一, 石津 帆高, 宮崎 拓自, 小川 拓也, 高橋 大介, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 94 - 94 1343-3873 2023
• Angulated Innominate Osteotomyにおける術中三次元矯正と術後1年単純X線との関連

  小川 拓也, 高橋 大介, 清水 智弘, 宮崎 拓自, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 95 - 95 1343-3873 2023
• 乳児股関節健診推奨項目は発育性股関節形成不全の予測因子となりうるか?

  大橋 佑介, 清水 智弘, 清水 寛和, 小川 拓也, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 95 - 95 1343-3873 2023
• 発育性股関節形成不全の二次検診受診時期による装具治療の有無の検討

  小川 拓也, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 96 - 96 1343-3873 2023
• リーメンビューゲル治療前に水平牽引を行うことで脱臼整復率は改善する

  小川 拓也, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 96 - 96 1343-3873 2023
• 北海道における先端的医療技術としてのAIと遠隔医療の取り組み 股関節周囲外傷・疾患診療におけるAIの活用

  清水 智弘, 山田 勝久, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (1) 18 - 20 1343-3873 2023
• 後縦靱帯骨化症患者は全身的な骨形成の亢進が示唆される アキレス腱と足底腱の骨化解析

  遠藤 努, 小池 良直, 山田 勝久, 大西 貴士, 筌場 大介, 岩崎 倫政, 高畑 雅彦, 金山 雅弘

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 14 - 14 1343-3873 2023
• AI技術により作成した3D腰神経MRI像を用いたL5/Sレベルの全内視鏡下椎間板ヘルニア摘出術シミュレーションの有用性

  山田 勝久, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 高畑 雅彦, 岩崎 倫政, 長濱 賢, 安倍 雄一郎, 須藤 英毅

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 15 - 15 1343-3873 2023
• 腰椎後方除圧術における棘上棘間靱帯・棘突起温存は、術後の二次性椎間板変性の進行を抑制する

  大西 貴士, 山田 勝久, 岩崎 倫政, 中下 並人, 楫野 知道, 久田 雄一郎, 須藤 英毅

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 15 - 15 1343-3873 2023
• 3次元デプスセンサーと人工知能を用いた側彎角の自動予測 着衣の有無による精度検証

  石川 蓉子, 小甲 晃史, 山田 勝久, 舘 弘之, 鈴木 久崇, 大西 貴士, 岩崎 倫政, 須藤 英毅, 安倍 雄一郎

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 16 - 16 1343-3873 2023
• 治療に苦慮した慢性再発性多発性骨髄炎(CRMO)を背景とした環軸椎回旋位固定の一例

  石田 健太, 遠藤 努, 高畑 雅彦, 須藤 英毅, 山田 勝久, 大西 貴士, 筌場 大介, 浦 勝郎, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 65 (142nd suppl) 18 - 18 1343-3873 2023
• Efficacy of a machine learning-based approach in predicting neurological prognosis of cervical spinal cord injury patients following urgent surgery within 24 h after injury.

  Tomoaki Shimizu, Kota Suda, Satoshi Maki, Masao Koda, Satoko Matsumoto Harmon, Miki Komatsu, Masahiro Ota, Hiroki Ushirozako, Akio Minami, Masahiko Takahata, Norimasa Iwasaki, Hiroshi Takahashi, Masashi Yamazaki

  Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 107 150 - 156 2023/01 

  We aimed to develop a machine learning (ML) model for predicting the neurological outcomes of cervical spinal cord injury (CSCI). We retrospectively analyzed 135 patients with CSCI who underwent surgery within 24 h after injury. Patients were assessed with the American Spinal Injury Association Impairment Scale (AIS; grades A to E) 6 months after injury. A total of 34 features extracted from demographic variables, surgical factors, laboratory variables, neurological status, and radiological findings were analyzed. The ML model was created using Light GBM, XGBoost, and CatBoost. We evaluated Shapley Additive Explanations (SHAP) values to determine the variables that contributed most to the prediction models. We constructed multiclass prediction models for the five AIS grades and binary classification models to predict more than one-grade improvement in AIS 6 months after injury. Of the ML models used, CatBoost showed the highest accuracy (0.800) for the prediction of AIS grade and the highest AUC (0.90) for predicting improvement in AIS. AIS grade at admission, intramedullary hemorrhage, longitudinal extent of intramedullary T2 hyperintensity, and HbA1c were identified as important features for these prediction models. The ML models successfully predicted neurological outcomes 6 months after injury following urgent surgery in patients with CSCI.
• Deep fibrous histiocytoma of the index finger: a case report.

  Hiroki Shibayama, Yuichiro Matsui, Daisuke Kawamura, Daisuke Momma, Takeshi Endo, Yuki Matsui, Yasutaka Yawaka, Kanako C Hatanaka, Emi Takakuwa, Hirokazu Sugino, Yutaka Hatanaka, Tadashi Hasegawa, Norimasa Iwasaki

  Case reports in plastic surgery & hand surgery 10 (1) 2207637 - 2207637 2023 

  Our patient presented with an elastic soft mass of his left index finger. Hematoxylin and eosin staining showed a high cellular density with spindle-shaped cells in a storiform pattern. Immunohistochemical staining was positive for CD68, factor XIIIa and α-smooth muscle actin, and negative for CD34, STAT6, S100 protein, and desmin.
• Three-stage total knee arthroplasty combined with deformity correction and leg lengthening using Taylor spatial frames and conversion to internal fixation for severe intra- and extra-articular deformities and hypoplasia in a patient with hemophilic knee arthropathy: A case report.

  Akira Fukushima, Koji Iwasaki, Ryousuke Hishimura, Shinji Matsubara, Zenta Joutoku, Masatake Matsuoka, Tomoyuki Endo, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki

  The Knee 40 90 - 96 2023/01 

  BACKGROUND: Hemophilic arthropathy is a cause of severe knee deformity, because chronic synovitis due to repeated hemarthrosis affects the area of the epiphyseal plates in juvenile cases. Total knee arthroplasty (TKA) is the standard treatment for end-stage knee arthropathy. However, it is difficult to perform one-stage TKA in patients with severe intra- and extra-articular deformities. CASE PRESENTATION: We reported a case of hemophilic arthropathy in a 55-year-old male with leg length discrepancy of 4 cm, limited range of knee motion (-40° extension and 85° flexion), intra-articular deformity (medial proximal tibial angle: 69°; mechanical lateral distal femoral angle: 79°), extra-articular deformity at the distal femoral metaphyseal (30° valgus and 45° flexion deformity), and varus malalignment (% mechanical axis: 33%). We planned a three-stage TKA. Firstly, we performed gradual correction and lengthening of the distal femur using Taylor spatial flame. Six months after surgery, we performed conversion surgery from external fixation to internal fixation. Finally, we performed TKA with rotating hinged type implant. Two years after surgery, physical examination showed a normal gait, leg length discrepancy of 2 cm (the right leg was shorter), improvement in the range of knee motion (0° extension and 100° flexion). CONCLUSION: To the best of our knowledge, this presents the first combination of three-stage TKA with correction of femoral deformity and leg lengthening using a Taylor spatial frame and conversion to internal fixation in a patient with hemophilic knee arthropathy and severe intra- and extra-articular deformities.
• Early Changes in Postural Balance Following Inverted V-Shaped High Tibial Osteotomy in Patients With Knee Osteoarthritis.

  Kento Sabashi, Takeshi Chiba, Koji Iwasaki, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki, Harukazu Tohyama

  Journal of applied biomechanics 39 (2) 1 - 6 2023/01/01 

  Patients with knee osteoarthritis and varus knee deformity have impaired postural balance, resulting in decreased walking performance and an increased risk of falls. This study aimed to investigate the early changes in the postural balance following inverted V-shaped high tibial osteotomy (HTO). Fifteen patients with medial knee osteoarthritis were recruited. Postural balance was assessed using the center-of-pressure (COP) data during single-leg standing before and 6 weeks after inverted V-shaped HTO. The maximum range, mean velocity, and area of COP movements in the anteroposterior and mediolateral directions were analyzed. Preoperative and postoperative visual analog scale for knee pain was assessed. The maximum range of COP in the mediolateral direction decreased (P = .017), whereas the mean velocity of COP in the anteroposterior direction increased 6 weeks postoperatively (P = .011). The visual analog scale score for knee pain significantly improved at 6 weeks postoperatively (P = .006). Valgus correction with inverted V-shaped HTO resulted in improved postural balance in the mediolateral direction and good short-term clinical outcomes early following surgery. Early rehabilitation after inverted V-shaped HTO should focus on postural balance in the anteroposterior direction.
• Radiolunate Arthrodesis in the Rheumatoid Wrist: A Retrospective Clinical and Radiologic Long-Term Follow-up

  Hiroki Hamano, Daisuke Kawamura, Makoto Motomiya, Yuichiro Matsui, Atsushi Urita, Norimasa Iwasaki

  The Journal of Hand Surgery 0363-5023 2023/01 

  PURPOSE: This study aimed to determine the results of radiolunate arthrodesis for rheumatoid arthritis (RA) after a long-term follow-up period of up to 20 years under tight postoperative medical control of RA. We also compared the results between patients with and without degenerative changes in the midcarpal joints at follow-up. We determined the radiologic factors predictive of secondary degenerative changes in the midcarpal joint. METHODS: This was a long-term retrospective analysis of 16 wrists of 14 patients with RA treated with radiolunate arthrodesis first reported in 2013. The mean follow-up period was 14 years (range, 8-23 years; SD, 4.6 years). Ten wrists had a Larsen classification of grade III, whereas 6 wrists had grade IV. The range of motion was assessed, and clinical outcomes were graded using the Mayo Wrist Score and Stanley classification system. The Carpal Height Index, Ulnar Translation Index, and changes in the midcarpal joint contour were determined from radiographs. We categorized the changes in the midcarpal joint as unchanged or degenerative. RESULTS: At final follow-up, the clinical scores improved; however, the extension and flexion range of motion was significantly reduced compared with that before surgery. The Carpal Height Index and Ulnar Translation Index improved immediately after surgery and remained stable at final follow-up. The changes in the midcarpal joint were categorized as unchanged in 6 wrists and degenerative in 10 wrists. The clinical outcomes were similar between the groups. The mean preoperative Ulnar Translation Index was significantly higher in the degenerative group than in the unchanged group. CONCLUSIONS: Radiolunate arthrodesis in patients with RA maintained good clinical results and corrected alignment, even during long-term follow-up. Preoperative severe ulnar translation deformity was a risk factor for postoperative degeneration of the midcarpal joint, and pre-existing degenerative changes at the midcarpal joint might lead to loss of wrist range of motion. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
• Strong relationship between dyslipidemia and the ectopic ossification of the spinal ligaments.

  Tsutomu Endo, Masahiko Takahata, Ryo Fujita, Yoshinao Koike, Ryota Suzuki, Yuichi Hasegawa, Toshifumi Murakami, Misaki Ishii, Katsuhisa Yamada, Hideki Sudo, Norimasa Iwasaki

  Scientific reports 12 (1) 22617 - 22617 2022/12/30 

  Obesity and metabolic disturbances are prevalent in ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF); however, the involvement of dyslipidemia (DL) in OPLL/OLF remains uncertain. We investigated the association between dyslipidemia and OPLL/OLF using a dataset of 458 individuals receiving health screening tests, including computed tomography. Subjects were grouped according to the presence or location of OPLL/OLF: controls (no OPLL/OLF, n = 230), OLF (n = 167), cervical OPLL (n = 28), and thoracic OPLL (n = 33). They were also grouped according to the presence of dyslipidemia (DL[+], n = 215; DL[-], n = 243). The proportion of dyslipidemia in the OLF and OPLL groups was 1.6-2.2 times higher than that in the control group. The proportion of OLF and OPLL in the DL(+) group was significantly higher than that in the DL(-) group (OLF, 43% vs. 29%; cervical OPLL, 14.4% vs. 3.2%; thoracic OPLL, 11.1% vs. 3.7%). Multivariate logistic regression analysis showed an association between all ossification types and dyslipidemia. This study demonstrated an association of dyslipidemia with OPLL/OLF; further investigation on the causal relationship between dyslipidemia and ectopic spinal ligament ossification is warranted to develop a therapeutic intervention for OPLL/OLF.
• Effects of Posterior Spinal Correction and Fusion on Postural Stability in Patients with Adolescent Idiopathic Scoliosis.

  Satoshi Osuka, Hideki Sudo, Katsuhisa Yamada, Hiroyuki Tachi, Kentaro Watanabe, Fuma Sentoku, Takeshi Chiba, Norimasa Iwasaki, Masahiko Mukaino, Harukazu Tohyama

  Journal of clinical medicine 12 (1) 2022/12/29 

  The present study aimed to assess the effects of posterior spinal correction and fusion on postural stability in patients with adolescent idiopathic scoliosis (AIS). The study included 41 female patients with AIS at our institution. All patients performed three 10 s single-leg standing trials on a force plate. The center of pressure (COP) was measured preoperatively, and at 1 week and 6 months postoperatively. The postural stability parameters were absolute minimum time-to-boundary (TTB), mean of the minimum TTB, mean COP velocity, standard deviation, range, and 95% confidence ellipse area. One-way repeated analysis of variance or Friedman test was applied to the postural stability parameters. Multiple comparisons were performed using the Bonferroni correction. The absolute minimum TTB and the mean minimum TTB showed a significant increase 6 months post-operation as compared to preoperatively and 1 week postoperatively. The COP velocity significantly decreased at 6 months post-operation compared to preoperatively and 1 week postoperatively. These changes in postural stability indicate that spinal correction and fusion can be considered to improve postural stability during single-leg standing tests in the postoperative period.
• Spinal Canal and Spinal Cord in Rat Continue to Grow Even after Sexual Maturation: Anatomical Study and Molecular Proposition.

  Akihito Sotome, Ken Kadoya, Yuki Suzuki, Norimasa Iwasaki

  International journal of molecular sciences 23 (24) 2022/12/16 

  Although rodents have been widely used for experimental models of spinal cord diseases, the details of the growth curves of their spinal canal and spinal cord, as well as the molecular mechanism of the growth of adult rat spinal cords remain unavailable. They are particularly important when conducting the experiments of cervical spondylotic myelopathy (CSM), since the disease condition depends on the size of the spinal canal and the spinal cord. Thus, the purposes of the present study were to obtain accurate growth curves for the spinal canal and spinal cord in rats; to define the appropriate age in weeks for their use as a CSM model; and to propose a molecular mechanism of the growth of the adult spinal cord in rats. CT myelography was performed on Lewis rats from 4 weeks to 40 weeks of age. The vertical growth of the spinal canal at C5 reached a plateau after 20 and 12 weeks, and at T8 after 20 and 16 weeks, in males and females, respectively. The vertical growth of the C5 and T8 spinal cord reached a plateau after 24 weeks in both sexes. The vertical space available for the cord (SAC) of C5 and T8 did not significantly change after 8 weeks in either sex. Western blot analyses showed that VEGFA, FGF2, and BDNF were highly expressed in the cervical spinal cords of 4-week-old rats, and that the expression of these growth factors declined as rats grew. These findings indicate that the spinal canal and the spinal cord in rats continue to grow even after sexual maturation and that rats need to be at least 8 weeks of age for use in experimental models of CSM. The present study, in conjunction with recent evidence, proposes the hypothetical model that the growth of rat spinal cord after the postnatal period is mediated at least in part by differentiation of neural progenitor cells and that their differentiation potency is maintained by VEGFA, FGF2, and BDNF.
• Implications of navigation system use for glenoid component placement in reverse shoulder arthroplasty.

  Hiroaki Kida, Atsushi Urita, Daisuke Momma, Yuki Matsui, Takeshi Endo, Daisuke Kawamura, Hiroshi Taneichi, Norimasa Iwasaki

  Scientific reports 12 (1) 21190 - 21190 2022/12/07 

  Recently, three-dimensional (3D) planning, patient-specific instruments, and navigation system have been developed to improve the accuracy of baseplate placement in reverse shoulder arthroplasty (RSA). The purpose of this study was to evaluate baseplate placement using the navigation system. Sixty-four shoulders in 63 patients who underwent RSA for rotator cuff tear arthropathy or irreparable rotator cuff tears were enrolled. Conventional RSA was performed in 31 shoulders and navigated RSA using pre-operative planning software was performed in 33 shoulders. The use of augmented baseplates, the version and inclination of the baseplate, and screw length were compared between conventional RSA and navigated RSA. Augmented baseplates were used more frequently in navigated RSA than in conventional RSA (20 vs 9 shoulders, p = 0.014). Baseplate alignment was 1.0° (SD 5.1) of retroversion and 2.4° (SD 6.8) of superior inclination in conventional RSA and 0.2° (SD 1.9) of anteversion and 0.3° (SD 1.7) of superior inclination in navigated RSA. Compared with conventional RSA, precision of baseplate version and inclination were higher in navigated RSA (both p < 0.001). Superior, inferior, and posteroinferior screws were significantly longer in navigated RSA than in conventional RSA (p = 0.021, 0.001 and < 0.001, respectively). Precision of superior and inferior screw lengths was significantly higher in navigated RSA than in conventional RSA (both p = 0.001). Our results suggest that adoption of pre-operative planning software increased augmented baseplate use to minimize the glenoid reaming. The navigation system allows placement of the baseplate accurately, according to the pre-operative plan. Furthermore, the navigation system enables monitoring of screw length and direction in real time.
• Safety of early posterior fusion surgery without endovascular embolization for asymptomatic vertebral artery occlusion associated with cervical spine trauma.

  Mitsuru Asukai, Hiroki Ushirozako, Kota Suda, Satoko Matsumoto Harmon, Miki Komatsu, Akio Minami, Masahiko Takahata, Norimasa Iwasaki, Yukihiro Matsuyama

  European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 31 (12) 3392 - 3401 2022/12 

  PURPOSE: Vertebral artery occlusion (VAO) is an increasingly recognized complication of cervical spine trauma. However, the management strategy of VAO remains heavily debated. Therefore, the aim of this retrospective study was to investigate the safety of early fusion surgery for traumatic VAO. METHODS: This study included a total of 241 patients (average age 64.7 years; 201 men) who underwent early surgical treatment for acute cervical spine injury between 2012 and 2019. The incidence of VAO, cerebral infarction rates, the recanalization rates, and cerebral thromboembolism after recanalization were retrospectively analyzed. RESULTS: VAO occurred in 22 patients (9.1%). Of the 22 patients with VAO, radiographic cerebral infarction was detected in 4 patients (21.1%) at initial evaluation, including 1 symptomatic medullar infarction (4.5%) and 3 asymptomatic cerebrum infarctions. A patient who experienced right medullar infarction showed no progression of the neurologic damage. Follow-up imaging revealed that the VAOs of 9 patients (40.9%) were recanalized, and the recanalization did not correlate with clinical adverse outcomes. The arteries of the remaining 13 (59.1%) patients remained occluded and clinically silent until the final follow-up (mean final follow-up 33.0 months). CONCLUSION: Despite the lack of a concurrent control group with preoperative antiplatelet therapy or endovascular embolization for VAO, our results showed low symptomatic stroke rate (4.5%), high recanalization rate (40.9%), and low mortality rate (0%). Therefore, we believe that the indication for early stabilization surgery as management strategy of asymptomatic VAO might be one of the safe and effective treatment options for prevention of symptomatic cerebral infarction.
• Efficacy of the microscopic parachute end-to-side technique for creating large-to-small venous anastomoses in free flaps in the extremities.

  Makoto Motomiya, Naoya Watanabe, Mitsutoshi Ota, Kohei Shimoda, Daisuke Kawamura, Norimasa Iwasaki

  JPRAS open 34 189 - 198 2022/12 

  PURPOSE: The availability of reliable and suitably sized veins is limited for creating free flaps to treat severe trauma and infection, and it is important to manage vessel size discrepancy between the recipient and flap veins. We evaluated the clinical outcomes of free flaps with large-to-small venous end-to-side (ETS) anastomoses using the microscopic parachute end-to-side (MPETS) anastomosis in soft tissue defects in the extremities. This procedure comprises mainly a wide-slit venotomy and parachute procedure at the heel. METHODS: We examined 24 free flaps in 23 patients given a large-to-small venous anastomosis using the MPETS technique. Patient demographics, details of vessel anastomoses, and flap outcomes and complications were obtained from medical records. RESULTS: Two veins were anastomosed in six flaps. Thirty anastomosed veins were assessed, and 24 deep veins, all of which accompanied main arteries, were chosen as recipient veins. The mean diameters were 1.5 mm in the recipient veins and 2.7 mm in the flap veins, and the mean vessel size discrepancy was 1.8-fold (range 1.3-3.3 fold). Because of the presence of venous valves at the anastomotic site, trimming of venous cusps was performed in six veins. All flaps survived, though one venous thrombosis occurred because of pedicle kinking in a case with a short pedicle. CONCLUSIONS: The MPETS technique is simple, reliable, and useful for performing various types of venous anastomoses regardless of a vessel size discrepancy and the presence of a venous valve. This may be a good option for large-to-small venous anastomosis in free flaps.
• The Impact of Carpal Tunnel Release on Two-Point Discrimination, Quick Disabilities of Arm, Shoulder and Hand Score and Distal Motor Latency - A Multi-centre Prospective Study.

  Yukinobu Kamiya, Akio Minami, Yasuaki Tojo, Yoji Mikami, Norimasa Iwasaki, Akinori Sakai

  The journal of hand surgery Asian-Pacific volume 27 (6) 991 - 999 2022/12 

  Background: The authors conducted a prospective, multi-centre study to assess the impact of carpal tunnel release (CTR) on Two-Point Discrimination (2-PD), Quick Disabilities of Arm, Shoulder and Hand Score (Q-DASH), and Distal Motor Latency (DL). The primary aim was to determine the change in outcome measurements (2-PD, Q-DASH and DL) preoperatively and postoperatively at 6 months and 1 year. The secondary aims of the study were to determine whether the postoperative outcomes were different at the 6-month and 1-year follow-up and if there was difference in outcomes based on the preoperative severity of carpal tunnel syndrome (CTS). Methods: A total of 205 hands in 171 patients underwent CTR at five hospitals over a 2-year period. A total of 110 hands in 94 patients were followed-up and analysed. The 2-PD, Q-DASH and DL were measured for all patients preoperatively and at 6 months and 1 year postoperatively. Patients were divided into two groups 'mild' and 'severe' based on pre-operative DL score (mild ≤ 8.1 msec). The change in preoperative and postoperative 2-PD, Q-DASH and DL values were compared. The change in pre-operative and post-operative 2-PD and Q-DASH values were also compared between the 'mild' and 'severe' groups. Results: The 2-PD, Q-DASH and DL showed significant improvement at 6-month and 1-year follow-ups compared to pre-operative values. However, there were no significant differences in all three parameters between the 6-month and 1-year measurements. There was significant improvement in preoperative and postoperative 2-PD and Q-DASH scores between the mild and severe groups. Conclusions: CTR is an effective treatment for patients with CTS with significant improvement in all three outcome parameters (2-PD, Q-DASH and DL). The improvement in outcome plateaus at 6 months and additional follow-up may not be useful. Level of Evidence: Level II (Therapeutic).
• Changes in wrist joint contact area following radial shortening osteotomy for Kienböck’s disease

  Junki Shiota, Daisuke Momma, Yuichiro Matsui, Nozomu Inoue, Eiji Kondo, Norimasa Iwasaki

  Scientific Reports 12 (1) 4001 - 4001 2022/12 

  Abstract We hypothesized that the contact area of the articular surface of the wrist joint could be evaluated using a custom-designed analytical program. The aim of the study was to compare the articular contact area of the wrist joint before and after radial shortening osteotomy for Kienböck’s disease. Nine wrists of 9 patients underwent radial shortening osteotomy for Kienböck’s disease. Computed tomography (CT) images of the wrist joint were reconstructed using a 3D reconstruction software package. Radioscaphoid and radiolunate joint contact areas and translation of the joint contact area from preoperative to postoperative were calculated using customized software. The mean Modified Mayo Wrist Score was significantly improved from 50.6 preoperatively to 83.3 at final follow-up (p < .001). Preoperatively, the pain was reported as severe in five wrists and moderate in four wrists, while at final follow-up, five patients were free from pain and four patients had mild pain with vigorous activity. The preoperative radioscaphoid joint contact area was 133.4 ± 49.5 mm² and the postoperative radioscaphoid joint contact area was 156.4 ± 73.1 mm². The preoperative radiolunate joint contact area was 194.8 ± 92.1 mm² and the postoperative radiolunate joint contact area was 148.3 ± 97.9 mm². The radial translation distance was 0.4 ± 1.2 mm, the dorsal translation distance was 0.6 ± 1.2 mm, and the proximal translation distance was 0.2 ± 0.4 mm. CT-based analysis revealed that the center of the contact area translated radially following radial shortening.
• Perioperative Complications of Open Spine Surgery in Older Adults over 90 Years of Age.

  Takeru Tsujimoto, Masahiro Kanayama, Kota Suda, Fumihiro Oha, Miki Komatsu, Yukitoshi Shimamura, Masaru Tanaka, Daisuke Ukeba, Yuichi Hasegawa, Tomoyuki Hashimoto, Masahiko Takahata, Norimasa Iwasaki

  Spine surgery and related research 6 (6) 664 - 670 2022/11/27 

  INTRODUCTION: Despite perioperative risks in nonagenarian patients who undergo open spine surgery for degeneration disorder or spinal trauma being of great interest, the prevalence of complications in this group remains unclear. This study aims to examine the perioperative complications of open spine surgery in the elderly over 90 years of age. METHODS: Preoperative and intraoperative characteristics including the American Society of Anesthesiologists Physical Status (ASA-PS) class, type of surgery, and complications within 30 postoperative days were retrospectively collected from the medical records of nonagenarians who underwent open spine surgery between April 2004 and July 2019 at our spine centers. RESULTS: A total of 48 patients met the inclusion criteria of this study. All belong to ASA-PS class 2 (69%) or 3. Preoperative American Spinal Injury Association Impairment Scale grades in trauma group were grade A in 4 cases, B in 1 case, C in 5 cases, D in 11 cases, and E in 1 case. Major complications (deep surgical site infection, cardiac event, respiratory disorder, gastrointestinal hemorrhage, and renal failure) occurred in 13 cases, and the rate of overall perioperative complications was 45.8%. One patient who underwent cervical stabilization for cervical fracture dislocation died at postoperative 13 days due to respiratory disorder. The rates of major complications and overall perioperative complications were 3.6% and 14.3% in the degenerative group and 45.5% and 81.8% in the trauma group, respectively. Especially in the trauma group, respiratory disorder occurred in 7 cases, delirium in 11 cases, and urinary tract infection in 5 cases. CONCLUSIONS: Although the perioperative complication rate reached 81.8% in spinal trauma cases, the complication rate in degenerative disorders was relatively low as 14.3%. Open spine surgery for degenerative disorders can be relatively safe even in nonagenarians, whereas the risks of perioperative complications, including respiratory disorder and delirium, were high in spinal trauma cases.
• Posterolateral full-endoscopic debridement and irrigation is effective in treating thoraco-lumbar pyogenic spondylodiscitis, except in cases with large abscess cavities

  Katsuhisa Yamada, Masahiko Takahata, Ken Nagahama, Akira Iwata, Tsutomu Endo, Ryo Fujita, Hiroyuki Hasebe, Takashi Ohnishi, Hideki Sudo, Manabu Ito, Norimasa Iwasaki

  European Spine Journal 32 (3) 859 - 866 0940-6719 2022/11/24 

  PURPOSE: To determine the efficacy and poor prognostic factors of posterolateral full-endoscopic debridement and irrigation (PEDI) surgery for thoraco-lumbar pyogenic spondylodiscitis. METHODS: We included 64 patients (46 men, 18 women; average age: 63.7 years) with thoracic/lumbar pyogenic spondylodiscitis who had undergone PEDI treatment and were followed up for more than 2 years. Clinical outcomes after PEDI surgery were retrospectively investigated to analyze the incidence and risk factors for prolonged and recurrent infection. RESULTS: Of 64 patients, 53 (82.8%) were cured of infection after PEDI surgery, and nine (17.2%) had prolonged or recurrent infection. Multivariate analysis demonstrated that significant risk factors for poor prognosis included a large intervertebral abscess cavity (P = 0.02) and multilevel intervertebral infections (P < 0.05). CONCLUSION: PEDI treatment is an effective, minimally invasive procedure for pyogenic spondylodiscitis. However, a large intervertebral abscess space could cause instability at the infected spinal column, leading to prolonged or recurrent infection after PEDI. In cases with a large abscess cavity with or without vertebral bone destruction, endoscopic drainage alone may have a poor prognosis, and spinal fixation surgery could be considered.
• Risk factors of AIS C incomplete cervical spinal cord injury for poor prognosis-The significance of anorectal evaluation.

  Osahiko Tsuji, Kota Suda, Takehiro Michikawa, Masahiko Takahata, Masahiro Ozaki, Tsunehiko Konomi, Satoko Harmon-Matsumoto, Miki Komatsu, Chikara Ushiku, Yusuke Menjo, Seiji Iimoto, Kota Watanabe, Masaya Nakamura, Morio Matsumoto, Akio Minami, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 28 (6) 1227 - 1233 2022/11/02 

  BACKGROUND: Although the prognosis of incomplete cervical spinal cord injury (SCI) diagnosed as American Spinal Injury Association Impairment Scale grade C (AIS C) is generally favorable, some patients remain non-ambulatory. The present study explored the clinical factors associated with the non-ambulatory state of AIS C patients. METHODS: This study was a single-center retrospective observational study. Seventy-three participants with AIS C on admission were enrolled and divided into two groups according to ambulatory ability after one year. Prognostic factors of SCI were compared in ambulatory (A-group) and non-ambulatory participants (NA-group). Univariable and multivariable logistic regression analyses were performed on demographic information, medical history, mechanism of injury, presence of fracture, ASIA motor scores (MS) of the extremities, neurological findings, including an anorectal examination on admission, and imaging findings. RESULTS: Forty-one patients were included in the A-group and 32 in the NA-group. Univariable analysis revealed that the following factors were related to poor outcomes (p < 0.05): older age, history of cerebrovascular disorder, impairment/absence of S4-5 sensory score, deep anal pressure (DAP) (-), voluntary anal contraction (VAC) (-), anorectal tone (-), anal wink reflex (-), and low MS of the upper and lower extremities. In the multivariable analysis using age, presence or absence of sacral abnormality, and history of cerebrovascular disorders (adjusted for these three factors), older age and presence of sacral abnormality on admission were independent risk factors for a non-ambulatory state at the 1-year follow-up. CONCLUSIONS: Incomplete AIS C SCI individuals with older age and/or impairment of anorectal examination could remain non-ambulatory at 1-year follow-up.
• 乳児股関節健診推奨項目は発育性股関節形成不全の予測因子となりうるか

  大橋 佑介, 清水 智弘, 清水 寛和, 小川 拓也, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本小児整形外科学会雑誌 (一社)日本小児整形外科学会 31 (3) S54 - S54 0917-6950 2022/11
• 発育性股関節形成不全の二次検診受診時期による装具治療の有無の検討

  小川 拓也, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本小児整形外科学会雑誌 (一社)日本小児整形外科学会 31 (3) S54 - S54 0917-6950 2022/11
• リーメンビューゲル治療前に水平牽引を行うことで脱臼整復率は改善する

  小川 拓也, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本小児整形外科学会雑誌 (一社)日本小児整形外科学会 31 (3) S66 - S66 0917-6950 2022/11
• Angulated Innominate Osteotomyにおける術中三次元矯正と術後1年単純X線との関連

  小川 拓也, 高橋 大介, 清水 智弘, 宮崎 拓自, 岩崎 倫政

  日本小児整形外科学会雑誌 (一社)日本小児整形外科学会 31 (3) S71 - S71 0917-6950 2022/11
• 最先端医療の今 免疫細胞由来因子Cardiotrophin-Like Cytokine Factor 1(CLCF1)の骨粗鬆症モデルマウスにおける検討

  横田 隼一, 高橋 大介, 照川 アラー, 清水 智弘, 岩崎 倫政

  Medical Science Digest (株)ニュー・サイエンス社 48 (12) 604 - 608 1347-4340 2022/11 

  免疫細胞由来分子であるCLCF1の発現が,閉経後の骨粗鬆症患者で減少していることが報告されており,CLCF1が骨代謝制御に関与すると考えられる。そこで本研究では,骨粗鬆症におけるCLCF1の機能を検証した。CLCF1投与により,卵巣摘出骨粗鬆症モデルマウスの骨量減少が抑制された。同様に,in vitroでCLCF1は破骨細胞数と象牙質スライスでの骨吸収領域が有意に減少させ,骨芽細胞の分化には抑制効果を示さなかった。RNA-seqによる網羅的解析により,CLCF1の作用にはインターフェロンシグナル(IFN)活性化とNF-κBシグナル抑制が関与していた。これらの結果から,CLCF1はIFN活性化とNF-κB抑制を介して,骨芽細胞の骨形成に影響を与えずに,破骨細胞分化と骨吸収を抑制する。CLCF1は骨粗鬆症の新規治療薬として有用である可能性が示唆された。(著者抄録)
• 人工関節置換術後無菌性緩みに対するポリエチレンライナー放射線架橋線量の検討

  塩田 惇喜, アラー照川, 高橋 大介, 清水 智弘, 松前 元, 江畑 拓, 横田 隼一, 西田 善郎, 北原 圭介, 徳廣 泰貴, 岩崎 倫政

  日本バイオマテリアル学会大会予稿集 日本バイオマテリアル学会 44回 145 - 145 2022/11
• Ferroptosisを標的としたポリエチレン摩耗粉による炎症性骨吸収抑制効果

  横田 隼一, 照川 アラー, 照川 ヘンド, 西田 善郎, 塩田 惇喜, 北原 圭太, 徳廣 泰貴, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本バイオマテリアル学会大会予稿集 日本バイオマテリアル学会 44回 410 - 410 2022/11
• Utility of thermal image scanning in screening for febrile patients in cold climates.

  Takuya Ogawa, Yukinori Tsukuda, Yuki Suzuki, Shigeto Hiratsuka, Ryo Inoue, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 27 (6) 1333 - 1337 2022/11 

  BACKGROUND: Infrared thermography (IRT) for fever screening systems was introduced in not only general hospitals, but also orthopedic hospitals as a countermeasure against the spread of coronavirus disease 2019 (COVID-19). Despite the widespread use of IRT, various results have shown low and high efficacies, so the utility of IRT is controversial, especially in cold climates. The aims of this study were to investigate the utility of IRT in screening for fever in a cold climate and to devise suitable fever screening in orthopedic surgery for COVID-19. METHODS: A total of 390 orthopedic surgery patients were enrolled to the outdoor group and 210 hospital staff members were enrolled to the indoor group. Thermographic temperature at the front of the face in the outdoor group was immediately measured after entering our hospital from a cold outdoor environment. Measurements for the indoor group were made after staying in the hospital (environmental temperature, 28 °C) for at least 5 h. Body temperature was then measured using an axillary thermometer >15 min later in both groups. RESULTS: In the outdoor group, mean thermographic temperature was significantly lower than axillary temperature and IRT could not detect febrile patients with axillary temperatures >37.0 °C. Mean thermographic temperature was significantly lower in the outdoor group than in the indoor group. Sensitivity was 11.5% for the outdoor group, lower than that for the indoor group. CONCLUSIONS: We verified that IRT was not accurate in a cold climate. IRT is inadequate as a screening method to accurately detect febrile individuals, so we believe that stricter countermeasures for second screening need to be employed to prevent nosocomial infections and disease clusters of COVID-19, even in orthopedic hospitals.
• Long-Term Clinical Course of Patients After Decompression and Posterior Instrumented Fusion Surgery for Thoracic Ossification of the Posterior Longitudinal Ligament: An Average Follow-Up of 18 years

  Masahiko Takahata, Tsutomu Endo, Yoshinao Koike, Kuniyoshi Abumi, Kota Suda, Ryo Fujita, Toshifumi Murakami, Hideki Sudo, Katsuhisa Yamada, Takashi Ohnishi, Katsuro Ura, Daisuke Ukeba, Norimasa Iwasaki

  Global Spine Journal 14 (4) 219256822211355 - 219256822211355 2192-5682 2022/10/15 

  Study Design Retrospective observational study. Objectives To evaluate the long-term recurrence rates and functional status of patients with thoracic ossification of the posterior longitudinal ligament (OPLL) after decompression and posterior fusion surgery. Methods Thirty-seven consecutive patients who underwent posterior thoracic spine surgery at a single institution were retrospectively reviewed. The long-term neurological and functional outcomes of 25 patients who were followed up for ≥10 years after surgery were assessed. Factors associated with the recurrence of myelopathy were also analyzed. Results The mean preoperative Japanese Orthopaedic Association score was 3.7, which improved to 6.5 at postoperative year 2 and declined to 6.0 at a mean follow-up of 18 years. No patient experienced a relapse of myelopathy due to OPLL within the instrumented spinal segments. However, 15 (60%) patients experienced late neurological deterioration, 10 of whom had a relapse of myelopathy due to OPLL or ossification of the ligamentum flavum (OLF) in the region outside the primary operative lesion, while 4 developed myelopathy due to traumatic vertebral fracture of the ankylosed spine. Young age, a high body mass index, and lumbar OPLL are likely associated with late neurological deterioration. Conclusions Decompression and posterior instrumented fusion surgery is a reliable surgical procedure with stable long-term clinical outcomes for thoracic OPLL. However, as OPLL may progress through the spine, attention should be paid to the recurrence of paralysis due to OPLL or OLF in regions other than the primary operative lesion and vertebral fractures of the ankylosed spine after surgery for thoracic OPLL.
• Molecular and Regenerative Characterization of Repair and Non-repair Schwann Cells.

  Tomoaki Suzuki, Ken Kadoya, Takeshi Endo, Norimasa Iwasaki

  Cellular and molecular neurobiology 43 (5) 2165 - 2178 2022/10/12 

  Although evidence has accumulated to indicate that Schwann cells (SCs) differentiate into repair SCs (RSCs) upon injury and that the unique phenotype of these cells allow them to provide support for peripheral nerve regeneration, the details of the RSCs are not fully understood. The findings of the current study indicate that the RSCs have enhanced adherent properties and a greater capability to promote neurite outgrowth and axon regeneration after peripheral nerve injury, compared to the non-RSCs. Further, transcriptome analyses have demonstrated that the molecular signature of the RSCs is distinctly different from that of the non-RSCs. The RSCs upregulate a group of genes that are related to inflammation, repair, and regeneration, whereas non-RSCs upregulate genes related to myelin maintenance, Notch, and aging. These findings indicate that the RSCs have markedly different cellular, regenerative, and molecular characteristics compared to the non-RSCs, even though the RSCs were just derived from non-RSCs upon injury, thus providing the basis for understanding the mechanisms related to SC mediated repair after peripheral nerve injury.
• Histochemical assessment of accelerated bone remodeling and reduced mineralization in Il-6 deficient mice.

  Yasuhito Moritani, Tomoka Hasegawa, Tomomaya Yamamoto, Hiromi Hongo, Yimin, Miki Abe, Hirona Yoshino, Ko Nakanishi, Haruhi Maruoka, Hotaka Ishizu, Tomohiro Shimizu, Masahiko Takahata, Norimasa Iwasaki, Minqi Li, Kanchu Tei, Yoichi Ohiro, Norio Amizuka

  Journal of oral biosciences 64 (4) 410 - 421 2022/10/11 

  OBJECTIVES: Interleukin-6 (IL-6) contributes to the regulation of functions in various tissues and organs. Even though IL-6 has been reported to modulate bone metabolism in previous studies, this finding is controversial. This study aims to evaluate the possible involvement of IL-6 in bone metabolism by examining the histological activity of osteoblasts and osteoclasts in the femora of Il-6 deficient (Il-6-/-) mice. METHODS: Eight-week-old male Il-6-/- mice and their wild-type littermates were fixed with a paraformaldehyde solution, and their femora were extracted for micro-CT analysis, immunohistochemistry, and real-time PCR analysis. RESULTS: Il-6-/- femora showed an increased bone volume/tissue volume (TV) but a reduced bone mineral density compared with the wild-type. Furthermore, the tissue-nonspecific alkaline phosphatase positive area/TV ratio, the expression of Runx2, Osterix, and Rankl, and the number of tartrate-resistant acid phosphatase-positive osteoclasts were all increased in the Il-6-/- mice. A considerable number of unmineralized areas within the bone matrix and abundant sclerostin-reactive osteocytes were observed in Il-6-/- femoral metaphyses but not in the wild-type. Interestingly, the gene expression of Cd206 was elevated in Il-6-/- femora, and many F4/80-positive macrophages/monocytes and CD206-immunoreactive macrophages in the primary trabeculae had migrated closer to the growth plate, where intense RANKL immunoreactivity was detected. These results suggest that, in an IL-6-deficient state, CD206-positive macrophages may differentiate into osteoclasts when in contact with RANKL-reactive osteoblastic cells. CONCLUSION: In a state of IL-6 deficiency, the population and cell activities of osteoblast, osteoclasts, and macrophages seemed to be facilitated, except for the reduced mineralization in bone.
• Giant Geode at the Humeral Head in the Rheumatoid Shoulder Treated With Allograft Bone Grafting and Shoulder Arthroplasty.

  Atsushi Urita, Takeshi Endo, Norimasa Iwasaki, Hiroshi Taneichi

  The Journal of rheumatology 49 (10) 1174 - 1175 2022/10
• Occurrence Rate of Cyclops Lesion After Anatomic Double-Bundle ACL Reconstruction: Comparison Between Remnant Tissue Preservation and Resection Methods.

  Ryosuke Hishimura, Eiji Kondo, Yuki Suzuki, Masatake Matsuoka, Koji Iwasaki, Tomohiro Onodera, Daisuke Momma, Tomonori Yagi, Kazunori Yasuda, Norimasa Iwasaki

  Orthopaedic journal of sports medicine 10 (10) 23259671221130688 - 23259671221130688 2022/10 

  BACKGROUND: The occurrence rate of cyclops lesion after anatomic double-bundle anterior cruciate ligament (ACL) reconstruction with remnant tissue preservation remains unclear. HYPOTHESIS: The study hypotheses were as follows: (1) the occurrence rate of cyclops lesion will be comparable between the remnant-preserving and remnant-resecting ACL reconstruction methods, and (2) there will be no significant differences in clinical outcomes between the remnant-preserving and remnant-resecting procedures. METHODS: This retrospective comparative study involved 177 patients who underwent unilateral anatomic double-bundle ACL reconstruction using hamstring tendon autografts from 2014 to 2018 at our hospital. According to the Crain classification of ACL remnant tissue, 98 patients with remnant types I, II, or III underwent the remnant-preserving procedure (group A), and the remaining 79 patients with remnant type IV underwent the remnant-resecting procedure (group B). All patients underwent second-look arthroscopy. Patients were evaluated according to arthroscopic and clinical results at postoperative 15.2 ± 8.4 months (mean ± SD). Statistical comparisons between groups were made using the paired Student t test, chi-square test, and Fisher exact test. STUDY DESIGN: Cohort study; Level of evidence, 3. RESULTS: At second-look arthroscopy, the incidence of cyclops lesions was significantly higher in group B than in group A (29.1% vs 13.3%; P = .0139). Cyclops lesions were divided into 4 locations: femoral side (type 1), midsubstance (type 2), tibial side (type 3), and anterior (type 4) of the ACL graft. The ratio of the tibial-side cyclops lesion (type 3) was significantly higher in group B than in group A (P = .0354). There were no significant differences in the clinical evaluation scores between the procedures. Side-to-side anterior laxity was significantly less in group A than in group B (0.7 vs 1.6 mm; P = .0035). Concerning postoperative laceration and synovium coverage of the grafts, group A was significantly better than group B (P < .0001). CONCLUSION: In this cohort of patients undergoing double-bundle ACL reconstruction, resection of the ACL remnant was associated with a significantly higher rate of cyclops lesion formation when compared with preservation of the remnant.
• High-Throughput Screening Assay Identifies Berberine and Mubritinib as Neuroprotection Drugs for Spinal Cord Injury via Blood-Spinal Cord Barrier Protection.

  Yuki Suzuki, Shinsuke Nakagawa, Takeshi Endo, Akihito Sotome, Rufei Yuan, Tsuyoshi Asano, Satoko Otsuguro, Katsumi Maenaka, Norimasa Iwasaki, Ken Kadoya

  Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 19 (6) 1976 - 1991 2022/10 

  Because the breakdown of the blood-brain spinal cord barrier (BBSCB) worsens many central nervous system (CNS) diseases, prevention of BBSCB breakdown has been a major therapeutic target, especially for spinal cord injury (SCI). However, effective drugs that protect BBSCB function have yet to be developed. The purpose of the current study was 1) to develop a high-throughput screening assay (HTSA) to identify candidate drugs to protect BBSCB function, 2) to identify candidate drugs from existing drugs with newly developed HTSA, and 3) to examine the therapeutic effects of candidate drugs on SCI. Our HTSA included a culture of immortalized human brain endothelial cells primed with candidate drugs, stress with H2O2, and evaluation of their viability. A combination of the resazurin-based assay with 0.45 mM H2O2 qualified as a reliable HTSA. Screening of 1,570 existing drugs identified 90 drugs as hit drugs. Through a combination of reproducibility tests, exclusion of drugs inappropriate for clinical translation, and dose dependency tests, berberine, mubritinib, and pioglitazone were identified as a candidate. An in vitro BBSCB functional test revealed that berberine and mubritinib, but not pioglitazone, protected BBSCB from oxygen-glucose deprivation and reoxygenation stress. Additionally, these two drugs minimized BBSCB breakdown 1 day after cervical SCI in mice. Furthermore, berberine and mubritinib reduced neuronal loss and improved gait performance 8 weeks after SCI. Collectively, the current study established a useful HTSA to identify potential neuroprotective drugs by maintaining BBSCB function and demonstrated the neuroprotective effect of berberine and mubritinib after SCI.
• Neutrophils delay repair process in Wallerian degeneration by releasing NETs outside the parenchyma.

  Yasuhiro Yamamoto, Ken Kadoya, Mohamad Alaa Terkawi, Takeshi Endo, Kohtarou Konno, Masahiko Watanabe, Satoshi Ichihara, Akira Hara, Kazuo Kaneko, Norimasa Iwasaki, Muneaki Ishijima

  Life science alliance 5 (10) 2022/10 

  Although inflammation is indispensable for the repair process in Wallerian degeneration (WD), the role of neutrophils in the WD repair process remains unclear. After peripheral nerve injury, neutrophils accumulate at the epineurium but not the parenchyma in the WD region because of the blood-nerve barrier. An increase or decrease in the number of neutrophils delayed or promoted macrophage infiltration from the epineurium into the parenchyma and the repair process in WD. Abundant neutrophil extracellular traps (NETs) were formed around neutrophils, and its inhibition dramatically increased macrophage infiltration into the parenchyma. Furthermore, inhibition of either MIF or its receptor, CXCR4, in neutrophils decreased NET formation, resulting in enhanced macrophage infiltration into the parenchyma. Moreover, inhibiting MIF for just 2 h after peripheral nerve injury promoted the repair process. These findings indicate that neutrophils delay the repair process in WD from outside the parenchyma by inhibiting macrophage infiltration via NET formation and that neutrophils, NETs, MIF, and CXCR4 are therapeutic targets for peripheral nerve regeneration.
• Establishment of the removal method of undifferentiated induced pluripotent stem cells coexisting with chondrocytes using R-17F antibody.

  Takuji Miyazaki, Hisatoshi Hanamatsu, Tomohiro Onodera, Jun-Ichi Furukawa, Liang Xu, Kentaro Homan, Rikiya Baba, Toshisuke Kawasaki, Norimasa Iwasaki

  Regenerative medicine 17 (11) 793 - 803 2022/09/26 

  Aim: Tumorigenicity of residual undifferentiated induced pluripotent stem cells (iPSCs) is a major concern. The purpose of this study was to investigate the optimal conditions for removal of iPSCs using R-17F antibody, which recognizes specific glycosphingolipids glycans on undifferentiated iPSCs and exhibits selective cytotoxicity to iPSCs. Materials & methods: After adding of R-17F and secondary antibody to co-cultured iPSCs and chondrocytes, residual iPSCs were quantitatively evaluated by iPS specific glycome analysis. Results: Undifferentiated iPSCs were sufficiently removed using R-17F in combination with an equal amount of a secondary antibody. Furthermore, teratomas were not observed upon transplantation of co-cultured cells pretreated under the same conditions into testes of immunodeficient mice. Conclusion: This removal method incorporating R-17F may be useful for regenerative medicine using iPSCs.
• Glycosphingolipid GM3 prevents albuminuria and podocytopathy induced by anti-nephrin antibody.

  Nagako Kawashima, Shokichi Naito, Hisatoshi Hanamatsu, Masaki Nagane, Yasuo Takeuchi, Jun-Ichi Furukawa, Norimasa Iwasaki, Tadashi Yamashita, Ken-Ichi Nakayama

  Scientific reports 12 (1) 16058 - 16058 2022/09/26 

  Podocytopathy, which is characterized by injury to podocytes, frequently causes proteinuria or nephrotic syndrome. There is currently a paucity of effective therapeutic drugs to treat proteinuric kidney disease. Recent research suggests the possibility that glycosphingolipid GM3 maintains podocyte function by acting on various molecules including nephrin, but its mechanism of action remains unknown. Here, various analyses were performed to examine the potential relationship between GM3 and nephrin, and the function of GM3 in podocytes using podocytopathy mice, GM3 synthase gene knockout mice, and nephrin injury cells. Reduced amounts of GM3 and nephrin were observed in podocytopathy mice. Intriguingly, this reduction of GM3 and nephrin, as well as albuminuria, were inhibited by administration of valproic acid. However, when the same experiment was performed using GM3 synthase gene knockout mice, valproic acid administration did not inhibit albuminuria. Equivalent results were obtained in model cells. These findings indicate that GM3 acts with nephrin in a collaborative manner in the cell membrane. Taken together, elevated levels of GM3 stabilize nephrin, which is a key molecule of the slit diaphragm, by enhancing the environment of the cell membrane and preventing albuminuria. This study provides novel insight into new drug discovery, which may offer a new therapy for kidney disease with albuminuria.
• AIと診断・治療 経椎間孔アプローチ進入角度に基づいたKambin's triangleの三次元的形態解析 AIにて自動作成した3D腰椎神経根画像を用いて

  山田 勝久, 長濱 賢, 安倍 雄一郎, 日向寺 義則, 須藤 英毅, 遠藤 努, 大西 貴士, 長谷部 弘之, 藤田 諒, 高畑 雅彦, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (8) S1740 - S1740 0021-5325 2022/09
• ステロイド関連特発性大腿骨頭壊死症における多発骨壊死の関連因子

  菅原 悠太郎, 清水 智弘, 横田 隼一, 石津 帆高, 宮崎 拓自, 小川 拓也, 高橋 大介, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 41 (3) 148 - 148 1883-2873 2022/09
• 整形外科領域におけるAIの応用 ハイブリット人工知能を用いた寛骨臼形成不全の自動解析システムの開発

  清水 智弘, 高橋 大介, 清水 寛和, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 41 (3) 206 - 206 1883-2873 2022/09
• 急速破壊型股関節症におけるNLRP3インフラマソーム経路を介した高度滑膜炎関与の検証

  横田 隼一, 清水 智弘, 小川 拓也, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 41 (3) 229 - 229 1883-2873 2022/09
• CLCF1投与によるインターフェロンシグナルの活性化を介した骨粗鬆症モデルマウスの骨量減少抑制効果について

  横田 隼一, 松前 元, 江畑 拓, 照川 ヘンド, 清水 智弘, 高橋 大介, 照川 アラー, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (8) S1537 - S1537 0021-5325 2022/09
• アネキシンA1(AnxA1)の炎症性骨吸収抑制効果の検討 人工関節術後無菌性緩みの治療薬開発にむけて

  照川 ヘンド, 西田 善郎, 松前 元, 江畑 拓, 横田 隼一, 高橋 大介, 清水 智弘, 照川 アラー, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (8) S1543 - S1543 0021-5325 2022/09
• 骨リモデリング調節におけるアネキシンA1の機能解析

  西田 善郎, 松前 元, 江畑 拓, 横田 隼一, 照川 ヘンド, 塩田 惇喜, 北原 圭太, 清水 智弘, 高橋 大介, 照川 アラー, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (8) S1549 - S1549 0021-5325 2022/09
• 炎症収束型好中球由来細胞外小胞による軟骨細胞抗異化作用の検討

  北原 圭太, 江畑 拓, 清水 智弘, 浅野 毅, 照川 アラー, 高橋 大介, 角家 健, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (8) S1559 - S1559 0021-5325 2022/09
• 変性軟骨細胞が骨細胞機能に及ぼす影響 変形性関節症における軟骨-軟骨下骨連関機序の解明

  徳廣 泰貴, 江畑 拓, 濱崎 雅成, 松前 元, 高橋 大介, 清水 智弘, 照川 アラー, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (8) S1573 - S1573 0021-5325 2022/09
• 軟骨細胞パイロトーシス制御による軟骨変性抑制効果

  江畑 拓, 照川 アラー, 横田 隼一, 照川 ヘンド, 松前 元, 清水 智弘, 高橋 大介, 小野寺 智洋, 角家 健, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (8) S1580 - S1580 0021-5325 2022/09
• 人工股関節全置換術におけるヘッド延長の脚長、オフセット、可動域に与える影響 A computer simulation study

  宮崎 拓自, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (8) S1710 - S1710 0021-5325 2022/09
• 機械学習予測モデルを介した脆弱性骨折術後患者の再骨折予測因子抽出の検討

  清水 寛和, 清水 智弘, 遠田 健, 石田 雄介, 石津 帆高, 伊勢 昂生, 田中 伸哉, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (8) S1797 - S1797 0021-5325 2022/09
• 乳児股関節超音波画像に対する人工知能解析システムの開発

  清水 寛和, 清水 智弘, 遠田 健, 児矢野 英典, 高橋 大介, 石田 雄介, 小川 拓也, 田中 伸哉, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (8) S1797 - S1797 0021-5325 2022/09
• In Reply to the Letter to the Editor Regarding "Does Primary Tumor Resection in Patients with Metastatic Primary Mobile Vertebral Column Sarcoma Improve the Survivals?".

  Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Norimasa Iwasaki

  World neurosurgery 165 210 - 210 2022/09
• Matrix Vesicle-Mediated Mineralization and Osteocytic Regulation of Bone Mineralization.

  Tomoka Hasegawa, Hiromi Hongo, Tomomaya Yamamoto, Miki Abe, Hirona Yoshino, Mai Haraguchi-Kitakamae, Hotaka Ishizu, Tomohiro Shimizu, Norimasa Iwasaki, Norio Amizuka

  International journal of molecular sciences 23 (17) 2022/09/01 

  Bone mineralization entails two mineralization phases: primary and secondary mineralization. Primary mineralization is achieved when matrix vesicles are secreted by osteoblasts, and thereafter, bone mineral density gradually increases during secondary mineralization. Nearby extracellular phosphate ions (PO43-) flow into the vesicles via membrane transporters and enzymes located on the vesicles' membranes, while calcium ions (Ca2+), abundant in the tissue fluid, are also transported into the vesicles. The accumulation of Ca2+ and PO43- in the matrix vesicles induces crystal nucleation and growth. The calcium phosphate crystals grow radially within the vesicle, penetrate the vesicle's membrane, and continue to grow outside the vesicle, ultimately forming mineralized nodules. The mineralized nodules then attach to collagen fibrils, mineralizing them from the contact sites (i.e., collagen mineralization). Afterward, the bone mineral density gradually increases during the secondary mineralization process. The mechanisms of this phenomenon remain unclear, but osteocytes may play a key role; it is assumed that osteocytes enable the transport of Ca2+ and PO43- through the canaliculi of the osteocyte network, as well as regulate the mineralization of the surrounding bone matrix via the Phex/SIBLINGs axis. Thus, bone mineralization is biologically regulated by osteoblasts and osteocytes.
• Correlation between carpal rotational alignment and postoperative wrist range of motion following total wrist arthroplasty

  Mitsutoshi Ota, Yuichiro Matsui, Daisuke Kawamura, Atsushi Urita, Takeshi Endo, Norimasa Iwasaki

  BMC Musculoskeletal Disorders 23 (1) 821 - 821 2022/08/30 

  Abstract Background Although total wrist arthroplasty (TWA) has become a common treatment option for wrists with damage due to rheumatoid arthritis (RA), the optimal implant axial alignment for TWA has been inadequately studied. This study was performed to investigate the relationships between implant alignment and carpal rotational alignment and the wrist range of motion (ROM) following TWA. Methods This study included 18 patients who underwent TWA using a DARTS® Total Wrist System (Teijin Nakashima Medical, Okayama, Japan) for wrist RA. Pre- and 6-month postoperative computed tomography scans were performed, including the radial volar line (Rv), capitohamate axis (CH), and Rv-CH angle in axial scans. The wrist ROM was also measured. The relationship between the Rv-CH angle and ROM was examined. Results The mean Rv-CH angle showed significant wrist pronation from 73.0° to 83.4° postoperatively. We observed a significant positive correlation (0.58) between the postoperative Rv-CH angle and extension and a significant negative correlation (− 0.56) between the postoperative Rv-CH angle and flexion. Conclusions Implantation of the DARTS® TWA prosthesis resulted in pronation of the carpal axial alignment, which was correlated with postoperative wrist extension. The volar cortex of the distal radius can be a novel reference axis for adequate implant placement.
• Comparison of clinical features between patients with bone and soft tissue fibrosarcomas.

  Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Eiji Kondo, Norimasa Iwasaki

  Journal of surgical oncology 126 (7) 1299 - 1305 2022/08/08 

  BACKGROUND AND OBJECTIVES: Fibrosarcomas predominantly arise in soft tissues, but can also develop in bone. Because of their rarity, whether bone development has an impact on clinical features has not been addressed. METHODS: We included fibrosarcoma patients diagnosed between 1983 and 2016 in the Surveillance, Epidemiology, and End Results database. Differences in clinical features between fibrosarcoma of bone (FS-B) and fibrosarcoma of soft tissue (FS-ST) were investigated. RESULTS: After excluding patients without information regarding cause of death, site of origin, distant tumor or survival, 1443 patients were included. Of those, 98 patients had FS-B. Patients with FS-B were younger, more frequently male, with fibrosarcomas that more often developed in an extremity and were histologically high-grade. In contrast, no difference in potential to metastasize was observed. Survival was almost equal between FS-B and FS-ST (FS-B/FS-ST: cancer-specific survival, hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.8-1.7; overall survival, HR: 1.3, 95% CI: 0.9-1.7). CONCLUSIONS: Our results clearly indicated that patient backgrounds differed, such as younger age and greater tendencies to affect males, develop in an extremity and show high-grade tumor in patients with FS-B. In contrast, no differences were observed in distant metastatic potential or survival.
• 人工知能を用いた乳児股関節超音波健診システムの開発

  清水 寛和, 清水 智弘, 高橋 大介, 小川 拓也, 岩崎 倫政

  東日本整形災害外科学会雑誌 東日本整形災害外科学会 34 (3) 236 - 236 1342-7784 2022/08
• 臼蓋骨欠損に対してKT plateとMetal meshを用いた人工股関節再置換術の術後成績,X線学的指標の比較検討

  石津 帆高, 清水 智弘, 笹沢 史生, 金山 雅弘, 高橋 大介, 岩崎 倫政

  東日本整形災害外科学会雑誌 東日本整形災害外科学会 34 (3) 254 - 254 1342-7784 2022/08
• 機械学習予測モデルを介した脆弱性骨折術後患者の再骨折予測因子抽出の検討

  清水 寛和, 清水 智弘, 石津 帆高, 岩崎 倫政

  東日本整形災害外科学会雑誌 東日本整形災害外科学会 34 (3) 368 - 368 1342-7784 2022/08
• 骨粗鬆症の逐次療法 ビスホスホネートからの逐次療法

  清水 智弘, 石津 帆高, 有田 皓介, 岩崎 倫政

  日本骨粗鬆症学会雑誌 (一社)日本骨粗鬆症学会 8 (Suppl.1) 10 - 10 2189-8383 2022/08
• 大腿骨近位部骨折術後の骨粗鬆症治療状況と治療率改善への取り組み 骨折リエゾンサービス導入前後の比較

  小川 裕生, 下段 俊, 福島 瑛, 池 翔太, 竹内 博紀, 百貫 亮太, 梅本 貴央, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本骨粗鬆症学会雑誌 (一社)日本骨粗鬆症学会 8 (Suppl.1) 112 - 112 2189-8383 2022/08
• 閉経後女性ランナーと非女性ランナーにおける骨密度および骨代謝マーカーの検討

  後藤 佳子, 清水 智弘, 門間 太輔, 清水 幸衣, 小林 範子, 笠原 靖彦, 吉本 尚, 近藤 英司, 岩崎 倫政

  日本骨粗鬆症学会雑誌 (一社)日本骨粗鬆症学会 8 (Suppl.1) 119 - 119 2189-8383 2022/08
• コロナ禍で始まった大腿骨近位部骨折リエゾンサービス1年後の骨粗鬆症加療状況

  下段 俊, 清水 智弘, 梅本 貴央, 百貫 亮太, 竹内 博紀, 小川 裕生, 池 翔太, 福島 瑛, 佐藤 知哉, 高橋 大介, 岩崎 倫政

  日本骨粗鬆症学会雑誌 (一社)日本骨粗鬆症学会 8 (Suppl.1) 174 - 174 2189-8383 2022/08
• 脆弱性骨折をきたした関節リウマチ患者の再骨折リスク

  石津 帆高, 清水 寛和, 清水 智弘, 江畑 拓, 小川 裕生, 宮野 真博, 有田 皓介, 大橋 佑介, 岩崎 倫政

  日本骨粗鬆症学会雑誌 (一社)日本骨粗鬆症学会 8 (Suppl.1) 178 - 178 2189-8383 2022/08
• 脆弱性骨盤骨折患者の骨粗鬆症加療状況

  大上 哲郎, 下段 俊, 清水 智弘, 高橋 大介, 岩崎 倫政

  Hip Joint 日本股関節学会 48 401 - 403 0389-3634 2022/08 

  当院で2018～2020年に骨盤骨折の病名登録をされた患者のうち、交通事故などによる高エネルギー外傷、転移性骨腫瘍による病的骨折を除外した38例を対象とし、「脆弱性骨折既往の有無」「骨盤骨折受傷前後の骨粗鬆症治療の有無」「二次骨折の有無」などについて調査した。脆弱性骨折の既往は9例(24%)にあり、内訳は大腿骨近位部骨折6例、椎体骨折3例であった。骨盤骨折受傷前に骨粗鬆症治療を受けていたのは9例(24%)、受傷後に骨粗鬆症治療を受けたのは22例(58%)であった。二次骨折は6例(16%)に発生しており、内訳は大腿骨近位部骨折3例、椎体骨折3例であった。当院では大腿骨近位部骨折に骨粗鬆症治療介入のクリニカルパスがあり、受傷後の骨粗鬆症治療率は81%と骨盤骨折に比べて高い。今後、骨盤骨折に対してもクリニカルパス導入や骨折リエゾンサービス介入を行い、二次骨折を防止することが望まれる。
• 脱臼整復時にインプラント分解を生じた大腿骨頸部骨折後バイポーラー型人工骨頭の1例

  北原 圭太, 浅野 毅, 佐藤 恒明, 清水 智弘, 高橋 大介, 岩崎 倫政

  Hip Joint 日本股関節学会 48 585 - 588 0389-3634 2022/08 

  症例は82歳男性で、左股関節痛を主訴とした。胸部大動脈瘤に対するステント留置術後入院中に転倒して受傷した。左大腿骨頸部骨折の診断で、受傷9日目に後方アプローチでバイポーラー型人工骨頭挿入術を施行した。術後は順調に離床が進んでいたが、11日目にベッド上で患肢屈曲および内旋位となって下肢自動運動困難となっているところを発見され、透視下で後方脱臼を確認した。整復操作中にdisassemblyを生じたため、2日後に観血的再手術を施行しアウターヘッドおよびインナーヘッドのインプラントを交換した。再手術後はhip spicaを装着していたが、再びベッド上で人工骨頭のdisassemblyをきたした。再々手術では人工骨頭再置換術を行い、前捻角を増捻するとともにオフセットも増加させ、術後はdisassemblyを生じることなく経過した。脱臼肢位の理解が乏しい認知症などの症例に対しては人工股関節全置換術やモノポーラー型の使用も考慮され得る。
• 側臥位でtraction tableを使用した、大腿骨転子下骨折の治療成績

  紺野 拓也, 高橋 大介, 清水 智弘, 岩崎 倫政

  Hip Joint 日本股関節学会 48 594 - 597 0389-3634 2022/08 

  対象は2015年5月～2018年8月の22例(男性6例、女性16例、受傷時平均年齢76.3歳)で、経過観察期間は平均11.2ヵ月であった。使用固定器具はCM long 3例、CM short 2例、multifix long 2例、γ-long 15例であり、観血的整復は9例に必要とした。骨折型はSeinsheimer分類でType IIA 5例、IIB 1例、IIC 7例、IIIA 4例、V 5例であった。手術時間は平均105分、体位を取るのに要した時間は平均40分、出血量は平均154.2mLであった。術後直後の整復度はgood 13例、fair 7例、poor 2例であり、合併症は偽関節1例、遠位screw折損1例であった。仰臥位で通常通りトラクションテーブルで手術を行った転子下骨折4例と比較すると、体位を取るのに要した時間に違いはなかったが、手術時間と出血量は側臥位トラクションの方が多い傾向であった。
• 高齢者に対するpolished taperセメントステムを用いた人工股関節全置換術の成績

  山崎 秀, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  Hip Joint 日本股関節学会 48 193 - 196 0389-3634 2022/08 

  当院でpolished taperセメントステムによる人工股関節全置換術を行った高齢者62例65関節を対象に、これらを70歳代群49例と80歳代群13例に分け、術後成績を比較検討した。その結果、術後平均観察期間は70歳代群が53.9ヵ月、80歳代群が52.7ヵ月と有意差はみられなかった。また、HHS、JHEQは両群とも術後有意に改善し、術前後のHHS、JHEQの変化量も有意差は認められなかった。尚、いずれの群も術後骨折や脱臼を生じた例はなかった。
• 生物学的製剤による加療を行った特発性股関節軟骨融解症の一例

  松岡 知樹, 清水 智弘, 有田 皓介, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  Hip Joint 日本股関節学会 48 474 - 477 0389-3634 2022/08 

  12歳女児。誘因なく右鼠径部痛が生じたため近医を受診後、精査加療目的で当科へ紹介となった。所見ではX線で明らかな異常はみられなかったが、股関節MRIで関節液の貯留と大腿骨の骨髄浮腫がみられた。大腿骨頭軟骨下脆弱性骨折の診断のもと保存的に加療されるも、股関節は外転位となり、側彎が出現した。そこで再度、MRIを行ったところ、骨髄内の信号変化の場所が移動しており、関節穿刺では感染は否定的であった。だが、臨床経過と関節内のTNFαの上昇が認められたことから、本症例は特発性股関節軟骨融解症と診断された。治療としてNSAIDsを投与するも効果がなく、アダリムマブを投与した結果、3ヵ月後には疼痛や外転位・骨髄浮腫は改善し、関節内のTNFαも著明に減少した。
• Superior capsular reconstruction for recurrent anterior shoulder dislocation with irreparable rotator cuff tear: a case report.

  Keizumi Matsugasaki, Atsushi Urita, Yukinori Tsukuda, Hiroshi Taneichi, Norimasa Iwasaki

  JSES reviews, reports, and techniques 2 (3) 406 - 411 2022/08
• High Rate of Radiographic Union at the Fibular Osteotomy Site With No Complications After an Acute Oblique Osteotomy and Ligation Procedure to Shorten the Fibula in High Tibial Osteotomy.

  Daisuke Ueda, Kazunori Yasuda, Takuma Kaibara, Koji Yabuuchi, Jun Yamaguchi, Jun Onodera, Norimasa Iwasaki, Tomonori Yagi, Eiji Kondo

  Orthopaedic journal of sports medicine 10 (8) 23259671221117480 - 23259671221117480 2022/08 

  BACKGROUND: A fibular shortening osteotomy is needed to perform lateral closing-wedge high tibial osteotomy (LCW-HTO). To achieve this shortening, we have recently developed an acute oblique osteotomy and ligation (AO/L) procedure for the center of the fibular shaft, based on the AO procedure. PURPOSE: To compare the 2-year follow-up outcomes between the AO/L procedure and the AO procedure. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A prospective comparative cohort study was conducted involving 83 patients (83 knees) who underwent shortening osteotomy of the fibula in LCW-HTO between April 2017 and March 2019. The first consecutive 41 knees (AO group) underwent fibular osteotomy with the AO procedure. The remaining 42 knees (AO/L group) underwent fibular osteotomy with the AO/L procedure. All of the patients were evaluated for at least 2 years postoperatively via clinical and radiological assessments. To determine the time needed for complete union at the osteotomy site, we evaluated the radiographs using a radiographic union score for tibial fractures, which was modified for fibular osteotomy. Comparison of outcomes between the 2 groups was performed using the Student t test for continuous variables and the Mann-Whitney U test or Fisher exact test for discrete variables. RESULTS: Around the fibular osteotomy site, no perioperative complications were found in either group. The radiographic union score was significantly higher in the AO/L group than in the AO group (P < .0001 at 2, 3, and 6 months; P = .0290 at 12 and 24 months). The union rate at the fibular osteotomy site was significantly higher in the AO/L group (97.6%) than in the AO group (82.9%) at 12 months (P = .0290). CONCLUSION: The AO/L procedure significantly accelerated the formation of bridging callus at the fibular osteotomy site and provided a significantly higher union rate compared with the AO procedure. Both AO/L and AO procedures were free from perioperative complications. These results suggest that the AO/L procedure is clinically useful as an osteotomy procedure to shorten the fibula in LCW-HTO.
• Extra-Articular Corrective Osteotomy for Malunion of Intra-Articular Fracture of the Elbow in a Child: A Case Report.

  Hiroki Shibayama, Daisuke Kawamura, Norimasa Iwasaki

  Journal of orthopaedic case reports 12 (8) 27 - 32 2022/08 

  INTRODUCTION: Malunion of intra-articular fracture of the elbow in children is uncommon and may be difficult to treat. Intra-articular corrective osteotomies are still not commonly performed in children, and the main reason is the concern regarding the risk of osteonecrosis. We present a case of extra-articular corrective osteotomy for malunion after open reduction and internal fixation for fracture dislocation of the elbow. CASE REPORT: An 8-year-old boy was injured by a fall and he underwent an operation the day after the injury with diagnosis of lateral condyle fracture of the right humerus. He was referred to our department 4 months after the operation due to restricted range of motion. His elbow exhibited cubitus varus, and range of motion was 80° of flexion, -30° of extension, 55° of pronation, and 85° of supination. Plain radiographs showed malunion, a Baumann angle of 3°, and a tilting angle of 5°. We diagnosed this injury not as lateral condyle fracture but as posterolateral dislocation with Milch type 1 lateral condyle fracture associated with osteochondral flap fracture of the coronoid process with computed tomography images at the time of injury. Because the patient was only 8 years old, we decided to perform an extra-articular corrective osteotomy to encourage bone remodeling and improve the flexion range of motion. After the operation, the range of motion improved as 130° of flexion, -30o of extension, 85o of pronation, and 90° of supination 4 years after the operation. Plain radiographs showed that the epiphysis of the capitellum was closed, and the trochlea presented a fishtail deformity. CONCLUSION: We obtained relatively good outcomes with extra-articular corrective osteotomy, and long-term follow-up is necessary. Especially in the elbow, the injury itself may cause fishtail deformity due to avascular necrosis of the trochlea, and if an additional osteotomy is performed, the risk increases. Although there is concern about the occurrence of secondary osteoarthritis, we expect that the intra-articular deformity would be remodeled due to the patient's young age if normal elbow movement could be obtained.
• Total hip arthroplasty with femoral shortening osteotomy using polished cemented stem vs. modular cementless stem in patients with Crowe type IV developmental dysplasia of the hip.

  Takuji Miyazaki, Tomohiro Shimizu, Hisanori Ohura, Naoyuki Katayama, Norimasa Iwasaki, Daisuke Takahashi

  Archives of orthopaedic and trauma surgery 143 (6) 3487 - 3493 2022/08/01 

  INTRODUCTION: There is still little information regarding the advantages of a using a polished tapered stem for Crowe Type IV developmental dysplasia of the hip (DDH). This study aimed to investigate the mid-term clinical and radiological outcomes of primary total hip arthroplasty (THA) with femoral shortening osteotomy using modular and polished tapered stems and to compare the results between the modular and polished tapered stems. MATERIALS AND METHODS: This retrospective review included 32 patients (37 hips) with Crowe type IV DDH who underwent primary THA with femoral shortening osteotomy using a modular stem (cementless group, 14 hips) or a polished tapered stem (cement group, 23 hips) between 1996 and 2018. Clinical data and radiographic assessments were reviewed to analyze the differences between the two groups. RESULTS: The mean duration of patient follow-up of the cementless group (134.4 months) was longer than that of the cement group (75.5 months). There were no differences in clinical results, time of bone union, and survival rate between the two groups. However, the cementless group exhibited a higher ratio of intraoperative fracture and thinning of cortical bone including stress shielding, medullary changes, stem alignment changes, and osteolysis, compared to the cement group. CONCLUSIONS: The findings of this study suggest that THA with femoral shortening osteotomy using both cemented and modular stems can provide satisfactory results. However, considering the occurrence of intraoperative fracture and radiographic analysis in the current study, the cement stem may have an advantage for patients with bone fragility and deterioration in bone quality.
• Influence of differences in bone morphology on the distribution patterns of subchondral bone density across the trapeziometacarpal joint.

  Yukinori Tsukuda, Yuichiro Matsui, Kaori Endo, Yuki Matsui, Daisuke Kawamura, Norimasa Iwasaki

  Scientific reports 12 (1) 12368 - 12368 2022/07/20 

  We aimed to clarify the effects of morphological patterns of the trapezium and first metacarpal on the distribution of subchondral bone density across the articular surface of the trapeziometacarpal (TMC) joint using computed tomography osteoabsorptiometry. Thirty-three patients with normal TMC joints were evaluated. The percentages of the high-density areas in the radial-dorsal and ulnar-volar regions of the trapezium were significantly higher than that in the ulnar-dorsal region, and that of the ulnar-dorsal region of the first metacarpal was significantly lower than in the other three regions. The percentage of the high-density area of the radial-dorsal region of the trapezium and trapezial inclination (TI) showed a significant positive correlation, and the percentages of the high-density areas in the ulnar-dorsal and ulnar-volar regions had significant negative correlations with TI at the articular surface of the first metacarpal. These results indicate that bony morphologic differences in the trapezium affect the distribution pattern of subchondral bone density through the TMC joint.
• Inhibitory role of Annexin A1 in pathological bone resorption and therapeutic implications in periprosthetic osteolysis.

  Hend Alhasan, Mohamad Alaa Terkawi, Gen Matsumae, Taku Ebata, Yuan Tian, Tomohiro Shimizu, Yoshio Nishida, Shunichi Yokota, Fayna Garcia-Martin, Mahmoud M Abd Elwakil, Daisuke Takahashi, Mahmoud A Younis, Hideyoshi Harashima, Ken Kadoya, Norimasa Iwasaki

  Nature communications 13 (1) 3919 - 3919 2022/07/07 

  There is currently no therapy available for periprosthetic osteolysis, the most common cause of arthroplasty failure. Here, the role of AnxA1 in periprosthetic osteolysis and potential therapeutics were investigated. Reducing the expression of AnxA1 in calvarial tissue was found to be associated with increased osteolytic lesions and the osteolytic lesions induced by debris implantation were more severe in AnxA1-defecient mice than in wild-type mice. AnxA1 inhibits the differentiation of osteoclasts through suppressing NFκB signaling and promoting the PPAR-γ pathway. Administration of N-terminal-AnxA1 (Ac2-26 peptide) onto calvariae significantly reduced osteolytic lesions triggered by wear debris. These therapeutic effects were abrogated in mice that had received the PPAR-γ antagonist, suggesting that the AnxA1/PPAR-γ axis has an inhibitory role in osteolysis. The administration of Ac2-26 suppressed osteolysis induced by TNF-α and RANKL injections in mice. These findings indicate that AnxA1 is a potential therapeutic agent for the treatment of periprosthetic osteolysis.
• Liver metastasis in soft tissue sarcoma at initial presentation.

  Yuta Kawae, Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Eiji Kondo, Norimasa Iwasaki

  Journal of surgical oncology 126 (6) 1074 - 1079 2022/07/06 

  BACKGROUND AND OBJECTIVES: Noncontrast computed tomography of the chest is the standard imaging modality for cancer staging in patients with soft tissue sarcoma (STS), but appropriate candidates for liver screening have not been clarified. METHODS: We reviewed all patients with STS diagnosed between 2010 and 2018 in the Surveillance, Epidemiology, and End Results database. Incidence of liver metastasis at initial presentation and high incidence of liver metastasis by histological subtype were investigated. In addition, risk factors for liver metastasis were investigated by multiple logistic regression analysis. RESULTS: After excluding patients without information about liver metastasis, cause of death or primary liver tumor, 47 260 patients were included in this study. Of those, 1471 patients (3.2%) showed liver metastasis at initial presentation. The histological subtype showing the highest incidence of liver metastasis was desmoplastic small round cell tumor (30.3%), followed by malignant hemangioendothelioma (11.5%) and angiomyoliposarcoma (10.5%). Deep-rooted tumor, location in the body wall, retroperitoneum, or thorax/peritoneum, high histological grade, and higher T stage were associated with higher incidences of liver metastasis at initial presentation. CONCLUSION: Risk factors for liver metastasis were deep location, trunk development, larger tumor size, high histological grade, and specific histological subtypes.
• CLCF 1の骨代謝へ与える影響と、新規骨粗鬆症治療薬としての可能性

  横田 隼一, 松前 元, 照川 ヘンド, 西田 善郎, 清水 智弘, 照川 アラー, 岩崎 倫政

  日本骨代謝学会学術集会プログラム抄録集 (一社)日本骨代謝学会 40回 125 - 125 1349-0761 2022/07
• 骨リモデリング調節におけるアネキシンA1の機能解析

  西田 善郎, 松前 元, 江畑 拓, 横田 隼一, 照川 ヘンド, 塩田 惇喜, 北原 圭太, 清水 智弘, 高橋 大介, 照川 アラー, 岩崎 倫政

  日本骨代謝学会学術集会プログラム抄録集 (一社)日本骨代謝学会 40回 132 - 132 1349-0761 2022/07
• Establishment of a New Qualitative Evaluation Method for Articular Cartilage by Dynamic T2w MRI Using a Novel Contrast Medium as a Water Tracer

  Yoshiaki Hosokawa, Tomohiro Onodera, Kentaro Homan, Jun Yamaguchi, Kohsuke Kudo, Hiroyuki Kameda, Hiroyuki Sugimori, Norimasa Iwasaki

  CARTILAGE 13 (3) 19476035221111503 - 19476035221111503 1947-6035 2022/07 

  Objective In the early stages of cartilage damage, diagnostic methods focusing on the mechanism of maintaining the hydrostatic pressure of cartilage are thought to be useful. O-17-labeled water, which is a stable isotope of oxygen, has the advantage of no radiation exposure or allergic reactions and can be detected by magnetic resonance imaging (MRI). This study aimed to evaluate MRI images using O-17-labeled water in a rabbit model. Design Contrast MRI with O-17-labeled water and macroscopic and histological evaluations were performed 4 and 8 weeks after anterior cruciate ligament transection surgery in rabbits. A total of 18 T2-weighted images were acquired, and O-17-labeled water was manually administered on the third scan. The O-17 concentration in each phase was calculated from the signal intensity at the articular cartilage. Macroscopic and histological grades were evaluated and compared with the O-17 concentration. Results An increase in O-17 concentration in the macroscopic and histologically injured areas was observed by MRI. Macroscopic evaluation showed that the O-17 concentration significantly increased in the damaged site group. Histological evaluations also showed that O-17 concentrations significantly increased at 36 minutes 30 seconds after initiating MRI scanning in the Osteoarthritis Research Society International (OARSI) grade 3 (0.493 in grade 0, 0.659 in grade 1, 0.4651 in grade 2, and 0.9964 in grade 3, P < 0.05). Conclusion O-17-labeled water could visualize earlier articular cartilage damage, which is difficult to detect by conventional methods.
• Effect of the Inverted V-Shaped Osteotomy on Patellofemoral Joint and Tibial Morphometry as Compared With the Medial Opening Wedge High Tibial Osteotomy.

  Eiji Kondo, Koji Yabuuchi, Zenta Joutoku, Shinji Matsubara, Koji Iwasaki, Masatake Matsuoka, Tomohiro Onodera, Daisuke Momma, Masayuki Inoue, Tomonori Yagi, Norimasa Iwasaki, Kazunori Yasuda

  The American journal of sports medicine 50 (9) 2439 - 2452 2022/07 

  BACKGROUND: Recent studies have reported that medial opening wedge (OW) high tibial osteotomy (HTO) induces patella baja, resulting in degenerative changes in the patellofemoral joint. We have developed an inverted V-shaped (iV) HTO, which is classified as a neutral wedge osteotomy. HYPOTHESES: The study hypotheses were as follows: (1) patellar height, posterior tibial slope, and tibial length will not change between pre- and postoperative evaluations after iV-HTO; (2) the lateral shift ratio of the patella and the distance between the tibial tubercle and the trochlear groove may be significantly decreased after iV-HTO. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 191 patients (220 knees) who underwent HTO for medial osteoarthritis were enrolled retrospectively in this study: 107 knees underwent OW-HTO and 113 knees underwent iV-HTO. Clinical and radiological evaluations were performed before and at least 3 years after surgery. RESULTS: Postoperatively, the mean Caton-Deschamps ratio was significantly decreased (P < .0001) from 0.95 to 0.79 in the OW group, while there were no significant changes in the iV group. The mean posterior tibial slope was significantly increased (P < .0001) from 8.5° to 10.5° in the OW group, while there were no significant differences in the iV group. Although the entire leg length was significantly increased (P < .0003) in both groups after HTO, there were no significant differences in tibial length between the pre- and postoperative periods in the iV group. Regarding the congruity of the patellofemoral joint, the mean lateral shift ratio did not significantly change in the OW group, whereas it was significantly decreased (P = .0012) from 11.5% to 8.8% in the iV group. The mean tibial tubercle-trochlear groove distance was significantly decreased (P < .0001) from 12.8 to 9.7 mm in the iV group, while it was significantly increased in the OW group (P < .0001). Concerning the clinical outcome, the Japanese Orthopaedic Association (JOA) and Lysholm knee scores at final follow-up (OW vs iV: JOA, 91.2 vs 90.1; Lysholm, 92.5 vs 89.0) were significantly increased (P < .0001) as compared with the preoperative values (OW vs iV: JOA, 68.3 vs 66.8; Lysholm, 67.9 vs 61.0). CONCLUSION: Patellar height, posterior tibial slope, and tibial length did not change after the iV-HTO, while they were significantly changed after the OW-HTO. Although the preoperative degrees of varus knee and patellofemoral osteoarthritis were more severe in the iV group than the OW group, the iV-HTO led to altered patellofemoral joint congruity.
• Real-world persistence of twice-weekly teriparatide and factors associated with the discontinuation in patients with osteoporosis.

  Ryo Fujita, Tsutomu Endo, Masahiko Takahata, Kentaro Haraya, Hisataka Suzuki, Itaru Oda, Masahiro Kanayama, Tsuyoshi Asano, Keiichi Shigenobu, Akira Iwata, Katsuhisa Yamada, Hirohito Takeuchi, Hisanori Ohura, Daisuke Yoneoka, Norimasa Iwasaki

  Journal of bone and mineral metabolism 40 (5) 782 - 789 2022/06/27 

  INTRODUCTION: A 28.2 μg twice-weekly formulation of teriparatide (2/W-TPD) was developed to provide comparably high efficacy for osteoporosis to a 56.5 μg once-weekly formulation while improving the safety and persistence rate. In the current study, we aimed to elucidate the real-world persistence of 2/W-TPD and to identify the factors associated with the discontinuation of 2/W-TPD in patients with severe osteoporosis. MATERIALS AND METHODS: This retrospective study included 90 patients who were treated with 2/W-TPD at three hospitals in Japan. Patient information was collected, including age, sex, distance to the hospital, family structure, comorbidities, previous treatment for osteoporosis, timing of the injection, side effects and duration of 2/W-TPD treatment, barthel index (BI), and bone mineral density (BMD) of the lumbar spine and femoral neck. We examined the factors influencing 2/W-TPD discontinuation using the Cox proportional hazards model. RESULTS: The 12 month completion rate of 2/W-TPD therapy was 47.5%. The Cox hazard analysis identified side effects [Hazard Ratio (HR) = 14.59, P < 0.001], low BMD of the femoral neck (HR = 0.04, P = 0.002), and morning injection (HR = 3.29, P = 0.006) as risk factors influencing the discontinuation of 2/W-TPD. Other variables, including age, did not contribute to the continuation of 2/W-TPD. CONCLUSION: One year continuation rate of 2/W-TPD was higher than the previously reported value of the once-weekly formulation in real-world setting, probably due to the lower incidence of side effects. Introducing injection of 2/W-TPD may further improve the persistence of TPD therapy for osteoporosis.
• Genetic insights into ossification of the posterior longitudinal ligament of the spine

  Yoshinao Koike, Masahiko Takahata, Masahiro Nakajima, Nao Otomo, Hiroyuki Suetsugu, Xiaoxi Liu, Tsutomu Endo, Shiro Imagama, Kazuyoshi Kobayashi, Takashi Kaito, Satoshi Kato, Yoshiharu Kawaguchi, Masahiro Kanayama, Hiroaki Sakai, Takashi Tsuji, Takeshi Miyamoto, Hiroyuki Inose, Toshitaka Yoshii, Masafumi Kashii, Hiroaki Nakashima, Kei Ando, Yuki Taniguchi, Kazuhiro Takeuchi, Shuji Ito, Kohei Tomizuka, Keiko Hikino, Yusuke Iwasaki, Yoichiro Kamatani, Shingo Maeda, Hideaki Nakajima, Kanji Mori, Atsushi Seichi, Shunsuke Fujibayashi, Tsukasa Kanchiku, Kei Watanabe, Toshihiro Tanaka, Kazunobu Kida, Sho Kobayashi, Masahito Takahashi, Kei Yamada, Hiroshi Takuwa, Hsing-Fang Lu, Shumpei Niida, Kouichi Ozaki, Yukihide Momozawa, Masashi Yamazaki, Atsushi Okawa, Morio Matsumoto, Norimasa Iwasaki, Chikashi Terao, Shiro Ikegawa

  medRxiv 12 2022/06/17 [Not refereed]
   

  Abstract Background Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease, leading to severe neurological deficits. Its etiology and pathogenesis are mostly unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. Methods To clarify the etiology and pathogenesis of OPLL, we conducted a meta-analysis of genome-wide association studies (GAWSs) using 22,016 Japanese individuals. We classified OPLL into cervical, thoracic and the other types, and conducted GWAS sub-analyses. We conducted a gene- based association analysis and a transcriptome-wide Mendelian randomization approach to identify other potential causal genes. To investigate cell groups related to OPLL, we conducted cell type group enrichment analysis. To identify traits with a causal effect on OPLL, we evaluated the genetic correlation with 99 complex traits and then performed mendelian randomization (MR) analyses. Finally, we generated polygenic risk score (PRS) to investigate the genetic impact of the causal trait on OPLL subtypes. Results A GWAS meta-analysis identified 14 significant loci, including eight novel loci. GWAS sub-analyses identified subtype-specific signals. A Gene-based association analysis and a transcriptome-wide Mendelian randomization approach identified five and three potential causal genes, respectively. These loci/genes contained bone metabolism-related genes. Cell type group enrichment analysis observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells. Genetic correlations showed positive correlation with T2D and BMI and negative correlation with cerebral aneurysm and osteoporosis. MR analyses demonstrated a significant causal effect of increased BMI and high bone mineral density (BMD) on OPLL, but not of T2D, indicating that high BMI confounded the T2D correlation. A PRS for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Conclusion We identified multiple causative genes involved in bone metabolism that are candidates for future therapeutic targets. By MR analyses, we showed for the first time a causal relationship between the common metabolic conditions (high BMI and BMD) and OPLL. We successfully linked intervenable traits to OPLL.
• Retrograde Axonal Transport of Liposomes from Peripheral Tissue to Spinal Cord and DRGs by Optimized Phospholipid and CTB Modification.

  Takafumi Fukui, Hironao Tateno, Takashi Nakamura, Yuma Yamada, Yusuke Sato, Norimasa Iwasaki, Hideyoshi Harashima, Ken Kadoya

  International journal of molecular sciences 23 (12) 2022/06/15 

  Despite recent advancements in therapeutic options for disorders of the central nervous system (CNS), the lack of an efficient drug-delivery system (DDS) hampers their clinical application. We hypothesized that liposomes could be optimized for retrograde transport in axons as a DDS from peripheral tissues to the spinal cord and dorsal root ganglia (DRGs). Three types of liposomes consisting of DSPC, DSPC/POPC, or POPC in combination with cholesterol (Chol) and polyethylene glycol (PEG) lipid were administered to sciatic nerves or the tibialis anterior muscle of mature rats. Liposomes in cell bodies were detected with infrared fluorescence of DiD conjugated to liposomes. Three days later, all nerve-administered liposomes were retrogradely transported to the spinal cord and DRGs, whereas only muscle-administered liposomes consisting of DSPC reached the spinal cord and DRGs. Modification with Cholera toxin B subunit improved the transport efficiency of liposomes to the spinal cord and DRGs from 4.5% to 17.3% and from 3.9% to 14.3% via nerve administration, and from 2.6% to 4.8% and from 2.3% to 4.1% via muscle administration, respectively. Modification with octa-arginine (R8) improved the transport efficiency via nerve administration but abolished the transport capability via muscle administration. These findings provide the initial data for the development of a novel DDS targeting the spinal cord and DRGs via peripheral administration.
• Scrotal pain of a patient with ankylosing spondylitis successfully treated with TNF-alpha inhibitor: a case report.

  Hisataka Suzuki, Takeru Tsujimoto, Masahiro Ota, Yuichi Hasegawa, Fumihiro Oha, Yukitoshi Shimamura, Masaru Tanaka, Tomoyuki Hashimoto, Norimasa Iwasaki, Masahiro Kanayama

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 29 (1) 402 - 404 2022/06/08
• Histochemical examination of blood vessels in murine femora with intermittent PTH administration.

  Haruhi Maruoka, Shen Zhao, Hirona Yoshino, Miki Abe, Tomomaya Yamamoto, Hiromi Hongo, Mai Haraguchi-Kitakamae, Alireza Nasoori, Hotaka Ishizu, Yuhi Nakajima, Masayuki Omaki, Tomohiro Shimizu, Norimasa Iwasaki, Paulo Henrique Luiz de Freitas, Minqi Li, Tomoka Hasegawa

  Journal of oral biosciences 64 (3) 329 - 336 2022/05/15 

  OBJECTIVE: To verify the biological effects of parathyroid hormone (PTH) on the blood vessels in the bone, this study aimed to investigate histological alterations in endomucin-positive blood vessels and perivascular cells in murine femora after intermittent PTH administration. For comparison with blood vessels in the bone, we examined the distribution of endomucin-positive blood vessels and surrounding αSMA-immunoreactive perivascular cells in the liver, kidney, and aorta with or without PTH administration. METHODS: Six-week-old male C57BL/6J mice received hPTH [1-34] or vehicle for two weeks. All mice were fixed with a paraformaldehyde solution after euthanasia, and the right femora, kidney, liver, and aorta were extracted for immunohistochemical analysis of endomucin, αSMA, ephrinB2, EphB4, and HIF1α. Light microscopic observations of semi-thin sections and transmission electron microscopic (TEM) observations of ultra-thin sections were performed on the left femora. RESULTS: After intermittent PTH administration, αSMA-reactive/ephrinB2-positive stromal cells appeared around endomucin-positive/EphB4-immunoreactive blood vessels in the bone. In addition, intense immunoreactivities of EphB4 and HIF1α were seen in vascular endothelial cells after the PTH treatment. Several stromal cells surrounding PTH-treated blood vessels exhibited well-developed rough endoplasmic reticulum under TEM observations. In contrast to bone tissues, αSMA-positive stromal cells did not increase around the endomucin-positive blood vessels in the kidney, liver, or aorta, even after PTH administration. CONCLUSION: These findings show that intermittent PTH administration increases αSMA-reactive/ephrinB2-positive perivascular stromal cells in bone tissue but not in the kidney, liver, or aorta, suggesting that PTH preferentially affects blood vessels in the bone.
• IL4 stimulated macrophages promote axon regeneration after peripheral nerve injury by secreting uPA to stimulate uPAR upregulated in injured axons.

  Yuki Matsui, Ken Kadoya, Yusuke Nagano, Takeshi Endo, Masato Hara, Gen Matsumae, Tomoaki Suzuki, Yasuhiro Yamamoto, Mohamad Alaa Terkawi, Norimasa Iwasaki

  Cellular and molecular life sciences : CMLS 79 (6) 289 - 289 2022/05/10 

  Accumulating evidences suggest that M2 macrophages are involved with repair processes in the nervous system. However, whether M2 macrophages can promote axon regeneration by directly stimulating axons nor its precise molecular mechanism remains elusive. Here, the current study demonstrated that typical M2 macrophages, which were generated by IL4 simulation, had the capacity to stimulate axonal growth by their direct effect on axons and that the graft of IL4 stimulated macrophages into the region of Wallerian degeneration enhanced axon regeneration and improved functional recovery after PNI. Importantly, uPA (urokinase plasminogen activator)-uPA receptor (uPAR) was identified as the central axis underlying the axon regeneration effect of IL4 stimulated macrophages. IL4 stimulated macrophages secreted uPA, and its inhibition abolished their axon regeneration effect. Injured but not intact axons expressed uPAR to be sensitive to uPA. These results unveil a cellular and molecular mechanism underlying the macrophage related axon regeneration and provide a basis of a novel therapy for PNI.
• Low-Grade Inflammation in the Pathogenesis of Osteoarthritis: Cellular and Molecular Mechanisms and Strategies for Future Therapeutic Intervention.

  M Alaa Terkawi, Taku Ebata, Shunichi Yokota, Daisuke Takahashi, Tsutomu Endo, Gen Matsumae, Tomohiro Shimizu, Ken Kadoya, Norimasa Iwasaki

  Biomedicines 10 (5) 2022/05/10 

  Osteoarthritis (OA) is a musculoskeletal disease characterized by cartilage degeneration and stiffness, with chronic pain in the affected joint. It has been proposed that OA progression is associated with the development of low-grade inflammation (LGI) in the joint. In support of this principle, LGI is now recognized as the major contributor to the pathogenesis of obesity, aging, and metabolic syndromes, which have been documented as among the most significant risk factors for developing OA. These discoveries have led to a new definition of the disease, and OA has recently been recognized as a low-grade inflammatory disease of the joint. Damage-associated molecular patterns (DAMPs)/alarmin molecules, the major cellular components that facilitate the interplay between cells in the cartilage and synovium, activate various molecular pathways involved in the initiation and maintenance of LGI in the joint, which, in turn, drives OA progression. A better understanding of the pathological mechanisms initiated by LGI in the joint represents a decisive step toward discovering therapeutic strategies for the treatment of OA. Recent findings and discoveries regarding the involvement of LGI mediated by DAMPs in OA pathogenesis are discussed. Modulating communication between cells in the joint to decrease inflammation represents an attractive approach for the treatment of OA.
• Rare case of real-time observation of paralytic deterioration after cervical dislocation in the hyperacute phase.

  Tsutomu Endo, Kota Suda, Takafumi Fukui, Satoko Matsumoto, Miki Komatsu, Masahiro Ota, Chikara Ushiku, Junichi Yamane, Akio Minami, Masahiko Takahata, Norimasa Iwasaki

  BMC musculoskeletal disorders 23 (1) 412 - 412 2022/05/02 

  BACKGROUND: There have been no prior reports of real-time detailed records leading to complete quadriplegia immediately after fracture dislocation in high-energy trauma. Here, we report a case of cervical dislocation in which the deterioration to complete motor paralysis (modified Frankel B1) and complete recovery (Frankel E) could be monitored in real time after reduction in the hyperacute phase. CASE PRESENTATION: A 65-year-old man was involved in a car accident and sustained a dislocation at the C5/6 level (Allen-Ferguson classification: distractive flexion injury stage IV). His paralysis gradually deteriorated from Frankel D to C 2 hours after the injury and from Frankl C to B 5 hours after the injury. His final neurological status immediately before reduction was Frankel B1 (complete motor paralysis with sensation only in the perianal region). Reduction was completed within 6 h and 5 min after injury, and spinal fusion was subsequently performed. The patient exhibited rapid motor recovery immediately after surgery, and was able to walk independently on postoperative day 14. CONCLUSIONS: This case suggests that there is a mixture of cases in which the spinal cord has not been catastrophically damaged, even if the patient has complete motor paralysis. Prompt reduction has the potential to improve neurological function in such cases.
• Implantation of autogenous meniscal fragments wrapped with a fascia sheath induces fibrocartilage regeneration in a large meniscal defect in sheep: A histological and biomechanical study.

  Eiji Kondo, Yasuyuki Kawaguchi, Masashi Yokota, Jun Onodera, Yasuhito Tanaka, Norimasa Iwasaki, Kazunori Yasuda

  Orthopaedics & traumatology, surgery & research : OTSR 108 (3) 103225 - 103225 2022/05 

  INTRODUCTION: Currently, various studies have been reported to regenerate the meniscus tissue in a large defect after partial meniscectomy using biological or synthetic scaffolds with or without fibrochondrocytes. However, the clinical utility of those treatments has not been established as of yet. HYPOTHESIS: Purposes of this study were to develop a sheep model to evaluate feasibility of this new surgical strategy to treat the irreparable meniscus injury, and to test the hypothesis that implantation of autogenous meniscal fragments wrapped with a fascia sheath may significantly induce fibrocartilage regeneration in a large meniscal defect in the sheep model. METHODS AND METHODS: Twenty Suffolk sheep were used. In each animal, an anterior 10-mm width of the right medial meniscus was resected. Then, the animals were divided into the following 2 groups. In Group I, the defect was enveloped with a fascia from the left thigh. In Group II, the resected meniscus fragmented into small pieces was grafted into the defect. Then the defect was enveloped with a fascia. In each group, 5 of 10 sheep were used for histological and biomechanical evaluations, respectively, at 12 weeks after surgery. RESULTS: In Group I, the defect was incompletely filled with thin fibrous tissues, while fibrocartilage tissues rarely regenerated in the tissue. In Group II, all defects were completely filled with thick fibrocartilage tissues, which were richly stained with the safranin O staining. Both the gross and histological observation score of Group II was significantly (p=0.0005, p=0.0005) greater than that of Group I. Concerning the cross-sectional area of the regenerated tissue, Group II was significantly (p=0.0002) greater than Group I. In the biomechanical evaluation, the maximal load and the linear stiffness of the meniscus-tibia complex were significantly (p=0.0015, p=0.0283) greater in Group II than in Group I. DISCUSSION: Implantation of autogenous meniscal fragments wrapped with a fascia sheath significantly induces fibrocartilage regeneration into a large meniscal defect in the sheep model. LEVEL OF EVIDENCE: Not applicable; Controlled Laboratory Study, Experimental in vivo study.
• Minimum 5-Year Outcomes of Dorsal Intercarpal Ligament Capsulodesis With Scapholunate Interosseous Ligament Repair for Subacute and Chronic Static Scapholunate Instability: A Clinical Series of 5 Patients

  Hiroki Shibayama, Yuichiro Matsui, Daisuke Kawamura, Daisuke Momma, Takeshi Endo, Norimasa Iwasaki

  Journal of Hand Surgery Global Online 4 (3) 162 - 165 2589-5141 2022/05 

  PURPOSE: Treatment of subacute and chronic static scapholunate instability remains challenging. We aimed to determine 5- to 10-year outcomes of dorsal intercarpal ligament capsulodesis with scapholunate interosseous ligament repair for subacute and chronic static scapholunate instability. METHODS: Six patients with subacute and chronic static scapholunate instability underwent dorsal intercarpal ligament capsulodesis with scapholunate interosseous ligament repair between 2011 and 2015, and 5 of them were followed for at least 5 years after surgery. The clinical and radiological results were retrospectively investigated. All patients were male, and the mean age at surgery was 37 years (range, 21-47 years). The mean period from injury to surgery was 26.2 months (range, 2-113 months). The surgical procedure was a modification of a method reported by Szabo et al. RESULTS: The mean postoperative follow-up period was 8.1 years (range, 5.1-9.5 years). Median Disabilities of the Arm, Shoulder, and Hand and Mayo wrist scores improved from 23.3 to 1.7 and from 55 to 80, respectively, from before surgery to the final follow-up. Although the median flexion angle tended to be smaller, the median extension angle tended to be greater than before surgery. The median percent grip strength increased from 72.3% before surgery to 99.2% at the final follow-up. The median scapholunate gap improved from 4.2 mm before surgery to 2.1 mm at the final follow-up. The median scapholunate angle also improved from 95.7° before surgery to 71.3° at the final follow-up. Osteoarthritic changes were observed in 2 of 5 patients at the final follow-up. CONCLUSIONS: The scapholunate gap in all patients was within the normal range after a mean of 8.1 years of follow-up. Dorsal intercarpal ligament capsulodesis with scapholunate interosseous ligament repair is considered a good alternative for subacute and chronic static scapholunate instability based on these 5- to 10-year outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
• Clinical and radiological outcomes of posterior cervical decompression and fusion for severe cervical compressive-extension injury: A case series.

  Takeru Tsujimoto, Kota Suda, Miki Komatsu, Satoko Matsumoto Harmon, Mitsuru Asukai, Masahiko Takahata, Norimasa Iwasaki, Akio Minami

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 28 (4) 733 - 739 2022/04/28 

  BACKGROUND: Although severe cervical compressive-extension (CE) injuries are usually repaired using a combined anterior-posterior approach, the repair is possible using a posterior approach alone with reliable anchors. This study aimed to present the outcomes and imaging analysis results of posterior cervical decompression and fusion (PCDF) for severe CE injuries. METHODS: We retrospectively reviewed 16 patients who underwent PCDF surgery for severe CE injuries (>50% subluxation) between January 2012 and December 2018. All patients completed 1-year follow-up, and their mean age at the time of surgery was 63.5 years. American Spinal Injury Association Impairment Scale (AIS) grade, kyphotic angle of lower vertebra (KALV), and anterior defect area of lower vertebra (ADLV) were assessed preoperatively. RESULTS: Of 16 patients, nine patients improved at the final follow-up, and eight patients could walk with or without assistance. All patients achieved bone union postoperatively, but four patients showed progression of correction loss of ≥10°. Therefore, patients were divided into two groups: NL group with correction loss of <10°; L group with correction loss of ≥10°. All patients in L group showed KALV of ≥15°, while 10 of 12 patients in NL group showed KALV of <15°. Furthermore, all patients in L group showed ADLV of ≥50%, whereas all patients in NL group showed ADLV of <50%. CONCLUSIONS: PCDF is feasible and a favorable procedure for severe CE injuries that require early reduction and cervical spinal stabilization. However, in the cases of advanced destruction of the anterior vertebra, loss of correction after PCDF might occur postoperatively.
• Does Primary Tumor Resection in Patients with Metastatic Primary Mobile Vertebral Column Sarcoma Improve Survival?

  Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Akira Iwata, Eiji Kondo, Norimasa Iwasaki

  World neurosurgery 163 e647-e654  2022/04/18 

  BACKGROUND: Primary mobile vertebral column sarcoma is an exceedingly rare malignancy. Although primary tumor resection has been reported to prolong survival in patients with metastatic bone sarcoma, whether primary tumor resection in patients with advanced primary mobile vertebral column sarcoma is associated with survival remains unclear owing to the rarity of this pathological entity. METHODS: Using the Surveillance, Epidemiology, and End Results database, 182 patients with metastatic primary mobile vertebral column sarcoma were identified between 1983 and 2015. Of the 182 patients enrolled, 101 patients (55%) underwent primary tumor resection (Surgery group) and 81 patients (45%) did not undergo resection (No Surgery group). To account for imbalances in the basic characteristics of patients between groups, propensity score matching was performed. Survival analysis was performed by weighted Cox proportional hazards modeling to calculate hazard ratios. RESULTS: After adjusting for patient background characteristics, 138 patients were included for the analysis (Surgery group: 69 patients; No Surgery group: 69 patients). The Surgery group did not show improved cancer-specific survival (hazard ratio = 0.73, 95% CI 0.49-1.10). Similarly, the Surgery group did not show improved overall survival compared with the No Surgery group (hazard ratio = 0.80, 95% CI 0.55-1.16). CONCLUSIONS: To our knowledge, this is the first study to indicate that surgical resection for advanced primary mobile vertebral column sarcoma does not have a positive impact on survival.
• Comprehensive validation of a wearable foot sensor system for estimating spatiotemporal gait parameters by simultaneous three-dimensional optical motion analysis.

  Kentaro Homan, Keizo Yamamoto, Ken Kadoya, Naoki Ishida, Norimasa Iwasaki

  BMC sports science, medicine & rehabilitation 14 (1) 71 - 71 2022/04/17 

  BACKGROUND: Use of a wearable gait analysis system (WGAS) is becoming common when conducting gait analysis studies due to its versatility. At the same time, its versatility raises a concern about its accuracy, because its calculations rely on assumptions embedded in its algorithms. The purpose of the present study was to validate twenty spatiotemporal gait parameters calculated by the WGAS by comparison with simultaneous measurements taken with an optical motion capture system (OMCS). METHODS: Ten young healthy volunteers wore two inertial sensors of the commercially available WGAS, Physilog®, on their feet and 23 markers for the OMCS on the lower part of the body. The participants performed at least three sets of 10-m walk tests at their self-paced speed in the laboratory equipped with 12 high-speed digital cameras with embedded force plates. To measure repeatability, all participants returned for a second day of testing within two weeks. RESULTS: Twenty gait parameters calculated by the WGAS had a significant correlation with the ones determined by the OMCS. Bland and Altman analysis showed that the between-device agreement for twenty gait parameters was within clinically acceptable limits. The validity of the gait parameters generated by the WGAS was found to be excellent except for two parameters, swing width and maximal heel clearance. The repeatability of the WGAS was excellent when measured between sessions. CONCLUSION: The present study showed that spatiotemporal gait parameters estimated by the WGAS were reasonably accurate and repeatable in healthy young adults, providing a scientific basis for applying this system to clinical studies.
• Machine Learning Algorithms: Prediction and Feature Selection for Clinical Refracture after Surgically Treated Fragility Fracture.

  Hirokazu Shimizu, Ken Enda, Tomohiro Shimizu, Yusuke Ishida, Hotaka Ishizu, Koki Ise, Shinya Tanaka, Norimasa Iwasaki

  Journal of clinical medicine 11 (7) 2022/04/05 

  BACKGROUND: The number of patients with fragility fracture has been increasing. Although the increasing number of patients with fragility fracture increased the rate of fracture (refracture), the causes of refracture are multifactorial, and its predictors are still not clarified. In this issue, we collected a registry-based longitudinal dataset that contained more than 7000 patients with fragility fractures treated surgically to detect potential predictors for clinical refracture. METHODS: Based on the fact that machine learning algorithms are often used for the analysis of a large-scale dataset, we developed automatic prediction models and clarified the relevant features for patients with clinical refracture. Formats of input data containing perioperative clinical information were table data. Clinical refracture was documented as the primary outcome if the diagnosis of fracture was made at postoperative outpatient care. A decision-tree-based model, LightGBM, had moderate accuracy for the prediction in the test and the independent dataset, whereas the other models had poor accuracy or worse. RESULTS: From a clinical perspective, rheumatoid arthritis (RA) and chronic kidney disease (CKD) were noted as the relevant features for patients with clinical refracture, both of which were associated with secondary osteoporosis. CONCLUSION: The decision-tree-based algorithm showed the precise prediction of clinical refracture, in which RA and CKD were detected as the potential predictors. Understanding these predictors may improve the management of patients with fragility fractures.
• 【発育性股関節形成不全の基礎と臨床】DDHの超音波検査

  高橋 大介, 清水 智弘, 宮嵜 拓自, 岩崎 倫政

  関節外科 (株)メジカルビュー社 41 (4) 342 - 352 0286-5394 2022/04 

  ＜文献概要＞発育性股関節形成不全(developmental dysplasia of the hip;DDH)の画像診断では超音波診断が最も有用である。近年の大規模研究により,処女歩行が開始される1歳以降に発見された「診断遅延症例」の増加が明らかとなり,乳児股関節脱臼検診において単純X線よりも診断精度の高い超音波検査(Graf法)の重要性が高まっている。本稿では,新生児期・乳児期の股関節の超音波解剖について述べた後に,Graf法について基本的手技から画像の読み方について概説する。
• Intra-articular osteoid osteoma at the elbow mimicking arthritis: a case report

  Ryuichi Fukuda, Masatake Matsuoka, Daisuke Kawamura, Takeshi Endo, Hiromi Kanno-Okada, Atsushi Urita, Yuichiro Matsui, Tomohiro Onodera, Norimasa Iwasaki

  Annals of Joint 7 20 - 20 2022/04 

  Osteoid osteomas are benign, typically intracortical lesions most often affecting the diaphysis of long bones. Nocturnal pain and characteristic symptoms that are relieved by administration of non-steroidal anti-inflammatory drugs (NSAIDs) are present and can help in the diagnosis of osteoid osteoma. We report a case of 18-year-old boy with an osteoid osteoma in the olecranon fossa with an atypical clinical manifestation. The initial manifestation was arthritis-like symptoms such as local heat, motion pain rather than pain at rest, and limited range-of-motion. Notably, NSAIDs were not effective at all for relieving his symptoms. Magnetic resonance imaging showed bone marrow edema around the elbow joint. The symptoms were resistant to conservative treatments, and thus, surgical resection was required. Histopathological examination showed that the lesion consisted of woven bones and osteoid tissues that anastomosed with each other. Combined with a tumor size that was less than 2 cm, clinicopathologically, the tumor was diagnosed as an osteoid osteoma. The pain was immediately relieved after the operation, and range-of-motion recovered at 2 months postoperatively. At 1 year after the surgery, the patient did not exhibit recurrence of the tumor or exacerbation of elbow pain and had a full range of elbow motion. Osteoid osteoma should be considered for the differential diagnosis of arthritis of the elbow in patients who are adolescents and young adults, which is the peak age of onset for osteoid osteoma.
• Pulsating Spinal Arachnoid Cyst as a Hidden Aggravating Factor for Thoracic Spondylotic Myelopathy: A Report of 3 Cases.

  Masahiko Takahata, Takamasa Watanabe, Tsutomu Endo, Yuki Ogawa, Souya Miura, Norimasa Iwasaki

  JBJS case connector 12 (2) 2022/04/01 

  CASE: We report 3 cases of thoracic myelopathy caused by vertebral osteophytes and coexisting intradural spinal arachnoid cyst (SAC), which was difficult to diagnose on preoperative magnetic resonance imaging. Intraoperative ultrasound sonography revealed spinal cord impingement because of osteophytes and a pulsating intradural SAC. Repeated pincer compression on the spinal cord seemed to be associated with their paraparetic symptoms. CONCLUSION: In treating patients presenting with unexplained progressive myelopathy with small ossified lesion in the thoracic spine, close attention should be paid to a coexisting SAC as a hidden aggravating factor for thoracic myelopathy.
• Finite Element Analysis of Optimal Positioning of Femoral Osteotomy in Total Hip Arthroplasty With Subtrochanteric Shortening.

  Daisuke Takahashi, Yoshihiro Noyama, Tomohiro Shimizu, Mohamad Alaa Terkawi, Norimasa Iwasaki

  Arthroplasty today 14 105 - 109 2022/04 

  Background: Total hip arthroplasty with femoral shortening is frequently recommended for patients with high hip dislocation. However, the possibility of postoperative rotational deviation of the stem presents a challenge for surgeons. We aimed to determine the optimal position for osteotomy in total hip arthroplasty under full weight-bearing and turning torque by using finite element analysis. Methods: Four models of femoral osteotomy with 30-mm transverse shortening at 30% (model 30), 40% (model 40), 50% (model 50), and 60% (model 60) from the proximal end of the full length of the Exeter stem were constructed. Using finite element analysis, the constructs were first analyzed under an axial load of 1500 N and then with an added torsional load of 10°. Results: The analyses under torsional loading conditions revealed that the maximum von Mises stress on the stem in each model occurred at the proximal end of the distal fragment and the distal side of the stem. The maximum stress values at the stem were 819 MPa (model 30), 825 MPa (model 40), 916 MPa (model 50), and 944 MPa (model 60). The maximum stress values at the osteotomy site of the medullary cavity side of the distal bone fragment were 761 MPa (model 30), 165 MPa (model 40), 187 MPa (model 50), and 414 MPa (model 60). Conclusions: The osteotomy level should be around the proximal 40% of the full length of the Exeter stem, which is most suitable for rotation stability in the early postoperative period.
• Diagnostic Utility of Superb Microvascular Imaging and Power Doppler Ultrasonography for Visualizing Enriched Microvascular Flow in Patients With Carpal Tunnel Syndrome

  Takeshi Endo, Yuichiro Matsui, Daisuke Kawamura, Atsushi Urita, Daisuke Momma, Mitsutoshi Ota, Hiroki Shibayama, Takahito Iwai, Mutsumi Nishida, Norimasa Iwasaki

  Frontiers in Neurology 13 832569 - 832569 2022/03/31 

  Recent studies suggest that blood flow changes in the median nerve may help confirm a diagnosis of carpal tunnel syndrome (CTS). Herein, we examined the utility of superb microvascular imaging (SMI), a new ultrasonographic (US) technique for visualizing microvascular flow, for detecting blood flow differences between CTS patients and healthy controls. We performed a retrospective analysis of 28 hands with suspected CTS. Patients received both nerve conduction and US examinations. Ten healthy volunteers were enrolled as the control group. The nerve compression ratio and the blood flow signal area were quantified using color Doppler US (CDUS), power Doppler US (PDUS), and SMI. Correlation analyses between the blood flow signal area, the compound muscle action potential of the thenar muscle, and the nerve compression ratio were performed. As a result, the mean nerve compression ratio was found to be significantly higher in the CTS group. There were no differences in the blood flow signal area between the groups using CDUS, while PDUS and SMI showed higher blood flow signals in the CTS group. The blood flow signal area measured by SMI had stronger correlations with the compound muscle action potential amplitude and the nerve compression ratio than those for PDUS. The diagnostic utility of SMI was equivalent to PDUS, but superior to conventional CDUS. Nevertheless, the blood flow signal by SMI was more strongly correlated with the electrophysiological severity and compression ratio than for PDUS. Use of SMI in future studies may help clarify the underlying mechanisms of blood flow changes in CTS.
• Bone biopsy findings in patients receiving long-term bisphosphonate therapy for glucocorticoid-induced osteoporosis.

  Masahiko Takahata, Tomohiro Shimizu, Satoshi Yamada, Tomomaya Yamamoto, Tomoka Hasegawa, Ryo Fujita, Hideyuki Kobayashi, Tsutomu Endo, Yoshinao Koike, Norio Amizuka, Masahiro Todoh, Jun-Ichiro Okumura, Tomomichi Kajino, Norimasa Iwasaki

  Journal of bone and mineral metabolism 40 (4) 613 - 622 2022/03/25 

  INTRODUCTION: Bisphosphonates (BPs) have been shown to reduce the incidence of vertebral fractures during the first year or two of glucocorticoid (GC) treatments and are therefore recommended as a first-line treatment for GC-induced osteoporosis (GIO). However, there are theoretical concerns about the long-term use of BPs in low-turnover osteoporosis caused by chronic GC therapy. MATERIALS AND METHODS: We analyzed the trabecular microarchitecture, bone metabolism, and material strength of iliac crest bone biopsy samples from 10 female patients with rheumatoid arthritis who received an average of 6.7 years of BP therapy for GIO (GIOBP group), compared with those of 10 age- and bone mineral density (BMD)-matched non-rheumatoid arthritis postmenopausal women (reference group). RESULTS: Patients in the GIOBP group had a significantly greater fracture severity index, as calculated from the number and the extent of vertebral fractures compared with the reference patients. Micro-computed tomography analysis showed that the degree of mineralization and trabecular microarchitecture were significantly lower in the GIOBP group than in the reference patients. Patients in the GIOBP group exhibited lower bone contact stiffness, determined by micro-indentation testing, than in the reference group. The contact stiffness of the bone was negatively correlated with the fracture severity index and the daily prednisolone dosage. Immunohistochemistry and serum bone turnover markers showed decreased osteoclastic activity, impaired mineralization, and an increased fraction of empty lacunae in the GIOBP group. CONCLUSION: Our findings indicate that patients receiving long-term BP for GIO are still at high risk for fragility fractures because of poor bone quality.
• Optical coherence tomography evaluation of the spatiotemporal effects of 3D bone marrow stromal cell culture using a bioreactor.

  Jun Yamaguchi, Tomohiro Onodera, Kentaro Homan, Xu Liang, Masatake Matsuoka, Takuji Miyazaki, Hosokawa Yoshiaki, Mitsuru Saito, Norimasa Iwasaki

  Journal of biomedical materials research. Part B, Applied biomaterials 110 (8) 1853 - 1861 2022/03/09 

  Performing cell culture in a three-dimensional (3D) environment has various advantages. In cartilage tissue engineering, 3D in vitro cultures utilizing biomaterials and bioreactors can mimic the biological environment. However, the biggest drawback of these 3D culture systems is a limited ability to evaluate 3D cell distribution. Optical coherence tomography (OCT) has recently been used to evaluate 3D cellular morphology and structure in a timely manner. Here, we showed that OCT could be used to visually assess the distribution and the morphology of bone marrow stromal cells under chondrogenic 3D cultivation using alginate gels and rotary culture. In particular, OCT was able to visualize living cells embedded in alginate gels in a non-destructive and 3D manner, as well as quantitatively evaluate cell distribution and spheroid volume. We also found that cells were centralized in rotary culture but peripherally distributed in static culture, while rotary culture enhanced the hypertrophy of marrow stromal cells (MSCs) embedded in alginate gels. Together, our findings demonstrate that OCT can be used to evaluate the spatiotemporal effects of 3D cultivation using alginate gels and rotary culture. Therefore, this method may allow the observation of pre-cultured tissue over time and the optimization of culture conditions for regenerative tissue engineering.
• Distinct progression pattern of ossification of the posterior longitudinal ligament of the thoracic spine versus the cervical spine: a longitudinal whole-spine CT study.

  Yuichiro Hisada, Tsutomu Endo, Yoshinao Koike, Masahiro Kanayama, Ryota Suzuki, Ryo Fujita, Katsuhisa Yamada, Akira Iwata, Hiroyuki Hasebe, Hideki Sudo, Norimasa Iwasaki, Masahiko Takahata

  Journal of neurosurgery. Spine 37 (2) 1 - 8 2022/03/04 

  OBJECTIVE: Data regarding risk factors for the progression of ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine are scarce. Therefore, in this study, the authors aimed to elucidate the difference in the radiographic progression pattern of OPLL and its risk factors between cervical and thoracic OPLL using longitudinally acquired whole-spine CT scans. METHODS: Overall, 123 patients with symptomatic OPLL who underwent repeated whole-spine CT examinations, with an average interval of 49 months (at least 3 years) between scans, were retrospectively reviewed. Progression of OPLL was assessed to compare the distribution of OPLL over the entire spine on the initial and final CT scans. Patients were divided into a cervical OPLL (C-OPLL) group and a thoracic OPLL (T-OPLL) group according to the location of the main lesion. The progression pattern of OPLL and its risk factors were compared between the two groups using the Student t-test or Mann-Whitney U-test. RESULTS: In the C-OPLL group, 15 (22.1%) of 68 patients had OPLL progression, of whom 12 patients (80.0%) had progression only in the cervical spine and 3 patients (20.0%) had progression in multiple regions (cervical and thoracic/lumbar). In the T-OPLL group, 16 (29.1%) of 55 patients had OPLL progression, of which 3 patients (18.8%) had progression only in the thoracic spine and 8 patients (50.0%) had progression in multiple regions. Young age was a common risk factor for OPLL progression regardless of the location of OPLL, and this trend was more pronounced in the T-OPLL group than in the C-OPLL group. High BMI, male sex, and multilevel, severe T-OPLL were identified as independent risk factors for progression of T-OPLL (OR 1.19, 95% CI 1.03-1.37; OR 10.5, 95% CI 1.39-81.94; and OR 1.24, 95% CI 1.16-1.45, respectively). CONCLUSIONS: Patients with T-OPLL are predisposed to diffuse progression of OPLL over the entire spine, whereas patients with C-OPLL are likely to have progression in only the cervical spine. Young age and high BMI are significant risk factors for OPLL progression, especially in patients with T-OPLL. Our study highlights the need for continued follow-up in patients with T-OPLL, especially in young patients and those with obesity, for early detection of spinal cord and cauda equina symptoms due to the progression of OPLL throughout the spine.
• 大菱形骨の骨形態の違いが母指CM関節における応力に及ぼす影響 CTOAM法を用いた解析

  佃 幸憲, 松井 雄一郎, 遠藤 香織, 松居 祐樹, 平塚 重人, 濱崎 雅成, 宮野 真博, 河村 太介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (3) S685 - S685 0021-5325 2022/03
• Modic type1の腰椎椎間板変性にアクネ菌は本当に存在するのか 141例の椎間板採取を用いたプロスペクティブ研究から

  八尋 雄平, 須田 浩太, 松本 聡子, 小松 幹, 太田 昌博, 後迫 宏紀, 三浪 明男, 冨永 博之, 谷口 昇, 高畑 雅彦, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (3) S1064 - S1064 0021-5325 2022/03
• 術前診断に苦慮し急性増悪をきたした悪性末梢神経鞘腫の一例

  藤田 諒, 遠藤 努, 岩田 玲, 山田 勝久, 大西 貴士, 長谷部 弘之, 須藤 英毅, 高畑 雅彦, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 63 (2) 151 - 151 1343-3873 2022/03
• 急速破壊型股関節症におけるインフラマソーム滑膜炎の関与について

  横田 隼一, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (2) S131 - S131 0021-5325 2022/03
• 脆弱性骨折を来した関節リウマチ患者の再骨折リスク

  石津 帆高, 清水 寛和, 清水 智弘, 村上 俊文, 松ヶ崎 圭純, 横田 隼一, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (2) S144 - S144 0021-5325 2022/03
• 発育性股関節形成不全に対するangulated innominate osteotomy(AIO)の三次元的評価

  小川 拓也, 高橋 大介, 清水 智弘, 宮崎 拓自, 中村 夢志郎, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (2) S313 - S313 0021-5325 2022/03
• 関節リウマチ患者の下肢手術数の傾向と併存症発生に関する調査

  糸賀 稜, 清水 智弘, 高橋 大介, 小野寺 智洋, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (2) S334 - S334 0021-5325 2022/03
• ハイブリッド人工知能を用いた寛骨臼形成不全の自動解析システムの開発

  清水 寛和, 清水 智弘, 遠田 健, 児矢野 英典, 高橋 大介, 小川 拓也, 田中 伸哉, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (2) S432 - S432 0021-5325 2022/03
• Graf法における教育の有無による精度と検査時間の比較

  清水 智弘, 中村 夢志郎, 小川 拓也, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (3) S682 - S682 0021-5325 2022/03
• 大腿骨近位部骨折術後の骨粗鬆症治療状況と治療率改善への取り組み 骨折リエゾンサービス導入前後の比較

  小川 裕生, 下段 俊, 福島 瑛, 池 翔太, 竹内 博紀, 百貫 亮太, 梅本 貴央, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (3) S696 - S696 0021-5325 2022/03
• 大腿骨近位部骨折に対する骨折リエゾンサービスの達成度 主要実績評価指標(KPI)を用いた経時的推移評価

  浅野 毅, 亀田 裕亮, 原谷 健太郎, 北原 圭太, 佐藤 恒明, 松岡 知樹, 高橋 大介, 清水 智弘, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (3) S697 - S697 0021-5325 2022/03
• 大腿骨寛骨臼インピンジメントと発育性股関節形成不全の股関節応力分布に与える影響の比較

  小川 裕生, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (3) S737 - S737 0021-5325 2022/03
• 短縮骨切り併用人工股関節全置換術におけるセメントステムとセメントレスステムの中期成績の比較

  宮崎 拓自, 高橋 大介, 清水 智弘, 中村 夢志郎, 大浦 久典, 片山 直行, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (3) S789 - S789 0021-5325 2022/03
• 高齢者に対するPolished Taperセメントステムを用いた人工股関節全置換術の成績

  山崎 秀, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (3) S789 - S789 0021-5325 2022/03
• 本邦の乳児股関節健診推奨項目と臼蓋発育不全の関連

  清水 智弘, 清水 寛和, 鈴木 久崇, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (3) S930 - S930 0021-5325 2022/03
• 乳児股関節脱臼ハイリスク児における超音波とX線を用いた経時的な画像評価

  大橋 佑介, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (3) S932 - S932 0021-5325 2022/03
• ハイブリッド人工知能を用いた乳児股関節X線画像の自動解析システムの開発

  清水 寛和, 高橋 大介, 児矢野 英典, 遠田 健, 清水 智弘, 下段 俊, 佐藤 恒明, 田中 伸哉, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (3) S932 - S932 0021-5325 2022/03
• 骨折リスクの高い閉経後骨粗鬆症に最適な骨粗鬆症治療

  清水 智弘, 有田 皓介, 石津 帆高, 中村 夢志郎, 藤田 諒, 室田 栄宏, 高橋 大介, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 96 (3) S1166 - S1166 0021-5325 2022/03
• 骨粗鬆症と骨代謝 脆弱性骨折をきたした関節リウマチ患者の再骨折リスク

  石津 帆高, 清水 寛和, 清水 智弘, 岩崎 倫政

  日本リウマチ学会総会・学術集会プログラム・抄録集 (一社)日本リウマチ学会 66回 382 - 382 2022/03
• 変形性関節症・軟骨 関節リウマチと酷似する急速破壊型股関節症におけるインフラマソーム滑膜炎の比較検討

  横田 隼一, 清水 智弘, 松前 元, 高橋 大介, 照川 アラー, 岩崎 倫政

  日本リウマチ学会総会・学術集会プログラム・抄録集 (一社)日本リウマチ学会 66回 428 - 428 2022/03
• 関節リウマチの骨関節破壊におけるCCN3の機能解析

  松前 元, 照川 アラー, 横田 隼一, 清水 智弘, 高橋 大介, 岩崎 倫政

  日本リウマチ学会総会・学術集会プログラム・抄録集 (一社)日本リウマチ学会 66回 569 - 569 2022/03
• 関節リウマチ患者の下肢手術数の傾向と併存症に関する調査

  糸賀 稜, 清水 智弘, 小野寺 智洋, 岩崎 倫政

  日本リウマチ学会総会・学術集会プログラム・抄録集 (一社)日本リウマチ学会 66回 623 - 623 2022/03
• Double-bundle anterior cruciate ligament reconstruction using autologous hamstring tendon hybrid grafts in a patient with hypermobile Ehlers-Danlos Syndrome: A case report.

  Ryosuke Hishimura, Eiji Kondo, Masatake Matsuoka, Koji Iwasaki, Yasuyuki Kawaguchi, Yuki Suzuki, Tomohiro Onodera, Daisuke Momma, Norimasa Iwasaki

  The Knee 35 81 - 86 2022/03 

  BACKGROUND: Ehlers-Danlos syndrome (EDS) is a connective tissue disorder characterized by skin hyperextensibility, joint hypermobility, and tissue friability. Hypermobile type Ehlers-Danlos syndrome (hEDS) is considered one of the EDS subtypes characterized by generalized joint hypermobility. Although there have been a few case reports which described surgical considerations for anterior cruciate ligament (ACL) reconstructions in patients with other types of EDS, no reports have described those in patients with hEDS. CASE PRESENTATION: We report a case of ACL injury in an 18-year-old male patient with hEDS. The patient was successfully treated with an anatomic double-bundle ACL reconstruction using autologous hamstring tendon hybrid grafts which consist of hamstring tendons connected in a series with commercially available polyester tape. The autogenous tendon portion of the anteromedial and posterolateral bundles were composed of 4 and 2 strands of hamstring tendons, respectively. After 2 weeks of knee joint immobilization, continuous passive motion exercise of the knee joint and partial weight-bearing was allowed. A hinged knee brace was used for a period of 5 months postoperatively. Second-look arthroscopy at 30 months showed that the ACL graft had no laceration and an excellent coverage of the synovium. At 36 months after surgery, the side-to-side differences in the anterior laxity was remarkably improved. The operated knee showed negative Lachman test and had a full range of motion. CONCLUSIONS: To the best of our knowledge, this represents the first report of anatomic double-bundle ACL reconstruction in patients with hEDS and demonstrates excellent clinical and functional outcomes.
• Differential effects of anti-RANKL monoclonal antibody and zoledronic acid on necrotic bone in a murine model of Staphylococcus aureus-induced osteomyelitis.

  Hideyuki Kobayashi, Ryo Fujita, Shigeto Hiratsuka, Tomohiro Shimizu, Dai Sato, Hiroki Hamano, Norimasa Iwasaki, Masahiko Takahata

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society 40 (3) 614 - 623 2022/03 

  Osteomyelitis is characterized by progressive inflammatory bone destruction accompanied by severe pain and disability. However, with the exception of antibiotic therapies, there is no established therapy to protect the bone from infectious osteolysis. The anti-receptor activator of nuclear factor-kB ligand (RANKL) monoclonal antibody (anti-RANKL Ab) is a potential drug based on its proven effectiveness in preventing joint bone erosion in rheumatoid arthritis; however, the efficacy and adverse effects of anti-RANKL Ab in osteomyelitis remain to be investigated. In this study, we investigated the effects of anti-mouse RANKL Ab on acute osteomyelitis and compared them with those of zoledronic acid (ZA) using a murine model. Mice were inoculated with bioluminescent Staphylococcus aureus (Xen 29) on their left femur and then treated with ZA, anti-RANKL Ab, or phosphate-buffered saline as control. A 21-day longitudinal observational study using microcomputed tomography showed that both anti-RANKL Ab and ZA had an osteoprotective effect against infectious osteolysis. However, it was also demonstrated through bioluminescence imaging that ZA delayed the spontaneous reduction of bacterial load and through histology that it increased the amount of necrotic bone, while anti-RANKL Ab did not. Findings from histopathological and in vitro studies suggest that an intense inflammatory response around the necrotic bone could induce osteoclasts in a RANKL-independent manner, leading to the removal of necrotic bone, even after administration of the anti-RANKL Ab therapy. Collectively, anti-RANKL Ab may exert an osteoprotective effect without hampering the removal of the necrotic bone, which serves as a nidus for infection in osteomyelitis.
• Association between obesity and ossification of spinal ligaments in 622 asymptomatic subjects: a cross-sectional study.

  Tsutomu Endo, Masahiko Takahata, Yoshinao Koike, Ryo Fujita, Ryota Suzuki, Yuichiro Hisada, Yuichi Hasegawa, Hisataka Suzuki, Katsuhisa Yamada, Akira Iwata, Hideki Sudo, Daisuke Yoneoka, Norimasa Iwasaki

  Journal of bone and mineral metabolism 40 (2) 337 - 347 2022/03 

  INTRODUCTION: Previous studies on patients with symptoms of spinal ligament ossification, including ossification of the posterior longitudinal ligament (OPLL) and ligamentum flavum (OLF), have not clarified whether obesity is a cause or consequence of these diseases and were limited by selection bias. Thus, we investigated the association between obesity and the prevalence of spinal ligament ossification in randomly selected asymptomatic subjects. MATERIALS AND METHODS: Between April 2020 and March 2021, 622 asymptomatic Japanese subjects who underwent computed tomography of neck to pelvis for medical check-up purposes were included. All subjects were divided into the following three groups: normal weight (body mass index [BMI] < 25 kg/m2), obese I (25 ≤ BMI < 30 kg/m2), and obese II (BMI ≥ 30 kg/m2). The relationship between factors affecting the presence of each spinal ligament ossification was evaluated using multivariate logistic regression analysis. RESULTS: The proportion of subjects with thoracic OPLL was significantly higher in the obese II group than in the other two groups (vs. normal weight, P < 0.001; vs. obese I, P < 0.001). BMI was associated with the prevalence of OLF, cervical OPLL, thoracic OPLL, and ossification of the anterior longitudinal ligament (OALL). BMI was most significantly associated with the prevalence of thoracic OPLL (β, 0.28; 95% confidence interval, 0.17-0.39). CONCLUSION: BMI was associated with the prevalence of OALL, cervical OPLL, thoracic OPLL, and OLF in asymptomatic subjects, suggesting that obesity is associated with the development of heterotopic ossification of the spinal ligaments.
• Primary Malignant Osseous Neoplasms in the Hand.

  Shota Ike, Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Eiji Kondo, Norimasa Iwasaki

  Anticancer research 42 (3) 1635 - 1640 2022/03 

  BACKGROUND: Primary malignant osseous neoplasms of the hand are rare malignancies. Comprehensive demographic and survival data regarding primary malignant osseous neoplasms of the hand are lacking in the literature. PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified all patients with primary malignant osseous neoplasms of the hand diagnosed between 1983 and 2015. Demographic data were searched for primary osseous neoplasms in the hand and higher incidence of histological subtype. RESULTS: A total of 197 patients were analyzed: 103 patients were diagnosed with histologically low-grade tumor, and 31 were diagnosed with high-grade tumor. Five-year cancer-specific and overall survival rates for the entire cohort were 91.4% and 81.9%, respectively. Histological high tumor grade and regional stage from SEER historic stage data were associated with unfavorable cancer-specific survival. CONCLUSION: Special caution is required if patients have histologically high-grade tumor or tumor extending beyond the periosteum into surrounding joints, as these features worsen cancer-specific mortality.
• Inflammasome activation in the hip synovium of rapidly destructive coxopathy patients and its relationship with the development of synovitis and bone loss

  Shunichi Yokota, Tomohiro Shimizu, Gen Matsumae, Taku Ebata, Hend Alhasan, Daisuke Takahashi, Mohamad Alaa Terkawi, Norimasa Iwasaki

  The American Journal of Pathology 192 (5) 794 - 804 0002-9440 2022/03 

  Rapidly destructive coxopathy (RDC), a rare disease of unknown etiology, is characterized by the rapid destruction of the hip joint. In the current study, the potential involvement of inflammasome signaling in the progression of RDC was investigated. Histopathologic changes and the gene expression of inflammasome activation markers in hip synovial tissues collected from patients with RDC were evaluated and compared with those of osteoarthritis and osteonecrosis of the femoral head patients. The synovial tissues of patients with RDC exhibited remarkable increases in the number of infiltrated macrophages and osteoclasts, and the expression of inflammasome activation markers was also increased compared with those of osteoarthritis and osteonecrosis of the femoral head patients. To further understand the histopathologic changes in the joint, a co-culture model of macrophages and synoviocytes that mimicked the joint environment was developed. Remarkably, the gene expression levels of NLRP3, GSDMD, IL1B, TNFA, ADMTS4, ADMTS5, MMP3, MMP9, and RANKL were significantly elevated in the synoviocytes that were co-cultured with activated THP-1 macrophages, suggesting the association between synovitis and inflammasome activation. Consistent with these findings, osteoclast precursor cells that were co-cultured with stimulated synoviocytes exhibited an increased number of tartrate-resistant acid phosphatase-positive cells, compared with cells that were co-cultured with non-stimulated synoviocytes. These findings suggest that the activation of inflammasome signaling in the synovium results in an increase in local inflammation and osteoclastogenesis, thus leading to the rapid bone destruction in RDC.
• Four-dimensional computed tomography evaluation of shoulder joint motion in collegiate baseball pitchers.

  Daisuke Momma, Alejandro A Espinoza Orías, Tohru Irie, Tomoyo Irie, Eiji Kondo, Norimasa Iwasaki, Nozomu Inoue

  Scientific reports 12 (1) 3231 - 3231 2022/02/25 

  The purpose of this study is to evaluate the glenohumeral contact area, center of glenohumeral contact area, and center of humeral head during simulated pitching motion in collegiate baseball pitchers using four-dimensional computed tomography (4D CT). We obtained 4D CT data from the dominant and non-dominant shoulders of eight collegiate baseball pitchers during the cocking motion. CT image data of each joint were reconstructed using a 3D reconstruction software package. The glenohumeral contact area, center of glenohumeral contact area, center of humeral head, and oblateness of humeral head were calculated from 3D bone models using customized software. The center of glenohumeral contact area translated from anterior to posterior during maximum external rotation to maximum internal rotation (0.58 ± 0.63 mm on the dominant side and 0.99 ± 0.82 mm on the non-dominant side). The center of humeral head translated from posterior to anterior during maximum external rotation to maximum internal rotation (0.76 ± 0.75 mm on the dominant side and 1.21 ± 0.78 mm on the non-dominant side). The increase in anterior translation of the center of glenohumeral contact area was associated with the increase in posterior translation of the center of humeral head. Also, the increase in translation of the center of humeral head and glenohumeral contact area were associated with the increase in oblateness of the humeral head. 4D CT analyses demonstrated that the center of humeral head translated in the opposite direction to that of the center of glenohumeral contact area during external rotation to internal rotation in abduction in the dominant and non-dominant shoulders. The oblateness of the humeral head may cause this diametric translation. 4D CT scanning and the software for bone surface modeling of the glenohumeral joint enabled quantitative assessment of glenohumeral micromotion and be used for kinematic evaluation of throwing athletes.
• Biomaterials and Cell-Based Regenerative Therapies for Intervertebral Disc Degeneration with a Focus on Biological and Biomechanical Functional Repair: Targeting Treatments for Disc Herniation.

  Katsuhisa Yamada, Norimasa Iwasaki, Hideki Sudo

  Cells 11 (4) 2022/02/09 

  Intervertebral disc (IVD) degeneration is a common cause of low back pain and most spinal disorders. As IVD degeneration is a major obstacle to the healthy life of so many individuals, it is a major issue that needs to be overcome. Currently, there is no clinical treatment for the regeneration of degenerated IVDs. However, recent advances in regenerative medicine and tissue engineering suggest the potential of cell-based and/or biomaterial-based IVD regeneration therapies. These treatments may be indicated for patients with IVDs in the intermediate degenerative stage, a point where the number of viable cells decreases, and the structural integrity of the disc begins to collapse. However, there are many biological, biomechanical, and clinical challenges that must be overcome before the clinical application of these IVD regeneration therapies can be realized. This review summarizes the basic research and clinical trials literature on cell-based and biomaterial-based IVD regenerative therapies and outlines the important role of these strategies in regenerative treatment for IVD degenerative diseases, especially disc herniation.
• Determination of optimal concentration of vitamin E in polyethylene liners for producing minimal biological response to prosthetic wear debris.

  Gen Matsumae, Hiroaki Kida, Daisuke Takahashi, Tomohiro Shimizu, Taku Ebata, Shunichi Yokota, Hend Alhasan, Mahmoud Khamis Aly, Tomoyo Yutani, Keita Uetsuki, Mohamad Alaa Terkawi, Norimasa Iwasaki

  Journal of biomedical materials research. Part B, Applied biomaterials 110 (7) 1587 - 1593 2022/02/05 

  The introduction of vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) for use in prosthetic components of hip implants has resulted in the production of implants that have excellent mechanical properties and substantially less adverse cellular responses. Given the importance of a biological response to wear in the survival of a prosthesis, we generated wear debris from UHMWPE that had been prepared with different concentrations of vitamin E of 0.1, 0.3, 0.5, and 1% and evaluated their biological reaction in vitro and in vivo. All types of VE-UHMWPE debris promoted a significantly lower expression of Tnf-α in murine peritoneal macrophages than that induced by conventional UHMWPE debris. However, levels of Tnf-α were not significantly different among the macrophages that were stimulated with VE-UHMWPE wear at the concentrations tested. The ability of wear debris to induce inflammatory osteolysis was assessed in a mouse calvarial osteolysis model. The expressions of Tnf-α, Il-6, and Rankl in granulomatous tissue formed around the wear debris were significantly reduced in mice that had been implanted with 0.3%VE-UHMWPE debris as compared to the corresponding values for mice that had been implanted with UHMWPE debris. Consistent with this finding, 0.3%VE-UHMWPE debris showed the lowest osteolytic activity, as evidenced by the reduced bone resorption area, the degree of infiltration of inflammatory cells and the TRAP staining area. Our results suggested that a 0.3% vitamin E concentration is the most appropriate concentration for use in prosthetic components with a reduced adverse cellular response for prolonging the life-span of the implant.
• Interplay between Inflammation and Pathological Bone Resorption: Insights into Recent Mechanisms and Pathways in Related Diseases for Future Perspectives.

  M Alaa Terkawi, Gen Matsumae, Tomohiro Shimizu, Daisuke Takahashi, Ken Kadoya, Norimasa Iwasaki

  International journal of molecular sciences 23 (3) 2022/02/04 

  Bone is a mineralized and elastic connective tissue that provides fundamental functions in the human body, including mechanical support to the muscles and joints, protection of vital organs and storage of minerals. Bone is a metabolically active organ that undergoes continuous remodeling processes to maintain its architecture, shape, and function throughout life. One of the most important medical discoveries of recent decades has been that the immune system is involved in bone remodeling. Indeed, chronic inflammation has been recognized as the most significant factor influencing bone homeostasis, causing a shift in the bone remodeling process toward pathological bone resorption. Bone osteolytic diseases typified by excessive bone resorption account for one of the greatest causes of disability worldwide, with significant economic and public health burdens. From this perspective, we discuss the recent findings and discoveries highlighting the cellular and molecular mechanisms that regulate this process in the bone microenvironment, in addition to the current therapeutic strategies for the treatment of osteolytic bone diseases.
• The effect of local injection of tranexamic acid into peri-articular tissue versus drain clamping in total knee arthroplasty: a randomized controlled trial.

  Ryosuke Hishimura, Tomohiro Onodera, Yasumitsu Ohkoshi, Kazufumi Okada, Masatake Matsuoka, Shinji Matsubara, Koji Iwasaki, Eiji Kondo, Norimasa Iwasaki

  BMC musculoskeletal disorders 23 (1) 111 - 111 2022/02/02 

  BACKGROUND: Tranexamic acid (TXA) is used as a synthetic anti-fibrinolytic agent for total knee arthroplasty (TKA) to reduce postoperative bleeding. Though the effects on bleeding reduction of several methods of administering TXA have been demonstrated, the optimal method remains controversial. Recently, the hemostatic effect of periarticular local injection of TXA during TKA was reported. Although this method can be expected to suppress postoperative bleeding without placing a drain, its hemostatic effect has not yet been assessed in comparison with local injection and other methods of administering TXA. The aim of this randomized, prospective study was to assess the efficacy of local injection of TXA during TKA. METHODS: To confirm the effect of the local injection of TXA, drain clamping was set as the control. The subjects included a prospective series of 109 patients randomly divided into 2 groups: the local injection (group L) and the drain clamping (group D). The main outcome measure was postoperative bleeding. Secondary outcomes included pain, physical measurements, and laboratory findings. RESULTS: The calculated total blood loss (CTBL) in groups L and D was nearly equal and did not show the non-inferiority of group L to group D (883 ± 248 vs. 841 ± 257 ml, P = .564). Drained blood loss was significantly higher in group L than in group D (395 ± 130 vs 276 ± 78.8 ml, P < .0001). There was no significant difference in hidden blood loss between the groups (488 ± 269 vs 565 ± 261 ml, P = .131). The other laboratory findings and physical measurements were identical between the groups. CONCLUSIONS: Although CTBL in group L did not show non-inferiority to group D, the local injection of TXA was considered to be superior for suppressing bleeding considering the risk of the adverse effects of using a drain. TRIAL REGISTRATION: This was a randomized, prospective study registered with UMIN Clinical Trials Registry (Registration number: UMIN000036146, date of disclosure: 10/3/2019).
• Discrepancy in the Distribution Patterns of Subchondral Bone Density Across the Ankle Joint After Medial Opening-Wedge and Lateral Closing-Wedge High Tibial Osteotomy.

  Shinji Matsubara, Tomohiro Onodera, Koji Iwasaki, Ryosuke Hishimura, Masatake Matsuoka, Eiji Kondo, Norimasa Iwasaki

  The American journal of sports medicine 50 (2) 478 - 485 2022/02 

  BACKGROUND: High tibial osteotomy (HTO) changes the alignment and dynamics of the ankle joint; however, differences in the stress distribution of the ankle joint after opening-wedge HTO (OWHTO) and closing-wedge HTO (CWHTO) are not understood. It is believed that subchondral bone density of the articular surface reflects the pattern of cumulative stress distribution across the joint surface. PURPOSE: To clarify the effects of OWHTO and CWHTO on the distribution patterns of subchondral bone density across the ankle joint using computed tomography (CT)-osteoabsorptiometry. STUDY DESIGN: Cohort study; Level of evidence, 4. METHODS: Radiographic and CT data of 18 cases who underwent OWHTO (OW group), 12 cases who underwent CWHTO (CW group), and 11 cases with unilateral anterior cruciate ligament injury serving as controls were retrospectively reviewed. The subchondral bone density of the distal tibia was assessed in the 3 groups using CT-osteoabsorptiometry. The distal tibial surface of the ankle joint was divided into 4 parts in the coronal direction, and the percentage of the high-density area (%HDA) to each subregion was compared before and after HTO. RESULTS: Preoperatively, comparing %HDA among the 3 groups, there were no significant differences in any regions. In the OW group, postoperative %HDA in the most medial region was significantly increased compared with preoperative %HDA (49.3% to 53.0%; P = .011), and postoperative %HDA in the most lateral region was significantly decreased (21.4% to 17.2%; P = .003). On the other hand, in the CW group, postoperative %HDA in the most medial region was significantly decreased (55.7% to 35.7%; P = .001), and %HDA in the second lateral region was significantly increased (23.6% to 29.2%; P = .002). CONCLUSION: The ankle distribution pattern of subchondral bone density shifted significantly medially after OWHTO without fibular osteotomy, whereas the distribution pattern shifted laterally after CWHTO with fibular osteotomy. When the OWHTO is performed for patients with medial ankle osteoarthritis, surgeons should pay attention to potential postoperative progression of ankle osteoarthritis due to medial shift of the stress distribution in the ankle joint.
• Mature but not developing Schwann cells promote axon regeneration after peripheral nerve injury.

  Takeshi Endo, Ken Kadoya, Tomoaki Suzuki, Yuki Suzuki, Mohamad Alaa Terkawi, Daisuke Kawamura, Norimasa Iwasaki

  NPJ Regenerative medicine 7 (1) 12 - 12 2022/01/28 

  Since Schwann cells (SCs) support axonal growth at development as well as after peripheral nerve injury (PNI), developing SCs might be able to promote axon regeneration after PNI. The purpose of the current study was to elucidate the capability of developing SCs to induce axon regeneration after PNI. SC precursors (SCPs), immature SCs (ISCs), repair SCs (RSCs) from injured nerves, and non-RSCs from intact nerves were tested by grafting into acellular region of rat sciatic nerve with crush injury. Both of developing SCs completely failed to support axon regeneration, whereas both of mature SCs, especially RSCs, induced axon regeneration. Further, RSCs but not SCPs promoted neurite outgrowth of adult dorsal root ganglion neurons. Transcriptome analysis revealed that the gene expression profiles were distinctly different between RSCs and SCPs. These findings indicate that developing SCs are markedly different from mature SCs in terms of functional and molecular aspects and that RSC is a viable candidate for regenerative cell therapy for PNI.
• Effect of periacetabular osteotomy on the distribution pattern of subchondral bone mineral density in patients with hip dysplasia.

  Tomohiro Shimizu, Daisuke Takahashi, Yumejiro Nakamura, Takuji Miyazaki, Shunichi Yokota, Hotaka Ishizu, Norimasa Iwasaki

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society 40 (11) 2626 - 2631 2022/01/25 

  Despite the availability of long-term follow-up data, the effect of pelvic osteotomy on the natural history of osteoarthritis is not yet fully understood, partly because there is untapped potential for radiographs to better describe osteoarthritis. Therefore, this study aimed to assess the distribution of subchondral bone mineral density (BMD) across the acetabulum in patients with hip dysplasia immediately (2 weeks) and 1 year after undergoing periacetabular osteotomy (PAO). To that end, we reviewed 40 hips from 33 patients with developmental dysplasia of the hip who underwent PAO between January 2016 and July 2019 at our institution. We measured subchondral BMD through the articular surface of the acetabulum using computed tomography osteoabsorptiometry, dividing the distribution map into nine segments. We then compared the subchondral BMD between 2 weeks and 1 year after PAO in each area. At 2 weeks after PAO, the high-density area tended to be localized particularly in the lateral part of the acetabulum, whereas 1 year after PAO, the high-density area moved to the central and lateral parts. The percentage ratios of the subchondral BMD for the central-posterior, lateral-central, and lateral-posterior areas relative to the central-central area were significantly decreased at 1 year after PAO, as compared to those at 2 weeks after PAO. These findings suggest that loading was altered by PAO to be more similar to physiological loading. A long follow-up observational study is warranted to confirm the association between early changes in subchondral BMD by PAO and joint degeneration.
• Causes of and Molecular Targets for the Treatment of Intervertebral Disc Degeneration: A Review.

  Takashi Ohnishi, Norimasa Iwasaki, Hideki Sudo

  Cells 11 (3) 2022/01/24 

  Intervertebral disc degeneration (IVDD) is a pathological condition that can lead to intractable back pain or secondary neurological deficits. There is no fundamental cure for this condition, and current treatments focus on alleviating symptoms indirectly. Numerous studies have been performed to date, and the major strategy for all treatments of IVDD is to prevent cell loss due to programmed or regulated cell death. Accumulating evidence suggests that several types of cell death other than apoptosis, including necroptosis, pyroptosis, and ferroptosis, are also involved in IVDD. In this study, we discuss the molecular pathway of each type of cell death and review the literature that has identified their role in IVDD. We also summarize the recent advances in targeted therapy at the RNA level, including RNA modulations through RNA interference and regulation of non-coding RNAs, for preventing cell death and subsequent IVDD. Therefore, we review the causes and possible therapeutic targets for RNA intervention and discuss the future direction of this research field.
• Combination of ultra-purified stem cells with an in situ-forming bioresorbable gel enhances intervertebral disc regeneration.

  Daisuke Ukeba, Katsuhisa Yamada, Takashi Suyama, Darren R Lebl, Takeru Tsujimoto, Takayuki Nonoyama, Hirokazu Sugino, Norimasa Iwasaki, Masatoki Watanabe, Yumi Matsuzaki, Hideki Sudo

  EBioMedicine 76 103845 - 103845 2022/01/24 

  BACKGROUND: Lumbar intervertebral disc (IVD) herniations are associated with significant disability. Discectomy is the conventional treatment option for IVD herniations but causes a defect in the IVD, which has low self-repair ability, thereby representing a risk of further IVD degeneration. An acellular, bioresorbable, and good manufacturing practice (GMP)-compliant in situ-forming gel, which corrects discectomy-associated IVD defects and prevents further IVD degeneration had been developed. However, this acellular matrix-based strategy has certain limitations, particularly in elderly patients, whose tissues have low self-repair ability. The aim of this study was to investigate the therapeutic efficacy of using a combination of newly-developed, ultra-purified, GMP-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs) and the gel for IVD regeneration after discectomy in a sheep model of severe IVD degeneration. METHODS: RECs and nucleus pulposus cells (NPCs) were co-cultured in the gel. In addition, RECs combined with the gel were implanted into IVDs following discectomy in sheep with degenerated IVDs. FINDINGS: Gene expression of NPC markers, growth factors, and extracellular matrix increased significantly in the co-culture compared to that in each mono-culture. The REC and gel combination enhanced IVD regeneration after discectomy (up to 24 weeks) in the severe IVD degeneration sheep model. INTERPRETATION: These findings demonstrate the translational potential of the combination of RECs with an in situ-forming gel for the treatment of herniations in degenerative human IVDs. FUNDING: Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.
• Radical resection for solitary thoracic spinous-process metastasis: a case report and technical note.

  Chikako Ishii, Akira Iwata, Katsuhisa Yamada, Tsutomu Endo, Takeru Tsujimoto, Hideki Sudo, Ai Shimizu, Norimasa Iwasaki, Masahiko Takahata

  Spinal cord series and cases 8 (1) 8 - 8 2022/01/17 

  INTRODUCTION: Bone metastases confined to the posterior elements of the spine are rarely treated, as there exist no established radical surgical treatment options for this area. Herein, we present a case report of and technical note on a patient who underwent radical resection for a metastatic tumor in the thoracic spinous process. CASE PRESENTATION: A 34-year-old male presented with a nasopharyngeal carcinoma with a solitary metastatic focus in the spinous process of the 10th thoracic vertebra. Imaging revealed that the tumor was confined to the spinous process and the surrounding soft tissues. No tumor was noted in the pedicles, vertebral body, and cortical bone on the ventral side of the lamina, as well as within the spinal canal. As treatment for this solitary metastatic lesion, we decided to perform radical resection with sufficient margins that would include the involved spinous process and all surrounding soft tissues exhibiting evidence of tumor infiltration. The posterior elements of the 9th-11th vertebrae, multifidus muscles, and skin were widely resected en bloc using a T-saw. The posterior elements of the spinal column were resected at the level of pedicles without full visualization of the involved dural sac. The tumor-infiltrated soft tissues surrounding the T10 vertebral spinous process were excised without full visualization of the tumor. Adjuvant therapy was not administered postoperatively. During the second year of follow-up, no signs of recurrence or metastasis were noted. DISCUSSION: Our proposed technique allows wide resection of a solitary focus of metastasis in the posterior elements of the spine.
• Cervical Myelopathy Caused by Non-Rheumatic Retro-Odontoid Pseudotumor: An Investigation of Underlying Mechanisms and Optimal Surgical Strategy.

  Masahiko Takahata, Ryota Hyakkan, Shigeki Oshima, Itaru Oda, Masahiro Kanayama, Takahiko Hyakumachi, Ryo Fujita, Tsutomu Endo, Tomomichi Kajino, Norimasa Iwasaki

  Global spine journal 13 (7) 21925682211069542 - 21925682211069542 2022/01/10 

  STUDY DESIGN: Retrospective case-control study. OBJECTIVE: This study aimed to identify the underlying pathologies of non-rheumatic retro-odontoid pseudotumors (NRPs), which would help establish an appropriate surgical strategy for myelopathy caused by NRP. METHODS: We identified 35 patients with myelopathy caused by NRP who underwent surgery between 2006 and 2017. An age- and sex-matched control group of 70 subjects was selected from patients with degenerative cervical myelopathy. Radiographic risk factors for NRP were compared between cases and controls. We also assessed surgical outcomes following occipital-cervical (O-C) fusion, atlantoaxial (C1-2) fusion, or C1 laminectomy. RESULTS: Patients with NRP had significantly lower C1 sagittal inner diameter, C2-7 range of motion (ROM), C2-7 Cobb angle, and C7 tilt, as well as significantly higher C1-2 ROM, atlantodental interval (ADI), and C1-2 to O-C7 ROM ratio. Multivariate regression analysis revealed that ADI, C2-7 ROM, and C7 tilt were independent risk factors for NRP. Neurological recovery and pseudotumor size reduction were comparable among surgical procedures, whereas post-operative cervical spine function was significantly lower in the O-C fusion group than in the other groups. CONCLUSION: Non-rheumatic retro-odontoid pseudotumor was associated with an increase in ADI, suggesting that spinal arthrodesis surgery is a reasonable strategy for NRP. C1-2 fusion is preferable over O-C fusion because of the high prevalence of ankylosis in the subaxial cervical spine. Given that 29% of patients with NRP have C1 hypoplasia, such cases can be treated by posterior decompression alone. Our study highlights the need to select appropriate surgical procedures based on the underlying pathology in each case.
• Simultaneous Bilateral Proximal Humerus Fractures Treated with Single-Stage Bilateral Reverse Shoulder Arthroplasty.

  Taiki Tokuhiro, Atsushi Urita, Yusuke Kameda, Makoto Motomiya, Naoya Watanabe, Norimasa Iwasaki

  Case reports in orthopedics 2022 2162331 - 2162331 2022 

  INTRODUCTION: Simultaneous bilateral fractures of the proximal humerus are infrequent, and simultaneous bilateral three- or four-part fractures are even rarer. Reverse shoulder arthroplasty (RSA) is being used increasingly for the treatment of three- and four-part fractures of the proximal humerus. However, treatment of simultaneous bilateral fractures of the proximal humerus is difficult because of concern about postoperative immobilization and rehabilitation. Case Presentation. A 75-year-old woman presented with bilateral shoulder pain subsequent to a fall on the street. Physical examination and radiographs showed simultaneous bilateral fractures of the proximal humerus. The right side fracture was classified as a four-part fracture and the left side fracture as a three-part fracture, according to Neer's classification. The right shoulder had a risk of avascular necrosis of the humeral head. For the left shoulder, the fracture type had caused ischemia of the humeral head. Single-stage bilateral RSA was performed 9 days after the injury. An abduction pillow was applied for 5 weeks postoperatively. Passive motion exercises were permitted starting at 4 weeks postoperatively, and active range of motion exercises were permitted at 6 weeks postoperatively. At the patient's most recent follow-up 30 months after surgery, the patient reported no restriction of the activities of daily living. Radiographs revealed no lucent line on the humerus and glenoid components, although bone resorption and superior retraction of the tuberosities on both sides were observed. CONCLUSIONS: Single-stage bilateral RSA improved shoulder function, but healing of the greater tuberosity can affect the improvement in external rotation after the operation. Although a long-term follow-up is needed, single-stage bilateral RSA appears to be a viable treatment option.
• Evaluation of biological responses to micro-particles derived from a double network hydrogel

  Gen Matsumae, Mohamad Alaa Terkawi, Takayuki Nonoyama, Takayuki Kurokawa, Daisuke Takahashi, Tomohiro Shimizu, Ken Kadoya, Jian Ping Gong, Kazunori Yasuda, Norimasa Iwasaki

  Biomaterials Science 10 (9) 2182 - 2187 2047-4830 2022 

  Double network hydrogels have been proven to be a substitute biomaterial for cartilage. For further applications as articular cartilages, it is essential to understand the biological reactions that might be initiated by their micro-particles.
• Rheumatoid Arthritis is a Risk Factor for Refracture in Patients with Fragility Fractures.

  Hotaka Ishizu, Hirokazu Shimizu, Tomohiro Shimizu, Taku Ebata, Yuki Ogawa, Masahiro Miyano, Kosuke Arita, Yusuke Ohashi, Norimasa Iwasaki

  Modern rheumatology 32 (6) 1017 - 1022 2021/12/03 

  OBJECTIVES: To determine whether patients with rheumatoid arthritis (RA) who have had fragility fractures are at an increased risk of refractures. METHODS: Patients with fragility fractures who were treated surgically at ten hospitals from 2008 to 2017 and who underwent follow-up for more than 24 months were either categorized into a group comprising patients with RA or a group comprising patients without RA (controls). The groups were matched 1:1 by propensity score matching. Accordingly, 240 matched participants were included in this study. The primary outcome was the refracture rate in patients with RA as compared to in the controls. Multivariable analyses were also conducted on patients with RA to evaluate the odds ratios (ORs) for the refracture rates. RESULTS: Patients with RA were significantly associated with increased rates of refractures during the first 24 months (OR: 2.714, 95% confidence interval [95% CI]: 1.015-7.255; P = 0.040). Multivariable analyses revealed a significant association between increased refracture rates and long-term RA (OR: 6.308, 95% CI: 1.195-33.292; P=0.030). CONCLUSIONS: Patients with RA who have experienced fragility fractures are at an increased risk of refractures. Long-term RA is a substantial risk factor for refractures.
• Surgical resection of primary tumor in the extremities improves survival for metastatic soft-tissue sarcoma patients: a population-based study of the SEER database.

  M Matsuoka, T Onodera, I Yokota, K Iwasaki, S Matsubara, R Hishimura, E Kondo, N Iwasaki

  Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 23 (12) 2474 - 2481 2021/12 

  PURPOSE: The objectives of this study were to clarify whether resection of primary tumor in the extremities for patients with metastatic soft-tissue sarcoma (STS) improves survival, and to clarify patient groups for whom primary tumor resection should be considered. METHODS/PATIENTS: Using the surveillance, epidemiology, and end results database, we identified 1453 patients with metastatic STS of the extremities at initial presentation between 1983 and 2016. Of these 1453 patients, 898 patients underwent primary tumor resection (Surgery group), and 555 patients did not (No-surgery group). RESULTS: After adjusting for patient background by propensity score matching, a total of 804 patients were included for analysis. Patients in the Surgery group showed improved survival (cancer-specific survival (CSS) hazard ratio (HR) = 0.59, 95% confidence interval (CI) 0.50-0.71 overall survival rate (OS) HR = 0.60, 95% CI 0.51-0.70). In subclass analysis, patients with high-grade STS, undifferentiated pleomorphic sarcoma, leiomyosarcoma, or synovial sarcoma showed improved survival in the Surgery group (high grade-CSS HR = 0.57, 95% CI 0.45-0.72, OS HR = 0.58, 95% CI 0.48-0.71; undifferentiated pleomorphic sarcoma-CSS HR = 0.60, 95% CI 0.42-0.84, OS HR = 0.61, 95% CI 0.46-0.82; leiomyosarcoma-CSS HR = 0.50, 95% CI 0.33-0.75, OS HR = 0.50, 95% CI 0.35-0.72; synovial sarcoma-CSS HR = 0.46, 95% CI 0.31-0.68, OS HR = 0.43, 95% CI 0.30-0.62). CONCLUSIONS: Our results indicated that primary tumor resection in metastatic STS exerts positive impacts on survival. Further clinical research is needed to confirm these results.
• Quantification of Cartilage Surface Degeneration by Curvature Analysis Using 3D Scanning in a Rabbit Model.

  Dawei Liang, Tomohiro Onodera, Masanari Hamasaki, Ryosuke Hishimura, Kentaro Homan, Liang Xu, Yuan Tian, Satoshi Kanai, Norimasa Iwasaki

  Cartilage 13 (2_suppl) 1734S-1741S  2021/12 

  OBJECTIVE: Accurate analysis to quantify cartilage morphology is critical for evaluating degenerative conditions in osteoarthritis (OA). Three-dimensional (3D) optical scanning provides 3D data for the entire cartilage surface; however, there is no consensus on how to quantify it. Our purpose was to validate a 3D method for evaluating spatiotemporal alterations in degenerative cartilages in a rabbit OA model by analyzing their curvatures at various stages of progression. DESIGN: Twelve rabbits underwent anterior cruciate ligament transection (ACLT) unilaterally and were divided into 4 groups: 4 weeks control, 4 weeks OA, 8 weeks control, and 8 weeks OA. 3D scanning, India ink staining, and histological assessments were performed in all groups. In 3D curvature visualization, the surfaces of the condyles were divided into 8 areas. The standard deviations (SD) of mean curvatures from all vertices of condylar surfaces and subareas were calculated. RESULTS: Regarding the site of OA change, curvature analysis was consistent with India ink scoring. The SD of mean curvature correlated strongly with the India ink Osteoarthritis Research Society International (OARSI) score. In curvature histograms, the curvature distribution in OA was more scattered than in control. Of the 8 areas, significant OA progression in the posterolateral part of the lateral condyle (L-PL) was observed at 4 weeks. The histology result was consistent with the 3D evaluation in terms of representative section. CONCLUSIONS: This study demonstrated that 3D scanning with curvature analysis can quantify the severity of cartilage degeneration objectively. Furthermore, the L-PL was found to be the initial area where OA degeneration occurred in the rabbit ACLT model.
• Cardiotrophin Like Cytokine Factor 1 (CLCF1) alleviates bone loss in osteoporosis mouse models by suppressing osteoclast differentiation through activating interferon signaling and repressing the nuclear factor-κB signaling pathway.

  Shunichi Yokota, Gen Matsumae, Tomohiro Shimizu, Tomoka Hasegawa, Taku Ebata, Daisuke Takahashi, Cai Heguo, Yuan Tian, Hend Alhasan, Masahiko Takahata, Ken Kadoya, Mohamad Alaa Terkawi, Norimasa Iwasaki

  Bone 153 116140 - 116140 2021/12 

  A growing body of evidence suggests that immune factors that regulate osteoclast differentiation and bone resorption might be promising therapeutic agents for the treatment of osteoporosis. The expression of CLCF1, an immune cell-derived molecule, has been reported to be reduced in patients with postmenopausal osteoporosis. This suggests that it may be involved in bone remodeling. Thus, we explored the functional role of CLCF1 in osteoclastogenesis and bone loss associated with osteoporosis. Surprisingly, the administration of recombinant CLCF1 repressed excessive bone loss in ovariectomized mice and prevented RANKL-induced bone loss in calvarial mouse model. Likewise, the addition of recombinant CLCF1 to RANKL-stimulated monocytes resulted in a significant suppression in the number of differentiated osteoclasts with small resorption areas being observed on dentine slices in vitro. At the same dosage, CLCF1 did not exhibit any detectable negative effects on the differentiation of osteoblasts. Mechanistically, the inhibition of osteoclast differentiation by the CLCF1 treatment appears to be related to the activation of interferon signaling (IFN) and the suppression of the NF-κB signaling pathway. Interestingly, the expression of the main components of IFN-signaling namely, STAT1 and IRF1, was detected in macrophages as early as 1 h after stimulation with CLCF1. Consistent with these results, the blockade of STAT1 in macrophages abolished the inhibitory effect of CLCF1 on osteoclast differentiation in vitro. These collective findings point to a novel immunoregulatory function of CLCF1 in bone remodeling and highlight it as a potentially useful therapeutic agent for the treatment of osteoporosis.
• Stress distribution pattern in the distal radioulnar joint before and after ulnar shortening osteotomy in patients with ulnar impaction syndrome

  Kazutoshi Hontani, Yuichiro Matsui, Daisuke Kawamura, Atsushi Urita, Daisuke Momma, Hiroki Hamano, Norimasa Iwasaki

  Scientific Reports 11 (1) 17891 - 17891 2021/12 

  Ulnar shortening osteotomy (USO) for ulnar impaction syndrome potentially leads to degenerative changes of the distal radioulnar joint (DRUJ). This study was performed to evaluate the effect of the sigmoid notch morphology on the stress distribution pattern of the DRUJ using computed tomography (CT) osteoabsorptiometry (CT-OAM). We reviewed the pre- and postoperative transverse CT images of 15 wrists that had undergone USO. The examined wrists were classified into two groups based on the sigmoid notch morphology: the linear-type notch (type L) and the curved-type notch (type C). We calculated and statistically compared the percentage of the high-density area (%HDA) in each divided region of the sigmoid notch. In type L, %HDA was significantly larger in the distal-dorsal region of the sigmoid notch before USO. Postoperatively, in type L, no specific regions showed a significantly different %HDA. In type C, %HDA was significantly larger in the distal-volar region of the sigmoid notch before USO. Postoperatively, %HDA of type C was significantly larger in the proximal-volar region. Our results suggest that in patients with ulnar impaction syndrome, morphological evaluation of the sigmoid notch can serve as a predictor of osteoarthritis in the DRUJ with or without USO.
• No patella resurfacing total knee arthroplasty leads to reduction in the thickness of patellar cartilage to less than half within 5 years: a quantitative longitudinal evaluation using MRI.

  Dai Sato, Masayuki Inoue, Takuro Sasaki, Jun Uchida, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki

  Journal of experimental orthopaedics 8 (1) 107 - 107 2021/11/24 

  PURPOSE: Patellar resurfacing in total knee arthroplasty (TKA) remains controversial as recent meta-analyses have not shown its clear superiority; however, most authors recommend it because it is associated with less frequent anterior knee pain and need for reoperation. We aimed to clarify the changes in patellar cartilage thickness in no patellar resurfacing TKA using a ceramic femoral component on magnetic resonance imaging (MRI). METHODS: Between 2009 and 2014, 40 consecutive patients (59 knees) were included in this study. All patients underwent TKA using zirconia ceramic femoral implants without patellar resurfacing. Indications for no patellar resurfacing TKA were absence of anterior knee pain, patellar compression pain, and osteoarthritic changes in the patellofemoral joint on plain radiography. The mean postoperative follow-up duration was 81.5 months (range, 25-131 months). Clinical and radiological evaluations were performed preoperatively and 5 years after TKA. Patellar cartilage thickness was evaluated preoperatively and every year for 5 years after TKA using MRI T2-weighted imaging. The patellar cartilage was divided into three regions of interest: medial, central, and lateral. To standardise the variation in patellar thickness among patients, the percent cartilage thickness was calculated. RESULTS: The implant's position was appropriate in all cases. Compared to preoperative scores, 5 years postoperatively, the Japanese Orthopedic Association score and Oxford knee score significantly improved from 52.1 to 84.7; mean tilting angle and congruence angle did not change significantly; mean lateral shift ratio significantly increased from 7.1% to 14.6%; cartilage thickness significantly decreased (P < 0.05); and the percentage cartilage thickness of the central, medial, and lateral cartilage zones gradually thinned to less than half. Four patients underwent conversion to patellar resurfacing due to anterior knee pain, without loosening the femoral and tibial implants. CONCLUSION: The patellar cartilage thickness decreased to less than half its preoperative level within 5 years after no patellar resurfacing TKA; this would led to clinical problems and conversion to patellar resurfacing. LEVEL OF EVIDENCE: Level III.
• Computed tomography revealed the correlation between radiolucency and alignment of all-polyethylene pegged glenoid component more than 10 years after total shoulder arthroplasty in the Japanese population.

  Yuki Matsui, Daisuke Momma, Naoki Suenaga, Atsushi Urita, Chika Yoshioka, Naomi Oizumi, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 28 (1) 131 - 137 2021/11/24 

  BACKGROUND: Anatomical total shoulder arthroplasty (TSA) provides successful long-term outcomes but complications can occur after 10 years that require revision. Computed tomography (CT) is a useful tool for assessing radiolucent lines around the glenoid component of TSA; however, the merits of long-term post-TSA follow up with CT are unclear. The purpose of this study was to evaluate the long-term outcomes after TSA of Japanese population and to identify factors related to radiolucency around the glenoid component using CT. METHODS: A retrospective review was conducted of TSA patients who had completed at least 10 years of clinical follow up. Radiographs and CT images of the affected shoulder obtained at the last follow up were evaluated for radiolucent lines around the stem and each peg, superior inclination and retroversion of the glenoid component, subluxation index, and critical shoulder angle (CSA). Shoulder ROM, Constant-Murley score and UCLA score were compared between the preoperative and last follow up period. RESULTS: Eighteen shoulders in 16 patients met the inclusion criteria. Mean patient age was 61 years, mean follow up period was 137 months, and mean Yian CT score was 19%. CT score was significantly highest in pegs located inferiorly (p < 0.05). Mean glenoid superior inclination was 12.6°, retroversion was -0.3°, subluxation index was 46%, and CSA was 33.7°. Glenoid superior inclination was significantly lower (p = 0.007) in shoulders with possible loosening than in cases with no loosening (5.0° vs 15.6°). Mean Constant score and UCLA score improved significantly after TSA, from 25.8 to 10.7 points preoperatively to 70.1 and 28.9 points postoperatively, respectively. Mean shoulder flexion, internal rotation, and external rotation also showed improvement postoperatively. CONCLUSION: TSA provides good long-term outcomes. Radiolucency was present most frequently around the inferior pegs of the glenoid component. Glenoid superior inclination may affect the formation of radiolucent lines around glenoid pegs. LEVEL OF EVIDENCE: Level IV; Case Series; Treatment study.
• ハイブリット人工知能システムを用いた寛骨臼形成不全の自動解析システムの開発

  清水 寛和, 清水 智弘, 高橋 大介, 小川 拓也, 岩崎 倫政

  日本小児整形外科学会雑誌 (一社)日本小児整形外科学会 30 (3) S56 - S56 0917-6950 2021/11
• 当院における発育性股関節形成不全に対するAngulated Innominate Osteotomy(AIO)の経時的変化の検討

  高橋 練也, 高橋 大介, 清水 智弘, 小川 拓也, 中村 夢志郎, 宮崎 拓自, 岩崎 倫政, 亀ヶ谷 真琴

  日本小児整形外科学会雑誌 (一社)日本小児整形外科学会 30 (3) S70 - S70 0917-6950 2021/11
• 乳児股関節脱臼ハイリスク児における超音波とX線を用いた経時的な画像評価

  大橋 佑介, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本小児整形外科学会雑誌 (一社)日本小児整形外科学会 30 (3) S82 - S82 0917-6950 2021/11
• 発育性股関節形成不全に対するAngulated Innominate Osteotomy(AIO)の3次元的評価

  小川 拓也, 清水 智弘, 宮崎 拓自, 中村 夢志郎, 高橋 大介, 岩崎 倫政

  日本小児整形外科学会雑誌 (一社)日本小児整形外科学会 30 (3) S85 - S85 0917-6950 2021/11
• 全身MRIを用いた特発性大腿骨頭壊死症患者の多発骨壊死の評価

  横田 隼一, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 浅野 毅, 高橋 大介, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 40 (3) 214 - 214 1883-2873 2021/11
• Modular型S-ROMステム、またはPolishedセメントステム用いた短縮骨切り併用THAの中期成績の比較検討

  宮崎 拓自, 清水 智弘, 中村 夢志郎, 高橋 要, 大浦 久典, 片山 直行, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 40 (3) 264 - 264 1883-2873 2021/11
• 偏心性寛骨臼回転骨切り術における応力分布の縦断的評価

  中村 夢志郎, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 40 (3) 266 - 266 1883-2873 2021/11
• 関節リウマチ患者の2010年以降の下肢手術数の動向と併存症発生に関する調査

  糸賀 稜, 清水 智弘, 高橋 大介, 小野寺 智洋, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 40 (3) 285 - 285 1883-2873 2021/11
• 脆弱性骨折をきたした関節リウマチ患者の再骨折リスク

  石津 帆高, 清水 寛和, 清水 智弘, 横田 隼一, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 40 (3) 287 - 287 1883-2873 2021/11
• 高齢者に対するPolished Taperセメントステムを用いた人工股関節全置換術の成績

  山崎 秀, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 40 (3) 300 - 300 1883-2873 2021/11
• Serum C-reactive protein is an early, simple and inexpensive prognostic marker for the progression of intramedullary lesion on magnetic resonance imaging from acute to subacute stage in patients with spinal cord injury.

  Masahiro Ozaki, Kota Suda, Tsunehiko Konomi, Satoko Matsumoto Harmon, Miki Komatsu, Akio Minami, Morio Matsumoto, Masaya Nakamura, Masahiko Takahata, Norimasa Iwasaki

  Spinal cord 59 (11) 1155 - 1161 2021/11 

  STUDY DESIGN: Retrospective chart audit. OBJECTIVES: This study aimed to identify conventional routine blood testing biomarkers associated with the progression of intramedullary injured area in patients with spinal cord injury (SCI). SETTING: A spinal cord injury center in Hokkaido, Japan. METHODS: We retrospectively reviewed 71 consecutive adults with acute SCI who were admitted within 24 h after injury and diagnosed as American Spinal Injury Association Impairment Scale Grade A or B at admission. Participants were divided into the progression (P group) and no progression group (NP group) based on the change of the hyperintense signal abnormality in the spinal cord on magnetic resonance imaging from the time of admission to 4 weeks after injury. Individual characteristics and blood testing data obtained in the first 4 weeks after injury were compared between groups. RESULTS: The P and NP groups were comprised of 16 and 55 participants, respectively. In univariate analyses, white blood cell (WBC) count on day 3 was significantly higher in group P than group NP (P = 0.021), as was serum C-reactive protein (CRP) level on day 3 (P = 0.015) and day 7 (P = 0.047). Multivariable analysis identified serum CRP level on day 3 as a significant independent prognostic factor for the progression of secondary SCI (OR, 1.138; 95% confidence interval, 1.01-1.28; P = 0.034). CONCLUSIONS: Serum CRP level on day 3 after injury was a good predictor for the progression of intramedullary signal intensity change on MRI from acute to subacute stage in patients with SCI.
• Brain Metastasis in Soft Tissue Sarcoma at Initial Presentation.

  Ryo Itoga, Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Shinji Matsubara, Ryosuke Hishimura, Yuki Suzuki, Akira Iwata, Eiji Kondo, Norimasa Iwasaki

  Anticancer research 41 (11) 5611 - 5616 2021/11 

  BACKGROUND/AIM: Brain metastasis is a rare condition among patients with soft tissue sarcoma (STS), and its precise incidence remains unclear. The aim of this study was to investigate which patients should be screened for brain metastasis. PATIENTS AND METHODS: We identified all patients with STS diagnosed between 2010 and 2015 in the SEER database. Incidence of brain metastasis at initial presentation and higher incidence of brain metastasis by histological subtype were investigated. In addition, risk factors for brain metastasis were examined. RESULTS: A total of 26,676 patients were included for analysis, of whom 162 patients (0.6%) had brain metastasis. Alveolar soft part sarcoma (6.3%), malignant hemangioendothelioma (3.1%) and malignant schwannoma (2.6%) showed higher incidence of brain metastasis. Deep-rooted tumor, trunk tumor, and histological high-grade tumor tended to show higher incidence of brain metastasis. CONCLUSION: Risk factors for brain metastasis were deep location, trunk development and histologically high-grade tumor, or specific histological subtypes.
• Hydroxyapatite‐hybridized double‐network hydrogel surface enhances differentiation of bone marrow‐derived mesenchymal stem cells to osteogenic cells

  Takuma Kaibara, Lei Wang, Masumi Tsuda, Takayuki Nonoyama, Takayuki Kurokawa, Norimasa Iwasaki, Jian Ping Gong, Shinya Tanaka, Kazunori Yasuda

  Journal of Biomedical Materials Research Part A 110 (4) 747 - 760 1549-3296 2021/10/28 

  Recently, we have developed a hydroxyapatite (HAp)-hybridized double-network (DN) hydrogel (HAp/DN gel), which can robustly bond to the bone tissue in the living body. The purpose of this study is to clarify whether the HAp/DN gel surface can differentiate the bone marrow-derived mesenchymal stem cells (MSCs) to osteogenic cells. We used the MSCs which were harvested from the rabbit bone marrow and cultured on the polystyrene (PS) dish using the autogenous serum-supplemented medium. First, we confirmed the properties of MSCs by evaluating colony forming unit capacity, expression of MSC markers using flow cytometry, and multidifferential capacity. Secondly, polymerase chain reaction analysis demonstrated that the HAp/DN gel surface significantly enhanced mRNA expression of the eight osteogenic markers (TGF-β1, BMP-2, Runx2, Col-1, ALP, OPN, BSP, and OCN) in the cultured MSCs at 7 days than the PS surfaces (p < 0.0001), while the DN gel and HAp surfaces provided no or only a slight effect on the expression of these markers except for Runx2. Additionally, the alkaline phosphatase activity was significantly higher in the cells cultured on the HAp/DN gel surface than in the other three material surfaces (p < 0.0001). Thirdly, when the HAp/DN gel plug was implanted into the rabbit bone marrow, MSC marker-positive cells were recruited in the tissue generated around the plug at 3 days, and Runx2 and OCN were highly expressed in these cells. In conclusion, this study demonstrated that the HAp/DN gel surface can differentiate the MSCs into osteogenic cells.
• Glenohumeral joint preservation using continuous intramedullary perfusion of high-concentration antibiotics in a patient with septic shoulder arthritis and proximal humerus osteomyelitis: A case report.

  Mitsutoshi Ota, Atsushi Urita, Hiroki Shibayama, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 28 (6) 1548 - 1551 2021/10/26
• Aggravation of Ossified Ligamentum Flavum Lesion Is Associated With the Degree of Obesity.

  Tsutomu Endo, Yoshinao Koike, Yuichiro Hisada, Ryo Fujita, Ryota Suzuki, Masaru Tanaka, Takeru Tsujimoto, Yukitoshi Shimamura, Yuichi Hasegawa, Masahiro Kanayama, Katsuhisa Yamada, Akira Iwata, Hideki Sudo, Misaki Ishii, Norimasa Iwasaki, Masahiko Takahata

  Global spine journal 13 (5) 21925682211031514 - 21925682211031514 2021/10/06 

  STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVES: There is insufficient data on the clinical features of ossification of the ligamentum flavum (OLF) of the thoracic spine and the risk of progression of ossified lesions. The link between obesity and ossification of the posterior longitudinal ligament (OPLL), which frequently coexists with OLF, has been demonstrated. However, the link between obesity and OLF has not been recognized. We aimed to determine the prevalence of obesity in thoracic OLF and whether the severity of OLF is associated with the degree of obesity. METHODS: A total of 204 symptomatic Japanese subjects with thoracic OLF and 136 subjects without spinal ligament ossification as controls were included. OLF subjects were divided into 3 groups: 1) localized OLF (OLF <2-intervertebral regions); 2) multilevel OLF (OLF ≥3-intervertebral regions); and 3) OLF + OPLL. The severity of OLF was quantified using the OLF index using computed tomography imaging of the entire spine. RESULTS: The proportion of severely obese subjects (BMI ≥ 30 kg/m2) was significantly higher both in the multilevel OLF group (25.5%) and the OLF + OPLL group (44.3%) than in the localized OLF group (3.6%) and the control group (1.4%) (P < 0.01). BMI, age, and coexistence of cervical OPLL and lumbar OLF were associated with thoracic OLF index in the multiple regression analysis. CONCLUSIONS: Our findings demonstrated that obesity is a distinct feature of multilevel OLF in the thoracic spine and that the severity of OLF is associated with the degree of obesity.
• Extrusion of the medial meniscus is a potential predisposing factor for post-arthroscopy osteonecrosis of the knee.

  Jun Yamaguchi, Kazunori Yasuda, Eiji Kondo, Takuma Kaibara, Daisuke Ueda, Koji Yabuuchi, Jun Onodera, Norimasa Iwasaki, Mitsuru Saito, Tomonori Yagi

  BMC musculoskeletal disorders 22 (1) 852 - 852 2021/10/05 

  BACKGROUND: Post-arthroscopic osteonecrosis of the knee (PAONK) is a rare condition. No studies have analyzed the relationship between the meniscus extrusion and PAONK. The purpose of this retrospective study is to test a hypothesis that the degree of the medial meniscus (MM) extrusion might be significantly greater in the knees with PAONK than in the matched control knees both before and after the meniscectomy. METHODS: Ten knees with PAONK were detected out of a total of 876 knees which had undergone arthroscopic partial meniscectomy of the MM. Ten matched control knees were randomly selected out of the remaining 866 knees without PAONK. The clinical data of these 20 patients were retrospectively collected from the medical records. To evaluate the location of the menisci on the joint line, Extrusion width and Inner width were defined on a coronal section of magnetic resonance imaging (MRI). The intra- and inter-rater reliability was evaluated by calculating the intra- and inter-class coefficients. Statistical comparisons between the 2 groups were made using the 3 non-parametric tests. RESULTS: Before the meniscectomy, the Extrusion width of the MM (mean 4.7 ± 1.4 mm) was significantly greater than that (3.0 ± 1.3 mm) in the Control group (P = 0.0195). In the MRI taken in a range from 3 to 50 weeks after the meniscectomy, the Extrusion width of the MM (5.9 ± 1.1 mm) in the PAONK group was significantly greater than that (3.4 ± 1.4 mm) in the Control group (P = 0.0009), and the Inner width of the MM (0.6 ± 1.7 mm) in the PAONK group was significantly less than that (3.9 ± 1.0 mm) in the Control group (P = 0.0001). CONCLUSION: A significant relationship was found between the degree of the MM extrusion and the onset of PAONK. This study suggested that the extrusion of the MM is a potential predisposing factor for PAONK.
• Changes in elbow joint contact area in symptomatic valgus instability of the elbow in baseball players.

  Kyosuke Numaguchi, Daisuke Momma, Yuki Matsui, Jun Oohinata, Takayoshi Yamaguchi, Nozomu Inoue, Eiji Kondo, Norimasa Iwasaki

  Scientific reports 11 (1) 19782 - 19782 2021/10/05 

  The aim of this study was to evaluate the joint contact area of the dominant side and that of the non-dominant side without valgus instability in symptomatic pitchers. Ten symptomatic elbow medial ulnar collateral ligament (UCL) deficient baseball pitchers participated in this study. Computed tomography (CT) data from the dominant and non-dominant elbows were obtained with and without elbow valgus stress. The CT imaging data of each elbow joint were reconstructed using a 3D reconstruction software package, and the radiocapitellar and ulnohumeral joint contact areas were calculated. The center of the contact area and the translation from the position without stress to the position with valgus stress were also calculated. With elbow valgus stress, the contact area changed, and the center of the radiocapitellar joint contact area translated significantly more laterally in the dominant elbow than in the non-dominant elbow (p = 0.0361). In addition, the center of the ulnohumeral joint contact area translated significantly more posteriorly in the dominant elbow than in the non-dominant elbow (p = 0.0413). These changes in contact areas could be the reason for cartilage injury at the posterior trochlea in pitchers with UCL deficiency.
• 関節リウマチにおける軟骨細胞の新たな役割 IL-6アンプとTMEM147

  太田 光俊, 田中 勇希, 岩崎 倫政, 村上 正晃

  リウマチ科 (有)科学評論社 66 (4) 393 - 403 0915-227X 2021/10
• Blood flow distribution after end-to-side anastomosis with wide arteriotomy in extremity free flap surgery.

  Makoto Motomiya, Naoya Watanabe, Shunichi Nakamura, Yusuke Kameda, Daisuke Kawamura, Norimasa Iwasaki

  Journal of plastic, reconstructive & aesthetic surgery : JPRAS 74 (10) 2495 - 2503 2021/10 

  PURPOSE: Although many studies have investigated the optimal anastomotic procedure for the end-to-side (ETS) procedure with a free flap, no study has focused on the size of the arteriotomy. Some surgeons have recently described the effectiveness of ETS with wide arteriotomy, but the postoperative haemodynamics remains unclear for free flaps created using this technique. The aim of this study was to use ultrasonography to evaluate the postoperative blood flow distribution after ETS with a wide arteriotomy in extremity free flap surgery. METHODS: We evaluated 20 free flaps in 18 consecutive patients who received an ultrasonographic examination after free flap surgery using the ETS technique with wide arteriotomy for arterial anastomosis. All flaps were examined after surgery and blood flow was calculated for the flap and recipient vessels. RESULTS: All 20 flaps survived, but one flap developed asymptomatic arterial thrombosis and 19 flaps were analysed. For the ETS technique with wide arteriotomy, peripheral circulation was well preserved in all flaps. Comparison of flap types showed that blood flow was significantly higher in myocutaneous flaps than in fasciocutaneous flaps, but there was no significant difference according to the size of the arteriotomy. CONCLUSIONS: Given the range of arteriotomy performed using the ETS with a wide arteriotomy technique, the blood flow volume in the flap depended on the type of flap but not on the size of the arteriotomy. A steal phenomenon related to the creation of a wide window in the receipt artery was not found in the analysed retrospective cohort.
• Stress on the posteromedial region of the proximal tibia increased over time after anterior cruciate ligament injury.

  Soya Miura, Koji Iwasaki, Eiji Kondo, Kaori Endo, Shinji Matsubara, Masatake Matsuoka, Tomohiro Onodera, Norimasa Iwasaki

  Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 30 (5) 1744 - 1751 2021/09/10 

  PURPOSE: Anterior cruciate ligament (ACL) injury induces anterior and rotatory instability of the knee. However, the effect of this instability on the stress distribution in the knee joint in living participants is not clear. The aim of this study was to compare the distribution pattern of subchondral bone density across the proximal tibia in the knees with and without ACL injury, and to investigate the correlation between the distribution patterns of the subchondral bone density and the duration of ACL-deficiency. METHODS: Radiographic and computed tomography (CT) data pertaining to 20 patients with unilateral ACL injury without combined injury (ACL-deficient group) and 19 nontraumatic subjects (control group) were collected retrospectively. Subchondral bone density of the proximal tibia was assessed using CT-osteoabsorptiometry. Both the medial and lateral compartments of the proximal tibia were divided into three subregions of equal width in the sagittal direction. The percentage of high subchondral bone density areas (HDA%) in each subregion was quantitatively analyzed. RESULTS: HDA% of the posteromedial region was significantly higher in the ACL-deficient group (mean: 21.6%) than in the control group (14.7%) (p = 0.002). In contrast, HDA% of the anteromedial region was significantly lower in the ACL-deficient group (9.4%) than in the control group (15.3%) (p = 0.048). The logarithm of the time elapsed from ACL injury to CT examination showed a significant correlation with HDA% in the posteromedial region (p = 0.032). CONCLUSIONS: Subchondral bone density in the posteromedial region significantly increased after ACL injury and correlated with the duration of ACL-deficiency in semi-log manner in meniscus intact knees. The increase in stress on the posteromedial region after ACL injury, which induces a change in the subchondral bone density, justifies early ACL reconstruction after ACL injury.
• Thrombocytopenia Associated with Unrecognized Non-Alcoholic Fatty Liver Disease Is an Independent Predictor of Perioperative Significant Blood Loss in Cervical Laminoplasty.

  Ryota Suzuki, Yoshinao Koike, Masahiro Ota, Tsutomu Endo, Yuichiro Hisada, Takeru Tsujimoto, Masahiro Kanayama, Yoichi M Ito, Hideki Sudo, Akira Iwata, Katsuhisa Yamada, Norimasa Iwasaki, Masahiko Takahata

  World neurosurgery 155 e797-e804  2021/09/09 

  OBJECTIVE: To identify risk factors for significant blood loss (SBL) in cervical laminoplasty, especially regarding thrombocytopenia and coagulopathy resulting from non-alcoholic fatty liver disease (NAFLD). METHODS: We retrospectively investigated differences in patient background data, laboratory data at the time of admission, and surgery-related data of 317 patients who underwent cervical laminoplasty and were divided into SBL (estimated blood loss [EBL] + drainage [D] ≥500 g) and non-SBL (EBL + D < 500 g) groups. To evaluate liver status, we used the fibrous 4 index and considered fibrous 4 index ≥1.85 as a representative phenotype for NAFLD with liver fibrosis. In addition, the risk factor for perioperative SBL was investigated using multiple logistic regression analysis, and the cutoff value was calculated. RESULTS: Incidence of perioperative SBL in cervical laminoplasty was 7.3% (23/317). Compared with the non-SBL group, the SBL group demonstrated significantly lower platelet count (PLT), lower aspartate aminotransferase, longer operation time, and greater number of opened laminae. According to multivariate analysis, lower PLT and a greater number of opened laminae were identified as significant risk factors for perioperative SBL. The cutoff value of PLT for predicting SBL was determined to be 16.7 × 104/μL using a receiver operating characteristic curve. The liver fibrosis group revealed significantly lower PLT and greater EBL + D than the non-liver fibrosis group. CONCLUSIONS: Thrombocytopenia is an independent predictor of perioperative SBL in cervical laminoplasty. Thus, patients with mild thrombocytopenia that may be associated with NAFLD must be carefully monitored to avoid perioperative SBL.
• Short-term efficacy and safety of zoledronate acid or denosumab in Japanese patients with postmenopausal osteoporosis.

  Yumejiro Nakamura, Tomohiro Shimizu, Tsuyoshi Asano, Shun Shimodan, Hotaka Ishizu, Daisuke Takahashi, Masahiko Takahata, Norimasa Iwasaki

  Journal of bone and mineral metabolism 39 (5) 824 - 832 2021/09 

  INTRODUCTION: We aimed to compare the efficacy after switching from either bisphosphonates (BPs) or non-BPs (NBPs) to combination therapies of denosumab (DMAb) or zoledronic acid (Zol) with eldecalcitol (ELD) in bone mineral density (BMD) and bone metabolism and investigate the prognostic and risk factors of side effects of this therapy. MATERIALS AND METHODS: One-hundred forty-eight patients with postmenopausal osteoporosis were recruited; their therapy was switched from BPs or NBPs to Zol or DMAb plus ELD (BP-Zol: 43, NBP-Zol: 32, BP-DMAb: 35, and NBP-DMAb: 38). Longitudinal changes in bone metabolic markers (P1NP and TRACP-5b) and BMD were evaluated. RESULTS: In the BP-Zol group, P1NP did not change after 6 months and increased by 38.9% after 12 months. TRACP-5b decreased 15.8% after 6 months, but came back to baseline values 12 months after administration. In the rest of the groups, the bone metabolic markers remained suppressed after 6 and 12 months. Compared with baseline, all groups showed increase in BMD after 6 and 12 months. Bone metabolic markers at baseline were correlated with %change in lumbar spine BMD from baseline to 12 months. P1NP and 25-hydroxy vitamin D levels at baseline were identified as potential predictors of development of acute-phase reactions. CONCLUSIONS: The combination therapy of Zol or DMAb and ELD may increase BMD at 12 months after the first administration in Japanese patients with postmenopausal osteoporosis, regardless of BPs pretreatment. Bone metabolic markers at baseline may be useful predictors for reaction to the therapy and side effects caused by these combination therapies in postmenopausal osteoporosis.
• Effects after starting or switching from bisphosphonate to romosozumab or denosumab in Japanese postmenopausal patients.

  Tomohiro Shimizu, Kosuke Arita, Eihiro Murota, Shigeto Hiratsuka, Ryo Fujita, Hotaka Ishizu, Tsuyoshi Asano, Daisuke Takahashi, Masahiko Takahata, Norimasa Iwasaki

  Journal of bone and mineral metabolism 39 (5) 868 - 875 2021/09 

  PURPOSE: We aimed to investigate the longitudinal changes in bone metabolic markers and bone mineral density (BMD) after starting or switching from bisphosphonate (BP) to romosozumab (ROMO) or denosumab (DENO) therapies over 12 months and to determine predictors that establish associations with changes in BMD among the patients received the ROMO therapy. METHODS: Postmenopausal osteoporosis patients with a high risk of fracture-154 in total-were recruited; their therapies were switched to ROMO or DENO from BP/naïve or vitamin D (ND) (ND-ROMO: 43, BP-ROMO: 38, ND-DENO: 38, and BP-DENO: 35). Longitudinal changes in bone metabolic markers and BMD were evaluated. RESULTS: ROMO groups showed significant increases in BMD of the lumbar spine at 6 and 12 months and femoral neck at 12 months compared to the DENO groups. Although BP-ROMO showed significant increase in the lumbar spine BMD compared to BP-DENO, there were no significant differences in femoral neck and total hip BMDs between BP-ROMO and BP-DENO. Among the ROMO groups, % changes of BMD from baseline to 12 months were associated with bone metabolic markers at baseline and changes in TRACP-5b from baseline to 3 months. CONCLUSIONS: ROMO continuously increased BMD for 12 months and performed better than DENO. On the other hand, effects of ROMO switched from BP on BMD of femoral neck and total hip were almost same with DENO. Bone metabolic markers at baseline and changes in TRACP-5b from baseline to 3 months may predict the efficacy of ROMO after 12 months of administration.
• Risks vs. benefits of switching therapy in patients with postmenopausal osteoporosis.

  Hotaka Ishizu, Kosuke Arita, Mohamad Alaa Terkawi, Tomohiro Shimizu, Norimasa Iwasaki

  Expert review of endocrinology & metabolism 16 (5) 217 - 228 2021/09 

  Introduction: Osteoporosis is characterized by the fragility of bones, leading to fractures and, consequently, the deterioration of functional capacity and quality of life. Postmenopausal women, in particular, are prone to osteoporosis and often require anti-osteoporosis treatment. In the last few decades, various anti-osteoporosis drugs have been approved for clinical use. In an aging society, osteoporosis cannot be treated using a single agent; therefore, switching therapy is an important treatment strategy.Areas covered: This review covers switching therapy in patients with postmenopausal osteoporosis. It's extremely important to understand the characteristics of each drug including; limitations on the duration of use, side effects due to long-term use (such as atypical femur fracture and osteonecrosis of the jaw) or discontinuation (such as rebound phenomenon), compliance, and ability to prevent fractures. We review and summarize the risks and benefits of switching therapy.Expert opinion: When switching therapy, the order of drug administration is important. Routine monitoring should be continued after switching treatments. We recommend first using osteoanabolic agents in postmenopausal women with severe osteoporosis. In addition, identifying predictors of the efficacy and side effects of treatment may help prevent the inappropriate use of drugs for the treatment of osteoporosis.
• Targeting thymidine phosphorylase as a potential therapy for bone loss associated with periprosthetic osteolysis.

  Gen Matsumae, Tomohiro Shimizu, Yuan Tian, Daisuke Takahashi, Taku Ebata, Hend Alhasan, Shunichi Yokota, Ken Kadoya, Mohamad Alaa Terkawi, Norimasa Iwasaki

  Bioengineering & translational medicine 6 (3) e10232  2021/09 

  Macrophages are generally thought to play a key role in the pathogenesis of aseptic loosening through initiating periprosthetic inflammation and pathological bone resorption. The aim of this study was to identify macrophage-derived factors that promote osteoclast differentiation and periprosthetic bone destruction. To achieve this, we examined the effects of 12 macrophage-derived factors that were identified by RNA-seq analysis of stimulated macrophages on osteoclast differentiation. Surprisingly, thymidine phosphorylase (TYMP) was found to trigger significant number of osteoclasts that exhibited resorbing activities on dentine slices. Functionally, TYMP knockdown reduced the number of osteoclasts in macrophages that had been stimulated with polyethylene debris. TYMP were detected in serum and synovial tissues of patients that had been diagnosed with aseptic loosening. Moreover, the administration of TYMP onto calvariae of mice induced pathological bone resorption that was accompanied by an excessive infiltration of inflammatory cells and osteoclasts. The RNA-seq for TYMP-induced-osteoclasts was then performed in an effort to understand action mode of TYMP. TYMP stimulation appeared to activate the tyrosine kinase FYN signaling associated with osteoclast formation. Oral administration of saracatinib, a FYN kinase inhibitor, significantly suppressed formation of bone osteolytic lesions in a polyethylene debris-induced osteolysis model. Our findings highlight a novel molecular target for therapeutic intervention in periprosthetic osteolysis.
• Close association between non-alcoholic fatty liver disease and ossification of the posterior longitudinal ligament of the spine.

  Tsutomu Endo, Yoshinao Koike, Hideaki Miyoshi, Yuichiro Hisada, Ryo Fujita, Ryota Suzuki, Masaru Tanaka, Takeru Tsujimoto, Yukitoshi Shimamura, Yuichi Hasegawa, Masahiro Kanayama, Tomoyuki Hashimoto, Fumihiro Oha, Naoki Noro, Kiyofumi Komano, Misaki Ishii, Yoichi M Ito, Norimasa Iwasaki, Masahiko Takahata

  Scientific reports 11 (1) 17412 - 17412 2021/08/31 

  Ossification of the posterior longitudinal ligament (OPLL) of the spine is a disease of unknown etiology occurring frequently in individuals with metabolic disturbances. Obesity has been suggested as a potential risk factor for the severity of OPLL. We aimed to investigate whether non-alcoholic fatty liver disease (NAFLD) is associated with OPLL severity. We assessed the severity of NAFLD by a liver-to-spleen (L/S) ratio on computed tomography (CT) scans of 85 symptomatic OPLL patients at a single institution in Japan. We also assessed the severity of OPLL by CT reconstruction sagittal and axial images. The prevalence of NAFLD in middle-aged patients (age < 70 years, n = 50) was 80.3%, which was 2.5-8 times higher than that in the general Japanese population (9-30%). The ossification index of the spinal ligaments increased in proportion to the severity of fatty liver. The L/S ratio was revealed as a significant risk factor associated with the total ossification index (standardized β: -0.40, 95% confidence interval - 54.34 to - 4.22). This study suggests the potential contribution of NAFLD to the progression of OPLL. The close association between NAFLD and OPLL demonstrated in this study warrants further study to elucidate the causal nature of this relationship.
• Functional reconstructions using only ulnar nerve and ulnar nerve-innervated muscles for traumatic musculocutaneous, median and radial nerve palsies.

  Makoto Motomiya, Naoya Watanabe, Daisuke Kawamura, Norimasa Iwasaki

  BMJ case reports 14 (8) 2021/08/20 

  A 20-year-old right-handed fisherman experienced a severe injury in a high-energy traffic accident. These injuries included a shaft fracture of the right humerus, open comminuted fracture of the right forearm and multiple peripheral nerve palsies involving the musculocutaneous, median and radial nerves. Six months after the initial treatment, the patient was referred to our hand surgeons for further treatment. Several operations for functional reconstruction using only the ulnar nerve and ulnar nerve-innervated muscles were performed: the main procedures included a partial ulnar nerve transfer for elbow flexion, flexor carpi ulnaris transfer for reconstruction of wrist and finger extension and opponensplasty using the abductor digiti minimi. Three years after the initial injury, the patient had relatively good function including elbow flexion and stable side pinch and grasp. Functional reconstruction using a combination of the ulnar nerve and ulnar nerve-innervated muscles may be useful in specific cases involving multiple peripheral nerve injuries.
• Medial closed-wedge distal femoral osteotomy with local bone grafts for large collapsed steroid-induced osteonecrosis of the lateral femoral condyle: A case report.

  Takuma Kaibara, Eiji Kondo, Masatake Matsuoka, Koji Iwasaki, Tomohiro Onodera, Daisuke Momma, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 28 (6) 1470 - 1477 2021/08/04
• Radiological predictors associated with success of treatment for developmental dysplasia of hip using the Pavlik harness: A retrospective study.

  Takuya Ogawa, Tomohiro Shimizu, Tsuyoshi Asano, Norimasa Iwasaki, Daisuke Takahashi

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 27 (5) 1067 - 1072 2021/08/04 

  BACKGROUND: While various predictors of treatment outcome of Pavlik harness have been reported, appropriate indications for treatment and relationships between patient characteristics and outcome are unclear. The present study aimed to identify radiological predictors for successful Pavlik harness treatment of DDH at the initiation of treatment and investigate the progression of radiological characteristics after successful treatment. METHODS: One-hundred-forty-two of 527 infants who visited our hospital for secondary screening of DDH were treated with the Pavlik harness. One-hundred-eight hips of 108 infants experienced successful treatment and could be followed up until 3 years of age (group S); treatment was unsuccessful within the first 2 weeks for 22 hips of 21 infants (group F). We investigated the Graf classification and radiological parameters. RESULTS: We observed the ipsilateral-side measurements of distance A and B as defined by Yamamuro and Chene's method to be significantly smaller and greater, respectively, in group F compared with those of group S. Group F tended to exhibit the smaller distance A and larger distance B compared to the group S among the same Graf type. The cut-off values for successful treatment at were >7.4 mm at initiation of treatment for distance A and <11.2 mm for distance B. The acetabular index (AI) of the ipsilateral side at the initiation of treatment was significantly correlated with that at 1 and 3 years of age. Patients with an AI of >32° at the initiation of harness treatment were more likely to exhibit hip dysplasia at 3 years of age. CONCLUSIONS: Radiographic parameters prior to the Pavlik harness could be predictors of treatment failure and DDH in the future. This study showed that AI at the initiation of treatment is associated with residual acetabular dysplasia, suggesting that radiographic assessment may be useful even considering the risks associated with radiation exposure.
• 大腿骨顆間外側壁における骨密度分布 前十字靱帯の大腿骨付着部についての考察

  菅原 悠太郎, 岩崎 浩司, 遠藤 香織, 菱村 亮介, 松原 新史, 松岡 正剛, 門間 太輔, 小野寺 智洋, 近藤 英司, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 95 (8) S1715 - S1715 0021-5325 2021/08
• Morphological analysis of Kambin's triangle using 3D CT/MRI fusion imaging of lumbar nerve root created automatically with artificial intelligence.

  Katsuhisa Yamada, Ken Nagahama, Yuichiro Abe, Yoshinori Hyugaji, Masahiko Takahata, Norimasa Iwasaki

  European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 30 (8) 2191 - 2199 2021/08 

  PURPOSE: We developed a software program that automatically extracts a three-dimensional (3D) lumbar nerve root image from magnetic resonance imaging (MRI) lumbar nerve volume data using artificial intelligence. The aim of this study is to evaluate the morphology of Kambin's triangle in three dimensions based on an actual endoscopic transforaminal surgical approach using three-dimensional (3D) computed tomography (CT)/ magnetic resonance imaging (MRI) fusion images of the lumbar spine and nerve tissue. METHODS: Three-dimensional lumbar spine/nerve images of 100 patients (31 males and 69 females; mean age, 66.8 years) were used to evaluate the relationship between the superior articular process (SAP), exiting nerve root (ENR), and dural canal at the L2/3, L3/4, and L4/5 levels at 45° and 60° approach angles. RESULTS: The SAP-ENR distance at 60° was the greatest at L4/5 and was significantly greater at L2/3 and L4/5 than at L3/4 (P < 0.01, P < 0.01, respectively). The SAP-ENR distance at 45° was the greatest at L2/3, and it was larger in L2/3 and L4/5 than in L3/4 (P < 0.01, P < 0.01, respectively). The SAP-ENR distances at L4/5 were significantly greater at 60° than at 45° (P < 0.01). The dural canal was located within Kambin's triangle on the plane of the upper endplate of the lower vertebra at L2/3 in 41.5% of the cases and at L3/4 in 14% of the cases at 60° but not at L4/5. CONCLUSION: The 3D lumbar spine/nerve image enabled a combined assessment of the positional relationship between the SAP, ENR, and dural canal to quantify the safety zone of practical endoscopic spinal surgery using a transforaminal approach. Three-dimensional lumbar spine/nerve images could be useful for examining parameters, including bones and nerves, to ensure the safety of surgery.
• Exceptional Conditions for Favorable Neurological Recovery After Laminoplasty in Cases with Cervical Myelopathy Caused by K-line (-) Ossification of Posterior Longitudinal Ligament.

  Takeru Tsujimoto, Tsutomu Endo, Yusuke Menjo, Masahiro Kanayama, Itaru Oda, Kota Suda, Ryo Fujita, Yoshinao Koike, Yuichiro Hisada, Norimasa Iwasaki, Masahiko Takahata

  Spine 46 (15) 990 - 998 2021/08/01 

  STUDY DESIGN: A retrospective observational study. OBJECTIVE: To clarify the exceptional conditions for a favorable neurological recovery after laminoplasty (LMP) for cervical myelopathy caused by K-line (-) ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: The K-line-based classification of cervical OPLL was developed to predict insufficient neurological recovery after LMP. For patients with K-line (-) OPLL, LMP generally yields the least improvement because of inadequate decompression of the spinal cord; however, there are some exceptional cases wherein LMP promotes favorable neurological recoveries. METHODS: We retrospectively reviewed the medical records of 106 consecutive patients who underwent LMP for cervical OPLL to determine the demographic data, radiographic findings, and neurological recoveries of the patients as assessed preoperatively and 2 years postoperatively by their Japanese Orthopedic Association (JOA) scores. The factors associated with favorable outcomes after LMP in patients with K-line (-) were then investigated. RESULTS: Of 106 total patients, 31 were classified as K-line (-), of whom 21 achieved the least neurological recovery after LMP (JOA recovery rate <50%), while the remaining 10 patients achieved favorable outcomes (JOA recovery rate ≥50%). Among the K-line (-) group patients, those with ext-K-line (+), which changed to K-line (+) in the neck-extended position, and the patients with up-K-line (-), in whom the lesion responsible for myelopathy in the upper cervical spine (C3 or above), showed favorable neurological recoveries after LMP. CONCLUSION: Our data shows that, even for patients with K-line (-) OPLL, a favorable neurological recovery can be expected after LMP in cases in which the OPLL is in the upper cervical spine or the K-line changes to (+) in the neck-extended position. This means that K-line-based predictions of surgical outcomes after LMP should be indicated for patients with OPLL in the middle and lower cervical spine with limited extension mobility.Level of Evidence: 4.
• Dynamic Evaluation of Intraneural Microvascularity of the Ulnar Nerve Using Contrast-Enhanced Ultrasonography in Patients With Cubital Tunnel Syndrome

  Yuichiro Matsui, Tatsunori Horie, Tadanao Funakoshi, Daisuke Kawamura, Mutsumi Nishida, Norimasa Iwasaki

  The Journal of Hand Surgery 47 (7) 687.e1-687.e8  0363-5023 2021/08 

  PURPOSE: The purpose of this study was to compare the intraneural microvascular patterns of the ulnar nerve at 2 elbow flexion angles in asymptomatic volunteers and patients with cubital tunnel syndrome (CuTS) and to evaluate the effects of surgery on the microvascular pattern in patients with CuTS by using contrast-enhanced ultrasonography (CEUS). METHODS: This study included 10 elbows in 10 asymptomatic volunteers (control group) and 10 elbows in 10 patients with CuTS who underwent anterior subcutaneous transposition of the ulnar nerve (CuTS group). The CuTS group underwent clinical and electrophysiologic examinations and CEUS before surgery and at 1, 2, and 3 months after surgery. The intraneural enhancement pattern was calculated as an area under the curve (AUC) value in the entrapment site of the ulnar nerve within the cubital tunnel and in the area 1 cm proximal to the site (proximal site) at elbow flexion angles of 20° and 110°. RESULTS: Serial electrophysiologic examinations showed improvements at 1, 2, and 3 months after surgery compared with before surgery. In the control group, the AUC values of the central part of the cubital tunnel and proximal sites showed no substantial changes with the increase in elbow flexion. In the CuTS group, the AUC in the proximal site at 110° of elbow flexion was decreased compared with that at 20° of flexion before surgery. The AUC values for both the entrapment and proximal sites at 20° and 110° of elbow flexion were the most increased at 2 months after surgery compared with before surgery. CONCLUSIONS: Increased elbow flexion in patients with CuTS influences the intraneural blood flow of the ulnar nerve. Surgery for CuTS alters the intraneural blood flow. CLINICAL RELEVANCE: Quantitative evaluation of the intraneural blood flow of the ulnar nerve using CEUS may be a new supplementary diagnostic tool for CuTS and an indicator for the evaluation of postoperative recovery from nerve damage.
• Delayed Onset of Infectious Foreign Body Granuloma for Nonabsorbable Sutures After Open Achilles Tendon Repair: A Case Report.

  Ryo Itoga, Masatake Matsuoka, Tomohiro Onodera, Ai Shimizu, Koji Iwasaki, Shinji Matsubara, Ryosuke Hishimura, Eiji Kondo, Norimasa Iwasaki

  The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons 60 (6) 1297 - 1300 2021/07/20 

  Foreign body granulomas from sutures are more common among non-absorbable sutures compared to absorbable sutures and have been reported as a postoperative complication in a variety of medical fields. However, only a few cases of delayed foreign body reaction have been reported and addressed with orthopedics. We present a patient with systemic lupus erythematosus who developed an infectious suture granuloma that extended to the entire Achilles tendon and was induced by nonabsorbable sutures that were used for open Achilles tendon repair 20 years before. This granuloma was resistant to antibiotic treatment and drainage and required surgical intervention. The tumor was marginally resected, and the continuity of the Achilles tendon was preserved. Histopathological examination detected many suture materials surrounded by xanthochromic necrotic lesions and the lesion was diagnosed as a foreign body granuloma. At 1 year after the operation, the patient did not exhibit exacerbation of infection or recurrence of the tumor, and she became able to walk by herself. To the best of our knowledge, this represents the first report of an infectious delayed foreign body granuloma in autoimmune disorder patient after open Achilles tendon repair. Surgical intervention should be considered, as treatment with conservative therapy such as antibiotics may be difficult.
• Ulnar nerve morphology during elbow flexion in patients with and without cubital tunnel syndrome: a sonographic study

  Yuichiro Matsui, Tatsunori Horie, Norimasa Iwasaki

  Journal of Hand Surgery (European Volume) 47 (2) 175319342110261 - 175319342110261 1753-1934 2021/06/30
• Flightless I is a catabolic factor of chondrocytes that promotes hypertrophy and cartilage degeneration in osteoarthritis.

  Taku Ebata, Mohamad Alaa Terkawi, Masanari Hamasaki, Gen Matsumae, Tomohiro Onodera, Mahmoud Khamis Aly, Shunichi Yokota, Hend Alhasan, Tomohiro Shimizu, Daisuke Takahashi, Kentaro Homan, Ken Kadoya, Norimasa Iwasaki

  iScience 24 (6) 102643 - 102643 2021/06/25 

  Synovial macrophages that are activated by cartilage fragments initiate synovitis, a condition that promotes hypertrophic changes in chondrocytes leading to cartilage degeneration in OA. In this study, we analyzed the molecular response of chondrocytes under condition of this type of stimulation to identify a molecular therapeutic target. Stimulated macrophages promoted hypertrophic changes in chondrocytes resulting in production of matrix-degrading enzymes of cartilage. Among the top-upregulated genes, FliI was found to be released from activated chondrocytes and exerted autocrine/paracrine effects on chondrocytes leading to an increase in expression of catabolic and hypertrophic factors. Silencing FliI in stimulated cells significantly reduced expression of catabolic and hypertrophic factors in cocultured chondrocytes. Our further results demonstrated that the FliI-TLR4-ERK1/2 axis is involved in the hypertrophic signaling of chondrocytes and catabolism of cartilage. Our findings provide a new insight into the pathogenesis of OA and identify a potentially new molecular target for diagnostics and therapeutics.
• In vivo deformation of anatomically pre-bent rods in thoracic adolescent idiopathic scoliosis.

  Hideki Sudo, Hiroyuki Tachi, Terufumi Kokabu, Katsuhisa Yamada, Akira Iwata, Tsutomu Endo, Masahiko Takahata, Yuichiro Abe, Norimasa Iwasaki

  Scientific reports 11 (1) 12622 - 12622 2021/06/16 

  Some surgical strategies can maintain or restore thoracic kyphosis (TK); however, next-generation surgical schemes for adolescent idiopathic scoliosis (AIS) should consider anatomical corrections. A four-dimensional correction could be actively achieved by curving the rod. Thus, anatomically designed rods have been developed as notch-free, pre-bent rods for easier anatomical reconstruction. This study aimed to compare the initial curve corrections obtained using notch-free rods and manually bent, notched rods for the anatomical reconstruction of thoracic AIS. Two consecutive series of 60 patients who underwent anatomical posterior correction for main thoracic AIS curves were prospectively followed up. After multilevel facetectomy, except for the lowest instrumented segment, either notch-free or notched rods were used. Patient demographic data, radiographic measurements, and sagittal rod angles were analyzed within 1 week after surgery. Patients with notch-free rods had significantly higher postoperative TK than patients with notched rods (P < .001), but both groups achieved three-dimensional spinal corrections and significantly increased postoperative rates of patients with T6-T8 TK apex (P = .006 for notch-free rods and P = .008 for notched rods). The rod deformation angle at the concave side was significantly lower in the notch-free rods than in the notched rods (P < .001). The notch-free, pre-bent rod can maintain its curvature, leading to better correction or maintenance of TK after anatomical spinal correction surgery than the conventional notched rod. These results suggest the potential benefits of anatomically designed notch-free, pre-bent rods over conventional, manually bent rods.
• An algorithm for using deep learning convolutional neural networks with three dimensional depth sensor imaging in scoliosis detection.

  Terufumi Kokabu, Satoshi Kanai, Noriaki Kawakami, Koki Uno, Toshiaki Kotani, Teppei Suzuki, Hiroyuki Tachi, Yuichiro Abe, Norimasa Iwasaki, Hideki Sudo

  The spine journal : official journal of the North American Spine Society 21 (6) 980 - 987 2021/06 

  BACKGROUND CONTEXT: Timely intervention in growing individuals, such as brace treatment, relies on early detection of adolescent idiopathic scoliosis (AIS). To this end, several screening methods have been implemented. However, these methods have limitations in predicting the Cobb angle. PURPOSE: This study aimed to evaluate the performance of a three-dimensional depth sensor imaging system with a deep learning algorithm, in predicting the Cobb angle in AIS. STUDY DESIGN: Retrospective analysis of prospectively collected, consecutive, nonrandomized series of patients at five scoliosis centers in Japan. PATIENT SAMPLE: One hundred and-sixty human subjects suspected to have AIS were included. OUTCOME MEASURES: Patient demographics, radiographic measurements, and predicted Cobb angle derived from the deep learning algorithm were the outcome measures for this study. METHODS: One hundred and sixty data files were shuffled into five datasets with 32 data files at random (dataset 1, 2, 3, 4, and 5) and five-fold cross validation was performed. The relationships between the actual and predicted Cobb angles were calculated using Pearson's correlation coefficient analyses. The prediction performances of the network models were evaluated using mean absolute error and root mean square error between the actual and predicted Cobb angles. The shuffling into five datasets and five-fold cross validation was conducted ten times. There were no study-specific biases related to conflicts of interest. RESULTS: The correlation between the actual and the mean predicted Cobb angles was 0.91. The mean absolute error and root mean square error were 4.0° and 5.4°, respectively. The accuracy of the mean predicted Cobb angle was 94% for identifying a Cobb angle of ≥10° and 89% for that of ≥20°. CONCLUSIONS: The three-dimensional depth sensor imaging system with its newly innovated convolutional neural network for regression is objective and has significant ability to predict the Cobb angle in children and adolescents. This system is expected to be used for screening scoliosis in clinics or physical examination at schools.
• Stress-Distribution Pattern Across the Glenohumeral Joint in Collegiate and Professional Baseball Players: A Computed Tomography Osteoabsorptiometry Study.

  Kyosuke Numaguchi, Daisuke Momma, Yuki Matsui, Masashi Yokota, Jun Oohinata, Eiji Kondo, Norimasa Iwasaki

  Orthopaedic journal of sports medicine 9 (6) 23259671211009185 - 23259671211009185 2021/06 

  Background: The influence of long-term loading conditions on the articular surfaces of the glenohumeral joint can be determined by measuring stress-distribution patterns. Long-term pitching activity changes the stress distribution across the glenohumeral joint surface; however, the influence of competitive level on stress-distribution patterns remains unclear. Purpose: To use computed tomography (CT) osteoabsorptiometry (CTOAM) to evaluate the distribution of subchondral bone density across the glenohumeral joint in collegiate and professional baseball players as well as to determine the effects of pitching activity on the articular surfaces. Study Design: Descriptive laboratory study. Methods: We evaluated 73 shoulders in 50 baseball players. CT imaging data were obtained from the dominant-side shoulder of 12 professional pitchers (PP group) and 15 professional fielders (PF group). CT imaging data were also obtained from both shoulders of 12 asymptomatic collegiate pitchers (CP group) and 11 collegiate fielders (CF group). The pattern of distribution of subchondral bone density across the articular surfaces of each glenohumeral joint was assessed by CTOAM. As a measure of bone density, the mean Hounsfield units (HU) were obtained for each joint surface, and the absolute values of the dominant shoulder were compared for each group. Results: Stress-distribution patterns over the articular surfaces differed between the dominant and nondominant sides in the CP group as well as between both collegiate groups versus the PP group. In the CP group, the mean HU of the humeral head surface were greater on the nondominant versus dominant side (P = .035). On the dominant side, the mean HU of the humeral head surface and glenoid were greater in the CP versus the PP group (P = .001 and .027, respectively). Conclusion: Stress distribution on the articular surface of the glenohumeral joint was affected by pitching ability and competitive level. Our analysis indicates that the traction force on the glenohumeral joint surface might be greater than compression force during pitching. Clinical Relevance: The present findings suggest that pitching activity results in low stress to the articular surfaces of the glenohumeral joint. This supports the notion that mechanical conditions play a crucial role in the etiology of disorders specific to pitching activity.
• Exploratory clinical trial on the safety and capability of dMD-001 in lumbar disc herniation: Study protocol for a first-in-human pilot study

  Katsuhisa Yamada, Maeda Kenichiro, Yoichi M. Ito, Fujio Inage, Toshiyuki Isoe, Nozomi Yokota, Osamu Sugita, Norihiro Sato, Khin Khin Tha, Norimasa Iwasaki, Teruyo Arato, Hideki Sudo

  Contemporary Clinical Trials Communications 23 100805 - 100805 2451-8654 2021/06 

  Herniated nucleus pulposus (NP), one of the most common diseases of the spine, is surgically treated by removing the sequestered NP. However, intervertebral disc (IVD) defects may remain after discectomy, leading to inadequate tissue healing and predisposing patients to IVD degeneration. An acellular, bioresorbable, ultra-purified alginate (UPAL) gel (dMD-001) implantation system can be used to fill any IVD defects in order to prevent IVD degeneration after discectomy. This first-in-human pilot study aims to determine the feasibility, safety, and perceived patient response to a combined treatment involving discectomy and UPAL gel implantation for herniated NP. We designed a one-arm, double-centre, open-label, pilot trial. The study started in November 2018 and will run until a sample of 40 suitable participants is established. Patients aged 20-49 years, diagnosed with isolated lumbar IVD herniation and scheduled for discectomy represent suitable candidates. All eligible participants who provide informed consent undergo standard discectomy followed by UPAL gel implantation. The primary outcomes of the trial will be the feasibility and safety of the procedure. Secondary outcomes will include self-assessed clinical scores and magnetic resonance imaging-based measures of morphological and compositional quality of the IVD tissue. Initial outcomes will be published at 24 weeks. Analysis of feasibility and safety will be performed using descriptive statistics. Both intention-to-treat and per-protocol analyses of treatment trends of effectiveness will be conducted.
• Ultrapurified Alginate Gel Containing Bone Marrow Aspirate Concentrate Enhances Cartilage and Bone Regeneration on Osteochondral Defects in a Rabbit Model

  Liang Xu, Atsushi Urita, Tomohiro Onodera, Ryosuke Hishimura, Takayuki Nonoyama, Masanari Hamasaki, Dawei Liang, Kentaro Homan, Jian Ping Gong, Norimasa Iwasaki

  The American Journal of Sports Medicine 49 (8) 036354652110141 - 036354652110141 0363-5465 2021/06/01 

  Ultrapurified alginate (UPAL) gel implantation has been demonstrated as effective in cartilage repair for osteochondral defects; however, cell transplantation within UPAL gels would be required to treat larger defects. The combination of UPAL gel and bone marrow aspirate concentrate (BMAC) would enhance cartilage repair and subchondral bone repair for large osteochondral defects. Controlled laboratory study. A total of 104 osteochondral defects (1 defect per knee) of 52 rabbits were randomly divided into 4 groups (26 defects per group): defects without any treatment (Defect group), defects treated using UPAL gel alone (UPAL group), defects treated using UPAL gel containing allogenic bone marrow mesenchymal stromal cells (UPAL-MSC group), and defects treated using UPAL gel containing BMAC (UPAL-BMAC group). At 4 and 16 weeks postoperatively, macroscopic and histologic evaluations and measurements of repaired subchondral bone volumes of reparative tissues were performed. Collagen orientation and mechanical properties of the reparative tissue were assessed at 16 weeks. The defects in the UPAL-BMAC group were repaired with hyaline-like cartilage with well-organized collagen structures. The histologic scores at 4 weeks were significantly higher in the UPAL-BMAC group (16.9 ± 2.0) than in the Defect group (4.7 ± 1.9; P < .05), the UPAL group (10.0 ± 3.3; P < .05), and the UPAL-MSC group (12.2 ± 2.9; P < .05). At 16 weeks, the score in the UPAL-BMAC group (24.4 ± 1.7) was significantly higher than those in the Defect group (9.0 ± 3.7; P < .05), the UPAL group (14.2 ± 3.9; P < .05), and the UPAL-MSC group (16.3 ± 3.6; P < .05). At 4 and 16 weeks, the macroscopic evaluations were significantly superior in the UPAL-BMAC group compared with the other groups, and the values of repaired subchondral bone volumes in the UPAL-BMAC group were significantly higher than those in the Defect and UPAL groups. The mechanical properties of the reparative tissues were significantly better in the UPAL-BMAC group than in the other groups. The implantation of UPAL gel containing BMAC-enhanced hyaline-like cartilage repair and subchondral bone repair of osteochondral defects in a rabbit knee model. These data support the potential clinical application of 1-step treatment for large osteochondral defects using biomaterial implantation with cell transplantation.
• Differential effects of anti-RANKL monoclonal antibody and zoledronic acid on necrotic bone in a murine model of Staphylococcus aureus-induced osteomyelitis.

  Hideyuki Kobayashi, Ryo Fujita, Shigeto Hiratsuka, Tomohiro Shimizu, Dai Sato, Hiroki Hamano, Norimasa Iwasaki, Masahiko Takahata

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2021/05/15 

  Osteomyelitis is characterized by progressive inflammatory bone destruction accompanied by severe pain and disability. However, with the exception of antibiotic therapies, there is no established therapy to protect the bone from infectious osteolysis. The anti-receptor activator of nuclear factor-kB ligand (RANKL) monoclonal antibody (anti-RANKL Ab) is a potential drug based on its proven effectiveness in preventing joint bone erosion in rheumatoid arthritis; however, the efficacy and adverse effects of anti-RANKL Ab in osteomyelitis remain to be investigated. In this study, we investigated the effects of anti-mouse RANKL Ab on acute osteomyelitis and compared them with those of zoledronic acid (ZA) using a murine model. Mice were inoculated with bioluminescent Staphylococcus aureus (Xen 29) on their left femur and then treated with ZA, anti-RANKL Ab, or phosphate-buffered saline as control. A 21-day longitudinal observational study using microcomputed tomography showed that both anti-RANKL Ab and ZA had an osteoprotective effect against infectious osteolysis. However, it was also demonstrated through bioluminescence imaging that ZA delayed the spontaneous reduction of bacterial load and through histology that it increased the amount of necrotic bone, while anti-RANKL Ab did not. Findings from histopathological and in vitro studies suggest that an intense inflammatory response around the necrotic bone could induce osteoclasts in a RANKL-independent manner, leading to the removal of necrotic bone, even after administration of the anti-RANKL Ab therapy. Collectively, anti-RANKL Ab may exert an osteoprotective effect without hampering the removal of the necrotic bone, which serves as a nidus for infection in osteomyelitis.
• Concomitant arthrodesis of the distal interphalangeal joint with surface replacement arthroplasty of the proximal interphalangeal joint: a comparative study in 11 patients.

  Hiroki Hamano, Daisuke Kawamura, Norimasa Iwasaki

  The Journal of hand surgery, European volume 46 (4) 416 - 417 2021/05
• Total shoulder arthroplasty with an anteriorly augmented glenoid component for glenohumeral osteoarthritis with anterior glenoid bone loss: a case report.

  Shusei Kurashige, Atsushi Urita, Norimasa Iwasaki

  JSES international 5 (3) 365 - 370 2021/05
• Patient characteristics affecting knowledge of the possibility of surgical reconstruction for rheumatoid hand and wrist deformities.

  Makoto Motomiya, Naoki Nishimoto, Atsushi Urita, Daisuke Kawamura, Yuka Shimizu, Norimasa Iwasaki

  Modern rheumatology 31 (3) 614 - 620 2021/05 

  OBJECTIVES: We aimed to investigate patient characteristics affecting their knowledge of surgical reconstruction for rheumatoid hand and wrist deformities, and to investigate such characteristics affecting their hope of receiving hand surgery if patients with rheumatoid arthritis (RA) knew surgical reconstruction options. METHODS: We carried out a questionnaire survey for all patients with RA who came to our outpatient department of rheumatology. Multivariate logistic regression analysis was performed to examine significant characteristics associated with the knowledge of surgical reconstruction and patients' hope of receiving hand surgery. RESULTS: In total, 687 patients were evaluated in this study and 337 (49%) reported knowledge about surgical reconstruction. A multivariate logistic regression analysis showed that patients with good control of disease activity and with long-lasting hand and wrist deformities were significantly associated with having knowledge of surgical reconstruction. Among the 337 patients with knowledge, only 122 (36%) expressed a hope of receiving hand surgery. The statistical analysis showed that younger age and surgical history were significantly associated with the hope of receiving surgery. CONCLUSION: Surgeons and rheumatologists should enlighten patients about the importance of hand surgery to achieve functional remission in this new era of treatment for patients with RA.
• Efficacy and safety of sodium RISedronate for glucocorticoid-induced OsTeoporosis with rheumaTOid arthritis (RISOTTO study): A multicentre, double-blind, randomized, placebo-controlled trial.

  Yuichiro Fujieda, Tetsuya Horita, Naoki Nishimoto, Kazuhide Tanimura, Yoshiharu Amasaki, Hideki Kasahara, Shin Furukawa, Tsuyoshi Takeda, Shinji Fukaya, Kazuo Matsui, Akito Tsutsumi, Akira Furusaki, Akira Sagawa, Kou Katayama, Kaoru Takeuchi, Kazuaki Katsumata, Takashi Kurita, Peter Shane, Masaru Kato, Kenji Oku, Shinsuke Yasuda, Masahiko Takahata, Norimasa Iwasaki, Tatsuya Atsumi

  Modern rheumatology 31 (3) 593 - 599 2021/05 

  OBJECTIVE: No evidence has shown the efficacy of Sodium Risedronate (Risedronate) for glucocorticoid-induced osteoporosis (GIO) in patients with Rheumatoid arthritis (RA). The aim of this study was to explore the effectiveness and safety of Risedronate for GIO complicated with RA. METHODS: This was a six-month randomized, double-blind, placebo-controlled trial of 95 patients with GIO complicated with RA from 19 centers. The primary endpoint was the change from baseline in lumbar spine bone mineral density (L-BMD). Secondary endpoints included changes in femoral neck and total hip BMD and bone turnover markers, as well as rheumatoid arthritis Disease Activity Score with 28-joint counts. Incident of non-traumatic spine fractures and adverse events were tracked as safety endpoints. RESULTS: Increase in L-BMD was significantly greater in the Risedronate group compared to the Placebo group (Risedronate: 3.49% [95% CI: 1.92-5.05] vs Placebo: 0.12% [95% CI: -2.07 to 2.30], p < .0001). No significant difference was found in the femoral neck and total hip BMD. Although adverse events were observed in 28 patients, none were considered serious. Non-traumatic vertebral fractures were identified in 10 patients. CONCLUSION: Risedronate was effective in increasing L-BMD and was well tolerated in patients with GIO complicated with RA.
• Effect of High Tibial Osteotomy on the Distribution of Subchondral Bone Density Across the Proximal Tibial Articular Surface of the Knee With Medial Compartment Osteoarthritis.

  Koji Iwasaki, Eiji Kondo, Shinji Matsubara, Masatake Matsuoka, Kaori Endo, Isao Yokota, Tomohiro Onodera, Norimasa Iwasaki

  The American journal of sports medicine 49 (6) 1561 - 1569 2021/05 

  BACKGROUND: The effect of high tibial osteotomy (HTO) on the stress distribution across the knee joint is not completely understood. Subchondral bone density is considered to reflect the pattern of stress distribution across a joint surface. PURPOSE: To assess the distribution of subchondral bone density across the proximal tibia in nonarthritic knees and in the knees of patients with osteoarthritis (OA) before and after HTO. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We retrospectively collected radiological and computed tomography data from 16 patients without OA (control group) and 17 patients with OA. Data from the OA group were collected before and 1.5 years after HTO. Subchondral bone density of the proximal tibia was assessed with computed tomography-osteoabsorptiometry. The locations and percentages represented by high-density areas (HDAs) on the articular surface were quantitatively analyzed. RESULTS: The ratio of the HDA of the medial compartment to the total HDA (medial ratio) was significantly higher in the preoperative OA group (mean, 80.1%) than in the control group (61.3%) (P < .001). After HTO, the medial ratio decreased significantly to 75.1% (P = .035 in comparison with preoperative values) and was significantly correlated with the hip-knee-ankle angle in both groups: control (r = -0.551; P = .033) and OA (r = -0.528; P = .043). The change in medial ratio after HTO was significantly correlated with the change in hip-knee-ankle angle (r = 0.587; P = .035). In the medial compartment, the HDA in the most lateral region of 4 subregions increased after HTO, but that in 3 medial subregions decreased. CONCLUSION: In this exploratory study, HTO shifted the HDA of the medial compartment of the proximal tibial articular surface toward the lateral compartment. In contrast, the HDA of the most lateral region of the medial compartment increased after HTO. This change in subchondral bone density may result from the change in stress distribution.
• Flightless I is a catabolic factor of chondrocytes that promotes hypertrophy and cartilage degeneration in osteoarthritis

  Taku Ebata, Mohamad Alaa Terkawi, Masanari Hamasaki, Gen Matsumae, Tomohiro Onodera, Mahmoud Khamis Aly, Shunichi Yokota, Hend Alhasan, Tomohiro Shimizu, Daisuke Takahashi, Kentaro Homan, Ken Kadoya, Norimasa Iwasaki

  iScience 102643 - 102643 2589-0042 2021/05
• Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review.

  Takashi Ohnishi, Yuki Ogawa, Kota Suda, Miki Komatsu, Satoko Matsumoto Harmon, Mitsuru Asukai, Masahiko Takahata, Norimasa Iwasaki, Akio Minami

  International journal of molecular sciences 22 (9) 2021/04/24 

  Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.
• Delayed lumbar plexus palsy due to giant psoas hematoma associated with vertebral compression fracture and direct oral anticoagulants: a case report.

  Chikako Ishii, Miki Komatsu, Kota Suda, Masahiko Takahata, Satoko Matsumoto Harmon, Masahiro Ota, Takamasa Watanabe, Mitsuru Asukai, Norimasa Iwasaki, Akio Minami

  BMC musculoskeletal disorders 22 (1) 377 - 377 2021/04/22 

  BACKGROUND: Osteoporotic vertebral compression fractures (VCFs) are commonly observed in elderly people and can be treated by conservatively with minimal risk of complications in most cases. However, utilization of direct oral anticoagulants (DOACs) increases the risks of secondary hematoma even after insignificant trauma. The use of DOACs increased over the past decade because of their approval and recommendation for both stroke prevention in non-valvular atrial fibrillation and treatment of venous thromboembolism. It is well known that DOACs are safer anticoagulants than warfarin in terms of major and nonmajor bleeding; however, we noted an increase in the number of bleeding events associated with DOACs that required medical intervention. This report describes the first case of delayed lumbar plexus palsy due to DOAC-associated psoas hematoma after VCF to draw attention to potential risk of severe complication associated with this type of common and stable trauma. CASE PRESENTATION: An 83-year-old man presented with his left inguinal pain and inability to ambulate after falling from standing position and was prescribed DOACs for chronic atrial fibrillation. Computed tomography angiography revealed a giant psoas hematoma arising from the ruptured segmental artery running around fractured L4 vertebra. Because of motor weakness of his lower limbs and expansion of psoas hematoma revealed by contrast computed tomography on day 8 of his hospital stay, angiography aimed for transcatheter arterial embolization was tried, but could not demonstrate any major active extravasation; therefore spontaneous hemostasis was expected with heparin replacement. On day 23 of his stay, hematoma turned to decrease, but dysarthria and motor weakness due to left side cerebral infarction occurred. His pain improved and bone healing was achieved about 2 months later from his admission, however the paralysis of the left lower limb and aftereffects of cerebral infarction remained after 1 year. CONCLUSION: In patients using DOACs with multiple risk factors, close attention must be taken in vertebral injury even if the fracture itself is a stable-type such as VCF, because segmental artery injury may cause massive psoas hematoma followed by lumbar plexus palsy and other complications.
• Bone Marrow Aspirate Concentrate Combined with in Situ Forming Bioresorbable Gel Enhances Intervertebral Disc Regeneration in Rabbits.

  Daisuke Ukeba, Katsuhisa Yamada, Takeru Tsujimoto, Katsuro Ura, Takayuki Nonoyama, Norimasa Iwasaki, Hideki Sudo

  The Journal of bone and joint surgery. American volume 103 (8) e31  2021/04/21 

  BACKGROUND: The current surgical procedure of choice for intervertebral disc (IVD) herniation is discectomy, which induces postoperative IVD degeneration. Thus, cell-based therapies, as a 1-step simple procedure, are desired because of the poor capacity of IVDs for self-repair. The aim of this study was to investigate the repair efficacy of ultra-purified alginate (UPAL) gels containing bone marrow aspirate concentrate (BMAC) for the treatment of discectomy-associated IVD degeneration in rabbits. METHODS: The mechanical properties of 3 types of gels-UPAL, UPAL containing bone marrow-derived mesenchymal stem cells (BMSCs), and UPAL containing BMAC-were evaluated. Forty rabbits were assigned to 5 groups: intact control, discectomy (to make the cavity), UPAL (implantation of the UPAL gel after discectomy), BMSCs-UPAL (implantation of a combination of autogenic BMSCs and UPAL gel after discectomy), and BMAC-UPAL (implantation of a combination of BMAC and UPAL gel after discectomy). The gels were implanted at 4 weeks after induction of IVD degeneration. At 4 and 12 weeks, magnetic resonance imaging (MRI) as well as histological and immunohistochemical analyses were performed to analyze IVD degeneration qualitatively and the viability of the implanted cells. RESULTS: There was no significant difference among the 3 types of gels in terms of the results of unconfined compression tests. The implanted cells survived for 12 weeks. The histological grades of the BMSCs-UPAL (mean and standard deviation, 2.50 ± 0.53; p < 0.001) and BMAC-UPAL (2.75 ± 0.64, p = 0.001) showed them to be more effective in preventing degeneration than UPAL gel alone (3.63 ± 0.52). The effectiveness of BMAC-UPAL was not significantly different from that of BMSCs-UPAL, except with respect to type-II collagen synthesis. CONCLUSIONS: BMAC-UPAL significantly enhanced the repair of IVD defects created by discectomy. This approach could be an effective therapeutic strategy owing to its simplicity and cost-effectiveness compared with cell therapy using culture-expanded BMSCs. CLINICAL RELEVANCE: Local administration of the BMAC combined with UPAL gel could be an effective therapeutic strategy to enhance IVD repair after discectomy.
• Bone Metabolism in the Healing Process of Lumbar Interbody Fusion-Temporal changes of bone turnover markers.

  Ryota Hyakkan, Masahiro Kanayama, Masahiko Takahata, Fumihiro Oha, Tomoyuki Hashimoto, Norimasa Iwasaki

  Spine 46 (23) 1645 - 1652 2021/04/19 

  STUDY DESIGN: Prospective longitudinal study. OBJECTIVE: The aim of this study was to evaluate temporal changes of bone turnover markers (BTMs) after lumbar spinal fusion in patients without osteoporosis. SUMMARY OF BACKGROUND DATA: Radiological studies are the standard method to monitor bony fusion, but they do not allow a timely assessment of bone healing. BTMs react rapidly to changes in bone metabolism during fusion process and could be an additional tool to monitor this process. METHODS: A total of 78 non-osteoporosis patients who had undergone one- or two-level transforaminal lumbar interbody fusion were included. Fusion status was assessed using CT sagittal and coronal images. Serum levels of bone specific alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP) and osteocalcin (OC) were measured to assess bone formation, and tartrate-resistant acid phosphatase 5b (TRACP-5b) was measured to assess bone resorption. Serum samples were obtained before surgery and at 1, 2, 4, 8, 13, 26, 39, and 52 weeks after surgery. RESULTS: A solid fusion was achieved in 71 of 78 patients (91%), and 7 patients resulted in pseudarthrosis. In the fusion group, the level of all BTMs once decreased at 1 postoperative week. Then, BAP and P1NP reached a peak at 4 weeks after surgery, and TRACP-5b and OC peaked at 8 weeks. Thereafter, the level of P1NP and TRACP-5b gradually got closer to the baseline over a year, and BAP kept high until 52 postoperative weeks. In the pseudarthrosis group, peak level of BTMs were significantly higher and the increased level of BAP and P1NP was kept until 52 weeks. CONCLUSIONS: The current study demonstrated dynamics of BTMs after lumbar spinal fusion in patients without osteoporosis. These normal population data contribute as a baseline to evaluate the effect of osteogenic agents on bone metabolism after spinal fusion.Level of Evidence: 2.
• Changes in the Contact Stress Distribution Pattern of the Patellofemoral Joint After Medial Open-Wedge High Tibial Osteotomy: An Evaluation Using Computed Tomography Osteoabsorptiometry.

  Toshiaki Kameda, Eiji Kondo, Tomohiro Onodera, Koji Iwasaki, Jun Onodera, Kazunori Yasuda, Norimasa Iwasaki

  Orthopaedic journal of sports medicine 9 (4) 2325967121998050 - 2325967121998050 2021/04 

  Background: Medial open-wedge high tibial osteotomy (OWHTO) theoretically causes distalization and lateralization of the tibial tuberosity and the patella. Purpose/Hypothesis: The purpose of the study was to identify any changes in the stress distribution of subchondral bone density across the patellofemoral (PF) joint before and after OWHTO through the use of computed tomography (CT) osteoabsorptiometry. We hypothesized that OWHTO would alter the distribution of contact stress in the PF joint. Study Design: Case series; Level of evidence, 4. Methods: A total of 17 patients (17 knees) who underwent OWHTO were enrolled in this study between September 2013 and September 2015. All patients underwent radiologic examination preoperatively and at 1 year postoperatively, and the distribution patterns of subchondral bone density through the articular surface of the femoral trochlea and patella were assessed preoperatively and >1 year postoperatively using CT osteoabsorptiometry. The quantitative analysis of the obtained mapping data focused on location of the high-density area (HDA) through the articular surface of the PF joint. The percentage of HDA at each divided region of the articular surface of the femoral trochlea and the patella was calculated. Results: In the radiologic evaluation, the Blackburne-Peel ratio was significantly reduced (P < .001) after surgery, and the tilting angle of the patella was significantly decreased (P < .001). On CT evaluation, the percentage of HDA in the lateral notch and lateral trochlea of the femur and in the medial portion of the lateral facet of the patella increased significantly after OWHTO surgery (P ≤ .038). Conclusion: OWHTO significantly increased the stress distribution pattern of the lateral trochlea of the femur and the medial portion of the lateral facet of the patella. The procedure significantly lowered the patellar height and significantly decreased the patellar tilting angle after surgery.
• Morphologic Changes in the Vertebral Artery Subsequent to Cervical Spine Degeneration and Aging: Analyses by Computed Tomography Angiography Using Multiplanar and 3-Dimensional Reconstructions.

  Takashi Ohnishi, Kota Suda, Miki Komatsu, Satoko Matsumoto Harmon, Takamasa Watanabe, Mitsuru Asukai, Ken Kadoya, Masahiko Takahata, Norimasa Iwasaki, Akio Minami

  World neurosurgery 150 e686-e695  2021/03/23 

  OBJECTIVE: To identify the morphologic changes in the vertebral artery (VA) subsequent to cervical spine degeneration and aging and to investigate the risk factors for iatrogenic VA injury or occlusion. METHODS: Eighty-eight consecutive patients (176 bilateral VAs) were retrospectively analyzed using radiographs, computed tomography, and computed tomography angiography images. The Kellgren and Lawrence (KL) score and its modified subscores were used to grade the severity of degenerative changes in the cervical spine. VA tortuosity widths and diameters were measured between the C2 and C6 transverse foramens. The outcome measures were statistically analyzed for difference, correlation, and explanatory variable. The level with a high prevalence of VA stenosis was also evaluated. RESULTS: There were significant positive correlations between the KL score and VA tortuosity width, and between age and VA tortuosity width. Osteophyte formation in the facet joint was the predominant explanatory variable for medial deviation of the VA. Significant positive correlations were evident between the dominant VA diameter and KL score or age. VA stenosis occurred at C3/C4 (24.5%) with the highest prevalence and it was caused by uncovertebral joint osteophytes (52.0%) with the highest incidence. CONCLUSIONS: The present study provides important evidence for decisions of surgical strategy and for avoiding catastrophic VA injury or occlusion in cervical spine surgeries.
• Finite element analysis of double-plate fixation using reversed locking compression-distal femoral plates for Vancouver B1 periprosthetic femoral fractures.

  Daisuke Takahashi, Yoshihiro Noyama, Tsuyoshi Asano, Tomohiro Shimizu, Tohru Irie, Mohamad Alaa Terkawi, Norimasa Iwasaki

  BMC musculoskeletal disorders 22 (1) 276 - 276 2021/03/13 

  BACKGROUND: Internal fixation is recommended for treating Vancouver B1 periprosthetic femoral fractures. Although several fixation procedures have been developed with high fixation stability and union rates, long-term weight-bearing constructs are still lacking. Therefore, the aim of the present study was to evaluate the stability of a double-plate procedure using reversed contralateral locking compression-distal femoral plates for fixation of Vancouver B1 periprosthetic femoral fractures under full weight-bearing. METHODS: Single- and double-plate fixation procedures for locking compression-distal femoral plates were analysed under an axial load of 1,500 N by finite element analysis and biomechanical loading tests. A vertical loading test was performed to the prosthetic head, and the displacements and strains were calculated based on load-displacement and load-strain curves generated by the static compression tests. RESULTS: The finite element analysis revealed that double-plate fixation significantly reduced stress concentration at the lateral plate place on the fracture site. Under full weight-bearing, the maximum von Mises stress in the lateral plate was 268 MPa. On the other hand, the maximum stress in the single-plating method occurred at the defect level of the femur with a maximum stress value of 1,303 MPa. The principal strains of single- and double-plate fixation were 0.63 % and 0.058 %, respectively. Consistently, in the axial loading test, the strain values at a 1,500 N loading of the single- and double-plate fixation methods were 1,274.60 ± 11.53 and 317.33 ± 8.03 (× 10- 6), respectively. CONCLUSIONS: The present study suggests that dual-plate fixation with reversed locking compression-distal femoral plates may be an excellent treatment procedure for patients with Vancouver B1 fractures, allowing for full weight-bearing in the early postoperative period.
• Evaluation of whole-body modalities for diagnosis of multifocal osteonecrosis-a pilot study.

  Shunichi Yokota, Keita Sakamoto, Yukie Shimizu, Tsuyoshi Asano, Daisuke Takahashi, Kohsuke Kudo, Norimasa Iwasaki, Tomohiro Shimizu

  Arthritis research & therapy 23 (1) 83 - 83 2021/03/11 

  BACKGROUND: This study aimed to investigate the ability of whole-body bone scintigraphy (WB-BS) in the detection of multifocal osteonecrosis (ON) compared to whole-body magnetic resonance imaging (WB-MRI) and to clarify the characteristics of patients with multifocal ON among those with ON of the femoral head (ONFH) using WB-MRI. METHODS: Forty-six patients who had symptomatic ONFH and underwent surgery in our hospital from April 2019 to October 2020 were included in the study. Data on patient demographics, including age, sex, body mass index (BMI), history of corticosteroid intake, alcohol abuse, smoking, and symptomatic joints, were collected from their medical records. All patients underwent WB-MRI and WB-BS before surgery. RESULTS: The agreement in the detection of ON by WB-MRI vs the uptake lesions by WB-BS in the hip joints was moderate (κ = 0.584), while that in other joints was low (κ < 0.40). Among the 152 joints with ON detected by WB-MRI, 92 joints (60.5%) were symptomatic, and 60 joints (39.5%) were asymptomatic. Twelve out of the 46 (26.0%) patients had multifocal (three or more distinct anatomical sites) ON. Nonetheless, while WB-BS detected symptomatic ON detected by WB-MRI as uptake lesions in 82.6% (76/92) of the joints, asymptomatic ON detected by WB-MRI was detected as uptake lesions in 21.7% (13/60) of the joints. All patients with multifocal ON had a history of steroid therapy, which was significantly higher than that in patients with oligofocal ON (P = 0.035). The patients with a hematologic disease had multifocal ON at a higher rate (P = 0.015). CONCLUSIONS: It might be difficult for WB-BS to detect the asymptomatic ON detected by WB-MRI compared to symptomatic ON. Considering the cost, examination time, and radiation exposure, WB-MRI might be useful for evaluating multifocal ON. Larger longitudinal studies evaluating the benefits of WB-MRI for detecting the risk factors for multifocal ON are required.
• Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model.

  Yuan Tian, Tomohiro Onodera, Mohamad Alaa Terkawi, Koji Iwasaki, Ryosuke Hishimura, Dawei Liang, Takuji Miyazaki, Norimasa Iwasaki

  International journal of molecular sciences 22 (5) 2021/03/04 

  Systemic injection of a nerve growth factor (NGF) antibody has been proven to have a significant relevance in relieving osteoarthritis (OA) pain, while its adverse effects remain a safety concern for patients. A local low-dose injection is thought to minimize adverse effects. In this study, OA was induced in an 8-week-old male Sprague-Dawley (SD) rat joint by monoiodoacetate (MIA) injection for 2 weeks, and the effect of weekly injections of low-dose (1, 10, and 100 µg) NGF antibody or saline (control) was evaluated. Behavioral tests were performed, and at the end of week 6, all rats were sacrificed and their knee joints were collected for macroscopic and histological evaluations. Results showed that 100 µg NGF antibody injection relieved pain in OA rats, as evidenced from improved weight-bearing performance but not allodynia. In contrast, no significant differences were observed in macroscopic and histological scores between rats from different groups, demonstrating that intra-articular treatment does not worsen OA progression. These results suggest that local administration yielded a low effective NGF antibody dose that may serve as an alternative approach to systemic injection for the treatment of patients with OA.
• 頸椎変性と加齢に伴い生じる椎骨動脈の形態的異常 術中椎骨動脈損傷と術後閉塞を回避するための新たなエビデンス

  大西 貴士, 須田 浩太, 小松 幹, 松本 聡子, 渡辺 尭仁, 飛鳥井 光, 角家 健, 高畑 雅彦, 東條 泰明, 神谷 行宣, 岩崎 倫政, 三浪 明男

  日本整形外科学会雑誌 (公社)日本整形外科学会 95 (3) S984 - S984 0021-5325 2021/03
• Acellular Cartilage Repair Technique Based on Ultrapurified Alginate Gel Implantation for Advanced Capitellar Osteochondritis Dissecans

  Daisuke Momma, Tomohiro Onodera, Daisuke Kawamura, Atsushi Urita, Yuichiro Matsui, Rikiya Baba, Tadanao Funakoshi, Makoto Kondo, Toshiya Endo, Eiji Kondo, Norimasa Iwasaki

  Orthopaedic Journal of Sports Medicine 9 (3) 232596712198967 - 232596712198967 2325-9671 2021/03/01 

  One of the most important limitations of osteochondral autograft transplant is the adverse effect on donor sites in the knee. Ultrapurified alginate (UPAL) gel is a novel biomaterial that enhances hyaline-like cartilage repair for articular defects. To avoid the need for knee cartilage autografting when treating osteochondritis dissecans (OCD) of the capitellum, we developed a surgical procedure involving a bone marrow stimulation technique (BMST) augmented by implantation of UPAL gel. BMST augmented by UPAL gel implantation improves the cartilage repair capacity and provides satisfactory clinical outcomes in OCD of the capitellum. Case series; Level of evidence, 4. A total of 5 athletes with advanced capitellar OCD in the dominant elbow underwent BMST augmented by implantation of UPAL gel. The osteochondral defects were filled with UPAL gel after BMST. At a mean follow-up of 97 weeks, all patients were evaluated clinically and radiographically. At final follow-up, all 5 patients had returned to competitive-level sports, and 4 patients were free from elbow pain. The mean Timmerman-Andrews score significantly improved from 100 to 194 points. Radiographically, all patients exhibited graft incorporation and a normal contour of the subchondral cortex. Magnetic resonance imaging showed that the preoperative heterogeneity of the lesion had disappeared, and the signal intensity had returned to normal. Arthroscopic examinations consistently exhibited improvement in the International Cartilage Regeneration and Joint Preservation Society (ICRS) grade of lesions from 3 or 4 to 1 or 2 in 4 patients at 85 weeks postoperatively. Histologic analysis of biopsy specimens revealed an average total ICRS Visual Assessment Scale II histologic score of 1060. The acellular cartilage repair technique using UPAL gel for advanced capitellar OCD provided satisfactory clinical and radiographic results. The present results suggest that this novel technique is a useful, minimally invasive approach for treating cartilaginous lesions in athletes.
• Impact of multilevel facetectomy on segmental spinal flexibility in patients with thoracic adolescent idiopathic scoliosis.

  Terufumi Kokabu, Yuichiro Abe, Katsuhisa Yamada, Norimasa Iwasaki, Hideki Sudo

  Clinical biomechanics (Bristol, Avon) 83 105296 - 105296 2021/03 

  BACKGROUND: The aim of this study was to intraoperatively assess the effects of multilevel facetectomy on segmental spinal flexibility in patients with thoracic adolescent idiopathic scoliosis. METHODS: Twenty patients who underwent posterior thoracic adolescent idiopathic scoliosis curve correction were evaluated. Compressive or distractive loaded force of 50N was applied on the handle of a compressor or distractor connected to the necks of pedicle screws inserted at T7 to T11. Segmental spinal flexibility rates were calculated based on the distance between screw heads under the loaded and unloaded conditions. In addition, the flexibility rates were obtained before and after multilevel facetectomy. FINDINGS: Absolute flexibility rates of all segments significantly increased after multilevel facetectomy under both compressive and distractive forces (P < 0.01). The absolute change in the flexibility rate was significantly higher at the concave side than at the convex side under both compressive (P < 0.01) and distractive loaded forces (P = 0.046). No significant correlation was found between change in the flexibility rates and preoperative Cobb angle or preoperative curve flexibility. INTERPRETATION: From a biomechanical point of view, multilevel facetectomy provides proper spinal flexibility to improve the correction rate of posterior adolescent idiopathic scoliosis surgery. The effects are higher at the concave side than at the convex side.
• Risk Factor Analysis of Proximal Junctional Kyphosis after Surgical Treatment of Adult Spinal Deformity with Oblique Lateral Interbody Fusion.

  Yoshinao Koike, Yoshihisa Kotani, Hidemasa Terao, Norimasa Iwasaki

  Asian spine journal 15 (1) 107 - 116 2021/02 

  STUDY DESIGN: A single-center retrospective study. PURPOSE: To investigate the prevalence of proximal junctional kyphosis (PJK) and its risk factors after surgical treatment of adult spinal deformity (ASD) with oblique lateral interbody fusion (OLIF). OVERVIEW OF LITERATURE: Correction of ASD using OLIF has been developed because it is less invasive, and enables correction of severe deformities. Although PJK is a well-recognized complication after the correction of spinal deformity, few studies have evaluated the prevalence and risk factors for PJK after OLIF for ASD. METHODS: We reviewed 74 patients who underwent surgery for ASD. PJK was defined as a proximal junction sagittal Cobb angle exceeding 10°, and at least 10° greater than the preoperative measurement. We investigated the following as risk factors: age, sex, body mass index, medical history, number of fused segments, number of interbody fusions, number of OLIFs, number of osteotomies, level of upper instrumented vertebrae, lowest instrumented vertebrae, and radiographic parameters. RESULTS: The mean follow-up duration was 22.4 months and the mean age of the patients was 73.6 years. PJK was present in 19/74 patients (25.7%) and absent in 55/74 (74.3%). In the univariate analysis, those with PJK had a significantly higher proportion of patients with a history of vertebral compression fracture (7/19 patients [36.8%] vs. 6/55 patients [10.9%], p=0.027). Those with PJK had a significantly higher proportion of patients with fusion to the pelvis (18/19 patients [94.7%] vs. 34/55 patients [61.8%], p=0.016). According to the multivariate analysis, fusion to the pelvis was a significant risk factor for PJK. CONCLUSIONS: Fusion to the pelvis was the most important risk factor for PJK. A history of vertebral compression fracture served as an additional risk factor for PJK. Clinicians should consider these factors before treating ASD patients with OLIF.
• Comparison of Outcomes of Oblique Lateral Interbody Fusion with Percutaneous Posterior Fixation in Lateral Position and Minimally Invasive Transforaminal Lumbar Interbody Fusion for Degenerative Spondylolisthesis.

  Yoshinao Koike, Yoshihisa Kotani, Hidemasa Terao, Norimasa Iwasaki

  Asian spine journal 15 (1) 97 - 106 2021/02 

  STUDY DESIGN: Single-center retrospective study. PURPOSE: To compare the physical function and quality of life (QOL) parameters of two minimally invasive surgical (MIS) procedures: oblique lateral interbody fusion with percutaneous posterior fixation in lateral position (OLIF-LPF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for single-level degenerative spondylolisthesis (DS). OVERVIEW OF LITERATURE: To date, many options for the surgical treatment of lumbar DS and reports have described the effectiveness of minimally invasive lateral access surgery and MIS-TLIF. However, there is still a paucity of comparative data regarding the physical function and QOL outcomes of OLIF and MIS-TLIF. METHODS: Eighty-six patients were enrolled in this study (group O: OLIF-LPF, n=38; group T: MIS-TLIF, n=48). We evaluated the operation time, estimated blood loss (EBL), postoperative laboratory data, preoperative and postoperative radiographic parameters, overall functional outcome with the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) effectiveness rate, and Visual Analog Scale (VAS) score for low back pain, leg pain, and leg numbness. RESULTS: No statistical differences in operation time, EBL, and C-reactive protein level, 5 days postoperatively, between groups O and T. With respect to radiological outcome, preoperative and postoperative disc height change was significantly greater in group O than in group T (3.8 vs. 1.8 mm, p<0.05). Both groups showed postoperative improvements in the clinical outcome scores of all JOABPEQ domains, but the effectiveness rate increase in the psychological domain was significantly higher in group O than in group T (47.1% vs. 14.6%, p<0.05). No differences in the preoperative and postoperative VAS score change were noted between the two groups in any of the items. CONCLUSIONS: The changes in physical function and QOL parameters after OLIF-LPF and MIS-TLIF were almost equivalent; however, OLIF-LPF had significant superiority in the psychological domain.
• Association Between Vitamin A Intake and Disease Severity in Early-Onset Heterotopic Ossification of the Posterior Longitudinal Ligament of the Spine.

  Tsutomu Endo, Shiro Imagama, Satoshi Kato, Takashi Kaito, Hiroaki Sakai, Shiro Ikegawa, Yoshiharu Kawaguchi, Masahiro Kanayama, Yuichiro Hisada, Yoshinao Koike, Kei Ando, Kazuyoshi Kobayashi, Itaru Oda, Kazufumi Okada, Ryo Takagi, Norimasa Iwasaki, Masahiko Takahata

  Global spine journal 12 (8) 2192568221989300 - 2192568221989300 2021/01/25 

  STUDY DESIGN: A sex- and age-matched case-control study and a cross-sectional study. OBJECTIVE: In our previous study, patients with early-onset (<50 years of age) ossification of the posterior longitudinal ligament (OPLL) had distinct features such as morbid obesity, a high prevalence of lifestyle-related diseases, and diffuse ossified lesions mainly affecting the thoracic spine. Our goals were to determine whether early-onset OPLL patients have unbalanced dietary habits and to identify nutritional factors associated with OPLL exacerbation. METHODS: In Study 1, the simple brief-type self-administered diet history questionnaire (BDHQ) was used to compare nutrient intake levels of early-onset OPLL patients (n = 13) with those of sex- and age-matched non-OPLL controls (n = 39) or with those of common OPLL (onset age ≥ 50 years, n = 62). In Study 2, serological validation was conducted for thoracic OPLL patients (n = 77) and non-OPLL controls (n = 101) in a nationwide multicenter study in Japan. RESULTS: The BDHQ showed that the early-onset OPLL patients had significantly lower intakes of vitamins A and B6 than non-OPLL controls. These results were validated by lower serum vitamins A and B6 levels in the early-onset thoracic OPLL patients. The severity of OPLL negatively correlated with serum vitamin A levels in male early-onset OPLL patients. The multiple regression analysis revealed that the severity of thoracic OPLL had an association with onset age and serum vitamin A level. CONCLUSIONS: Vitamin A deficiency resulting from unbalanced dietary habits is associated with exacerbation of male early-onset OPLL.
• Three-dimensional distribution of CT attenuation in the lumbar spine pedicle wall.

  Tomoyo Y Irie, Tohru Irie, Alejandro A Espinoza Orías, Kazuyuki Segami, Norimasa Iwasaki, Howard S An, Nozomu Inoue

  Scientific reports 11 (1) 1709 - 1709 2021/01/18 

  This study investigated in vivo the three-dimensional distribution of CT attenuation in the lumbar spine pedicle wall measured in Hounsfield Unit (HU). Seventy-five volunteers underwent clinical lumbar spine CT scans. Data was analyzed with custom-written software to determine the regional variation in pedicle wall attenuation values. A cylindrical coordinate system oriented along the pedicle's long axis was used to calculate the pedicular wall attenuation distribution three-dimensionally and the highest attenuation value was identified. The pedicular cross-section was divided into four quadrants: lateral, medial, cranial, and caudal. The mean HU value for each quadrant was calculated for all lumbar spine levels (L1-5). The pedicle wall attenuation was analyzed by gender, age, spinal levels and anatomical quadrant. The mean HU values of the pedicle wall at L1 and L5 were significantly lower than the values between L2-4 in both genders and in both age groups. Furthermore, the medial quadrant showed higher HU values than the lateral quadrant at all levels and the caudal quadrant showed higher HU values at L1-3 and lower HU values at L4-5 than the cranial quadrant. These findings may explain why there is a higher incidence of pedicle screw breach in the pedicle lateral wall.
• Ultra-purified alginate gel implantation decreases inflammatory cytokine levels, prevents intervertebral disc degeneration, and reduces acute pain after discectomy.

  Katsuro Ura, Katsuhisa Yamada, Takeru Tsujimoto, Daisuke Ukeba, Norimasa Iwasaki, Hideki Sudo

  Scientific reports 11 (1) 638 - 638 2021/01/12 

  Lumbar intervertebral disc (IVD) herniation causes severe low back pain (LBP), which results in substantial financial and emotional strains. Despite the effectiveness of discectomy, there is no existing treatment for post-operative LBP induced by progressive IVD degeneration. Two key factors of LBP are intradiscal inflammation, indicated by tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and sensory nerve ingrowth into the inner layer of the annulus fibrosus, triggered by nerve growth factor/high-affinity tyrosine kinase A (TrkA) signalling. In an animal models of discectomy, the bioresorbable ultra-purified alginate (UPAL) gel with an extremely low-toxicity has been effective in acellular tissue repair. We aimed to investigate whether UPAL gel can alleviate LBP using a rat nucleus pulposus (NP) punch model and a rabbit NP aspirate model. In both models, we assessed TNF-α and IL-6 production and TrkA expression within the IVD by immunohistochemistry. Further, histological analysis and behavioural nociception assay were conducted in the rat model. UPAL gel implantation suppressed TNF-α and IL-6 production, downregulated TrkA expression, inhibited IVD degeneration, and reduced nociceptive behaviour. Our results suggest the potential of UPAL gel implantation as an innovative treatment for IVD herniation by reducing LBP and preventing IVD degeneration after discectomy.
• Risk factors of multidrug-resistant pyogenic spondylitis in thoraco-lumbar spine: A retrospective study of 122 cases.

  Katsuhisa Yamada, Masahiko Takahata, Manabu Ito, Ken Nagahama, Akira Iwata, Tsutomu Endo, Hideki Sudo, Nobuhisa Ishiguro, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 27 (1) 95 - 100 2021/01/06 

  BACKGROUND: The number of spinal infections has been increasing in developed countries due to the increase of aged or immunosuppressed patients. Spondylitis caused by multidrug-resistant (MDR) bacterial infection often become intractable and require long-term antibiotic therapy and multiple surgeries. Therefore, it is of great importance to understand risk factors for MDR spinal infections. The aim of this study was to elucidate the risk factors for MDR bacterial spondylitis. METHODS: A total of 122 patients (82 men, 40 women; average age: 63.8 y) with thoracic/lumbar spondylitis who underwent posterolateral full-endoscopic debridement and irrigation were included. The organisms detected by this endoscopic procedure were investigated, and the incidence and risk factors for MDR bacterial infection were retrospectively analyzed. RESULTS: Cultures of specimens obtained by endoscopic procedures were positive in 78 patients (63.9%). Among 68 isolated bacteria, MDR bacteria accounted for 47.1%. Multivariate analysis showed that significant risk factors for MDR bacterial infection included autoimmune connective tissue disease (P = 0.03) and central venous catheter (P = 0.02). The incidence of MDR bacteria in patients who were administered a broad-spectrum antibiotic for more than 1 month preoperatively was 64.0%, which was significantly higher than in patients who were administered a broad-spectrum antibiotic for less than 1 month and patients who were administered a narrow-spectrum antibiotic (P < 0.01, P < 0.01, respectively). CONCLUSIONS: The significant risk factors for MDR bacterial spondylitis included immunosuppressed conditions, such as autoimmune connective tissue disease, presence of central venous catheter, and longer administration periods of a broad-spectrum antibiotic. In patients with pyogenic spondylitis who could not be controlled with previous antibiotics and whose result of culture was negative, administration of anti-MRSA antibiotics would be considered when they have the risk factors identified in this study.
• 大腿骨顆間窩外側壁における骨密度分布 前十字靱帯の大腿骨付着部に関する考察

  菅原 悠太郎, 遠藤 香織, 菱村 亮介, 松原 新史, 松岡 正剛, 小野寺 智洋, 岩崎 倫政, 岩崎 浩司, 門間 大輔, 近藤 英司

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 63 (139th suppl) 36 - 36 1343-3873 2021
• 末梢神経損傷後の好中球の時空間的変化に関する検討

  山本 康弘, 角家 健, 岩崎 倫政, 市原 理司, 石島 旨章

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 63 (139th suppl) 61 - 61 1343-3873 2021
• Hallux Valgus With Second Brachymetatarsia Discovered Accidentally: A Case Report.

  Shinji Matsubara, Tomohiro Onodera, Koji Iwasaki, Ryosuke Hishimura, Masatake Matsuoka, Eiji Kondo, Norimasa Iwasaki

  The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons 60 (5) 1060 - 1062 2021 

  Hallux valgus deformity is one of the most common foot and ankle diseases, while brachymetatarsia is a rare foot anomaly with pathological shortening of a metatarsal bone. We present a case of hallux valgus deformity possibly due to second brachymetatarsia. As the hallux valgus was associated with dorsal dislocation of the second toe that made it difficult to evaluate the length of the second toe, the patient was unaware of the second metatarsal shortening until the lengths of the toes compared by manual reposition of the second MTP joint. In this case, proximal osteotomy of the first metatarsal on the hallux valgus and single-stage bone lengthening of the second metatarsal with iliac bone grafting on the second brachymetatarsia were performed. One year after the operation, the callosity of the third toe resolved and the clinical scores were improved. In the case of a hallux valgus deformity with second dorsal dislocation of the toes, surgeons should consider that there are rare cases with second metatarsal shortening. When hallux valgus associated with second brachymetatarsia is diagnosed, second metatarsal lengthening should be considered in addition to hallux valgus surgery.
• Micro-computed tomography analysis of the lumbar pedicle wall.

  Tomoyo Y Irie, Tohru Irie, Alejandro A Espinoza Orías, Kazuyuki Segami, Norimasa Iwasaki, Howard S An, Nozomu Inoue

  PloS one 16 (7) e0253019  2021 

  BACKGROUND: Although the pedicle is routinely used as a surgical fixation site, the pedicle wall bone area fraction (bone area per unit area) and its distribution at the isthmus of the pedicle remain unknown. The bone area fraction at the pedicle isthmus is an important factor contributing to the strength of pedicle screw constructs. This study investigates the lumbar pedicle wall microstructure based on micro-computed tomography. METHODS: Six fresh-frozen cadaveric lumbar spines were analyzed. Left and right pedicles of each vertebra from L1 to L5 were resected for micro-computed tomography scanning. Data was analyzed with custom-written software to determine regional variation in pedicle wall bone area fraction. The pedicular cross-section was divided into four regions: lateral, medial, cranial, and caudal. The mean bone area fraction values for each region were calculated for all lumbar spine levels. RESULTS: The lateral region showed lower bone area fraction than the medial region at all spinal levels. Bone area fraction in the medial region was the highest at all levels except for L4, and the median values were 99.8% (95.9-100%). There were significant differences between the lateral region and the caudal region at L1, L2 and L3, but none at L4 and L5. The bone area fraction in the lateral region was less than 64% at all spinal levels and that in the caudal region was less than 67% at the L4 and L5 levels. CONCLUSIONS: This study provides initial detailed data on the lumbar pedicle wall microstructure based on micro-computed tomography. These findings may explain why there is a higher incidence of pedicle screw breach in the pedicle lateral and caudal walls.
• Impact of Smoking History on Pulmonary Metastasis-free Survival in Patients With Soft-tissue Sarcoma.

  Masatake Matsuoka, Masanori Okamoto, Tamotsu Soma, Isao Yokota, Ryuta Arai, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki, Hiroaki Hiraga

  Cancer diagnosis & prognosis 1 (2) 89 - 94 2021 

  BACKGROUND/AIM: Although smoking history is predictive of poor pulmonary metastasis-free survival (PMFS) in patients with epithelial tumors, the impact of smoking history on PMFS in those with soft-tissue sarcoma (STS) is not known. PATIENTS AND METHODS: Patients undergoing treatment for STS at our institutes between 2008 and 2017 were enrolled. Patients were excluded if they had metastatic lesion, or had a histopathological classification demonstrating small round-cell sarcoma. The impact of smoking history on PMFS and overall survival was examined with multivariate analysis using a Cox proportional hazards model. RESULTS: A total of 250 patients were retrospectively reviewed. Patients with smoking history had worse PMFS on multivariate analysis (hazard ratio=2.00, 95% confidence interval=1.12-3.60). On the other hand, smoking history did not significantly affect overall survival (hazard ratio=1.26, 95% confidence interval=0.61-2.58). CONCLUSION: Patients with STS need to be followed-up by frequent clinical assessments if they have a smoking history.
• Surgical Outcome Prediction Using a Four-Dimensional Planning Simulation System With Finite Element Analysis Incorporating Pre-bent Rods in Adolescent Idiopathic Scoliosis: Simulation for Spatiotemporal Anatomical Correction Technique.

  Hiroyuki Tachi, Koji Kato, Yuichiro Abe, Terufumi Kokabu, Katsuhisa Yamada, Norimasa Iwasaki, Hideki Sudo

  Frontiers in bioengineering and biotechnology 9 746902 - 746902 2021 

  An optimal surgical strategy for adolescent idiopathic scoliosis (AIS) is to provide maximal deformity correction while preserving spinal mobile segments as much as possible and obtaining a balanced posture. From a spatiotemporal deformity correction standpoint, we recently showed that anatomical four-dimensional (4D) spinal correction could be accomplished by curving the rod. In the surgical procedure, two rods are bent identically to confirm spinal anatomical alignment without referring to the intraoperative alignment of the deformity. Therefore, anatomically designed rods have been developed as notch-free, pre-bent rods for easier anatomical reconstruction. In addition to providing the best spinal instrumentation configurations as pre-bent rods, prediction of surgical outcome along with its biomechanical impact can be obtained by simulation of the surgical procedures with computer modeling. However, an objective model that can simulate the surgical outcome in patients with AIS has not been completely elucidated. The present study aimed to compare simulated deformity corrections based on our newly developed spatiotemporal morphological 4D planning simulation system incorporating pre-bent rods and actual deformity corrections in patients with AIS. A consecutive series of 47 patients who underwent anatomical posterior correction for AIS curves were prospectively evaluated. After multilevel facetectomy, except for the lowest instrumented segment, 11 types of pre-bent rods were used. Patient demographic data, radiographic measurements, and sagittal rod angles were analyzed within 1 week of surgery. Our simulation system incorporating pre-bent rods showed a significant correlation with the actual postoperative spinal alignment. The present study demonstrated the feasibility of our simulation system and the ability to simulate the surgical procedure using the pre-bent rods. The simulation system can be used to minimize the differences between the optimal and possible outcomes related to the instrumentation levels and rod shapes. Preoperative assumption of rod shape and length can contribute to a reduction in operative time which decreases blood loss and risk of infection. The results of the finite element analysis in the simulation system measured for each individual patient would also provide a more realistic representation of the surgical procedures.
• Unintentional Fusion in Preserved Facet Joints without Bone Grafting after Percutaneous Endoscopic Transforaminal Lumbar Interbody Fusion.

  Katsuhisa Yamada, Ken Nagahama, Yuichiro Abe, Eihiro Murota, Shigeto Hiratsuka, Masahiko Takahata, Norimasa Iwasaki

  Spine surgery and related research 5 (6) 390 - 396 2021 

  INTRODUCTION: A percutaneous endoscopic transforaminal lumbar interbody fusion (PETLIF) procedure has been previously developed. During postoperative follow-up, in some patients, bone fusion occurred between opened facet joints, despite not having bone grafting in the facet joints. Here, we investigated facet fusion's frequency and tendencies following PETLIF. METHODS: A retrospective analysis was conducted on a prospectively collected, nonrandomized series of patients. Forty-two patients (6 males and 36 females, average age: 69.9 years) who underwent single-level PETLIF at our hospital from February 2016 to March 2019 were included in this study. Patients were assessed with lumbar X-ray images and computed tomography (CT) prior to, immediately after, and 1 year after surgery. RESULTS: Pseudarthrosis was not observed in any patients, and facet fusion was observed in 26 of 42 post-PETLIF patients (61.9%) by CT 1 year postoperatively. The average interfacet distance increased from 1.3 mm preoperatively to 4.5 mm postoperatively, and facet fusion was observed under the opened conditions of 3.8 mm at 1 year. Segmental lordotic angle of the fusion segment in the lumbar X-ray images was significantly larger in the facet fusion subgroup prior to surgery, immediately following surgery, and 1 year after surgery compared to the facet non-fusion group (p=0.02, p<0.01, p=0.01, respectively). There were no significant differences in patient background, correction loss of segmental lordosis, interfacet distance, or clinical score between the facet fusion and facet non-fusion subgroups. CONCLUSIONS: Facet fusion was achieved over time within the facet joints that were opened through indirect decompression after PETLIF. We hypothesized that the preserved facet joints potentially became the base bed for spontaneous bone fusion due to the preserved facet joint capsule and surrounding soft tissue, which maintained cranio-caudal facet traffic and blood circulation in the facet joints. The complete preservation of the facet joints was a key advantage of minimally invasive lumbar interbody fusion procedures. LEVEL OF EVIDENCE: Level III.
• Angiosarcoma after revision total knee arthroplasty.

  Ryuichi Fukuda, Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Daisuke Tanaka, Hiroaki Hiraga, Hiromi Kanno-Okada, Yoshihiro Matsuno, Eiji Kondo, Norimasa Iwasaki

  The Knee 28 151 - 158 2021/01 

  BACKGROUND: Hemarthrosis after total knee arthroplasty (TKA) is a relatively rare complication. Although most cases are effectively treated with conservative therapy, some cases require angiographic embolization or surgical intervention. Angiosarcoma is a rare malignant tumor derived from the vascular endothelium with neovascular hyperplasia and mainly arises in the skin and superficial soft tissue, and less frequently in deep soft tissue and bone. Although malignant neoplasms such as angiosarcoma in the vicinity of orthopedic implants were reported, the causal relationship between development of the malignant tumor and the orthopedic implant is widely debated in the literature. CASE PRESENTATION: We report the case of a 68-year-old female with angiosarcoma that developed in the knee joint 2 years after revision TKA. The patient exhibited severe persistent bleeding, which reached 1000-1400 ml per day for 4 months. Histological analysis of the synovial tissue in the knee joint showed large cells with nuclear atypia. Immunohistochemical staining showed cells that were positive for CD31, CD34, and D2-40, and she was diagnosed with angiosarcoma. The patient underwent an amputation at the level of the thigh, and her general condition immediately improved after the operation. The patient did not exhibit bleeding from the site of amputation, and no local recurrence or distant metastases were detected 1 year after the amputation. CONCLUSIONS: To the best of our knowledge, this represents the first report of angiosarcoma 2 years after revision TKA. Further careful follow up is needed, given the high-grade malignancy.
• Histological observation on the initial stage of vascular invasion into the secondary ossification of murine femoral epiphyseal cartilage.

  Keiji Hashimoto, Tomoka Hasegawa, Tomomaya Yamamoto, Hiromi Hongo, Y Imin, Miki Abe, Alireza Nasoori, Ko Nakanishi, Haruhi Maruoka, Yasuhito Morimoto, Keisuke Kubota, Tomohiro Shimizu, Mai Haraguchi, Masahiko Takahata, Norimasa Iwasaki, Minqi Li, Toshiaki Fujisawa, Norio Amizuka

  Biomedical research (Tokyo, Japan) 42 (4) 139 - 151 2021 

  It remains unknown whether the histology of vascular invasion during secondary ossification of epiphyseal cartilage is the same as that seen in primary ossification; we examined the initial processes of vascular invasion of secondary ossification in the murine femora. Many endomucin-immunoreactive blood vessels gathered at the central region of the articular surface, and buds of soft tissue, including glomerular loops of endomucin-immunoreactive blood vessels and TNALPase- immunopositive osteoblastic cells accompanied by TRAP-positive osteoclasts, had begun to invade the epiphyseal cartilage. The invading soft tissues formed cartilage canals displaying MMP9 immunoreactivity in the tip region, and cartilaginous collagen fibrils were not visible in the vicinity of the vascular wall of the blood vessels. Thus, the histological profile marked by invading glomerular vasculature and the erosion of the cartilage matrix near the vascular walls during secondary ossification differs from that seen during primary ossification.
• Histochemical characteristics on minimodeling-based bone formation induced by anabolic drugs for osteoporotic treatment.

  Tomomaya Yamamoto, Tomoka Hasegawa, Paulo Henrique Luiz de Fraitas, Hiromi Hongo, Shen Zhao, Tsuneyuki Yamamoto, Alireza Nasoori, Miki Abe, Haruhi Maruoka, Keisuke Kubota, Yasuhito Morimoto, Mai Haraguchi, Tomohiro Shimizu, Masahiko Takahata, Norimasa Iwasaki, Minqi Li, Norio Amizuka

  Biomedical research (Tokyo, Japan) 42 (5) 161 - 171 2021 

  Modeling, the changes of bone size and shape, often takes place at the developmental stages, whereas bone remodeling-replacing old bone with new bone-predominantly occurs in adults. Unlike bone remodeling, bone formation induced by modeling i.e., minimodeling (microscopic modeling in cancellous bone) is independent of osteoclastic bone resorption. Although recently-developed drugs for osteoporotic treatment could induce minimodeling-based bone formation in addition to remodeling-based bone formation, few reports have demonstrated the histological aspects of minimodeling-based bone formation. After administration of eldecalcitol or romosozumab, unlike teriparatide treatment, mature osteoblasts formed new bone by minimodeling, without developing thick preosteoblastic layers. The histological characteristics of minimodeling-based bone formation is quite different from remodeling, as it is not related to osteoclastic bone resorption, resulting in convex-shaped new bone and smooth cement lines called arrest lines. In this review, we will show histological properties of minimodeling-based bone formation by osteoporotic drugs.
• Reliable free flaps using the microscopic parachute end-to-side technique in severe extremity injuries.

  Makoto Motomiya, Naoya Watanabe, Daisuke Kawamura, Keigo Yasui, Akira Adachi, Norimasa Iwasaki

  Journal of plastic, reconstructive & aesthetic surgery : JPRAS 73 (12) 2239 - 2260 2020/12 

  PURPOSE: Although end-to-side anastomosis is an essential method for the transfer of free flaps in traumatic extremity injuries, orthoplastic surgeons have no standard technique for performing this procedure. We describe a simple and reliable end-to-side technique is modified from that commonly used by cardiovascular surgeons for free-flap transfer. METHODS: Our microscopic parachute end-to-side technique consists primarily of two simple steps. First, the donor vessel is cut and widened with microscissors, and a wide slit is made in the recipient vessel. Second, the heel of the vessel is sutured using the parachute technique, followed by suturing of the vessel wall with a continuous suture to control blood leakage from the widely opened window. We retrospectively evaluated the clinical outcomes of 18 flaps in which the microscopic parachute end-to-side technique was used for both arterial and venous anastomoses. RESULTS: All microscopic parachute end-to-side procedures achieved flap survival without complications related to anastomosis. The mean size of the vesselotomy was 4.8 mm, and the mean expansion rate of the donor vessel was 2.7 times. CONCLUSIONS: Compared with the conventional end-to-side technique, the microscopic parachute end-to-side technique has three advantages: easy vesselotomy, avoidance of anastomotic narrowing, and easy control of blood leakage from the anastomotic site. We believe that the microscopic parachute end-to-side technique might make free flaps easier and improve their clinical outcomes in severe extremity injuries.
• Alterations of Glycosphingolipid Glycans and Chondrogenic Markers during Differentiation of Human Induced Pluripotent Stem Cells into Chondrocytes.

  Liang Xu, Hisatoshi Hanamatsu, Kentaro Homan, Tomohiro Onodera, Takuji Miyazaki, Jun-Ichi Furukawa, Kazutoshi Hontani, Yuan Tian, Rikiya Baba, Norimasa Iwasaki

  Biomolecules 10 (12) 2020/12/01 

  Due to the limited intrinsic healing potential of cartilage, injury to this tissue may lead to osteoarthritis. Human induced pluripotent stem cells (iPSCs), which can be differentiated into chondrocytes, are a promising source of cells for cartilage regenerative therapy. Currently, however, the methods for evaluating chondrogenic differentiation of iPSCs are very limited; the main techniques are based on the detection of chondrogenic genes and histological analysis of the extracellular matrix. The cell surface is coated with glycocalyx, a layer of glycoconjugates including glycosphingolipids (GSLs) and glycoproteins. The glycans in glycoconjugates play important roles in biological events, and their expression and structure vary widely depending on cell types and conditions. In this study, we performed a quantitative GSL-glycan analysis of human iPSCs, iPSC-derived mesenchymal stem cell like cells (iPS-MSC like cells), iPS-MSC-derived chondrocytes (iPS-MSC-CDs), bone marrow-derived mesenchymal stem cells (BMSCs), and BMSC-derived chondrocytes (BMSC-CDs) using glycoblotting technology. We found that GSL-glycan profiles differed among cell types, and that the GSL-glycome underwent a characteristic alteration during the process of chondrogenic differentiation. Furthermore, we analyzed the GSL-glycome of normal human cartilage and found that it was quite similar to that of iPS-MSC-CDs. This is the first study to evaluate GSL-glycan structures on human iPS-derived cartilaginous particles under micromass culture conditions and those of normal human cartilage. Our results indicate that GSL-glycome analysis is useful for evaluating target cell differentiation and can thus support safe regenerative medicine.
• Fibroma of tendon sheath of the hand in a 3-year-old boy: a case report.

  Hiroki Shibayama, Yuichiro Matsui, Daisuke Kawamura, Atsushi Urita, Chikako Ishii, Tamotsu Kamishima, Mutsumi Nishida, Ai Shimizu, Norimasa Iwasaki

  BMC musculoskeletal disorders 21 (1) 732 - 732 2020/11/10 

  BACKGROUND: Fibroma of tendon sheath (FTS) is a rare benign soft tissue tumor that often occurs in the upper extremities. It manifests as a slow-growing mass, often without tenderness or spontaneous pain. FTS occurs most commonly in people aged 20-40 years and is extremely rare in young children. Because FTS presents with atypical physical and imaging findings, it might be misdiagnosed as another soft tissue tumor such as a ganglion cyst or tenosynovial giant cell tumor (TSGCT). Although marginal resection is usually performed, a high rate of local recurrence is reported. CASE PRESENTATION: A boy aged 3 years and 1 month visited our outpatient clinic with a complaint of a mass of the left hand. An elastic hard mass approximately 20 mm in diameter could be palpated on the volar side of his left little finger. This mass was initially diagnosed as a ganglion cyst at another hospital. Ultrasonography revealed a well-circumscribed hypoechoic mass with internal heterogeneity on the flexor tendon. On magnetic resonance imaging (MRI), the mass showed iso signal intensity to muscle on T1-weighted images, and homogeneously low signal intensity to muscle on T2-weighted images. The mass was peripherally enhanced after contrast administration. FTS was initially suspected as the diagnosis on the basis of these imaging features. Because of the limited range of motion of his little finger, surgery was performed when he was 4 years old. Histopathological findings indicated the mass was well-circumscribed and contained scattered spindle cells embedded in a prominent collagenous matrix. The spindle cells contained elongated and cytologically bland nuclei with a fine chromatin pattern. Nuclear pleomorphism and multinucleated giant cells were not observed. On the basis of these findings, we made a diagnosis of FTS. One year after surgery, no signs of local recurrence were observed. CONCLUSIONS: We experienced an extremely rare case of FTS in the hand of a 3-year-old child. We especially recommend ultrasonography for hand tumors of young children to diagnose or eliminate ganglion cysts. MRI helped differentially diagnose FTS from TSGCT. Although marginal resection can be performed as a treatment, great care should be taken postoperatively because FTS has a high possibility of local recurrence.
• Lactone-Driven Ester-to-Amide Derivatization for Sialic Acid Linkage-Specific Alkylamidation.

  Jun-Ichi Furukawa, Hisatoshi Hanamatsu, Takashi Nishikaze, Hiroshi Manya, Nobuaki Miura, Hirokazu Yagi, Ikuko Yokota, Keiko Akasaka-Manya, Tamao Endo, Motoi Kanagawa, Norimasa Iwasaki, Koichi Tanaka

  Analytical chemistry 92 (21) 14383 - 14392 2020/11/03 

  Sialic acid attached to nonreducing ends of glycan chains via different linkages is associated with specific interactions and physiological events. Linkage-specific derivatization of sialic acid is of great interest for distinguishing sialic acids by mass spectrometry, specifically for events governed by sialyl linkage types. In the present study, we demonstrate that α-2,3/8-sialyl linkage-specific amidation of esterified sialyloligosaccharides can be achieved via an intramolecular lactone. The method of lactone-driven ester-to-amide derivatization for sialic acid linkage-specific alkylamidation, termed LEAD-SALSA, employs in-solution ester-to-amide conversion to directly generate stable and sialyl linkage-specific glycan amides from their ester form by mixing with a preferred amine, resulting in the easy assignments of sialyl linkages by comparing the signals of esterified and amidated glycan. Using this approach, we demonstrate the accumulation of altered N-glycans in cardiac muscle tissue during mouse aging. Furthermore, we find that the stability of lactone is important for ester-to-amide conversion based on experiments and density functional theory calculations of reaction energies for lactone formation. By using energy differences of lactone formation, the LEAD-SALSA method can be used not only for the sialyl linkage-specific derivatization but also for distinguishing the branching structure of galactose linked to sialic acid. This simplified and direct sialylglycan discrimination will facilitate important studies on sialylated glycoconjugates.
• Stress Distribution Patterns Across the Shoulder Joint in Gymnasts: A Computed Tomography Osteoabsorptiometry Study.

  Daisuke Momma, Wataru Iwamoto, Kaori Endo, Kazuki Sato, Norimasa Iwasaki

  Orthopaedic journal of sports medicine 8 (11) 2325967120962103 - 2325967120962103 2020/11 

  BACKGROUND: The distribution pattern of subchondral bone density is an indicator of stress distribution over a joint surface under long-term physiologic loading. The biomechanical characteristics of the articular surfaces of the shoulder joint in gymnasts can be determined by measuring this distribution pattern. PURPOSE: To evaluate the distribution of subchondral bone density across the shoulder joint in male collegiate gymnasts and to determine the effects of gymnastic activities on its articular surfaces under long-term loading conditions using computed tomography osteoabsorptiometry (CTOAM). STUDY DESIGN: Descriptive laboratory study. METHODS: CT image data were obtained from both shoulders of 12 asymptomatic male collegiate gymnasts (gymnast group; mean age, 19.4 years; range, 18-22 years) and 10 male collegiate volunteers (control group; mean age, 20.2 years; range, 18-22 years). The distribution pattern of subchondral bone density across the articular surfaces of each shoulder joint was assessed by CTOAM. Quantitative analysis was performed of the locations and percentages of high-density areas on the articular surface. RESULTS: Stress distribution patterns over the articular surfaces differed between the gymnasts and the controls. In the gymnasts, high-density areas were detected on the posterosuperior articular surface of the humeral head and the anterosuperior and/or posterosuperior articular surface of the glenoid. Mean bone density was greater in the gymnasts than in the controls (P < .0001). CONCLUSION: Stress distribution over the articular surfaces of the shoulder joint was affected by gymnastic activities. Stress was concentrated over the superior part of the glenohumeral joint in male collegiate gymnasts. CLINICAL RELEVANCE: The present findings suggest that gymnastic activities increase stress to the articular surfaces of the superior glenohumeral joint. This supports the notion that mechanical conditions play a crucial role in the origin of disorders particular to gymnastic activities.
• Long-term Stress Distribution Patterns Across the Ankle Joint in Soccer Players: A Computed Tomography Osteoabsorptiometry Study.

  Junki Shiota, Daisuke Momma, Takayoshi Yamaguchi, Norimasa Iwasaki

  Orthopaedic journal of sports medicine 8 (11) 2325967120963085 - 2325967120963085 2020/11 

  BACKGROUND: The distribution pattern of subchondral bone density is considered to accurately reflect the stress distribution over a joint under long-term physiologic loading. The biomechanical characteristics of the surface of the ankle joint in soccer players can be determined by measuring this distribution pattern under long-term loading. PURPOSE: To evaluate the distribution of subchondral bone density across the ankle joint in soccer players and to determine the effects of soccer activities, including kicking motion, on the ankle joint surface under long-term loading conditions by computed tomography (CT) osteoabsorptiometry (CTOAM). STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: CT imaging data were obtained from both ankles of 10 soccer players (soccer group) and 10 nonathletic volunteers (control group). The distribution patterns of subchondral bone density across the articular surface of the ankle joints were assessed by CTOAM. Quantitative analysis was performed of the locations and percentages of high-density areas on the articular surface. RESULTS: Stress distribution patterns over the ankle joint differed between the soccer players and controls. In the soccer players, the high-density areas were found in the anterior part of the distal tibia and proximal talus as well as the distal fibula. The percentages of high-density areas were greater in the soccer players compared with controls (P < .0001). CONCLUSION: Stress distribution over the articular surface of the ankle joint was affected by soccer activities. A high stress concentration was seen in soccer players in the anterior part of the tibia and talus and in the fibula; such excessive stress may lead to anterior impingement.
• Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20-89 years: A cross-sectional nationwide study in Japan.

  Keiko Yamada, Yoichi M Ito, Masao Akagi, Etsuo Chosa, Takeshi Fuji, Kenichi Hirano, Shinichi Ikeda, Hideaki Ishibashi, Yasuyuki Ishibashi, Muneaki Ishijima, Eiji Itoi, Norimasa Iwasaki, Ryoichi Izumida, Ken Kadoya, Masayuki Kamimura, Arihiko Kanaji, Hiroyuki Kato, Shunji Kishida, Naohiko Mashima, Shuichi Matsuda, Yasumoto Matsui, Toshiki Matsunaga, Naohisa Miyakoshi, Hiroshi Mizuta, Yutaka Nakamura, Ken Nakata, Go Omori, Koji Osuka, Yuji Uchio, Kazuteru Ryu, Nobuyuki Sasaki, Kimihito Sato, Masuo Senda, Akihiro Sudo, Naonobu Takahira, Hiroshi Tsumura, Satoshi Yamaguchi, Noriaki Yamamoto, Kozo Nakamura, Takashi Ohe

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 25 (6) 1084 - 1092 2020/11 

  BACKGROUND: The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. METHODS: We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. RESULTS: The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. CONCLUSION: The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex.
• Usefulness of ultrasonography for diagnosing iatrogenic spinal accessory nerve palsy after lymph node needle biopsy: a case report.

  Hisataka Suzuki, Yuichiro Matsui, Takahito Iwai, Mutsumi Nishida, Norimasa Iwasaki

  BMC musculoskeletal disorders 21 (1) 712 - 712 2020/10/31 

  BACKGROUND: Spinal accessory nerve (SAN) palsy is rare in clinical settings. Iatrogenicity is the most common cause, with cervical lymph node biopsy accounting for > 50% of cases. However, SAN palsy after lymph node needle biopsy is extremely rare, and the injury site is difficult to identify because of the tiny needle mark. CASE PRESENTATION: A 26-year-old woman was referred to our hospital with left neck pain and difficulty abducting and shrugging her left shoulder after left cervical lymph node needle biopsy. Five weeks earlier, a needle biopsy had been performed at the surgery clinic because of suspected histiocytic necrotizing lymphadenitis. No trace of the needle biopsy site was found on the neck, but ultrasonography (US) showed SAN swelling within the posterior cervical triangle. At 3 months after the injury, her activities of daily living had not improved. Therefore, we decided to perform a surgical intervention after receiving informed consent. We performed neurolysis because the SAN was swollen in the area consistent with the US findings, and nerve continuity was preserved. Shoulder shrugging movement improved at 1 week postoperatively, and the trapezius muscle manual muscle testing score recovered to 5 at 1 year postoperatively. The swelling diameter on US gradually decreased from 1.8 mm preoperatively to 0.9 mm at 6 months. CONCLUSION: We experienced a rare case in which US was useful for iatrogenic SAN palsy. Our results suggest that preoperative US is useful for localization of SAN palsy and that postoperative US for morphological evaluation of the SAN can help assess recovery.
• Three-dimensional hip joint congruity evaluation of the borderline dysplasia: Zonal-acetabular radius of curvature.

  Tohru Irie, Alejandro A Espinoza Orías, Tomoyo Y Irie, Shane J Nho, Daisuke Takahashi, Norimasa Iwasaki, Nozomu Inoue

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society 38 (10) 2197 - 2205 2020/10 

  In theory, a hemispherical acetabulum provides the ideal hip congruity in any hip position. However, it remains unknown how the three-dimensional acetabular morphology of borderline dysplastic and frank dysplastic hips compare to normal hips. This study inquires if borderline dysplastic zonal-acetabular curvatures in the anterior, superior, and posterior zones are different from normal or dysplastic hips three-dimensionally. One-hundred and fifteen hips, grouped as control (25°≤ LCEA <40°), 36 hips; borderline (20°≤ LCEA <25°), 32 hips; dysplasia (LCEA ≤20°), 47 hips were analyzed. The radii of acetabular curvature for the anterior, superior, and posterior zones were calculated as the zonal-acetabular radius of curvature (ZARC). The mean acetabular roof obliquity of the borderline (10.6 ± 4.3 [SD]°) was significantly larger than the control (3.0° ± 5.4°; P < .001) and smaller than the dysplasia (19.3° ± 5.7°; P < .001). Although the mean acetabular anteversion angle of the borderline (21.3° ± 3.7°) was significantly larger than control (17.9 ± 3.5°; P = .001), that of the borderline was not different from the dysplasia (23.3° ± 4.0°; P = .053). The mean anterior ZARC in the borderline (29.8 ± 2.6 mm) was significantly larger than the control (28.0 ± 2.2 mm; P = .011) and smaller than the dysplasia (31.5 ± 2.7 mm; P = .009). The mean superior ZARC in the borderline (25.7 ± 3.0 mm) was not different from the control (25.9 ± 2.2 mm; P = .934) or the dysplasia (25.8 ± 2.5 mm; P = .991). Although the mean posterior ZARC in the borderline (27.2 ± 2.5 mm) was not different from the control (26.4 ± 1.9 mm; P = .455), that of the borderline group was significantly smaller than the dysplasia (30.4 ± 3.3 mm; P < .001); that is, the severity of lateral under-coverage affects the anterior and/or posterior zonal-acetabular curvature.
• Computed Tomography-Based Three-Dimensional Analyses Show Similarities in Anterosuperior Acetabular Coverage Between Acetabular Dysplasia and Borderline Dysplasia.

  Tohru Irie, Alejandro A Espinoza Orías, Tomoyo Y Irie, Shane J Nho, Daisuke Takahashi, Norimasa Iwasaki, Nozomu Inoue

  Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association 36 (10) 2623 - 2632 2020/10 

  PURPOSE: (1) To compare the acetabular coverage between dysplasia, borderline dysplasia, and control acetabulum in a quantitative 3-dimensional manner; and (2) to evaluate correlations between the radiologic parameters and the 3-dimensional zonal-acetabular coverage. METHODS: We reviewed contralateral hip computed tomography images of patients 16 to 60 years of age who underwent 1 of 3 types of surgeries: eccentric rotational acetabular osteotomy, curved intertrochanteric varus osteotomy, and total hip replacement with minimum 1-year follow-up from January 2013 to April 2018. A point-cloud model of the acetabulum created from computed tomography was divided into 6 zones. Three-dimensional acetabular coverage was measured radially at intervals of 1°. Mean radial acetabular coverage for each zone was named ZAC (zonal acetabular coverage) and was compared among the 3 subgroups (control: 25° ≤lateral center-edge angle [LCEA] <40°; borderline: 20° ≤LCEA <25°; and dysplasia: LCEA ≤20°) statistically. Further, the correlations between the ZAC in each zone and the LCEA were analyzed using Pearson's correlation coefficient. RESULTS: One-hundred fifteen hips were categorized as control (36 hips), borderline (32 hips), and dysplasia (47 hips). The mean anterocranial ZAC in the borderline (87.5 ± 5.7°) was smaller than that in the control (92.6 ± 5.9°, P = .005) but did not differ compared with the dysplasia (84.5 ± 7.6°, P = .131). In contrast, the anterocaudal (71.2 ± 5.0°), posterocranial (85.0 ± 6.4°), and posterocaudal (82.4 ± 4.5°) mean ZACs in the borderline were not different from those in the control (anterocaudal, 74.3 ± 4.6°, P = .090; posterocranial, 87.9 ± 4.3°, P = .082; posterocaudal, 85.1 ± 5.0°, P = .069) respectively. Although there was a very strong positive correlation with supra-anterior ZAC and LCEA (r = 0.750, P < .001), the correlation between the anterocranial ZAC and LCEA was relatively weak (r = 0.574, P < .001). CONCLUSIONS: The anterosuperior acetabular coverage in the borderline dysplastic acetabulum is more similar to the dysplastic acetabulum than to the normal acetabulum. CLINICAL RELEVANCE: This study emphasizes the importance of evaluating not only the lateral but also the anterior coverage in borderline dysplasia.
• Non-tuberculosis Mycobacterium Tenosynovitis with Rice Bodies in a Patient with Systemic Lupus Erythematosus

  Yuichiro Fujieda, Keita Ninagawa, Yuichiro Matsui, Michihiro Kono, Tamotsu Kamishima, Norimasa Iwasaki, Tatsuya Atsumi

  Internal Medicine 59 (18) 2317 - 2320 0918-2918 2020/09/15 

  Infectious disease with various presentations in systemic lupus erythematosus often resembles lupus flare. A 37-year-old woman presented with a swollen left index finger that had not resolved, despite 7 years of immunosuppressive treatment. MRI showed rice-body formation in the flexor tendon sheath and tenosynovectomy demonstrated chronic synovitis with epithelioid granuloma. A mycobacterial culture confirmed invasive mycobacterial tenosynovitis due to Mycobacterium chelonae. The patient was treated with moxifloxacin and clarithromycin and completely recovered.
• 四次元CTを用いた肩甲上腕関節の解析

  門間 太輔, 井上 望, 遠藤 香織, 河村 太介, 瓜田 淳, 松井 雄一郎, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 94 (8) S1900 - S1900 0021-5325 2020/09
• Protective Role of Optineurin Against Joint Destruction in Rheumatoid Arthritis Synovial Fibroblasts.

  Wen Shi Lee, Masaru Kato, Eri Sugawara, Michihiro Kono, Yuki Kudo, Michihito Kono, Yuichiro Fujieda, Toshiyuki Bohgaki, Olga Amengual, Kenji Oku, Shinsuke Yasuda, Tomohiro Onodera, Norimasa Iwasaki, Tatsuya Atsumi

  Arthritis & rheumatology (Hoboken, N.J.) 72 (9) 1493 - 1504 2020/09 

  OBJECTIVE: Optineurin (OPTN) is an autophagy adaptor/receptor that acts as an intrinsic negative regulator of osteoclast differentiation. RANKL expressed by rheumatoid arthritis synovial fibroblasts (RASFs) is primarily responsible for the development of bone erosions in patients with RA. The aim of the present study was to explore the role of OPTN in the pathogenesis of joint destruction in RA. METHODS: RASFs were left untreated or incubated with tumor necrosis factor (TNF) or interferon-γ (IFNγ), and expression of OPTN by RASFs was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Expression of RANKL and osteoprotegerin (OPG) was evaluated in cultures of OPTN-reduced RASFs with or without TNF or IFNγ treatment. OPTN-reduced RASFs were cocultured with monocytes and stained for tartrate-resistant acid phosphatase (TRAP). IκBα, NF-κB1, and RelA protein levels were measured to evaluate NF-κB signaling. Expression of messenger RNA (mRNA) for matrix metalloproteinase 3 (MMP3), interleukin-6 (IL6), GATA binding protein 3 (GATA3), carbohydrate sulfotransferase 15 (CHST15), hyaluronan synthase 1 (HAS1), and GATA1 was analyzed by RT-qPCR. RESULTS: In RASFs incubated with TNF or IFNγ, OPTN expression was up-regulated and RANKL expression was increased, and these effects were further pronounced in OPTN-reduced RASFs (all P < 0.05 versus controls). OPG mRNA levels remained unchanged. Monocytes cocultured with OPTN-reduced RASFs differentiated to a greater extent into TRAP+ multinucleated cells compared to monocytes cocultured with control RASFs (P < 0.05). IκBα degradation and nuclear NF-κB1 expression following TNF treatment were both prolonged in OPTN-reduced RASFs (each P < 0.05 versus controls). MMP3 mRNA levels were up-regulated, while GATA3, CHST15, and HAS1 mRNA levels were down-regulated in OPTN-reduced RASFs (each P < 0.05 versus controls). CONCLUSION: OPTN plays a protective role in RA when it is up-regulated in RASFs in the presence of proinflammatory cytokines. Absence of OPTN might worsen RA by generating a joint-destructive state, as indicated by evidence of increased RANKL expression on RASFs and subsequent osteoclast differentiation.
• An Acute Oblique Osteotomy and Suture Ligation Procedure to Shorten the Fibula in Lateral Closing-Wedge High Tibial Osteotomy.

  Kazunori Yasuda, Eiji Kondo, Daisuke Ueda, Jun Onodera, Koji Yabuuchi, Yoshie Tanabe, Norimasa Iwasaki, Tomonori Yagi

  Arthroscopy techniques 9 (9) e1299-e1308  2020/09 

  The purpose of this description is to report an "acute oblique osteotomy and ligation" (AOOL) procedure to shorten the fibula in high tibial osteotomy (HTO). A 4-cm longitudinal skin incision is made at the lateral aspect of the leg. After the central portion of the fibula is circumferentially isolated from all the periosteal tissues, a simple osteotomy is performed at the mid-portion of the fibular diaphysis in the quasi-frontal plane, which is inclined by 25 to 30° to the long axis of the fibula. Two thin holes are created beside the osteotomy line on the lateral surface of the fibula. A polyester thread is passed through the 2 holes. After the HTO is completed, the surgeon easily reduces the displaced fibular ends using this thread. This thread is securely tied to keep the contact between the 2 osteotomized surfaces. The AOOL procedure is technically easy and safely performed. We believe that the AOOL procedure is clinically useful to shorten the fibular shaft in HTO.
• Large osteochondral defect in the lateral femoral condyle reconstructed by Atelocollagen-associated autologous chondrocyte implantation combined with anterior cruciate ligament reconstruction.

  Takuma Kaibara, Eiji Kondo, Masatake Matsuoka, Koji Iwasaki, Tomohiro Onodera, Daisuke Momma, Naoki Seito, Susumu Mikami, Norimasa Iwasaki

  BMC musculoskeletal disorders 21 (1) 494 - 494 2020/07/27 

  BACKGROUND: Articular surface damage commonly associated with rupture of the anterior cruciate ligament (ACL). Large osteochondral defect, which consists of a severe depression fracture and a large cartilage defect, need to be treated due to deformation of the articular surface as it can impact the clinical outcome of ACL reconstruction. Although autologous chondrocyte implantation is one of the useful options in such cases, it can be questioned whether the reconstruction of the ACL and osteochondral defect should be performed in one procedure alone. CASE PRESENTATION: We report a case of a 38-year-old male with a deep depression fracture extending to the edge of the lateral femoral condyle associated with ACL injury after twisting his right knee while skiing. The patient was successfully treated with tissue-engineered cartilage transplantation covered by the periosteum with an iliac bone graft combined with anatomic double-bundle ACL reconstruction. Histopathological examination of the transplanted cartilage taken at second-look arthroscopy showed a cartilage-like tissue in the middle to deep zone in which the extracellular matrix was largely stained with Safranin O. The patient was able to return to his previous level of skiing activity without any experience of knee pain. Magnetic resonance imaging at 4 years after surgery showed that the graft integrated to the border zone and subchondral bone. The operated knee showed negative Lachman test and had a full range of motion. CONCLUSIONS: To our knowledge, this is the first report of anatomic double-bundle ACL reconstruction with tissue-engineered cartilage transplantation and an iliac bone graft to restore the lateral edge of the femoral condyle.
• Association of neutrophil extracellular traps with the development of idiopathic osteonecrosis of the femoral head.

  Mayu Nonokawa, Tomohiro Shimizu, Miku Yoshinari, Yamato Hashimoto, Yusuke Nakamura, Daisuke Takahashi, Tsuyoshi Asano, Yuka Nishibata, Sakiko Masuda, Daigo Nakazawa, Satoshi Tanaka, Utano Tomaru, Norimasa Iwasaki, Akihiro Ishizu

  The American journal of pathology 190 (11) 2282 - 2289 2020/07/20 [Refereed][Not invited]
   

  Idiopathic osteonecrosis of the femoral head (ONFH) is defined as necrosis of osteocytes due to a non-traumatic ischemia of the femoral head. Iatrogenic glucocorticoid administration and habitual alcohol intake are regarded as risk factors. It has been suggested that glucocorticoid-induced activation of platelets contribute to the local blood flow disturbance of the femoral head. Both activated platelets and alcohol can induce neutrophil extracellular traps (NETs). To determine the association of NETs with the development of idiopathic ONFH, surgically resected femoral heads of patients with idiopathic ONFH and osteoarthritis (OA) were assessed for existence of NET-forming neutrophils by immunofluorescent staining. As a result, NET-forming neutrophils were present in small vessels surrounding the femoral head of patients with idiopathic ONFH but not OA. Moreover, Wistar-Kyoto rats were intravenously injected with NET-forming neutrophils or neutrophils without NET induction, and then the ischemic state of the tissue around the femoral head was evaluated by immunohistochemistry for hypoxia-inducible factor-1α (HIF-1α). NET-forming neutrophils circulated into the tissue around the femoral head, and HIF-1α expression in the tissue was higher compared to that of rats intravenously administered with neutrophils without NET induction. Furthermore, ischemic change of osteocytes was observed in the femoral head of rats given an intravenous injection of NET-forming neutrophils. The collective findings suggest that NETs are possibly associated with the development of idiopathic ONFH.
• Comparison of the Efficacy and Renal Safety of Bisphosphonate Between Low-Dose/High-Frequency and High-Dose/Low-Frequency Regimens in a Late-Stage Chronic Kidney Disease Rat Model.

  Ryo Fujita, Masahiro Ota, Dai Sato, Daigo Nakazawa, Hiromi Kimura-Suda, Fumiya Nakamura, Tomohiro Shimizu, Hideyuki Kobayashi, Norimasa Iwasaki, Masahiko Takahata

  Calcified tissue international 107 (4) 389 - 402 2020/07/15 [Refereed][Not invited]
   

  The efficacy and renal safety of low-dose/high-frequency (LDHF) dosing and high-dose/low-frequency (HDLF) dosing of bisphosphonates (BPs) are comparable in patients with normal kidney function but might be different in patients with late-stage chronic kidney disease (CKD). This study aimed to compare the efficacy and renal safety of two different dosage regimens of a BP, alendronate (ALN), in stage 4 CKD using a rat model. Male, 10-week-old Sprague-Dawley rats were subjected to either 5/6 nephrectomy or sham surgery. The animals received subcutaneous administration of vehicle (daily) or ALN in LDHF dosage regimen (LDHF-ALN: 0.05 mg/kg/day) or HDLF dosage regimen (HDLF-ALN: 0.70 mg/kg/2 weeks). Medications commenced at 20 weeks of age and continued for 10 weeks. Micro-computed tomography, histological analysis, infrared spectroscopic imaging, and serum and urine assays were performed to examine the efficacy and renal safety of the ALN regimens. Both LDHF-ALN and HDLF-ALN increased bone mass, improved micro-structure, and enhanced mechanical properties, without causing further renal impairment in CKD rats. Histologically, however, HDLF-ALN more efficiently suppressed bone turnover, leading to more mineralized trabecular bone, than LDHF-ALN in CKD rats, whereas such differences between LDHF-ALN and HDLF-ALN were not observed in sham rats. Both LDHF-ALN and HDLF-ALN showed therapeutic effects on high bone turnover osteoporosis in CKD stage 4 rats without causing further renal impairment. However, as HDLF-ALN more efficiently suppressed bone turnover than LDHF-ALN in late-stage CKD, HDLF-ALN might be more appropriate than LDHF-ALN for fracture prevention in high bone turnover osteoporosis patients with late-stage CKD.
• Predictive factors for irreversible motor paralysis following cervical spinal cord injury.

  Tsunehiko Konomi, Kota Suda, Masahiro Ozaki, Satoko Matsumoto Harmon, Miki Komatsu, Seiji Iimoto, Osahiko Tsuji, Akio Minami, Masahiko Takahata, Norimasa Iwasaki, Morio Matsumoto, Masaya Nakamura

  Spinal cord 59 (5) 554 - 562 2020/07/06 

  STUDY DESIGN: A retrospective observational study. OBJECTIVES: To elucidate predictive clinical factors associated with irreversible complete motor paralysis following traumatic cervical spinal cord injury (CSCI). SETTING: Hokkaido Spinal Cord Injury Center, Japan. METHODS: A consecutive series of 447 traumatic CSCI persons were eligible for this study. Individuals with complete motor paralysis at admission were selected and divided into two groups according to the motor functional outcomes at discharge. Initial findings in magnetic resonance imaging (MRI) and other clinical factors that could affect functional outcomes were compared between two groups of participants: those with and those without motor recovery below the level of injury at the time of discharge. RESULTS: Of the 73 consecutive participants with total motor paralysis at initial examination, 28 showed some recovery of motor function, whereas 45 remained complete motor paralysis at discharge, respectively. Multivariate logistic regression analysis showed that the presence of intramedullary hemorrhage manifested as a confined low intensity changes in diffuse high-intensity area and more than 50% of cord compression on MRI were significant predictors of irreversible complete motor paralysis (odds ratio [OR]: 8.4; 95% confidence interval [CI]: 1.2-58.2 and OR: 14.4; 95% CI: 2.5-82.8, respectively). CONCLUSION: The presence of intramedullary hemorrhage and/or severe cord compression on initial MRI were closely associated with irreversible paralysis in persons with motor complete paralysis following CSCI. Conversely, subjects with a negligible potential for recovery could be identified by referring to these negative findings.
• Long-Term Clinical and Radiological Outcomes of Primary Total Hip Arthroplasty with Modular Femoral Stem in Middle-Aged Asian Patients.

  Kaname Takahashi, Tomohiro Shimizu, Tsuyoshi Asano, Mohamad Alaa Terkawi, Norimasa Iwasaki, Daisuke Takahashi

  The Journal of arthroplasty 35 (12) 3650 - 3655 2020/06/30 [Refereed][Not invited]
   

  BACKGROUND: There is insufficient information regarding the outcome of primary total hip arthroplasty (THA) with the modular femoral stem in middle-aged patients. This study aimed to assess long-term clinical and radiological outcomes of primary THA using the original or modified modular hip system (S-ROM) in middle-aged Asian patients. METHODS: A retrospective review identified 98 primary THAs that used a modular stem and were undertaken between 1997 and 2009 in patients younger than 58 years, for whom at least 5 years of follow-up data were available. Clinical data and radiograph assessments were reviewed to analyze differences between the original and modified modular stem groups. RESULTS: The mean patient follow-up duration was 148.3 months, and the follow-up ratio was 89.1%. The Kaplan-Meier analysis revealed that the survival rate of both stems was 98.9% at 10 years and 89.8% at 15 years. Although no statistically significant differences in the survival rate were observed between the stem designs, the original stem group had increased incidence of thigh pain compared with the modified stem group. In total, 12 and 54 hips showed change in stem alignment and osteolysis, respectively. CONCLUSION: The findings of this study show that the modular stems have a high survival rate, and results suggest positive outcomes among the Asian population over the long term. Although there were very few differences between the stem designs, the results suggest that the modified modular stem could prevent thigh pain and that selection of the implant based on the bone shape is important for THA.
• Predictors of cartilage degeneration in patients with subchondral insufficiency fracture of the femoral head: a retrospective study.

  Tomohiro Shimizu, Shunichi Yokota, Yosuke Kimura, Tsuyoshi Asano, Hirokazu Shimizu, Hotaka Ishizu, Norimasa Iwasaki, Daisuke Takahashi

  Arthritis research & therapy 22 (1) 150 - 150 2020/06/22 [Refereed][Not invited]
   

  BACKGROUND: There is evidence that the cause of primary osteoarthritis (OA) is related to the changes in subchondral bone; however, the influence of subchondral insufficiency fracture (SIF) of the femoral head on the degeneration of the hip joint and the prognostic factors related to joint degeneration remain unclear. The objectives of this study were (1) to investigate the natural history of joint space width after the occurrence of SIF and (2) to investigate the associations between joint space narrowing and bone metabolic markers as well as magnetic resonance imaging (MRI) among the patients with SIF. METHODS: Between January 2010 and December 2019, 238 patients in whom band pattern of the femoral head were observed on MRI visited Hokkaido University Hospital. Among these patients, 44 hips in 41 patients were diagnosed with SIF and eligible for this retrospective study. We evaluated the joint space width (JSW) of the hip on the radiograph obtained at the first and last visits, length of the band lesion on MRI, bone mineral density by dual-energy X-ray absorptiometry, and bone metabolism markers. Similarly, the factors associated with the necessity of surgery and the progression of the narrowing of the joint space were evaluated. RESULTS: Fifteen of the 44 hips required total hip arthroplasty (THA). A significant decrease was observed in the JSW from the first visit to the final follow-up. Changes in the JSW were associated with the length of band patterns, serum type 1 procollagen-N-propeptide (P1NP), and tartrate-resistant acid phosphatase 5b (TRACP-5b) during diagnosis. Additionally, bone metabolic markers tended to be associated with the length of the band pattern. CONCLUSIONS: SIF could cause joint space narrowing and hip OA. In addition to MRI findings as prognostic predictors of SIF, as previously described, bone metabolic markers were equally associated with changes in JSW, suggesting that these parameters could be useful in predicting the prognosis of SIF. Considering that bone metabolic markers trended to be associated with the length of band pattern, they might reflect the local severity.
• Impact of lowest instrumented vertebra tilt and rotation on uninstrumented lumbar curve and L4 tilt in thoracic adolescent idiopathic scoliosis.

  Akira Iwata, Hideki Sudo, Kuniyoshi Abumi, Manabu Ito, Katsuhisa Yamada, Norimasa Iwasaki

  Journal of neurosurgery. Spine 1 - 9 2020/06/12 [Refereed][Not invited]
   

  OBJECTIVE: Controversy exists regarding the effects of lowest instrumented vertebra (LIV) tilt and rotation on uninstrumented lumbar segments in adolescent idiopathic scoliosis (AIS) surgery. Because the intraoperative LIV tilt from the inferior endplate of the LIV to the superior sacral endplate is not stable after surgery, the authors measured the LIV angle of the instrumented thoracic spine as the LIV angle of the construct. This study aimed to evaluate the effects of the LIV angle of the construct and the effects of LIV rotation on the postoperative uninstrumented lumbar curve and L4 tilt in patients with thoracic AIS. METHODS: A retrospective correlation and multivariate analysis of a prospectively collected, consecutive, nonrandomized series of patients at a single institution was undertaken. Eighty consecutive patients with Lenke type 1 or type 2 AIS treated with posterior correction and fusion were included. Preoperative and 2-year postoperative radiographic measurements were the outcome measures for this study. Outcome variables were postoperative uninstrumented lumbar segments (LIV tilt, LIV translation, uninstrumented lumbar curve, thoracolumbar/lumbar [TL/L] apical vertebral translation [AVT], and L4 tilt). The LIV angle of the construct was measured from the orthogonal line drawn from the upper instrumented vertebra to the LIV. Multiple stepwise linear regression analysis was conducted between outcome variables and patient demographics/radiographic measurements. There were no study-specific biases related to conflicts of interest. RESULTS: Predictor variables for postoperative uninstrumented lumbar curve were the postoperative LIV angle of the construct, number of uninstrumented lumbar segments, and flexibility of TL/L curve. Specifically, a lower postoperative uninstrumented lumbar curve was predicted by a lower absolute value of the postoperative LIV angle of the construct (p < 0.0001). Predictor variables for postoperative L4 tilt were postoperative LIV rotation, preoperative L4 tilt, and preoperative uninstrumented lumbar curve. Specifically, a lower postoperative L4 tilt was predicted by a lower absolute value of postoperative LIV rotation (p < 0.0001). CONCLUSIONS: The LIV angle of the construct significantly affected the LIV tilt, uninstrumented lumbar curve, and TL/L AVT. LIV rotation significantly affected the LIV translation and L4 tilt.
• Therapeutic effects and adaptive limits of an acellular technique by ultrapurified alginate (UPAL) gel implantation in canine osteochondral defect models.

  Tomohiro Onodera, Rikiya Baba, Yasuhiko Kasahara, Toshihiko Tsuda, Norimasa Iwasaki

  Regenerative therapy 14 154 - 159 2020/06 

  Background: The aim of this study was to clarify the objective therapeutic effects of an acellular technique by ultrapurified alginate (UPAL) gel implantation in canine osteochondral defect models. Methods: Two osteochondral defects (diameters: 3.0 and 5.0 mm) were created on each patellar groove in both knees of 10 dogs. Defects were divided into four groups (n = 10 each): Group 1, untreated 3.0-mm defect; Group 2, 3.0-mm defect with UPAL gel; Group 3, untreated 5.0-mm defect; and Group 4, 5.0-mm defect with UPAL gel. All surgical procedures were performed by individuals unfamiliar with the technique at an independent institution. Articular surfaces were evaluated grossly and histologically at 27 weeks after operation. Results: UPAL gel-treated osteochondral defects showed significantly improved gross appearance in Group 4 and histological appearance in Groups 2 and 4. Reparative tissues in the 3.0-mm defect with UPAL gel were replaced by hyaline-like cartilage tissue. The 5.0-mm defects with UPAL gel were mostly covered with fibrocartilaginous tissue, whereas UPAL gel-untreated defects mostly remained uncovered by any tissue. Conclusions: Although an acellular technique using UPAL gel implantation significantly enhanced osteochondral repair in canines, reparative tissues of the large defect with alginate gel comprised of fibrocartilaginous tissue. This surgical technique is effective, especially for small cartilage injuries. Further improvements are required before clinical application in cases of severe osteochondral defects in humans.
• Clinical Outcomes and Complications During and After Medial Open-Wedge High Tibial Osteotomy Using a Locking Plate: A 3- to 7-Year Follow-up Study.

  Koji Yabuuchi, Eiji Kondo, Jun Onodera, Tomohiro Onodera, Tomonori Yagi, Norimasa Iwasaki, Kazunori Yasuda

  Orthopaedic journal of sports medicine 8 (6) 2325967120922535 - 2325967120922535 2020/06 

  Background: Outcomes and complications at mid- or long-term follow-up after medial open-wedge high tibial osteotomy (MOWHTO) with the TomoFix locking plate have not been fully evaluated. Purpose: To evaluate the complications and midterm clinical outcomes after MOWHTO using a TomoFix. Study Design: Case series; Level of evidence, 4. Methods: Enrolled in this study were 80 patients (85 knees) who underwent MOWHTO with the TomoFix locking plate between 2009 and 2013. There were 66 women and 14 men, with a mean age of 61.5 years at the time of surgery. The diagnosis was medial osteoarthritis in 76 knees and spontaneous osteonecrosis of the knee in 9 knees. Metal removal and second-look arthroscopy were performed in all cases. Clinical and radiological examinations were performed at final follow-up after surgery (mean, 4.5 years). Results: The mean Japanese Orthopaedic Association score and Knee injury and Osteoarthritis Outcome Score improved significantly from pre- to postoperatively (P < .0001). The weightbearing line percentage shifted to pass through a point 67.7% lateral from the medial edge of the tibial plateau. The Caton-Deschamps index changed significantly from 0.88 to 0.66 at final follow-up (P < .0001). The mean posterior tibial slope changed significantly from 8.9° to 11.9° at final follow-up (P < .0001). Limb length was significantly increased after MOWHTO (10.3 mm; P < .0001). During plate removal, 14 locking screws were found to be broken in 9 knees (10.6%). The articular cartilage grade of the patellofemoral joint was significantly higher in the second arthroscopy than in the first arthroscopy (P < .0001). The cumulative rate of all complications was 41.2%, with major complications (ie, those requiring additional or extended treatment) in 24.7%. Conclusion: Postoperative outcome scores indicated significant improvement after MOWHTO, although the cumulative rate of all complications was 41.2% and the rate of major complications was 24.7%. These results indicate that MOWHTO with the TomoFix is a technically demanding procedure. Careful preoperative planning and meticulous surgical technique are needed to decrease the incidence of complications associated with MOWHTO.
• Siglec-15-targeting therapy protects against glucocorticoid-induced osteoporosis of growing skeleton in juvenile rats.

  Dai Sato, Masahiko Takahata, Masahiro Ota, Chie Fukuda, Tomoka Hasegawa, Tomomaya Yamamoto, Norio Amizuka, Eisuke Tsuda, Akiko Okada, Yoshiharu Hiruma, Ryo Fujita, Norimasa Iwasaki

  Bone 135 115331 - 115331 2020/06 

  Effective treatment of juvenile osteoporosis, which is frequently caused by glucocorticoid (GC) therapy, has not been established due to limited data regarding the efficacy and adverse effects of antiresorptive therapies on the growing skeleton. We previously demonstrated that sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) targeting therapy, which interferes with osteoclast terminal differentiation in the secondary, but not primary, spongiosa, increased bone mass without adverse effects on skeletal growth, whereas bisphosphonate, a first-line treatment for osteoporosis, increased bone mass but impaired long bone growth in healthy growing rats. In the present study, we investigated the efficacy of anti-Siglec-15 neutralizing antibody (Ab) therapy against GC-induced osteoporosis in a growing rat model. GC decreased bone mass and deteriorated mechanical properties of bone, due to a disproportionate increase in bone resorption. Both anti-Siglec-15 Ab and alendronate (ALN) showed protective effects against GC-induced bone loss by suppressing bone resorption, which was more pronounced with anti-Siglec-15 Ab treatment, possibly due to a reduced negative impact on bone formation. ALN induced histological abnormalities in the growth plate and morphological abnormalities in the long bone metaphysis but did not cause significant growth retardation. Conversely, anti-Siglec-15 Ab did not show any negative impact on the growth plate and preserved normal osteoclast and chondroclast function at the primary spongiosa. Taken together, these results suggest that anti-Siglec-15 targeting therapy could be a safe and efficacious prophylactic therapy for GC-induced osteoporosis in juvenile patients.
• Computed tomography osteoabsorptiometry changes following ulnar shortening osteotomy: observations in nine patients

  Yuichi Hasegawa, Yuichiro Matsui, Norimasa Iwasaki

  Journal of Hand Surgery (European Volume) 45 (5) 527 - 529 1753-1934 2020/06
• Role of Chondrocytes in the Development of Rheumatoid Arthritis Via Transmembrane Protein 147-Mediated NF-κB Activation.

  Mitsutoshi Ota, Yuki Tanaka, Ikuma Nakagawa, Jing-Jing Jiang, Yasunobu Arima, Daisuke Kamimura, Tomohiro Onodera, Norimasa Iwasaki, Masaaki Murakami

  Arthritis & rheumatology (Hoboken, N.J.) 72 (6) 931 - 942 2020/06 

  OBJECTIVE: We have previously reported that the coactivation of NF-κB and STAT3 in nonimmune cells, including synovial fibroblasts, enhances the expression of NF-κB target genes and plays a role in chronic inflammation and rheumatoid arthritis (RA). This study was undertaken to examine the role of NF-κB activation in chondrocytes and better understand the pathogenesis of RA. Furthermore, transmembrane protein 147 (TMEM147) was investigated as a representative NF-κB activator in chondrocytes. METHODS: Clinical samples from RA patients were analyzed by immunohistochemistry. Specimens obtained from patients with polydactyly were used as control samples. The functional contribution of chondrocytes and TMEM147 to arthritis was examined in several murine models of RA. In vitro experiments (quantitative polymerase chain reaction, RNA interference, immunoprecipitation, and confocal microscopy) were performed to investigate the mechanism of action of TMEM147 in chondrocytes. RESULTS: Samples obtained from RA patients and mouse models of RA showed coactivation of NF-κB and STAT3 in chondrocytes (P < 0.001). This coactivation induced a synergistic expression of NF-κB targets in vitro (P < 0.01). Chondrocyte-specific deletion of STAT3 significantly suppressed the development of cytokine-induced RA (P < 0.01). TMEM147 was highly expressed in chondrocytes from RA patient samples and the mouse models of RA. Gene silencing of TMEM147 or anti-TMEM147 antibody treatment inhibited the cytokine-mediated activation of NF-κB in vitro (P < 0.01) and suppressed cytokine-induced RA in vivo (P < 0.01). Mechanistically, TMEM147 molecules acted as scaffold proteins for the NF-κB complex, which included breakpoint cluster region and casein kinase 2, and enhanced NF-κB activity. CONCLUSION: These results suggest that chondrocytes play a role in the development of RA via TMEM147-mediated NF-κB activation and indicate a novel therapeutic strategy for RA.
• Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis.

  Masanari Hamasaki, Mohamad Alaa Terkawi, Tomohiro Onodera, Yuan Tian, Taku Ebata, Gen Matsumae, Hend Alhasan, Daisuke Takahashi, Norimasa Iwasaki

  Scientific reports 10 (1) 7558 - 7558 2020/05/05 [Refereed][Not invited]
   

  Accumulating evidence suggests that synovitis is associated with osteoarthritic process. Macrophages play principal role in development of synovitis. Our earlier study suggests that interaction between cartilage fragments and macrophages exacerbates osteoarthritic process. However, molecular mechanisms by which cartilage fragments trigger cellular responses remain to be investigated. Therefore, the current study aims at analyzing molecular response of macrophages to cartilage fragments. To this end, we analyzed the transcriptional profiling of murine macrophages exposed to cartilage fragments by RNA sequencing. A total 153 genes were differentially upregulated, and 105 genes were down-regulated in response to cartilage fragments. Bioinformatic analysis revealed that the most significantly enriched terms of the upregulated genes included scavenger receptor activity, integrin binding activity, TNF signaling, and toll-like receptor signaling. To further confirm our results, immunohistochemical staining was performed to detected regulated molecules in synovial tissues of OA patients. In consistence with RNA-seq results, MARCO, TLR2 and ITGα5 were mainly detected in the intima lining layer of synovial tissues. Moreover, blockade of TLR2 or ITGα5 but not Marco using specific antibody significantly reduced production of TNF-α in stimulated macrophages by cartilage fragments. Our data suggested that blocking TLR2 or ITGα5 might be promising therapeutic strategy for treating progressive osteoarthritis.
• Atypical osteochondroma of the hamate that presented clinically as carpal tunnel syndrome: report of an extremely rare case and literature review.

  Makoto Motomiya, Taiki Sakazaki, Norimasa Iwasaki

  BMC musculoskeletal disorders 21 (1) 231 - 231 2020/04/13 

  BACKGROUND: Osteochondroma is a benign tumor that occurs mainly at the metaphysis of long bones and seldom arises from carpal bones. We describe an extremely rare case of osteochondroma of the hamate without a typical cartilaginous cap and with a spiky bony protrusion in an elderly patient. CASE PRESENTATION: A 78-year-old right-handed female housekeeper had a multilobed osteochondroma of the hamate, which caused carpal tunnel syndrome and irritation of the flexor tendons. Radiological examinations showed a morphological abnormality of the hamate comprising a spiky bony protrusion into the carpal tunnel and a free body proximal to the pisiform. Open carpal tunnel release and resection of the spiky bony protrusion on the hook of the hamate were performed. The flexor digitorum profundus tendons of the ring and little fingers displayed synovitis and partial laceration in the carpal tunnel. Histological examination also showed atypical findings: only a few regions of cartilaginous tissue were seen in the spiky bony protrusion, whereas the free body proximal to the pisiform contained thick cartilaginous tissue such as a cartilaginous cap typical of osteochondroma. We speculated that the bony protrusion to the carpal tunnel had been eroded by mechanical irritation caused by gliding of the flexor tendon and had resulted in the protruding spiky shape with less cartilaginous tissue. The fractured cartilaginous cap had moved into the cavity within the carpal tunnel proximal to the pisiform and had become a large free body. CONCLUSIONS: Osteochondroma of the carpal bone may take various shapes because the carpal bone is surrounded by neighboring bones and tight ligaments, which can restrict tumor growth. This type of tumor is likely to present with various symptoms because of the close proximity of important structures including nerves, tendons, and joints. The diagnosis of osteochondroma of the carpal bone may be difficult because of its rarity and atypical radiological and histological findings, such as the lack of a round cartilaginous cap. We suggest that surgeons should have a detailed understanding of this condition and should make a definitive diagnosis based on the overall findings.
• Effects of Unweighting on Gait Kinematics During Walking on a Lower-Body Positive Pressure Treadmill in Patients with Hip Osteoarthritis

  Yoshiaki Kataoka, Tomohiro Shimizu, Ryo Takeda, Shigeru Tadano, Yuki Saito, Satoshi Osuka, Tomoya Ishida, Mina Samukawa, Tohru Irie, Daisuke Takahashi, Norimasa Iwasaki, Harukazu Tohyama

  BMC musculoskeletal disorders 22 (1) 46 - 46 2020/04/10 [Refereed][Not invited]
   

  Background: Hip osteoarthritis (OA) is a musculoskeletal condition that makes walking difficult due to pain induced by weight-bearing activity. Treadmills that support body weight reduce the load on the lower limbs, and those equipped with a lower-body positive pressure (LBPP) device, developed as a new method for unweighting, significantly reduce pain in patients with knee OA. However, the effects of unweighting on gait kinematics remain unclear in patients with hip OA. Therefore, we investigated the effects of unweighting on kinematics in patients with hip OA during walking on a treadmill equipped with an LBPP device.Methods: Fifteen women with hip OA and fifteen age-matched female controls wore a three-dimensional motion analysis system and walked at a comfortable speed on the LBPP treadmill. Data regarding hip pain using a numeric rating scale under three different unweighting conditions (100%, 75%, and 50% bodyweight) were collected. Sagittal plane lower-limb kinematics under each condition were calculated and compared.Results: In the hip OA group, numerical rating scores at the unweighted condition were significantly decreased compared to the 100% bodyweight condition, and sagittal kinematics in the hip and knee joints significantly decreased compared to the healthy controls. In both groups, unweighting significantly decreased the peak hip flexion angle and increased the peak ankle plantarflexion angle during walking.Conclusions: Although unweighting by LBPP decreased pain in the hip OA group, gait kinematics did not improve despite less load on the hip joint. Therefore, clinicians should consider the benefits of pain reduction, rather than improved gait, when considering LBPP treadmill for patients with hip OA.
• 脊髄損傷治療の現状と脊髄再生-東京オリンピック、パラリンピックを記念して- 急性期病院が脊髄再生に果たすべき役割 つなぐべき希望

  須田 浩太, 松本 聡子, 小松 幹, 大西 貴士, 渡辺 尭仁, 飛鳥井 光, 宇都宮 祥弘, 東條 泰明, 三浪 明男, 角家 健, 高畑 雅彦, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 94 (2) S26 - S26 0021-5325 2020/03
• 脊髄損傷患者における出血性イベントの危険因子とは? 完全運動麻痺と直接作用型傾向抗凝固薬はハイリスクである

  渡辺 尭仁, 須田 浩太, 小松 幹, 松本 聡子, 大西 貴士, 飛鳥井 光, 宇都宮 祥弘, 東條 泰明, 三浪 明男, 高畑 雅彦, 岩崎 倫政

  Journal of Spine Research (一社)日本脊椎脊髄病学会 11 (3) 591 - 591 1884-7137 2020/03
• A Minimum 5-Year Longitudinal Study of a New Total Wrist Arthroplasty in Patients With Rheumatoid Arthritis

  Yuichiro Matsui, Akio Minami, Makoto Kondo, Jyunichi Ishikawa, Makoto Motomiya, Norimasa Iwasaki

  The Journal of Hand Surgery 45 (3) 255.e1 - 255.e7 0363-5023 2020/03 

  PURPOSE: To evaluate the longitudinal clinical outcomes using a new semiconstrained wrist prosthesis for the treatment of severe rheumatoid arthritis of the wrist. METHODS: Twenty patients with rheumatoid arthritis (20 wrists) underwent total wrist arthroplasty with the prosthesis in a clinical trial. The preoperative Larsen classification was grade IV in 16 wrists and grade V in 4 wrists. Assessments were performed before surgery, 1.5 years after surgery, and at final follow-up (≥ 5 years after surgery) using the visual analog scale for pain, Figgie wrist score, Japanese version of the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, and plain radiographs. RESULTS: At final follow-up, no patient had wrist pain. The preoperative flexion-extension arc at final follow-up was similar to the preoperative range. The mean 1.5-year postoperative Figgie score was significantly improved and was unchanged at final follow-up. The DASH score significantly improved from before surgery to 1.5 years after surgery; the DASH score was improved further at final follow-up, but not significantly. Five of the 19 wrists evaluated had radiographic findings indicating carpal component loosening at final follow-up; however, all patients with the loosening were asymptomatic and had not undergone revision surgery. CONCLUSIONS: Total wrist arthroplasty using this wrist prosthesis leads to favorable clinical outcomes regarding pain relief and retained range of wrist motion. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
• Bone marrow mesenchymal stem cells combined with ultra-purified alginate gel as a regenerative therapeutic strategy after discectomy for degenerated intervertebral discs.

  Daisuke Ukeba, Hideki Sudo, Takeru Tsujimoto, Katsuro Ura, Katsuhisa Yamada, Norimasa Iwasaki

  EBioMedicine 53 102698 - 102698 2020/03 [Refereed][Not invited]
   

  BACKGROUND: Because the regenerative ability of intervertebral discs (IVDs) is restricted, defects caused by discectomy may induce insufficient tissue repair leading to further IVD degeneration. An acellular bioresorbable biomaterial based on ultra-purified alginate (UPAL) gel was developed to fill the IVD cavity and prevent IVD degeneration. However, an acellular matrix-based strategy may have limitations, particularly in the elderly population, who exhibit low self-repair capability. Therefore, further translational studies involving product combinations, such as UPAL gel plus bone marrow-derived mesenchymal stem cells (BMSCs), are required to evaluate the regenerative effects of BMSCs embedded in UPAL gel on degenerated IVDs. METHODS: Rabbit BMSCs and nucleus pulposus cells (NPCs) were co-cultured in a three-dimensional (3D) system in UPAL gel. In addition, rabbit or human BMSCs combined with UPAL gel were implanted into IVDs following partial discectomy in rabbits with degenerated IVDs. FINDINGS: Gene expression of NPC markers, growth factors, and extracellular matrix was significantly increased in the NPC and BMSC 3D co-culture compared to that in each 3D mono-culture. In vivo, whereas UPAL gel alone suppressed IVD degeneration as compared to discectomy, the combination of BMSCs and UPAL gel exerted a more potent effect to induce IVD regeneration. Similar IVD regeneration was observed using human BMSCs. INTERPRETATION: These findings demonstrate the therapeutic potential of BMSCs combined with UPAL gel as a regenerative strategy following discectomy for degenerated IVDs. FUNDING: Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.
• MicroRNA-9 ameliorates destructive arthritis through down-regulation of NF-κB1-RANKL pathway in fibroblast-like synoviocytes.

  Wen Shi Lee, Shinsuke Yasuda, Michihiro Kono, Yuki Kudo, Sanae Shimamura, Michihito Kono, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Tomohiro Shimizu, Tomohiro Onodera, Norimasa Iwasaki, Tatsuya Atsumi

  Clinical immunology (Orlando, Fla.) 212 108348 - 108348 2020/03 [Refereed][Not invited]
   

  We investigated the effect of miR-9 on fibroblast-like synoviocytes (FLS) from RA patients and animal arthritis model. The binding of miR-9 to NF-κB1 3'UTR was analyzed by luciferase reporter assay and immunoprecipitation. ChIP assay and luciferase promoter assay were performed to identify the binding of NF-κB1 to RANKL promoter and its activity. FLS were treated with miR-9/anti-miR-9 to evaluate cell proliferation and the expression of RANKL. Therapeutic effect of intra-articular miR-9 was evaluated in type-II collagen-induced arthritis in rats. miR-9 bound to the 3'-UTR of NF-κB1 and downregulated NF-κB1. NF-κB1 bound to RANKL promoter and increased the promoter activity of RANKL. RANKL was downregulated by miR-9. Proliferation of FLS was increased by miR-9 inhibitor. miR-9 dampened experimental arthritis by lowering inflammatory state, reducing RANKL and osteoclasts formation. Our findings revealed miR-9-NF-κB1-RANKL pathway in RA-FLS, further, miR-9 ameliorated inflammatory arthritis in vivo which propose therapeutic implications of miR- 9 in RA.
• Which Contributes to Meniscal Repair, the Synovium or the Meniscus? An In Vivo Rabbit Model Study With the Freeze-Thaw Method.

  WooYoung Kim, Tomohiro Onodera, Eiji Kondo, Mohamad Alaa Terkawi, Kentaro Homan, Ryosuke Hishimura, Norimasa Iwasaki

  The American journal of sports medicine 363546520906140 - 363546520906140 2020/02/27 [Refereed][Not invited]
   

  BACKGROUND: During meniscal tissue repair, the origin of the reparative cells of damaged meniscal tissue remains unclear. HYPOTHESIS: Comparison of the influence between meniscal and synovial tissues on meniscal repair by the in vivo freeze-thaw method would clarify the origin of meniscal reparative cells. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 48 mature Japanese white rabbits were divided into 4 groups according to the tissue (meniscal or synovial) that received freeze-thaw treatment. The meniscus of each group had a 2 mm-diameter cylindrical defect filled with alginate gel. Macroscopic and histologic evaluations of the reparative tissues were performed at 1, 3, and 6 weeks postoperatively. Additional postoperative measurements included cell density, which was the number of meniscal cells in the cut area per cut area (mm2) of meniscus; cell density ratio, which was the cell density of the sample from each group per the average cell density of the intact meniscus; and cell death rate, which was the number of cells stained by propidium iodide per the number of cells stained by Hoechst 33342 of the meniscal tissue adjacent to the defect. RESULTS: The macroscopic and histologic evaluations of the non-synovium freeze-thaw groups were significantly superior to those of the synovium freeze-thaw groups at 3 and 6 weeks postoperatively. Additionally, the meniscal cell density ratio and cell death rate in the freeze-thaw groups were significantly lower than those in the non-meniscal freeze-thaw groups at 3 and 6 weeks postoperatively. CONCLUSION: The freeze-thawed meniscus recovered few cells in its tissue even after 6 weeks. However, the defect was filled with fibrochondrocytes and proteoglycan when the synovium was intact. On the basis of these results, it is concluded that synovial cells are the primary contributors to meniscal injury repair. CLINICAL RELEVANCE: In meniscal tissue engineering, there is no consensus on the best cell source for meniscal repair. Based on this study, increasing the synovial activity and contribution should be the main objective of meniscal tissue engineering. This study can establish the foundation for future meniscal tissue engineering.
• Two case reports of 'locked spondyloptosis': the most severe traumatic cervical spondyloptosis with locked spinous process and vertebral arch into the spinal canal.

  Takeru Tsujimoto, Kota Suda, Satoko Matsumoto Harmon, Miki Komatsu, Masahiko Takahata, Norimasa Iwasaki, Akio Minami

  Spinal cord series and cases 6 (1) 10 - 10 2020/02/18 [Refereed][Not invited]
   

  INTRODUCTION: Traumatic cervical spondyloptosis, including compressive-extension stage 5 of Allen's classification of cervical spine injuries, is commonly observed; however, cases involving locked spinous process and vertebral arch into the spinal canal are extremely rare. CASE PRESENTATION: We present two individuals with spondyloptosis of C7 with locked spinous process of C6 and the vertebral arch into the spinal canal. Closed reduction was unable to be performed due to rigid locking of the cervical spine in the first case, whereas preoperative closed reduction was achieved with mild traction in a prone position after general anaesthesia in the second case. These two individuals underwent spinal fusion via a posterior approach after open or closed reduction. Six months after surgery, both individuals exhibited significant neurological recovery and acquired a stable gait. DISCUSSION: To the best of our knowledge, this is the first report of traumatic 'locked spondyloptosis' of the spinous process and vertebral arch into the spinal canal. Although high-grade compressive-extension injuries are usually repaired using a combined anterior-posterior approach, repair is possible with a posterior approach alone with reliable anchors, such as pedicle screws or multiple lateral mass screws. Urgent open reduction may be required for locked spondyloptosis when closed reduction is invalid due to rigid locking of the cervical spine.
• Is Bone Non-Union, Vertebral Deformity, or Spino-Pelvic Malalignment the Best Therapeutic Target for Amelioration of Low Back Pain after Osteoporotic Vertebral Fracture?

  Akira Iwata, Masahiro Kanayama, Fumihiro Oha, Yukitoshi Shimamura, Tomoyuki Hashimoto, Masahiko Takahata, Norimasa Iwasaki

  Spine 45 (13) E760-E767  2020/02/11 [Refereed][Not invited]
   

  STUDY DESIGN: Cohort study (level 3). OBJECTIVE: To identify independent risk factors for residual low back pain (LBP) following osteoporotic vertebral fracture (OVF). SUMMARY OF BACKGROUND DATA: Non-union has been proposed as the primary cause of residual LBP following OVF. However, LBP can occur even when union is maintained. Other reported causes of LBP after OVF include vertebral deformities and spino-pelvic malalignment. METHODS: Sixty-seven patients with single-level thoracolumbar OVF who had not received previous osteoporotic treatment were enrolled. Conservative treatment was conducted using a soft lumbosacral orthosis plus osteoporosis drugs, either weekly alendronate (bisphosphonate) or daily teriparatide. Pain scores, kyphosis angle of fractured vertebra (VKA), and spino-pelvic alignment, including pelvic incidence minus lumbar lordosis (PI-LL), were assessed periodically during treatment. Radiographic union was evaluated independently by three specialists at 24 weeks post-admission. Patients were divided by pain scores >40% at 24 weeks into the LBP (n = 36) and non-LBP (n = 31) groups. Temporal changes and statistical associations were examined to identify risk factors for LBP at 24 weeks. RESULTS: At 24 weeks, 25% of OVFs failed to achieve union. The LBP group consisted of 71% of non-union and 48% of union cases. Stepwise multinomial regression analysis showed VKA at 24 weeks over 25° was significant risk factor for the LBP group (odds ratio: 6.24, 95% confidence interval: 1.77 - 22.02, p = 0.004). Significant differences in VKA emerged during treatment in the LBP group, but PI-LL showed the tendency not to change throughout the treatment period. Non-union was correlated with VKA (area under the curve: 0.864). CONCLUSION: Although spino-pelvic malalignment is considered as a pre-existing factor for LBP, VKA exacerbated by non-union predominantly led to LBP after a new OVF. Each incidence of OVF should be treated to limit further morphological changes to the fractured vertebra. LEVEL OF EVIDENCE: 3.
• Charcot Arthropathy of the Shoulder Joint in a Patient with Guillain-Barré Syndrome: A Case Report.

  Tetsuya Yamaguchi, Atsushi Urita, Takeshi Endo, Mitsutoshi Ota, Norimasa Iwasaki

  JBJS case connector 10 (1) e0530  2020 

  CASE: A 53-year-old woman presented with Charcot arthropathy of the shoulder joint secondary to residual sensory neuropathy of Guillain-Barré syndrome, which was accompanied by swollen shoulder and restricted range of motion of the right shoulder. We performed a reverse shoulder arthroplasty (RSA). The range of motion had improved 15 months postoperatively, and there was no postoperative complication after RSA. CONCLUSION: Clinicians should be aware that Guillain-Barré syndrome can cause Charcot arthropathy of the shoulder joint. RSA is regarded as a useful treatment, although careful follow-up is needed.
• Three-dimensional curvature mismatch of the acetabular radius to the femoral head radius is increased in borderline dysplastic hips.

  Tohru Irie, Alejandro A Espinoza Orías, Tomoyo Y Irie, Shane J Nho, Daisuke Takahashi, Norimasa Iwasaki, Nozomu Inoue

  PloS one 15 (4) e0231001  2020 

  Whether borderline hip dysplasia is pathologic remains unclear. In order to evaluate the three-dimensional joint congruity, this study sought to answer the question: are borderline dysplastic hip curvature mismatch and eccentricity between the acetabulum and the femoral head different from dysplastic or control hips three-dimensionally? The 113 hips, categorized as: dysplastic (LCEA ≤ 20°), 47 hips; borderline (20° ≤ LCEA < 25°), 32 hips; and control (25° ≤ LCEA < 35°), 34 hips; were evaluated. Three-dimensional (3D) femoral and coxal bone models were reconstructed from CT images. Using a custom-written Visual C++ routine, the femoral head and acetabular radii of curvature, and the femoral head and the acetabular curvature center were calculated. Then the ratio of the acetabular radius to the femoral head radius (3D curvature mismatch ratio), and the distance between the acetabular curvature center and the femoral head center (3D center discrepancy distance) were calculated. These indices were compared statistically among the three groups using Tukey's post hoc test. The mean 3D curvature mismatch ratio in the borderline (1.13 ± 0.05) was smaller than in the dysplasia (1.23 ± 0.08, p < 0.001), and larger than in the control (1.07 ± 0.02, p < 0.001). The mean 3D center discrepancy distance in the borderline (3.2 ± 1.4 mm) was smaller than in the dysplasia (4.8 ± 2.3, p < 0.001) and larger than in the control (1.6 ± 0.7, p < 0.001). These results demonstrated that three-dimensional congruity of the borderline dysplastic hip is impaired, but its incongruity is not as severe as in dysplastic hips. The 3D curvature mismatch ratio and the 3D center discrepancy distance can be valuable signs of joint congruity in patients with borderline dysplasia. However, future studies are necessary to clarify any associations between curvature mismatch and pathogenesis of osteoarthritis in borderline dysplasia.
• Coronal Hamate Fractures with Carpometacarpal Dislocation Treated Effectively Using Headless Compression Screws with Percutaneous Pinning Fixation by Using the 2-Directional Approach: A Report of 2 Cases.

  Hirokazu Shimizu, Tomoya Matsuhashi, Akira Fukushima, Yusuke Menjo, Yoshihiro Hojo, Norimasa Iwasaki

  JBJS case connector 10 (2) e0361  2020 

  CASE: Coronal shear fractures of the hamate are relatively rare injuries. Surgical intervention is recommended for displaced fractures. However, there is no established surgical procedure for the displaced coronal shear fractures of the hamate. Therefore, we present 2 cases of the displaced coronal hamate fracture with metacarpal dislocations, which were successfully managed with open reduction and internal fixation, using the headless compression screw by the 2-directional approach. CONCLUSION: Our procedure ensured that the screw's distal end captured the hamate hook, and the displaced bone fragments were reduced considerably in both cases.
• Blockade of XCL1/Lymphotactin Ameliorates Severity of Periprosthetic Osteolysis Triggered by Polyethylene-Particles.

  Yuan Tian, Mohamad Alaa Terkawi, Tomohiro Onodera, Hend Alhasan, Gen Matsumae, Daisuke Takahashi, Masanari Hamasaki, Taku Ebata, Mahmoud Khamis Aly, Hiroaki Kida, Tomohiro Shimizu, Keita Uetsuki, Ken Kadoya, Norimasa Iwasaki

  Frontiers in immunology 11 1720 - 1720 2020 

  Periprosthetic osteolysis induced by orthopedic implant-wear particles continues to be the leading cause of arthroplasty failure in majority of patients. Release of the wear debris results in a chronic local inflammatory response typified by the recruitment of immune cells, including macrophages. The cellular mediators derived from activated macrophages favor the osteoclast-bone resorbing activity resulting in bone loss at the site of implant and loosening of the prosthetic components. Emerging evidence suggests that chemokines and their receptors are involved in the progression of periprosthetic osteolysis associated with aseptic implant loosening. In the current study, we investigated the potential role of chemokine C-motif-ligand-1 (XCL1) in the pathogenesis of inflammatory osteolysis induced by wear particles. Expressions of XCL1 and its receptor XCR1 were evident in synovial fluids and tissues surrounding hip-implants of patients undergoing revision total hip arthroplasty. Furthermore, murine calvarial osteolysis model induced by ultra-high molecular weight polyethylene (UHMWPE) particles was used to study the role of XCL1 in the development of inflammatory osteolysis. Mice received single injection of recombinant XCL1 onto the calvariae after implantation of particles exhibited significantly greater osteolytic lesions than the control mice. In contrast, blockade of XCL1 by neutralizing antibody significantly reduced bone erosion and the number of bone-resorbing mature osteoclasts induced by UHMWPE particles. In consistence with the results, transplantation of XCL1-soaked sponge onto calvariae caused osteolytic lesions coincident with excessive infiltration of inflammatory cells and osteoclasts. These results suggested that XCL1 might be involved in the development of periprosthetic osteolysis through promoting infiltration of inflammatory cells and bone resorbing-osteoclasts. Our further results demonstrated that supplementing recombinant XCL1 to cultured human monocytes stimulated with the receptor activator of nuclear factor kappa-B ligand (RANKL) promoted osteoclastogenesis and the osteoclast-bone resorbing activity. Moreover, recombinant XCL1 promoted the expression of inflammatory and osteoclastogenic factors, including IL-6, IL-8, and RANKL in human differentiated osteoblasts. Together, these results suggested the potential role of XCL1 in the pathogenesis of periprosthetic osteolysis and aseptic loosening. Our data broaden knowledge of the pathogenesis of aseptic prosthesis loosening and highlight a novel molecular target for therapeutic intervention.
• Conservatively Treated Femoral Intertrochanteric Fracture With Early Asymptomatic Novel Coronavirus Disease 2019 (COVID-19): A Case Report.

  Yuki Suzuki, Toshihiko Kasashima, Kazutoshi Hontani, Yasuhiro Yamamoto, Kanako Ito, Liang Xu, Masatake Matsuoka, Koji Iwasaki, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki

  Geriatric orthopaedic surgery & rehabilitation 11 2151459320969380 - 2151459320969380 2020 

  Introduction: The ongoing outbreak of novel coronavirus disease 2019 (COVID-19) is a worldwide problem. Although diagnosing COVID-19 in fracture patients is important for selecting treatment, diagnosing early asymptomatic COVID-19 is difficult. We describe herein a rare case of femoral intertrochanteric fracture concomitant with early asymptomatic novel COVID-19. Case presentation: An 87-year-old Japanese woman was transferred to our emergency room with a right hip pain after she fell. She had no fever, fatigue, or respiratory symptoms on admission and within the 14 days before presenting to our hospital, and no specific shadow was detected in chest X-ray. However, chest computed tomography (CT) was performed considering COVID-19 pandemic, and showed ground-glass opacities with consolidation in the dorsal segment of the right lower lung field. Then, qualitative real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) was carried out and turned out to be positive. She was diagnosed right femoral intertrochanteric fracture with concomitant COVID-19 infection. Conservative treatment was applied to the fracture due to infection. After admission, fever and oxygen demand occurred but she recovered from COVID-19. Throughout the treatment period, no cross-infection from the patient was identified in our hospital. Conclusion: This case highlights the importance of considering chest CT as an effective screening method for infection on hospital admission in COVID-19-affected areas, especially in trauma patients with early asymptomatic novel COVID-19.
• Long-term pulmonary function after posterior spinal fusion in main thoracic adolescent idiopathic scoliosis.

  Young Man Byun, Takahiro Iida, Katsuhisa Yamada, Kuniyoshi Abumi, Terufumi Kokabu, Akira Iwata, Norimasa Iwasaki, Hideki Sudo

  PloS one 15 (6) e0235123  2020 [Refereed][Not invited]
   

  BACKGROUND: Adolescent idiopathic scoliosis (AIS) patients typically undergo surgical treatment as teenagers, follow-ups of >5 years are necessary to evaluate effects on peak pulmonary reserves. However, limited data is available regarding the long-term (>10 years) effects of surgical intervention on pulmonary function (PF) in patients with thoracic AIS. OBJECTIVE: To provide long-term (>10 years) information on the PF after posterior spinal fusion for treating main thoracic AIS. We especially investigated whether surgical correction for AIS led to impairment of the PF. METHODS: A total of 35 patients with main thoracic AIS treated with posterior spinal fusion were included. Radiographs and PF tests, which included measurements of absolute and percent-predicted values of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1), were evaluated. RESULTS: Mean age at surgery was 14.9 years (12-19 years). Mean follow-up period was 15.1 years (10-24 years). Although the final postoperative FVC and FEV1 absolute values were higher than the preoperative values, the differences were not statistically significant (p = 0.22 and p = 0.08, respectively). Percent-predicted FVC and FEV1 values between preoperative and final postoperative measurements were not statistically different (p = 0.63 and p = 0.29, respectively). However, for the patients who presented with pulmonary impairment preoperatively, both the FVC and FEV1 significantly increased at the final follow-up (p = 0.01 and p = 0.01, respectively). CONCLUSIONS: Long-term results of AIS patients who underwent posterior spinal fusion in main thoracic curves demonstrated absolute and percent-predicted PF test values similar to preoperative measurements; thus, indicating that posterior spinal fusion did not decrease PF 15 years after the initial surgery. Instead, patients with severe preoperative pulmonary impairment might show some degree of improvement after surgery.
• Evaluation of Residual Human-Induced Pluripotent Stem Cells in Human Chondrocytes by Cell Type-Specific Glycosphingolipid Glycome Analysis Based on the Aminolysis-SALSA Technique.

  Takuji Miyazaki, Hisatoshi Hanamatsu, Liang Xu, Tomohiro Onodera, Jun-Ichi Furukawa, Kentaro Homan, Rikiya Baba, Toshisuke Kawasaki, Norimasa Iwasaki

  International journal of molecular sciences 21 (1) 2019/12/28 [Refereed][Not invited]
   

  Cartilage damage may eventually lead to osteoarthritis because it is difficult to repair. Human-induced pluripotent stem cell (iPSC)-derived chondrocytes may potentially be used to treat cartilage damage, but the tumorigenicity of iPSCs is a major concern for their application in regenerative medicine. Many glycoconjugates serve as stem cell markers, and glycosphingolipids (GSLs) including H type 1 antigen (Fucα1-2Galβ1-3GlcNAc) have been expressed on the surface of iPSCs. The purpose of the present study was to investigate whether GSL-glycome analysis is useful for quality control of residual iPSCs in chondrocytes. We performed GSL-glycome analysis of undifferentiated iPSCs in chondrocytes by combining glycoblotting and aminolysis-sialic acid linkage-specific alkylamidation (SALSA) method, enabling the detection of small quantities of iPSC-specific GSL-glycans from 5 × 104 cells. Furthermore, we estimated the residual amount of iPSCs using R-17F antibody, which possesses cytotoxic activity toward iPSCs that is dependent on the Lacto-N-fucopentaose I (LNFP I) of GSL. Moreover, we could detect a small number of LNFP I during mesenchymal stem cells (MSCs) differentiation from iPSCs. This is the first demonstration that GSL-glycome analysis is useful for detecting undifferentiated iPSCs, and can thereby support safe regenerative medicine.
• Caspase-3 knockout inhibits intervertebral disc degeneration related to injury but accelerates degeneration related to aging.

  Takashi Ohnishi, Katsuhisa Yamada, Koji Iwasaki, Takeru Tsujimoto, Hideaki Higashi, Taichi Kimura, Norimasa Iwasaki, Hideki Sudo

  Scientific reports 9 (1) 19324 - 19324 2019/12/18 [Refereed][Not invited]
   

  Approximately 40% of people under 30 and over 90% of people 55 or older suffer from moderate-to-severe levels of degenerative intervertebral disc (IVD) disease in their lumbar spines. Surgical treatments are sometimes effective; however, the treatment of back pain related to IVD degeneration is still a challenge; therefore, new treatments are necessary. Apoptosis may be important in IVD degeneration because suppressing cell apoptosis inside the IVD inhibits degeneration. Caspase-3, the primary effector of apoptosis, may be a key treatment target. We analyzed caspase-3's role in two different types of IVD degeneration using caspase-3 knockout (Casp-3 KO) mice. Casp-3 KO delayed IVD degeneration in the injury-induced model but accelerated it in the age-induced model. Our results suggest that this is due to different pathological mechanisms of these two types of IVD degeneration. Apoptosis was suppressed in the IVD cells of Casp-3 KO mice, but cellular senescence was enhanced. This would explain why the Casp-3 KO was effective against injury-induced, but not age-related, IVD degeneration. Our results suggest that short-term caspase-3 inhibition could be used to treat injury-induced IVD degeneration.
• Perioperative complications of spine surgery in patients 80 years of age or older: a multicenter prospective cohort study.

  Takamasa Watanabe, Masahiro Kanayama, Masahiko Takahata, Itaru Oda, Kota Suda, Yuichiro Abe, Junichiro Okumura, Yoshihiro Hojo, Norimasa Iwasaki

  Journal of neurosurgery. Spine 1 - 9 1547-5654 2019/12/17 [Refereed][Not invited]
   

  OBJECTIVE: The number of spine surgeries performed in elderly patients is consistently increasing. However, to date the prevalence of and risk factors for perioperative complications remain unclear, especially in patients 80 years of age or older. This study had two goals: 1) determine the perioperative complications of spine surgery associated with patients 80 years of age or older; and 2) investigate the risk factors for perioperative systemic complications. METHODS: In this paper, the authors describe a multicenter prospective cohort study. Seven spine centers with board-certified spine surgeons participated in this all-case investigation. A total of 270 consecutively enrolled patients (109 males and 161 females), 80 years of age or older, underwent spine surgery between January and December 2017. Patients with trauma, infection, or tumor were excluded in this cohort. Perioperative complications were defined as adverse events that occurred intraoperatively or within 30 days postoperatively. The patients' preoperative health status was determined using the following means of assessment: 1) the Charlson Comorbidity Index, 2) the American Society of Anesthesiologists Physical Status Classification System, 3) the Eastern Cooperative Oncology Group Performance Status (ECOG-PS), 4) the presence of sarcopenia, and 5) the Geriatric Nutritional Risk Index. Associations among patient age, preoperative health status, surgical factors (instrumentation surgery, operation time, number of spinal levels treated, and estimated blood loss), and perioperative systemic complications were analyzed. RESULTS: Overall perioperative, surgical site, and minor systemic complications were observed in 20.0%, 8.1%, and 14.8% of patients, respectively. Major systemic complications, on the other hand, were not observed. The reoperation rate was low-only 4.1%. Multivariate analysis revealed that the ECOG-PS (p = 0.013), instrumentation surgery (p = 0.024), and an operation time longer than 180 minutes (p = 0.016) were associated with minor systemic complications. CONCLUSIONS: To the best of the authors' knowledge, this is the first multicenter prospective all-case investigation of perioperative complications of spine surgery in elderly patients. Although decreased daily activity (ECOG-PS), instrumentation surgery, and longer operation time were associated with minor systemic complications, no major systemic complications were observed in these elderly patients. Thus, spine surgery can be safely performed in elderly patients 80 years of age or older.
• Long-term stress distribution patterns across the wrist joint in gymnasts assessed by computed tomography osteoabsorptiometry.

  Daisuke Momma, Wataru Iwamoto, Norimasa Iwasaki

  The Journal of hand surgery, European volume 44 (10) 1098 - 1100 2019/12
• Trapeziectomy with Ligament Reconstruction and Interposition Arthroplasty Using the Palmaris Longus Tendon: An Average 5-Year Follow-up.

  Daisuke Kawamura, Tadanao Funakoshi, Norimasa Iwasaki

  Clinics in orthopedic surgery 11 (4) 453 - 458 2019/12 

  BACKGROUND: Trapeziectomy with ligament reconstruction and tendon interposition (LRTI) with the flexor carpi radialis (FCR) tendon is one of the most common procedures for the treatment of trapeziometacarpal osteoarthritis. We modified the LRTI, using the palmaris longus (PL) tendon instead of the FCR tendon. The aim of this retrospective study was to evaluate the clinical outcomes of trapeziectomy with our modified LRTI procedure at a mean follow-up of 5 years. METHODS: Fourteen thumbs in 13 patients (12 women) with a mean age of 64 years (range, 50 to 77 years) were available for assessment for a mean duration of 62 months (range, 41 to 97 months). The patients were evaluated subjectively and objectively. RESULTS: The modified LRTI procedure provided good pain relief, motion, strength, and stability without any severe complications related to the PL tendon harvesting. Radiography showed that compared to the preoperative status, the trapezial space decreased by about 40% at the final follow-up. CONCLUSIONS: The modified LRTI procedure provided significant subjective and objective improvements without severe complications particularly related to the harvesting of the PL tendon. This procedure is a valuable surgical option for trapeziometacarpal osteoarthritis and could be a useful salvage modality if the FCR tendon ruptures during the conventional LRTI procedure.
• Breast cancer cells expressing cancer-associated sialyl-Tn antigen have less capacity to develop osteolytic lesions in a mouse model of skeletal colonization.

  Fujita R, Hamano H, Kameda Y, Arai R, Shimizu T, Ota M, Sato D, Kobayashi H, Iwasaki N, Takahata M

  Clinical & experimental metastasis 36 (6) 539 - 549 0262-0898 2019/12 [Refereed][Not invited]
   

  Breast cancer is one of the most prevalent malignancies in women, and approximately 75-80% of patients with advanced breast cancer develop bone metastasis. Expression of the cancer-associated carbohydrate antigen sialyl-Tn (STn) in breast cancer is associated with a poor prognosis; however, involvement of STn in the development of metastatic bone lesions remains unclear. We investigated whether STn expression on breast cancer cells influences intraosseous tumor growth and bone response in mice models of skeletal colonization. STn-positive (STn+) breast cancer cells were generated by stable transfection of an expression vector encoding ST6GaLNAc I into the breast cancer cell line MDA-MB-231. Parental MDA-MB-231 cells not expressing STn antigen were used as STn-negative (STn-) breast cancer cells. Contrary to expectations, STn expression attenuated the development of destructive bone lesions in the in vivo mice models. An in vitro study demonstrated that STn expression impaired adhesion of MDA-MB-231cells to bone marrow stromal cells. This finding in vitro was also confirmed by another breast cancer cell line MCF-7. Cell adhesion to fibronectin and type I collagen was also impaired in STn+ MDA-MB-231 cells compared to that in STn- MDA-MB-231 cells, suggesting integrin dysfunction. Given that the integrin β1 subunit is the main carrier of the STn epitope, it is likely that changes in glycan structure impaired the adhesive capacity of β1 integrin in the bone environment, leading to attenuation of tumor cell engraftment. In conclusion, breast cancer cells expressing STn antigen had less capacity for skeletal colonization, possibly due to impaired adhesive capability.
• Impact of Surgical Timing on Clinical Outcomes in Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction Using Hamstring Tendon Autografts.

  Rikiya Baba, Eiji Kondo, Koji Iwasaki, Zenta Joutoku, Jun Onodera, Tomohiro Onodera, Tomonori Yagi, Norimasa Iwasaki, Kazunori Yasuda

  Orthopaedic journal of sports medicine 7 (11) 2325967119880553 - 2325967119880553 2019/11 

  Background: To date, no studies have analyzed the influence on clinical outcomes of the interval between an anterior cruciate ligament (ACL) injury and double-bundle (DB) reconstruction with hamstring tendon autografts. Hypotheses: (1) Performing ACL reconstruction sooner after an injury will reduce postoperative anterior and rotatory knee instability, (2) postoperative range of knee motion or functional results will not be affected by different intervals between injury and surgery, and (3) preoperative isokinetic peak torque of the quadriceps and hamstring muscles will be lower in patients undergoing surgery earlier, while postoperative muscle strength will not be affected by surgery timing. Study Design: Cohort study; Level of evidence, 3. Methods: This study was conducted on a total of 171 patients who had undergone anatomic DB ACL reconstruction with hamstring tendon autografts. The patients were divided into 3 groups based on the time to surgery: (1) ≤1 month after the injury (group E; n = 25), (2) between 1 and 3 months after the injury (group M; n = 72), and (3) >3 months after the injury (group D; n = 74). Patients were assessed for a minimum of 2 years after surgery. Results: Concerning postoperative anterior laxity, 1-way analysis of variance demonstrated a significant difference (P = .0274) among the 3 groups. Anterior laxity was significantly less in group E than in group D (P = .0206). Spearman rank correlation analysis showed a significant correlation (ρ = 0.200; P = .0327) between anterior knee laxity and time to surgery. Also, a significant correlation (P = .0461) was found between the degree of the pivot-shift phenomenon and time to surgery. There were no significant differences in loss of knee extension or flexion among the 3 groups, nor were there any differences in the Lysholm knee score or International Knee Documentation Committee grade. Postoperatively, there were no significant differences in peak torque of the quadriceps or hamstring muscles among the 3 groups. Conclusion: Early DB reconstruction led to significantly less anterior laxity compared with delayed reconstruction. There were no significant differences in postoperative range of knee motion or functional results among the 3 time intervals between injury and surgery in this study.
• Retrospective study to evaluate the clinical significance of a second rise in C-reactive protein level following instrumented spinal fusion surgery.

  Fujita R, Takahata M, Kokabu T, Oda I, Kajino T, Hisada Y, Takeuchi H, Iwasaki N

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 24 (6) 963 - 968 0949-2658 2019/11 [Refereed][Not invited]
   

  BACKGROUND: This study aimed to identify the incidence and causes of a second rise in C-reactive protein (CRP) levels following spinal instrumentation surgery and to help determine how an abnormal CRP response should be interpreted and managed during postoperative care. METHODS: The medical records of 948 patients who underwent instrumented spine fusion surgery and met the inclusion criteria were retrospectively reviewed to assess the frequency and causes of a second rise (SR) of CRP. A SR of CRP was defined when the CRP level after postoperative day 7 increased by more than 0.5 mg/dl from that at the previous time-point. The diagnostic cut-off value of CRP elevation for detection of surgical site infection (SSI) was determined. Cut-off values were analyzed using receiver operating characteristic (ROC) curves. Bayes' theorem was used to determine blood test posterior probabilities for SSI-positive cases using cutoff values of re-evaluated CRP levels. RESULTS: SR of CRP occurred in 107 of the 948 patients. Of the patients with SR of CRP, 38 (35%) patients had developed SSI, 33 (31%) patients had causes other than SSI, and the remaining 36 patients had unidentified causes. Among the patients with SR, excluding those with causes other than SSI, the best diagnostic cut-off value of SR for detection of SSI was 3.04 mg/dl (area under the curve was 0.74). The posterior test probability was 84.4%. CONCLUSIONS: For patients with SR of CRP, who had no causes other than SSI, an SR value of 3.04 mg/dl correlated with a high probability of developing SSI.
• Assessment of valgus laxity after release of the medial structure in medial open-wedge high tibial osteotomy: an in vivo biomechanical study using quantitative valgus stress radiography.

  Dai Sato, Eiji Kondo, Koji Yabuuchi, Jun Onodera, Tomohiro Onodera, Tomonori Yagi, Keita Sakamoto, Akira Takasawa, Norimasa Iwasaki, Kazunori Yasuda

  BMC musculoskeletal disorders 20 (1) 481 - 481 2019/10/27 

  BACKGROUND: To perform medial open-wedge high tibial osteotomy (OWHTO), surgeons expose the medial-proximal tibia by releasing or cutting the superficial layer of the medial collateral ligament (sMCL). Biomechanically, the sMCL provides primary restraint against valgus forces. Therefore, any release of the sMCL can cause valgus instability of the knee joint. The purpose of this study was to assess valgus laxity after release of the medial structure of the knee during OWHTO. METHODS: Between 2009 and 2015, 84 consecutive patients (93 knees) who underwent OWHTO using a locking plate were enrolled in this study. All patients underwent radiological examinations before surgery, during surgery, 1 year after surgery, and after plate removal to objectively assess valgus laxity. The medial joint space (MJS) and the joint line convergence angle (JLCA) of the knee were evaluated using quantitative valgus stress radiography. Clinical evaluation was performed 2 years after surgery. RESULTS: The mean functional knee score improved significantly, from 65.5 to 91.1 points (p < 0.0001). The mechanical axis percentage shifted to pass through a point 69.7% lateral from the medial edge of the tibial plateau. The MJS and JLCA increased significantly during OWHTO surgery (11.0 mm, 7.4 °, p < 0.0001). However, no significant differences were noted in the MJS and JLCA among preoperative, 1-year postoperative periods and after plate removal. CONCLUSION: Valgus laxity was significantly greater after release of the sMCL. However, no significant differences were noted in valgus laxity in preoperative, 1-year postoperative periods and after plate removal. Complete release of the sMCL did not cause postoperative valgus laxity after OWHTO surgery. TRIAL REGISTRATION: Trial registration number: No.012-0360.
• Occipitoatlantoaxial rotatory fixation caused by minor traumatic occipitoatlantal rotatory fixation with compensatory counter-rotation in atlantoaxial joint: A case report.

  Hirokazu Shimizu, Tsutomu Endo, Masahiko Takahata, Keigo Yasui, Yohei Sodeyama, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 27 (4) 956 - 959 0949-2658 2019/10/10 [Refereed][Not invited]
  
• Evidence for cell-contact factor involvement in neurite outgrowth of dorsal root ganglion neurons stimulated by Schwann cells.

  Takeshi Endo, Ken Kadoya, Daisuke Kawamura, Norimasa Iwasaki

  Experimental physiology 104 (10) 1447 - 1454 2019/10 

  NEW FINDINGS: What is the central question of this study? Although the factors secreted from Schwann cells that promote axonal growth in the peripheral nervous system have been well studied, the effect of cell-contact factors on Schwann cells remains to be determined. What is the main finding and its importance? This study demonstrates that Schwann cells stimulate neurite outgrowth by direct contact with neurites and by secreting factors. Notably, the effect of cell-contact factors in neurite outgrowth is comparable to that of secreted factors, indicating that the identification of cell surface molecules on Schwann cells that promote neurite outgrowth could lead to development of a new therapy for peripheral nervous system injury. ABSTRACT: Schwann cells (SCs) play a variety of roles in the regeneration process after injury to the peripheral nervous system. The factors secreted from SCs that promote axonal growth have been well studied. However, the involvement of cell-contact factors on SCs remains to be determined. Here, we demonstrate a significant contribution of a cell-contact mechanism in the effect of SCs on promotion of neuronal outgrowth. Neurite outgrowth of adult sensory neurons from dorsal root ganglia was quantified during co-culture with adult SCs. Direct contact of SCs with neurons was eliminated by culturing SCs on an insert placed in the same well; this resulted in a 51% reduction in the length of neurite outgrowth. In addition, when dorsal root ganglion neurons were cultured on sparsely seeded SCs, neurons that made contact with SCs on their neurites had 118% longer neurites than neurons that lacked contacts with SCs. Collectively, these findings provide evidence that SCs stimulate neurite outgrowth via direct contact with neurites in addition to secreting factors. The identification of cell surface molecules on SCs that promote neurite outgrowth could lead to development of a new therapy for peripheral nervous system injury.
• Ten years change in post-fracture care for hip fracture patients.

  Shimodan S, Sato D, Takahashi K, Nakamura Y, Hyakkan R, Watanabe T, Hishimura R, Ota M, Shimizu H, Hojo Y, Hasegawa Y, Chubachi T, Yasui K, Tsujimoto T, Tsukuda Y, Asano T, Takahashi D, Takahata M, Iwasaki N, Shimizu T

  Journal of bone and mineral metabolism 38 (2) 222 - 229 0914-8779 2019/10 [Refereed][Not invited]
   

  INTRODUCTION: This multicenter, retrospective study aimed to clarify the changes in postoperative care provided by orthopaedic surgeons after hip fractures and clarify the incidence of secondary fractures requiring surgery. MATERIALS AND METHODS: Subjects were patients with hip fracture treated surgically in seven hospitals during the 10-year period from January 2008 to December 2017. Data on patient demographics, comorbidities, preoperative and postoperative osteoporosis treatments, and secondary fractures were collected from the medical records. RESULTS: In total, 4764 new hip fractures in 982 men and 3782 women (mean age: 81.3 ± 10.0 years) were identified. Approximately 10% of patients had a history of osteoporosis drug treatment and 35% of patients received postoperative drug treatment. The proportion of patients receiving postoperative drug therapy increased by approximately 10% between 2009 and 2010, 10% between 2010 and 2011, and 10% between 2011 and 2013. Although the rate of secondary fractures during the entire period and within 3 years decreased from 2011, the rate of secondary fracture within 1 year remained at around 2% every year. CONCLUSIONS: The approval of new osteoporosis drugs and the establishment of osteoporosis liaison services have had a positive effect on the use of postoperative drug therapy in the orthopedic field. Our finding that the rate of secondary fracture within 1 year of the initial fracture remained around 2% every year, despite improvements in postoperative drug therapy, suggests that both rehabilitation for preventing falls and early postoperative drug therapy are essential to prevent secondary fractures.
• 椎間板再生への挑戦 高純度硬化性ゲルによる椎間板再生

  辻本 武尊, 須藤 英毅, 東藤 正浩, 山田 勝久, 大西 貴士, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 93 (8) S1595 - S1595 0021-5325 2019/09
• A multi-centre study to explore the feasibility and acceptability of collecting data for complex regional pain syndrome clinical studies using a core measurement set: Study protocol.

  Sharon Grieve, Florian Brunner, Lisa Buckle, Francois Gobeil, Hitoshi Hirata, Norimasa Iwasaki, Lorimer Moseley, Gudson Sousa, Jean-Jacques Vatine, Nicole Vaughan-Spickers, Jijun Xu, Candida McCabe

  Musculoskeletal care 17 (3) 249 - 256 2019/09 

  OBJECTIVES: This international, multicentre study will inform the final data collection tools and processes which will comprise the first international, clinical research registry for complex regional pain syndrome (CRPS). This study will: (a) test the feasibility and acceptability of collecting outcome measurement data using a patient reported, questionnaire core measurement set (COMPACT [Core Outcome Measurement set for complex regional PAin syndrome Clinical sTudies]); and (b) test and refine an electronic data management system to collect and manage the data. METHODS: A maximum of 240 adults, meeting the Budapest diagnostic clinical criteria for CRPS type I or II, will be recruited across eight countries. The COMPACT questionnaire will be completed on two occasions: at baseline (T1) and 6 months later (T2). At T2, participants will choose to complete COMPACT using a paper or electronic version. Participants will be asked to feed back on their experience of completing COMPACT via a questionnaire. A separate questionnaire will ask clinicians to feed back their experience of data collection. ANALYSIS: The study is not aiming to derive statistically significant data but to ascertain the practicalities of collecting data, using the COMPACT questionnaire set, across a range of different cultures and populations. At the end of the study, a single workshop will be convened to review the findings and agree the final documents and processes for the international registry.
• Minimum Ten-Year Outcomes of Partial Ulnar Nerve Transfer for Restoration of Elbow Flexion in Patients with Upper Brachial Plexus Injury.

  Nagano Y, Kawamura D, Terkawi A, Urita A, Matsui Y, Iwasaki N

  The journal of hand surgery Asian-Pacific volume 24 (3) 283 - 288 2424-8355 2019/09 [Refereed][Not invited]
   

  Background: Partial ulnar nerve transfer to the biceps motor branch of the musculocutaneous nerve (Oberlin's transfer) is a successful approach to restore elbow flexion in patients with upper brachial plexus injury (BPI). However, there is no report on more than 10 years subjective and objective outcomes. The purpose of this study was to clarify the long-term outcomes of Oberlin's transfer based on the objective evaluation of elbow flexion strength and subjective functional evaluation of patients. Methods: Six patients with BPI who underwent Oberlin's transfer were reviewed retrospectively by their medical records. The mean age at surgery was 29.5 years, and the mean follow-up duration was 13 years. The objective functional outcomes were evaluated by biceps muscle strength using the Medical Research Council (MRC) grade at preoperative, postoperative, and final follow-up. The patient-derived subjective functional outcomes were evaluated using the Quick Disability of the Arm, Shoulder, and Hand (QuickDASH) questionnaire at final follow-up. Results: All patients had MRC grade 0 (M0) or 1 (M1) elbow flexion strength before operation. Four patients gained M4 postoperatively and maintained or increased muscle strength at the final follow-up. One patient gained M3 postoperatively and at the final follow-up. Although one patient achieved M4 postoperatively, the strength was reduced to M2 due to additional disorder. The mean score of QuickDASH was 36.5 (range, 7-71). Patients were divided into two groups; three patients had lower scores and the other three patients had higher scores of QuickDASH. Conclusions: Oberlin's transfer is effective in the restoration of elbow flexion and can maintain the strength for more than 10 years. Patients with upper BPI with restored elbow flexion strength and no complicated nerve disorders have over ten-year subjective satisfaction.
• Effects of Intradiscal Injection of Local Anesthetics on Intervertebral Disc Degeneration in Rabbit Degenerated Intervertebral Disc.

  Ura K, Sudo H, Iwasaki K, Tsujimoto T, Ukeba D, Iwasaki N

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society 37 (9) 1963 - 1971 0736-0266 2019/09 [Refereed][Not invited]
   

  Analgesic discoblock is widely used for the diagnosis or treatment of discogenic low back pain by injecting local anesthetics. The purpose of this study was to investigate the deleterious effects of local anesthetics on degenerated rabbit intervertebral disks (IVDs) using an organotypic culture model and in vivo long-term follow-up model. To induce IVD degeneration, a rabbit annular puncture model was used. For the organotypic culture model, degenerated IVDs were harvested 1 month after the initial annular puncture and cultured for 3 or 7 days after intradiscal injection of local anesthetics (1% lidocaine and 0.5% bupivacaine). To perform in vivo analysis, local anesthetics were injected into degenerated IVDs, and IVDs were prepared for histological analysis after 6 or 12 months. In the organotypic model, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive nucleus pulposus (NP) cells were significantly increased in the bupivacaine group compared with the other groups. In the in vivo study, the number of NP cells was significantly decreased in the saline and local anesthetics groups compared with the untreated control and puncture-only groups. However, there was no significant difference among the saline, lidocaine, and bupivacaine groups. In addition, histological analysis showed no significant difference of IVD degeneration among the puncture-only, saline, lidocaine, and bupivacaine groups. Although bupivacaine induced apoptotic NP cell death in the organotypic culture model, in vivo observations did not show any definitive proof to suggest that local anesthetics were capable of promoting degeneration in the degenerated IVD, except for pressurized injection-induced damage. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1963-1971, 2019.
• Mechanical Analysis of Notch-Free Pre-Bent Rods for Spinal Deformity Surgery.

  Yamada K, Sudo H, Iwasaki N, Chiba A

  Spine 45 (6) E312-E318  0362-2436 2019/09 [Refereed][Not invited]
   

  STUDY DESIGN: Experimental study of spinal rod as per the American Society for Testing Materials (ASTM) F2193 methodology for static and dynamic four-point bending. OBJECTIVE: The hypotheses underlying this study were that the notch-free, curved rod would have a significantly higher ultimate load and fatigue strength compared with conventional notched curved rods. This study aimed to analyze the mechanical properties of notch-free curved rods compared with conventional notched rods. SUMMARY OF BACKGROUND DATA: The goal of instrumented spinal fusion in the management of spinal deformities is to realign the spine and maintain the correction and stability in order to obtain arthrodesis. Although rod curvature could play an important role, intraoperative contouring of the straight rod induces notches into the rod, leading to decreased fatigue strength. METHODS: Commercially produced titanium alloy (ϕ6.0 mm) and cobalt chromium alloy (ϕ5.5 mm) spinal rods were assessed by four-point bending tests in accordance with the ASTM F2193. RESULTS: Static four-point bending tests for the curved spinal rods showed that cobalt chromium alloy rods had significantly higher stiffness compared with titanium alloy rods. Notch-free cobalt chromium alloy rods had a significantly higher ultimate load than the conventional notched cobalt chromium alloy and titanium alloy rods. The dynamic four-point bending test showed that force/displacement at a minimum force at 2,500,000 cycles was larger in the notch-free cobalt chromium alloy rod than in the notched cobalt chromium alloy rod. CONCLUSION: The notch-free curved cobalt chromium alloy rod is likely to maintain its curvature after spinal deformity surgery with a decreased risk of breakage and could overcome the problems of the conventional notched rod such as breakage and spring-back. LEVEL OF EVIDENCE: N/A.
• Clinical characteristics of patients with thoracic myelopathy caused by ossification of the posterior longitudinal ligament.

  Endo T, Takahata M, Koike Y, Iwasaki N

  Journal of bone and mineral metabolism 38 (1) 63 - 69 0914-8779 2019/07 [Refereed][Not invited]
   

  Although ossification of the posterior longitudinal ligament (OPLL) commonly develops in the cervical spine, it also occurs, albeit less commonly, in the thoracic spine. However, data are scarce regarding the characteristics of patients with thoracic OPLL. In the current study, we performed a cross-sectional study on a total of 133 patients with OPLL to clarify the clinical characteristics of patients with thoracic OPLL compared with those of patients with cervical OPLL. The subjects were divided into four groups according to the main region of OPLL and treatment type: C-OPLL-C, cervical OPLL treated conservatively; C-OPLL-S, cervical OPLL treated via surgery; T-OPLL-C, thoracic OPLL treated conservatively; and T-OPLL-S, thoracic OPLL treated via surgery. Symptoms developed at an earlier age in the T-OPLL-S group than in the C-OPLL groups. Current body mass index (BMI), maximum lifetime BMI, and BMI at the age of 20 years were significantly higher in the T-OPLL-S group than in the C-OPLL groups. Yearly weight gain from the age of 20 years to the age at which maximum body weight was attained was significantly greater in the T-OPLL-S group than in the C-OPLL groups. The T-OPLL group showed a higher rate of co-existence of OPLL at other regions or ossification of the ligamentum flavum compared to the C-OPLL groups. Our findings demonstrate that severe obesity, early-onset of symptoms, and diffuse ossification of spinal ligaments are distinct features of patients with myelopathy caused by thoracic OPLL.
• Three-dimensional depth sensor imaging to identify adolescent idiopathic scoliosis: a prospective multicenter cohort study

  Terufumi Kokabu, Noriaki Kawakami, Koki Uno, Toshiaki Kotani, Teppei Suzuki, Yuichiro Abe, Kenichiro Maeda, Fujio Inage, Yoichi M. Ito, Norimasa Iwasaki, Hideki Sudo

  Scientific Reports 9 (9678) 1 - 8 2019/07 [Refereed][Not invited]
   

  Adolescent idiopathic scoliosis is the most ordinary pediatric spinal disease that causes a three-dimensional deformity. Early detection of this potentially progressive deformity is considered crucial. The purpose of the present study was to report the potential for accurately diagnosis of adolescent idiopathic scoliosis using a newly developed, automated, noninvasive asymmetry-recognition system for the surface of the human back using a three-dimensional depth sensor. We included 170 subjects with suspected adolescent idiopathic scoliosis in this study. Outcomes measured included patient demographics, Cobbe angles from radiographic measurements, and asymmetry indexes. The coefficient of correlation between the asymmetry index and the Cobb angle was 0.85. For the prediction of scoliosis >10°, the area under the curve was 0.98, sensitivity was 0.97, specificity was 0.93, positive predictive value was 0.99, negative predictive value was 0.72, accuracy was 0.97, positive likelihood ratio was 13.55, and negative likelihood ratio was 0.04. The posterior test probability for the positive screen >10° was 98.9% if the asymmetry index was >1.268, three times in a row. This novel system automatically evaluated the back asymmetry. Therefore, this study demonstrates the outstanding discriminative ability of this newly developed system for deciding whether an examinee should undergo additional radiography to define scoliosis. This system can be used as an alternative to the forward bend test and scoliometer measurement in clinics. Future studies should seek to confirm these findings in a larger group and involve mass school scoliosis screening programs within the context of a multicenter trial.
• Inclination of Blumensaat's line influences on the accuracy of the quadrant method in evaluation for anterior cruciate ligament reconstruction.

  Iwasaki K, Inoue M, Kasahara Y, Tsukuda K, Kawahara H, Yokota I, Kondo E, Iwasaki N, Yasuda K

  Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 28 (6) 1885 - 1893 0942-2056 2019/07 [Refereed][Not invited]
   

  PURPOSE: The quadrant method is used to evaluate the bone tunnel position with the grid based on the Blumensaat's line in anterior cruciate ligament (ACL) reconstruction. This study aimed to clarify the influence of variation in the Blumensaat's line on the accuracy of the quadrant method measurements. METHODS: A retrospective review of the radiological records of patients aged 18-30 years who underwent computed tomography (CT) scanning of the knee joint was conducted. The Blumensaat's line inclination angle (BIA), along with the most posterior point of the posterior condyle (point P) position using the quadrant method and morphology of the Blumensaat's line were measured on true lateral transparent three-dimensional CT images of the distal femoral condyle in 147 patients. Statistical analysis was conducted to determine associations among these measurements. RESULTS: BIA was 37.5° (standard deviation 4.2°; range 27°-48°). The point P position was significantly correlated with BIA in the high/low (R2 = 0.590, P < 0.0001) and deep/shallow (R2 = 0.461, P < 0.0001) directions. The morphology of the Blumensaat's line was straight in 35 knees (23.8%); whereas, the remaining 112 knees (76.2%) were not straight but had some hill on the Blumensaat's line. No significant difference among the morphological variation of the Blumensaat's line was observed in BIA and the point P position. CONCLUSION: There was a strong correlation between BIA and the point P measured using the quadrant method, suggesting the influence of the Blumensaat's line on the accuracy of the quadrant method measurements in ACL reconstruction. As for the clinical relevance, surgeons should be careful in application of the quadrant method for ACL reconstruction, because the variation of the Blumensaat's line inclination influences the accuracy of this method.
• Alteration of the Total Cellular Glycome during Late Differentiation of Chondrocytes.

  Homan K, Hanamatsu H, Furukawa JI, Okada K, Yokota I, Onodera T, Iwasaki N

  International journal of molecular sciences 20 (14) 2019/07 [Refereed][Not invited]
   

  In normal articular cartilage, chondrocytes do not readily proliferate or terminally differentiate, and exhibit a low level of metabolism. Hypertrophy-like changes of chondrocytes have been proposed to play a role in the pathogenesis of osteoarthritis by inducing protease-mediated cartilage degradation and calcification; however, the molecular mechanisms underlying these changes are unclear. Glycans are located on the outermost cell surface. Dynamic cellular differentiation can be monitored and quantitatively characterized by profiling the glycan structures of total cellular glycoproteins. This study aimed to clarify the alterations in glycans upon late differentiation of chondrocytes, during which hypertrophy-like changes occur. Primary mouse chondrocytes were differentiated using an insulin-induced chondro-osteogenic differentiation model. Comprehensive glycomics, including N-glycans, O-glycans, free oligosaccharides, glycosaminoglycan, and glycosphingolipid, were analyzed for the chondrocytes after 0-, 10- and 20-days cultivation. The comparison and clustering of the alteration of glycans upon hypertrophy-like changes of primary chondrocytes were performed. Comprehensive glycomic analyses provided complementary alterations in the levels of various glycans derived from glycoconjugates during hypertrophic differentiation. In addition, expression of genes related to glycan biosynthesis and metabolic processes was significantly correlated with glycan alterations. Our results indicate that total cellular glycan alterations are closely associated with chondrocyte hypertrophy and help to describe the glycophenotype by chondrocytes and their hypertrophic differentiation. our results will assist the identification of diagnostic and differentiation biomarkers in the future.
• Correction osteotomy for bilateral varus knee deformity caused by premature epiphyseal closure induced by hypervitaminosis A: a case report.

  Masatake Matsuoka, Tomohiro Onodera, Tokifumi Majima, Koji Iwasaki, Daisuke Takahashi, Eiji Kondo, Norimasa Iwasaki

  BMC musculoskeletal disorders 20 (1) 287 - 287 2019/06/15 

  BACKGROUND: A vitamin A derivative, 13-cis-retinoic acid (isotretinoin), has been administered to treat several types of pediatric cancer and has improved survival rates in patients despite being known to induce premature epiphyseal closure. As the number of patients treated by 13-cis-retinoic acid increases, demands for salvage treatment after systemic retinoid therapy are emerging. However, few studies have described the surgical treatment of this disease. CASE PRESENTATION: We report a case with bilateral varus knee deformity due to premature epiphyseal closure that occurred during treatment with isotretinoin for neuroblastoma. The patient was successfully treated with correction osteotomy using a Taylor spatial frame in the right knee joint and femoral closed wedge osteotomy using a locking plate in left knee joint. Histopathological examination of the growth plate showed polar irregularity of chondrocytes and decreased cartilage matrix without apoptosis. In contrast, arthroscopic findings showed an intact joint surface. No recurrence of varus deformity was evident on follow-up at 1 year. CONCLUSIONS: To the best of our knowledge, this represents the first report of correction osteotomy for varus knee deformity due to premature epiphyseal closure that occurred during treatment with isotretinoin.
• Autologous living chondrocytes contained in the meniscal matrix play an important role in in vivo meniscus regeneration induced by in situ meniscus fragment implantation.

  Yasuyuki Kawaguchi, Eiji Kondo, Norimasa Iwasaki, Yasuhito Tanaka, Tomonori Yagi, Kazunori Yasuda

  Orthopaedics & traumatology, surgery & research : OTSR 105 (4) 683 - 690 2019/06 

  INTRODUCTION: Implantation of autogenous meniscal fragments wrapped with a fascia sheath significantly enhances fibrocartilage regeneration in vivo in defect cases at 12 weeks after implantation. The specific effects of the implanted autologous living chondrocytes and meniscal matrix have not been elucidated, however. The aim of this study was to clarify the role of autologous living chondrocytes contained in the meniscal matrix in in vivo meniscus regeneration induced by in situ meniscus fragment implantation. HYPOTHESIS: Implantation of meniscus fragments containing autologous living chondrocytes may result in significant in vivo meniscus regeneration. MATERIALS AND METHODS: Seventy-five rabbits were used in this study. A partial meniscectomy of the anterior one-third of the medial meniscus including the part of the anterior horn was performed. The rabbits were divided into 3 groups. In Group I, no treatment was applied to the defect. In Group II, the autogenous meniscal fragments devitalized by freeze-thaw treatment were reimplanted into the defect. In Group III, the autogenous meniscal fragments were reimplanted. In each group, the defect was covered with a fascia. Five rabbits from each group were subjected to morphologic and histologic evaluations at 3, 6, and 12 weeks, and 5 rabbits from each group were subjected to biomechanical evaluations at 6 and 12 weeks. RESULTS: Histologically, no cells were seen in the grafted meniscal fragments at 3 weeks in Group II, whereas chondrocytes in the grafted meniscal fragments were alive at 3 weeks in Group III. Histologic and biomechanical data for Group II were slightly but significantly better than those of Group I at 12 weeks after implantation (p=0.007 and p=0.002, respectively), whereas the data for Group III were significantly superior to those of Groups I and II at 12 weeks (p<0.0014 and p<0.0029, respectively). DISCUSSIONS: Grafted autologous living chondrocytes contained in the meniscal matrix play an important role in in vivo meniscus regeneration induced by in situ meniscus fragment implantation. STUDY DESIGN: II, Controlled laboratory study.
• Effects of femoral bone defect morphology on initial polished tapered stem stability in massive defect model: a biomechanical study.

  Irie T, Takahashi D, Asano T, Shimizu T, Arai R, Terkawi AM, Ito YM, Iwasaki N

  BMC Musculoskeletal Disorders 1;20(1):355 (1) 355 - 355 2019/06 [Refereed][Not invited]
   

  BACKGROUND: Good outcomes have been reported in revision total hip replacement with massive segmental defects using impaction bone grafting with circumferential metal meshes. However, the morphology of defects that require a mesh is poorly defined. The purpose of this study was to evaluate the effects of a variety of segmental defects on load transmission to the proximal femur under both axial and rotational loads. METHODS: Initial stability of the Exeter stem was investigated in a composite bone model using three medial bone defect morphologies: Long (length 5 cm × width 2 cm), Short (2.5 cm × 2 cm), Square (3.2 cm × 3.2 cm), Square with mesh (3.2 cm × 3.2 cm defect covered with metal mesh), and with no defect as control. Specimens (5 per group) were axially loaded and internally rotated up to 20° or to failure. Strain distributions of the femora were measured using a strain gauge. RESULTS: All Square group specimens failed while rotation was increasing. In the other four groups, failure was not observed in any specimens. Mean torsional stiffness in the Long (4.4 ± 0.3 Nm/deg.) and Square groups (4.3 ± 0.3 Nm/deg.) was significantly smaller than in the Control group (4.8 ± 0.3 Nm/deg.). In the medio-cranial region, the magnitude of the maximum principal strain in the Square group (1176.4 ± 100.9) was significantly the largest (Control, 373.2 ± 129.5, p < 0.001; Long, 883.7 ± 153.3, p = 0.027; Short, 434.5 ± 196.8, p < 0.001; Square with mesh, 256.9 ± 100.8, p < 0.001). Torsional stiffness, and both maximum and minimum principal strains in the Short group showed no difference compared to the Control group in any region. CONCLUSIONS: Bone defect morphology greatly affected initial stem stability and load transmission. If defect morphology is not wide and the distal end is above the lower end of the lesser trochanter, it may be acceptable to fill the bone defect region with bone cement. However, this procedure is not acceptable for defects extending distally below the lower end of the lesser trochanter or defects 3 cm or more in width.
• Bilateral subchondral insufficiency fractures of the femoral head in a normally active adolescent patient: A case report.

  Ishizu H, Shimizu T, Kaibara T, Asano T, Terkawi MA, Takahashi D, Iwasaki N

  The Journal of Orthopaedic Science S0949-2658(19)30148-4 (2) 492 - 494 2019/06 [Refereed][Not invited]
  
• A CRISPR Screen Using Subtilase Cytotoxin Identifies SLC39A9 as a Glycan-Regulating Factor.

  Toshiyuki Yamaji, Hisatoshi Hanamatsu, Tsuyoshi Sekizuka, Makoto Kuroda, Norimasa Iwasaki, Makoto Ohnishi, Jun-Ichi Furukawa, Kinnosuke Yahiro, Kentaro Hanada

  iScience 15 407 - 420 2019/05/31 [Refereed][Not invited]
   

  Subtilase cytotoxin (SubAB) is a virulence factor produced by locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli strains. The toxin recognizes sialoglycans for entry and cleaves an endoplasmic reticulum chaperon, binding immunoglobulin protein, to cause cell death. However, no systematic screening has yet been performed to identify critical host factors. Here, we performed a genome-wide CRISPR/Cas9 knockout screen for SubAB-induced cell death and identified various sialoglycan-related and membrane-trafficking genes. Analysis of glycan-deficient cells demonstrated that not only N-glycans but also O-glycans serve as SubAB receptors. In addition, SLC39A9, which is a predicted zinc transporter, as well as KDELRs and JTB, were required for SubAB to induce maximal cell death. Disruption of the SLC39A9 gene markedly reduced both complex-type N-glycans and core 1 O-glycans, and the O-glycan reduction was attributed to the reduction of core 1 synthase (C1GalT1). These results provide insights into the post-transcriptional regulation of glycosyltransferases by SLC39A9, as well as sialoglycan species as SubAB receptors.
• 骨粗鬆症性椎体骨折後早期に生じるドミノ骨折および椎体圧潰の病態

  高畑 雅彦, 岩田 玲, 遠藤 香織, 浦 勝郎, 岩崎 倫政

  日本骨形態計測学会雑誌 日本骨形態計測学会 29 (1) S80 - S80 0917-4648 2019/05
• Chondrogenic differentiation of mouse induced pluripotent stem cells using the three-dimensional culture with ultra-purified alginate gel.

  Kazutoshi Hontani, Tomohiro Onodera, Michiyo Terashima, Daisuke Momma, Masatake Matsuoka, Rikiya Baba, Zenta Joutoku, Shinji Matsubara, Kentaro Homan, Ryosuke Hishimura, Liang Xu, Norimasa Iwasaki

  Journal of biomedical materials research. Part A 107 (5) 1086 - 1093 1549-3296 2019/05 [Refereed][Not invited]
   

  As articular cartilages have rarely healed by themselves because of their characteristics of avascularity and low cell density, surgical intervention is ideal for patients with cartilaginous injuries. Because of structural characteristics of the cartilage tissue, a three-dimensional culture of stem cells in biomaterials is a favorable system on cartilage tissue engineering. Induced pluripotent stem cells (iPSCs) are a new cell source in cartilage tissue engineering for its characteristics of self-renewal capability and pluripotency. However, the optimal cultivation condition for chondrogenesis of iPSCs is still unknown. Here we show that a novel chondrogenic differentiation method of iPSCs using the combination of three-dimensional cultivation in ultra-purified alginate gel (UPAL gel) and multi-step differentiation via mesenchymal stem cell-like cells (iPS-MSCs) could efficiently and specifically differentiate iPSCs into chondrocytes. The iPS-MSCs in UPAL gel culture sequentially enhanced the expression of chondrogenic marker without the upregulation of that of osteogenic and adipogenic marker and histologically showed homogeneous chondrogenic extracellular matrix formation. Our results suggest that the pluripotency of iPSCs can be controlled when iPSCs are differentiated into iPS-MSCs before embedding in UPAL gel. These results lead to the establishment of an efficient three-dimensional system to engineer artificial cartilage tissue from iPSCs for cartilage regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1086-1093, 2019.
• Magnetic resonance imaging T1 and T2 mapping provide complementary information on the bone mineral density regarding cancellous bone strength in the femoral head of postmenopausal women with osteoarthritis.

  Endo K, Takahata M, Sugimori H, Yamada S, Tadano S, Wang J, Todoh M, Ito YM, Takahashi D, Kudo K, Iwasaki N

  Clinical biomechanics (Bristol, Avon) 65 13 - 18 0268-0033 2019/05 [Refereed][Not invited]
   

  BACKGROUND: Since bone mass is not the only determinant of bone strength, there has been increasing interest in incorporating the bone quality into fracture risk assessments. We aimed to examine whether the magnetic resonance imaging (MRI) T1 or T2 mapping value could provide information that is complementary to bone mineral density for more accurate prediction of cancellous bone strength. METHODS: Four postmenopausal women with hip osteoarthritis underwent 3.0-T MRI to acquire the T1 and T2 values of the cancellous bone of the femoral head before total hip arthroplasty. After the surgery, the excised femoral head was portioned into multiple cubic cancellous bone specimens with side of 5 mm, and the specimens were then subjected to microcomputed tomography followed by biomechanical testing. FINDINGS: The T1 value positively correlated with the yield stress (σy) and collapsed stress (σc). The T2 value did not correlate with the yield stress, but it correlated with the collapsed stress and strength reduction ratio (σc/σy), which reflects the progressive re-fracture risk. Partial correlation coefficient analyses, after adjusting for the bone mineral density, showed a statistically significant correlation between T1 value and yield stress. The use of multiple coefficients of determination by least squares analysis emphasizes the superiority of combining the bone mineral density and the MRI mapping values in predicting the cancellous bone strength compared with the bone mineral density-based prediction alone. INTERPRETATION: The MRI T1 and T2 values predict cancellous bone strength including the change in bone quality.
• Late Subaxial Lesion after Overcorrected Occipitocervical Reconstruction in Patients with Rheumatoid Arthritis.

  Iwata A, Abumi K, Takahata M, Sudo H, Yamada K, Endo T, Iwasaki N

  Asian spine journal 13 (2) 181 - 188 1976-1902 2019/04 [Refereed][Not invited]
   

  STUDY DESIGN: Retrospective case-control study, level 4. PURPOSE: To clarify the risk factors for late subaxial lesion after occipitocervical (O-C) reconstruction. We examined cases requiring fusion-segment-extended (FE) reconstruction in addition to/after O-C reconstruction. OVERVIEW OF LITERATURE: Patients with rheumatoid arthritis (RA) frequently require O-C reconstruction surgery for cranio-cervical lesions. Acceptable outcomes are achieved via indirect decompression using cervical pedicle screws and occipital plate-rod systems. However, late subaxial lesions may develop occasionally following O-C reconstruction. METHODS: O-C reconstruction using cervical pedicle screws and occipital plate-rod systems was performed between 1994 and 2007 in 113 patients with RA. Occipito-atlanto-axial (O-C2) reconstruction was performed for 89 patients, and occipito-subaxial cervical (O-under C2) reconstruction was performed for 24 patients. We reviewed the cases of patients requiring FE reconstruction (fusion extended group, FEG) and 26 consecutive patients who did not require FE reconstruction after a follow-up of >5 years (non-fusion extended group, NEG) as controls. RESULTS: FE reconstructions were performed for nine patients at an average of 45 months (range, 24-180 months) after O-C reconstruction. Of the 89 patients, three (3%) underwent FE reconstruction in cases of O-C2 reconstruction. Of the 24 patients, five (21%) underwent FE reconstruction in cases of O-under C2 reconstruction (p=0.003, Fisher exact test). Age, sex, RA type, and neurological impairment stage were not significantly different between FEG and NEG. O-under C2 reconstruction, larger correction angle (4° per number of unfixed segment), and O-C7 angle change after O-C reconstruction were the risk factors for late subaxial lesions on radiographic assessment. CONCLUSIONS: Overcorrection of angle at fusion segments requiring O-C7 angle change was a risk factor for late subaxial lesion in patients with RA with fragile bones and joints. Correction should be limited, considering the residual mobility of the cervical unfixed segments.
• CCL21/CCR7 axis regulating juvenile cartilage repair can enhance cartilage healing in adults.

  Zenta Joutoku, Tomohiro Onodera, Masatake Matsuoka, Kentaro Homan, Daisuke Momma, Rikiya Baba, Kazutoshi Hontani, Masanari Hamasaki, Shinji Matsubara, Ryosuke Hishimura, Norimasa Iwasaki

  Scientific reports 9 (1) 5165 - 5165 2045-2322 2019/03/26 [Refereed][Not invited]
   

  Juvenile tissue healing is capable of extensive scarless healing that is distinct from the scar-forming process of the adult healing response. Although many growth factors can be found in the juvenile healing process, the molecular mechanisms of juvenile tissue healing are poorly understood. Here we show that juvenile mice deficient in the chemokine receptor CCR7 exhibit diminished large-scale healing potential, whereas CCR7-depleted adult mice undergo normal scar-forming healing similar to wild type mice. In addition, the CCR7 ligand CCL21 was transiently expressed around damaged cartilage in juvenile mice, whereas it is rarely expressed in adults. Notably, exogenous CCL21 administration to adults decreased scar-forming healing and enhanced hyaline-cartilage repair in rabbit osteochondral defects. Our data indicate that the CCL21/CCR7 axis may play a role in the molecular control mechanism of juvenile cartilage repair, raising the possibility that agents modulating the production of CCL21 in vivo can improve the quality of cartilage repair in adults. Such a strategy may prevent post-traumatic arthritis by mimicking the self-repair in juvenile individuals.
• 脊椎・椎間板外傷に対する細胞死をターゲットとした分子標的治療の可能性

  大西 貴士, 須藤 英毅, 岩崎 浩司, 辻本 武尊, 山田 勝久, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 93 (3) S1177 - S1177 0021-5325 2019/03
• 頸椎化膿性脊椎炎の臨床的特徴と機能予後 後彎変形とQOLとの関連

  山田 勝久, 高畑 雅彦, 楫野 知道, 袖山 洋平, 岩田 玲, 小甲 晃史, 遠藤 努, 大西 貴士, 須藤 英毅, 石黒 信久, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 93 (3) S1180 - S1180 0021-5325 2019/03
• 膿胸・縦隔膿瘍を併発した胸椎化膿性脊椎炎に対する治療 難治例では椎間板・胸腔ドレナージが必要

  山田 勝久, 高畑 雅彦, 青木 佑介, 岩田 玲, 遠藤 努, 大西 貴士, 須藤 英毅, 石黒 信久, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 93 (3) S1181 - S1181 0021-5325 2019/03
• 胸椎特発性側彎症の固定下端椎の操作が腰椎非固定椎間配列と冠状面バランスに与える影響

  岩田 玲, 須藤 英毅, 安倍 雄一郎, 伊東 学, 鐙 邦芳, 山田 勝久, 遠藤 努, 大西 貴士, 高畑 雅彦, 岩崎 倫政

  Journal of Spine Research (一社)日本脊椎脊髄病学会 10 (3) 212 - 212 1884-7137 2019/03
• 合併症を生じやすい脊椎腫瘍手術の条件

  岩田 玲, 高畑 雅彦, 角家 健, 須藤 英毅, 山田 勝久, 遠藤 努, 大西 貴士, 伊東 学, 鐙 邦芳, 岩崎 倫政

  Journal of Spine Research (一社)日本脊椎脊髄病学会 10 (3) 272 - 272 1884-7137 2019/03
• 第5腰椎骨腫瘍摘出術における腸骨稜切離飜転の有用性

  岩田 玲, 高畑 雅彦, 須藤 英毅, 山田 勝久, 遠藤 努, 大西 貴士, 岩崎 倫政

  Journal of Spine Research (一社)日本脊椎脊髄病学会 10 (3) 396 - 396 1884-7137 2019/03
• 膿胸・縦隔膿瘍を併発した胸椎化膿性脊椎炎に対する治療 あまり知られていない危険な病態

  山田 勝久, 高畑 雅彦, 岩田 玲, 遠藤 努, 大西 貴士, 須藤 英毅, 石黒 信久, 岩崎 倫政

  Journal of Spine Research (一社)日本脊椎脊髄病学会 10 (3) 663 - 663 1884-7137 2019/03
• 若年発症の胸椎OPLL患者は高度肥満と強い骨化傾向の特徴をもつ

  遠藤 努, 高畑 雅彦, 岩田 玲, 山田 勝久, 大西 貴士, 須藤 英毅, 岩崎 倫政

  Journal of Spine Research (一社)日本脊椎脊髄病学会 10 (3) 687 - 687 1884-7137 2019/03
• 経時的応力計測可能なラメラ構造二重膜ヒドロゲルを用いたヒト関節靱帯における内部応力解析

  門間 太輔, 黒川 孝幸, 河村 太介, 瓜田 淳, 松井 雄一郎, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 93 (3) S1042 - S1042 0021-5325 2019/03
• Identification of IL-27 as potent regulator of inflammatory osteolysis associated with vitamin E-blended ultra-high molecular weight polyethylene debris of orthopedic implants

  Terkawi MA, Kadoya K, Takahashi D, Tian Y, Hamasaki M, Matsumae G, Alhasan H, Elmorsy S, Uetsuki K, Onodera T, Takahata M, Iwasaki N

  Acta Biomaterialia 89 242 - 251 2019/03 [Refereed][Not invited]
   

  Vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) is a newly introduced material for prosthetic components that has proven a better mechanical performance with lesser adverse cellular responses than conventional polyethylene in experimental animal models. However, the mechanisms by which VE-UHMWPE particles trigger a reduced osteolytic activity are unclear and remain to be investigated. Therefore, the current study aims at exploring a possible anti-osteolytic mechanism associated with VE-UHMWPE particles. Transcriptional profiling and bioinformatic analyses of human macrophages stimulated by VE-UHMWPE particles revealed a distinct transcriptional program from macrophages stimulated with UHMWPE particles. Out of the up-regulated genes, IL-27 was found to be significantly elevated in macrophages cultured with VE-UHMWPE particles as compared to these with UHMWPE particles (p = 0.0084). Furthermore, we studied the potential anti-osteolytic function of IL-27 in osteolysis murine model. Interestingly, administration of recombinant IL-27 onto calvariae significantly alleviated osteolytic lesions triggered by UHMWPE particles (p = 0.0002). Likewise, IL-27 inhibited differentiation of osteoclasts (p = 0.0116) and reduced inflammatory response (p < 0.0001) elicited by conventional UHMWPE particles in vitro. This is the first study demonstrating the involvement of IL-27 in macrophage response to VE-UHMWPE particles and its regulatory role in osteolysis. Our data highlight a novel therapeutic agent for treatment of inflammatory osteolysis induced by polyethylene debris. STATEMENT OF SIGNIFICANCE: Aseptic loosening due to inflammatory osteolysis remains the major cause of arthroplasty failure and represents a substantial economic burden worldwide. Ideal approach to prevent this failure should be directed to minimize inflammatory response triggered by wear particles at the site of implant. Understanding the mechanism by which VE-UHMWPE particles triggers lesser cellular responses and reduced osteolysis as compared to conventional UHMWPE particles may aid in discovery of regulatory factors. In the current study, we reported that IL-27 is a potent regulator of inflammatory osteolysis involved in the reduced biologic activities and osteolytic potentials associated with VE-UHMWPE particles. Initiating the production IL-27 in vivo after total joint arthroplasties might be a novel strategy to prolong the life-spam of implant.
• Effects of Ultra-Purified Alginate Gel Implantation on Meniscal Defects in Rabbits.

  Kim W, Onodera T, Kondo E, Kawaguchi Y, Terkawi MA, Baba R, Hontani K, Joutoku Z, Matsubara S, Homan K, Hishimura R, Iwasaki N

  The American journal of sports medicine 47 (3) 640 - 650 0363-5465 2019/03 [Refereed][Not invited]
   

  BACKGROUND: Many tissue-engineered methods for meniscal repair have been studied, but their utility remains unclear. HYPOTHESIS: Implantation of low-endotoxin, ultra-purified alginate (UPAL) gel without cells could induce fibrocartilage regeneration on meniscal defects in rabbits. STUDY DESIGN: Controlled laboratory study. METHODS: Forty-two mature Japanese White rabbits were divided into 2 groups of 21 animals each. In each animal, a cylindrical defect measuring 2 mm in diameter was created with a biopsy punch on the anterior horn of the medial meniscus. In the control group, no treatment was applied on the left medial meniscal defect. In the UPAL gel group, the right medial meniscal defect was injected with the UPAL gel and gelated by a CaCl2 solution. Samples were evaluated at 3, 6, and 12 weeks postoperatively. For biomechanical evaluation, 6 additional samples from intact animals were used for comparison. RESULTS: The macroscopic score was significantly greater in the UPAL gel group than in the control group at 3 weeks (mean ± SE: 5.6 ± 0.82 vs 3.4 ± 0.83, P = .010), 6 weeks (5.9 ± 0.72 vs 2.5 ± 0.75, P = .026), and 12 weeks (5.2 ± 1.21 vs 1.0 ± 0.63, P = .020). The histological score was significantly greater in the UPAL group than in the control group at 3 weeks (2.1 ± 0.31 vs 1.2 ± 0.25, P = .029) and 12 weeks (2.2 ± 0.55 vs 0.3 ± 0.21, P = .016). The mean stiffness of the reparative tissue in the UPAL gel group was significantly greater than that in the control group at 6 weeks (24.325 ± 3.920 N/mm vs 8.723 ± 1.190 N/mm, P = .006) and at 12 weeks (27.804 ± 6.169 N/mm vs not applicable [because of rupture]). CONCLUSION: The UPAL gel enhanced the spontaneous repair of fibrocartilage tissues in a cylindrical meniscal defect in rabbits. CLINICAL RELEVANCE: These results imply that the acellular UPAL gel may improve the repair of traumatic meniscal injuries.
• Preoperative radiographic and clinical factors associated with postoperative floating of the lesser toes after resection arthroplasty for rheumatoid forefoot deformity.

  Tomohiro Onodera, Hiroaki Nakano, Kentaro Homan, Eiji Kondo, Norimasa Iwasaki

  BMC musculoskeletal disorders 20 (1) 87 - 87 2019/02/19 [Refereed][Not invited]
   

  BACKGROUND: This study aimed to clarify the characteristics associated with postoperative floating of the lesser toes, especially focusing on the medial and lateral lessor toes, after arthrodesis of the first metatarsophalangeal joint and resection arthroplasty of the lessor toes in rheumatoid forefoot deformity. METHODS: Fourty-seven feet of 43 people who underwent resection arthroplasty of the metatarsal head of the lesser toes for rheumatoid arthritis of the metatarsophalangeal joints were included. We retrospectively evaluated the preoperative radiographic findings and clinical characteristics of the patients, and the occurrence of postoperative floating of the lesser toes. The mean duration of follow-up was 36.5 (range 12 to 114) months. RESULTS: Preoperative dislocation grades of the second and third toes that demonstrated postoperative floating were significantly higher than those of toes that did not experience postoperative floating. The hallux valgus deformity before surgery was significantly more severe in toes with postoperative floating of the second and third lessor toes than those with no floating (p < 0.05). In addition, the Japanese Society for Surgery of the Foot (JSSF) hallux scale scores before surgery in toes with postoperative floating of the fourth and fifth lessor toes were significantly worse than those in non-dislocating toes (p < 0.05). CONCLUSIONS: The preoperative condition of the first metatarsophalangeal joint, including hallux valgus deformity, pain, range of motion, activity of daily living, and function is significantly different between postoperative floating of the lesser toes and non-floating of them after resection arthroplasty for rheumatoid forefoot deformity.
• 経時的応力計測可能なラメラ構造二重膜ヒドロゲルを用いたヒト関節靱帯における内部応力解析

  門間 太輔, 黒川 孝幸, 河村 太介, 瓜田 淳, 松井 雄一郎, 岩崎 倫政

  日本肘関節学会雑誌 日本肘関節学会 26 (1) S4 - S4 1349-7324 2019/02
• Corticosteroid dose increase is a risk factor for nonalcoholic fatty liver disease and contralateral osteonecrosis of the femoral head: a case report.

  Shimizu H, Shimizu T, Takahashi D, Asano T, Arai R, Takakuwa Y, Iwasaki N

  BMC musculoskeletal disorders 20 (1) 88 - 88 2019/02 [Refereed][Not invited]
   

  BACKGROUND: The incidence of bilateral corticosteroid-induced osteonecrosis of the femoral head (ONFH) is high. Although the precise mechanism of corticosteroid-induced ONFH development is unclear, hepatic enzyme abnormalities such as low activity of hepatic cytochrome P450 3A could be one cause. Herein, we report the case of a patient who developed ONFH in the contralateral hip after the dose of corticosteroids for idiopathic thrombocytopenic purpura was increased. Liver biopsy was done to rule out autoimmune hepatitis. CASE PRESENTATION: A 32-year-old woman had been treated with continuous corticosteroids of up to 10 mg/day for Sjögren's syndrome for 25 years and corticosteroid-induced ONFH in the left side. At age 33, idiopathic thrombocytopenia developed, which was treated by increasing the corticosteroid dose (40 mg/day). Two months later, liver enzyme level began to increase slightly and continued to increase. A year after corticosteroid dose increase, contralateral ONFH developed, and a liver biopsy demonstrated nonalcoholic fatty liver disease (NAFLD). CONCLUSIONS: The current case indicates that corticosteroid dose increase is a potential risk factor for NAFLD and contralateral ONFH. Therefore, it would be useful and important for to screen and monitor patients with hepatic enzyme abnormality for ONFH occurrence.
• Long-Term Changes in Vertebral Morphology After Cervical Spinal Fusion in Adolescent Pediatric Patients: Retrospective Case Series with up to a Minimum 12 Years of Follow-up.

  Yuichiro Abe, Katsuhisa Yamada, Kuniyoshi Abumi, Norimasa Iwasaki, Hideki Sudo

  World neurosurgery 122 e765-e772  1878-8750 2019/02 [Refereed][Not invited]
   

  OBJECTIVE: The mechanical alteration in the adolescent/pediatric cervical spine after spinal fusion remains unknown. The purpose of this study was to investigate morphologic changes in the cervical spine in adolescent/pediatric patients who underwent spinal fusion. METHODS: Ten adolescent/pediatric patients (9-18 years) who underwent cervical spinal fusion were included. The anteroposterior diameter (AP-D) of the vertebral body was evaluated using lateral radiographs. The AP-D ratio was defined as the ratio of the AP-D at final follow-up to the postoperative value. The kyphosis angles at the fused level and cervical spine (C2-C7) also were measured. RESULTS: The mean follow-up period was 20.0 years (range, 12-40 years). The AP-D was reduced in 4 patients and increased or remained unchanged in 6 patients. The AP-D reduction was usually seen at the middle of the fused levels and was remarkable in patients who underwent kyphosis correction using posterior instrumentation combined with anterior fusion. The AP-D ratio was significantly correlated to segments of anterior fusion (P = 0.029) and the kyphosis angle of the fused levels (P = 0.016). CONCLUSIONS: Cervical kyphosis correction using posterior instrumentation combined with endplate destruction by anterior bone grafting is a risk factor for atrophic morphologic changes in the vertebral body in adolescent/pediatric patients. Endplate destruction and instrumentation-induced stress shielding could alter bone remodeling.
• Increased risk of symptomatic progression of instability following decompression for lumbar canal stenosis in patients receiving chronic glucocorticoids therapy.

  Shigeto Hiratsuka, Masahiko Takahata, Yoshihiro Hojo, Tomomichi Kajino, Yuichiro Hisada, Akira Iwata, Katsuhisa Yamada, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 24 (1) 14 - 18 0949-2658 2019/01 [Refereed][Not invited]
   

  BACKGROUND: Lumbar decompression surgery is a commonly used treatment for degenerative lumbar spinal stenosis; however, some patients develop symptomatic spinal instability following decompression surgery. The objective of this study was to reveal risk factors for delayed instability following decompression surgery for lumbar spinal stenosis. METHODS: One hundred ten patients who underwent single-level lumbar decompression between 2008 and 2014 were retrospectively reviewed. Surgical indication for decompression surgery was symptomatic lumbar canal stenosis without spondylolisthesis or with minimum spondylolisthesis (less than 4 mm translation). Patients with gross segmental motion (>10° in disc angle, >2 mm translation) on flexion-extension lumbar radiographs were excluded. Age, sex, body mass index, smoking history, diabetes mellitus, autoimmune connective tissue diseases including rheumatoid arthritis, and the use of glucocorticoids were investigated. Radiographic measurements included disc angle, disc height, slippage, facet angle, segmental motion (flexion-extension), lumbar alignment, facet effusion, and disc degeneration. Data were analyzed using multivariate forward selection stepwise logistic regression, chi-square tests, and Student t-test. RESULTS: Six of 110 patients (5.5%) developed symptomatic spinal instability at the operative level and underwent spinal fusion surgery at an average of 2.1 years postoperatively. Autoimmune connective tissue disorders and chronic use of glucocorticoids were associated with the occurrence of symptomatic spinal instability requiring spine fusion surgery, while there was no significant difference in radiographic parameters and demographic factors excluding autoimmune connective tissue diseases between reoperation and non-reoperation groups. CONCLUSIONS: Patients with autoimmune connective tissue disorders receiving chronic glucocorticoid therapy are more likely to develop symptomatic spinal instability following decompression surgery for lumbar canal stenosis without or with minimal spondylolisthesis.
• Identification of il-27 as potent regulator of osteolysis triggered by of orthopaedic implants debris

  Daisuke Takahashi, Mohamad Alaa Terkawi, Gen Matsumae, Yuan Tian, Hend Alhasan, Norimasa Iwasaki.

  Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium 40 612  1526-7547 2019 

  Statement of Purpose: Aseptic loosening due to inflammatory osteolysis remains the major postoperative complication of total joint arthroplasty that leads to prosthesis failure. Inflammation occurs when macrophages recognize wear debris derived from implant bearing surfaces and release an array of cytokines and chemokines that promote the recruitment of other inflammatory cells and the osteoclastic-bone resorbing activity [1]. Vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) is a newly developed material for prosthetic components that has proven greater clinical performance with lesser adverse cellular responses than conventional polyethylene in short-term clinical studies as well as in experimental animal models [2]. However, the mechanisms by which VE-UHMWPE debris triggers reduced osteolytic activity are largely unclear and remain to be investigated. Therefore, the current study aims at exploring a possible mechanism by which VE-UHMWPE debris triggers a reduced adverse cellular response. with macrophage response to debris.
• 転移性脊椎腫瘍術後合併症の危険因子

  岩田 玲, 山田 勝久, 遠藤 努, 大西 貴士, 角家 健, 高畑 雅彦, 岩崎 倫政, 須藤 英毅

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 61 (136th suppl) 8 - 8 1343-3873 2019
• 若年発症の胸椎OPLL患者は高度な肥満と強い骨化傾向の特徴をもつ

  遠藤 努, 高畑 雅彦, 岩田 玲, 山田 勝久, 大西 貴士, 須藤 英毅, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 61 (136th suppl) 11 - 11 1343-3873 2019
• 環軸椎脱臼により呼吸障害を生じた新生児の1例

  大西 貴士, 遠藤 努, 高畑 雅彦, 岩田 玲, 岩崎 倫政, 山田 勝久, 須藤 英毅

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 61 (136th suppl) 11 - 11 1343-3873 2019
• 受傷直後に生じた後頭環軸椎回旋位固定の稀な1例

  清水 寛和, 遠藤 努, 高畑 雅彦, 須藤 英毅, 岩田 玲, 山田 勝久, 大西 貴士, 岩崎 倫政, 安井 啓悟, 袖山 洋平

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 61 (136th suppl) 13 - 13 1343-3873 2019
• Septic embolizationによる脳塞栓を併発した腰椎化膿性脊椎炎の1例

  佐藤 恒明, 山田 勝久, 遠藤 努, 大西 貴士, 岩田 玲, 須藤 英毅, 高畑 雅彦, 岩崎 倫政, 大嶌 祐貴, 脇田 雅大

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 61 (136th suppl) 20 - 20 1343-3873 2019
• 胸椎骨化病変に合併した脊髄くも膜嚢胞の1例

  宮野 真博, 高畑 雅彦, 山田 勝久, 遠藤 努, 大西 貴士, 岩崎 倫政, 岩田 玲, 須藤 英毅

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 61 (136th suppl) 23 - 23 1343-3873 2019
• A Novel Experimental Model to Determine the Axon-Promoting Effects of Grafted Cells After Peripheral Nerve Injury.

  Takeshi Endo, Ken Kadoya, Yuki Suzuki, Daisuke Kawamura, Norimasa Iwasaki

  Frontiers in cellular neuroscience 13 280 - 280 2019 

  Although peripheral nerves can regenerate, clinical outcomes after peripheral nerve injuries are not always satisfactory, especially in cases of severe or proximal injuries. Further, autologous nerve grafting remains the gold standard for the reconstruction of peripheral nerves, although this method is still accompanied by issues of donor-site morbidity and limited supply. Cell therapy is a potential approach to overcome these issues. However, the optimal cell type for promoting axon regeneration remains unknown. Here, we report a novel experimental model dedicated to elucidation of the axon-promoting effects of candidate cell types using simple and standardized techniques. This model uses rat sciatic nerves and consists of a 25 mm-long acellular region and a crush site at each end. The acellular region was made by repeated freeze/thaw procedures with liquid nitrogen. Importantly, the new model does not require microsurgical procedures, which are technically demanding and greatly affect axon regeneration. To test the actual utility of this model, red fluorescent protein-expressing syngeneic Schwann cells (SCs), marrow stromal cells, or fibroblasts were grafted into the acellular area, followed by perfusion of the rat 2 weeks later. All types of grafted cells survived well. Quantification of regenerating axons demonstrated that SCs, but not the other cell types, promoted axon regeneration with minimum variability. Thus, this model is useful for differentiating the effects of various grafted cell types in axon regeneration. Interestingly, regardless of the grafted cell type, host SCs migrated into the acellular area, and the extent of axon regeneration was strongly correlated with the number of SCs. Moreover, all regenerating axons were closely associated with SCs. These findings suggest a critical role for SCs in peripheral nerve axon regeneration. Collectively, this novel experimental model is useful for elucidating the axon-promoting effects of grafted cells and for analyzing the biology of peripheral nerve axon regeneration.
• Glycans in osseous tissue and articulation

  Tadahisa Mikami, Hiroshi Kitagawa, Norimasa Iwasaki

  Glycoscience: Basic Science to Applications: Insights from the Japan Consortium for Glycobiology and Glycotechnology (JCGG) 221 - 226 2019/01/01 [Refereed][Not invited]
  
• Early surgical intervention may facilitate recovery of cervical spinal cord injury in DISH.

  Tsuji O, Suda K, Takahata M, Matsumoto-Harmon S, Komatsu M, Menjo Y, Watanabe K, Ishii K, Nakamura M, Matsumoto M, Minami A, Iwasaki N

  Journal of orthopaedic surgery (Hong Kong) 27 (1) 2309499019834783 - 2309499019834783 1022-5536 2019/01 [Refereed][Not invited]
   

  STUDY DESIGN: A retrospective study of consecutive surgically managed cases of cervical spinal fractures and diffuse idiopathic skeletal hyperostosis (DISH) at our hospital from October 2006 to April 2016. SUMMARY OF BACKGROUND DATA: Prognostic factors have not been determined for cervical fractures in DISH. OBJECTIVES: To assess demographics, surgical techniques, and complications in cervical spinal cord injury with DISH and to evaluate factors affecting neurological prognosis. METHODS: Patients' medical records and radiographs were reviewed and analyzed for demographics, injury characteristics, surgical outcomes, perioperative complications, additional surgeries, and neurological prognosis. Neurological status was assessed by the American Spinal Injury Association (ASIA) grade at admission and discharge. RESULTS: Of 38 patients (mean age 71.9 ± 8.8), 20 had type 1 fractures (through the disc space), 8 had type 2 (through the vertebral body), and 10 had type 3 (through disc and vertebral body). ASIA grades at admission included 14 ASIA-A, 4 ASIA-B, 7 ASIA-C, 8 ASIA-D, and 5 ASIA-E. All patients underwent posterior fusion with an average of 4.5 ± 2.5 instrumented vertebrae (range, 2-7) and six patients required secondary halo-vest fixation. Of 14 ASIA-A patients, 12 developed serious postsurgical pulmonary complications and 4 of these died within 6 months of surgery. Of the 38 patients, 13 improved more than one grade after treatment, 24 did not improve, and 1 deteriorated. In the 18 ASIA-A/B cases (complete motor paralysis), neither fracture type nor injury mechanism (e.g. a ground-level fall or high-energy trauma) correlated with neurological prognosis, but a time of 8 h or less from injury to surgery correlated significantly with an improvement from ASIA A/B to C/D ( p  <  0.01, Pearson's χ2 test). CONCLUSION: Patients with complete motor paralysis after a cervical fracture with DISH may recover to partial paralysis if surgically treated within 8 h of injury.
• Time Course of Respiratory Dysfunction and Motor Paralysis for 12 Weeks in Cervical Spinal Cord Injury without Bone Injury.

  Ushiku C, Suda K, Matsumoto S, Komatsu M, Takahata M, Iwasaki N, Minami A

  Spine surgery and related research 3 (1) 37 - 42 2432-261X 2019/01 [Refereed][Not invited]
   

  INTRODUCTION: Cervical spinal cord injury without bone injury (SCIWOBI) is a common cervical injury in the elderly population and is most likely to occur at the C3/C4 level. Respiratory dysfunction (RD) related to the damage of the spinal respiratory center, which is close to the C4 segment, is one of the greatest obstacles in improving the activities of daily living of patients with severe paralysis. We evaluated the time course of RD and motor function in cervical SCIWOBI to identify effective medical strategies. METHODS: We followed 54 patients (49 men, 5 women; mean age: 65 years old) who were treated for SCIWOBI at our medical center from 2011 to 2014. The patients were evaluated within 72 hours of injury and were monitored for at least 12 weeks. All patients began respiratory-muscle training the day after admission regardless of whether they were treated conservatively or surgically. The percent vital capacity (%VC), forced expiratory volume (FEV) in one second/forced vital capacity ratio (FEV 1.0%), and American Spinal Injury Association motor score (MS) were recorded at admission and again at weeks 4 and 12. We calculated the %VC rate of change and the MS improvement rate over the entire period. RESULTS: Fifty patients (92.6%) had restrictive ventilatory impairment at admission. The %VC correlated with the upper- and lower-limb MSs at admission, and the %VC and upper- and lower-limb MSs had improved by weeks 4 and 12 after the injury. The %VC rate of change was significantly correlated with the rate of improvement in lower-limb MS throughout the entire period. CONCLUSIONS: Lung capacity decreased in SCIWOBI owing to respiratory-muscle paralysis and upper- and lower-limb motor paralyses. Lung capacity improved as the lower limbs recovered their motor function. Respiratory rehabilitation should be continued for at least 12 weeks after SCIWOBI.
• Depletion of glycosphingolipids induces excessive response of chondrocytes under mechanical stress

  Matsubara S, Onodera T, Maeda E, Momma D, Matsuoka M, Homan K, Ohashi T, Iwasaki N

  Journal of biomechanics 94 22 - 30 2019 [Refereed][Not invited]
   

  Glycosphingolipids (GSLs) are ubiquitous membrane components that play an indispensable role in maintaining chondrocyte homeostasis. To gain better insight into roles of GSLs, we studied the effects of GSL-deletion on the physiological responses of chondrocytes to mechanical stress. Mice lacking Ugcg gene (Ugcg-/-) were genetically generated to obtain GSL-deficient mice, and their chondrocytes from the joints were used for functional analyses in vitro culture experiments. The cells were seeded in a three-dimensional collagen gel and subjected to 5%, 10% or 16% cyclic tensile strain for either 3 or 24 h. The gene expressions of chondrocyte anabolic and catabolic factors, and the induction of Ca2+ signaling were analyzed. Our results revealed that chondrocytes derived from GSL-deficient mice exhibited an elevation in the expression of catabolic factors (ADAMTS-5, MMP-13) following the exposure to strain with amplitudes of 10%. Likewise, applying cyclic tensile strain with these amplitudes resulted in an increased Ca2+ oscillation ratio in chondrocytes from GSL-deficient as compared to the ratio from control mice. These results demonstrated that deletion of GSL stimulated the catabolic responses of chondrocytes to mechanical stress via the augmentation of the sensitivity to mechanical stress that may lead to the cartilage deterioration. These findings suggest that the regulation of the physiological responses of chondrocytes by GSLs could be a potential target in a therapeutic intervention in osteoarthritis.
• A Novel Cartilage Fragments Stimulation Model Revealed that Macrophage Inflammatory Response Causes an Upregulation of Catabolic Factors of Chondrocytes In Vitro.

  Hamasaki M, Terkawi MA, Onodera T, Homan K, Iwasaki N

  Cartilage 12 (1947603519828426) 354 - 361 2019/01 [Refereed][Not invited]
   

  OBJECTIVE: Osteoarthritis is a progressive joint disease characterized by cartilage degradation and synovial inflammation. Presence of cartilage fragments in the joint due to degradation of cartilage is thought to be associated with local inflammatory response and progressive osteoarthritic process. Understanding the mechanism by which cartilage fragments elicit this destructive process should aid in designing novel therapeutic approaches. Therefore, objective of current study is to establish an in vitro model to examine the cross-talk between chondrocytes and cartilage fragments-stimulated macrophages. DESIGN: Cartilage fragments were prepared from femoral head cartilages of mice and analyzed using a scanning electron microscope and particle size analyzer. Bone marrow-derived macrophages were co-cultured with cartilage fragments and chondrocytes using transwell co-culture system. Macrophage inflammatory mediators in supernatant of cultures were determined by ELISA and gene expression of macrophages and chondrocyte were quantified by qRT-PCR. RESULTS: Shapes of cartilage fragments were irregular with sizes ranged between 0.54 and 55 μm. Macrophages cultured with cartilage fragments released significantly higher concentrations of TNF-α, IL-6, and NO than those of mock and control. Consistently, gene expressions of TNF-α, IL-6, and MMP-9 were significantly increased in stimulated macrophages. The elevation in production of pro-inflammatory molecules in stimulated macrophages cultures were coincident with an increase in gene expression of chondrocyte MMP-13, iNOS, and IL-6. CONCLUSION: We developed an in vitro co-culture model to study the impact of stimulation of macrophage by cartilage fragments on the expression of chondrocyte carbolic factors. Our results revealed that cartilage fragments triggered macrophages inflammatory response that enhanced the production of chondrocyte catabolic factors.
• Rapidly progressive cervical myelopathy had a high risk of developing deep venous thrombosis: a prospective observational study in 289 cases with degenerative cervical spine disease.

  Katsuhisa Yamada, Kota Suda, Satoko Matsumoto Harmon, Miki Komatsu, Chikara Ushiku, Masahiko Takahata, Akio Minami, Norimasa Iwasaki

  Spinal cord 57 (1) 58 - 64 1362-4393 2019/01 [Refereed][Not invited]
   

  STUDY DESIGN: A prospective observational study. OBJECTIVES: To determine the incidence of deep venous thrombosis (DVT) and to evaluate the risk factors for DVT development associated with degenerative cervical spine disease. SETTING: Hokkaido Spinal Cord Injury Center, Japan. METHODS: Between April 2008 and March 2015, patients with degenerative cervical spine disease, such as compressive myelopathy or radiculopathy, who underwent surgical treatment were prospectively assessed. Leg vein ultrasonography and D-dimer tests were performed preoperatively and at 4 days after surgery. All patients received treatment with intermittent pneumatic compression and elastic stockings for primary DVT prophylaxis. No anticoagulation medications were used for DVT prophylaxis. RESULTS: A total of 289 patients (203 males, 86 females; median age: 67 years (interquartile range, 58-76)) were included. Nine patients (3.1%) exhibited DVT during the perioperative period. All 9 cases were women who had distal DVT. The incidences of preoperative and postoperative DVT were 1.1% and 2.1%, respectively. The univariate analysis showed that statistically significant risk factors for perioperative DVT included female gender (P < 0.01), advanced age (P = 0.04), a low Japanese Orthopaedic Association score (P = 0.03), rapidly progressive myelopathy (P < 0.01), and inability to walk (P = 0.01). The multivariate analysis showed that rapidly progressive myelopathy (P = 0.04) was the most important risk factor. CONCLUSION: Female gender and rapidly progressive myelopathy are high-risk factors that predict the development of DVT during the perioperative period of cervical spine surgery. This result indicates that screening and treatment for DVT are needed in such high-risk patients.
• Osteochondral Autograft Transplantation Technique Augmented by an Ultrapurified Alginate Gel Enhances Osteochondral Repair in a Rabbit Model

  Ryosuke Hishimura, Tomohiro Onodera, Kazutoshi Hontani, Rikiya Baba, Kentaro Homan, Shinji Matsubara, Zenta Joutoku, WooYoung Kim, Takayuki Nonoyama, Takayuki Kurokawa, Jian Ping Gong, Norimasa Iwasaki

  American Journal of Sports Medicine 47 (2) 468 - 478 2019/01 [Refereed][Not invited]
   

  BACKGROUND: One of the most important limitations of osteochondral autograft transplantation (OAT) is the adverse effect on donor sites in the knee. To decrease the number and/or size of osteochondral defects, we devised a method with biomaterial implantation after OAT. HYPOTHESIS: OAT augmented by ultrapurified alginate (UPAL) gel enhances cartilage repair capacity. STUDY DESIGN: Controlled laboratory study. METHODS: Seventy-five osteochondral defects in rabbits were divided into 3 groups: osteochondral defects with OAT alone, defects with OAT augmented by UPAL gel (combined group), and defects without intervention as controls. Macroscopic and histological evaluations of the reparative tissues were performed at 4 and 12 weeks postoperatively. Histological evaluation of graft cartilage degradation was also performed. To evaluate the effects of UPAL gel on graft healing, repaired bone volumes and osseointegration of the graft were evaluated. Collagen orientation and the mechanical properties of the reparative tissue and graft cartilage were also evaluated qualitatively. RESULTS: The macroscopic and histological evaluations of the combined group were significantly superior to the other groups at 12 weeks postoperatively. Regarding degenerative change of the graft, the histological scores of the combined group were significantly higher than those of the OAT-alone group. The values of repaired subchondral bone volumes and osseointegration of the graft were almost identical in both groups. Collagen orientation and the mechanical properties of the reparative tissue and graft cartilage were significantly better in the combined group than in the other groups. CONCLUSION: Administration of UPAL gel in OAT enhanced cartilage repair and protected graft cartilage without inhibiting subchondral bone repair and graft survival. CLINICAL RELEVANCE: OAT augmented by UPAL gel decreases the number and/or size of osteochondral grafts, minimizing the risk of donor site morbidity. This combination technique has the potential to improve clinical outcomes and expand the surgical indications for OAT.
• Ectopic RASGRP2 (CalDAG-GEFI) expression in rheumatoid synovium contributes to the development of destructive arthritis.

  Hiroyuki Nakamura, Sanae Shimamura, Shinsuke Yasuda, Michihito Kono, Michihiro Kono, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Toshiyuki Bohgaki, Tomohiro Shimizu, Norimasa Iwasaki, Tatsuya Atsumi

  Annals of the rheumatic diseases 77 (12) 1765 - 1772 0003-4967 2018/12 [Refereed][Not invited]
   

  OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune polyarthritis, in which fibroblast-like synoviocytes (FLS) play a key role in cartilage and bone destruction through tumour-like proliferation and invasiveness. Considering still unsatisfactory remission rate in RA even under treatment with biological disease-modifying antirheumatic drugs, novel therapeutic strategy for treatment-resistant RA is still awaited. In this study, we analysed the expression and function of Ras guanine nucleotide-releasing proteins (RASGRPs), guanine exchange factors for small GTPase Ras, in FLS as a potential therapeutic target for RA. METHODS: The expression of RASGRPs mRNA was quantified by a real-time PCR assay in FLS isolated from synovial tissue samples. RASGRP2 protein was also evaluated immunohistochemically. Then, we transiently transfected FLS with RASGRP2 expression vector and assessed their proliferation, adhesion, migration and invasion by cellular functional assays and downstream signalling activation using immunoblot. Finally, the therapeutic effect of RASGRP2 silencing was evaluated in type-II collagen-induced arthritis rats. RESULTS: RASGRP2 was abundantly expressed in FLS from RA synovium, whereas scarcely found in those from osteoarthritis. Expression of RASGRP2 in RA-FLS was enhanced by transforming growth factor-beta. RASGRP2 activated RAP-1, subsequently affecting nuclear factor kappa-light-chain-enhancer of activated B cells pathway and actin dynamics in FLS. RASGRP2-overexpressed FLS had increased abilities of adhesion, migration and interleukin (IL)-6 production. Silencing of RASGRP2 using the intra-articular injection of Rasgrp2-specific siRNAs dampened experimental arthritis in rats by inhibiting pannus formation. CONCLUSIONS: RASGRP2 was identified to be involved in the pathogenesis of RA by promoting adhesion, migration and IL-6 production from FLS, proposed as a potential novel non-immunosuppressive therapeutic target for RA.
• Postoperative translation of the upper instrumented vertebra in thoracic adolescent idiopathic scoliosis.

  Katsuhisa Yamada, Hideki Sudo, Kiyoshi Kaneda, Yasuhiro Shono, Yuichiro Abe, Norimasa Iwasaki

  Journal of neurosurgery. Pediatrics 22 (6) 694 - 700 1933-0707 2018/12/01 [Refereed][Not invited]
   

  OBJECTIVEThe aim of this retrospective study was to analyze the influence of upper instrumented vertebra (UIV) translation from the C7 plumb line (C7PL) on the long-term postoperative results of patients with main thoracic (MT) adolescent idiopathic scoliosis (AIS).METHODSTwenty-five patients had been treated surgically for AIS with a Lenke type 1 curve and had been followed up for a mean period of 18.2 years. Radiographic parameters, pulmonary function measurements, and clinical outcomes were compared between the patients (n = 15) with UIV translation < 20 mm and those (n = 10) with UIV translation ≥ 20 mm at the final follow-up. Correlations between UIV translation and radiographic or pulmonary function parameters were analyzed.RESULTSPatients with ≥ 20 mm UIV translation at the final follow-up had a significantly larger preoperative UIV translation than that in the patients with < 20 mm UIV translation at follow-up. The former group also had a significantly lower correction rate of the MT curve, higher chest cage ratio, and lower radiographic shoulder height (p = 0.01, 0.005, and 0.025, respectively) at the final follow-up. The Scoliosis Research Society (SRS)-30 Questionnaire scores were equivalent between the two groups. Correlation analysis showed that the following parameters were significantly associated with UIV translation: MT curve correction rate (r = -0.481, p = 0.015), chest cage ratio (r = 0.673, p < 0.001), and percent-predicted forced expiratory volume in 1 second (r = -0.455, p = 0.033).CONCLUSIONSThe UIV translation should be considered an important factor that influences postoperative results. In MT AIS patients whose preoperative upper end vertebra (UEV) is distant from the C7PL, the UIV should be selected above the UEV to prevent large UIV translation at the postoperative follow-up.
• Effects of Remnant Tissue Preservation on Tunnel Enlargement After Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction Using the Hamstring Tendon.

  Tetsuro Masuda, Eiji Kondo, Jun Onodera, Nobuto Kitamura, Masayuki Inoue, Eiichi Nakamura, Tomonori Yagi, Norimasa Iwasaki, Kazunori Yasuda

  Orthopaedic journal of sports medicine 6 (12) 2325967118811293 - 2325967118811293 2018/12 

  Background: The effects of remnant tissue preservation on tunnel enlargement after anatomic double-bundle anterior cruciate ligament (ACL) reconstruction have not yet been established. Hypothesis: The preservation of ACL remnant tissue may significantly reduce the degree and incidence of tunnel enlargement after anatomic double-bundle ACL reconstruction, while the remnant-preserving procedure may not significantly increase the incidence of tunnel coalition after surgery. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 79 patients underwent anatomic double-bundle ACL reconstruction. Based on the Crain classification of ACL remnant tissue, 40 patients underwent the remnant-preserving procedure (group P), and the remaining 39 patients underwent the remnant-resecting procedure (group R). There were no differences between the 2 groups concerning all background factors, including preoperative knee instability and intraoperative tunnel positions. All patients were examined using computed tomography and a standard physical examination at 2 weeks and 1 year after surgery. Results: During surgery, the femoral and tibial anteromedial (AM) tunnel sizes in both groups averaged 6.6 and 6.5 mm, respectively. The femoral and tibial posterolateral (PL) tunnel sizes in both groups averaged 6 and 6 mm, respectively. There were no differences in the intraoperative tunnel positions and tunnel sizes between groups. Concerning the femoral AM tunnel, the degree of tunnel enlargement in the oblique coronal and oblique axial views in group P was significantly less than that in group R (P = .0068 and .0323, respectively). Regarding the femoral AM tunnel cross-sectional area, the degree and incidence of tunnel enlargement in group P were significantly less than those in group R (P = .0086 and .0278, respectively). There were no significant differences in tunnel coalition between groups. In each group, there were no significant relationships between tunnel enlargement and each clinical outcome. Conclusion: Remnant preservation in anatomic double-bundle ACL reconstruction reduced enlargement of the femoral AM tunnel and did not increase the incidence of tunnel coalition. This is one of the advantages of remnant-preserving ACL reconstruction.
• Automated noninvasive detection of idiopathic scoliosis in children and adolescents: A principle validation study.

  Sudo H, Kokabu T, Abe Y, Iwata A, Yamada K, Ito YM, Iwasaki N, Kanai S

  Scientific reports 8 (1) 17714 - 17714 2018/12 [Refereed][Not invited]
   

  Idiopathic scoliosis is the most common pediatric musculoskeletal disorder that causes a three-dimensional deformity of the spine. Early detection of this progressive aliment is essential. The aim of this study is to determine outcomes using a newly developed automated asymmetry-evaluation system for the surface of the human back using a three-dimensional depth sensor. Seventy-six human subjects suspected to have idiopathic scoliosis were included in this study. Outcome measures include patient demographics, radiographic measurements, and asymmetry indexes defined in the automated asymmetry-recognition system. The mean time from scanning to analysis was 1.5 seconds. For predicting idiopathic scoliosis of greater than 25°, the area under the curve was 0.96, sensitivity was 0.97, and specificity was 0.88. The coefficient of variation for repeatability analyses using phantom models was 1-4%. The intraclass correlation coefficient obtained for intra-observer repeatability for human subjects was 0.995. The system three-dimensionally scans multiple points on the back, enabling an automated evaluation of the back's asymmetry in a few seconds. This study demonstrated discriminative ability in determining whether an examinee requires an additional x-ray to confirm diagnosis.
• A novel technique of cervical pedicle screw placement with a pilot screw under the guidance of intraoperative 3D imaging from C-arm cone-beam CT without navigation for safe and accurate insertion.

  Masahiko Takahata, Katsuhisa Yamada, Iwata Akira, Tsutomu Endo, Hideki Sudo, Hidetoki Yokoyama, Norimasa Iwasaki

  European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 27 (11) 2754 - 2762 0940-6719 2018/11 [Refereed][Not invited]
   

  PURPOSE: The cervical pedicle screw (CPS) requires careful and accurate placement because of the critical risk for neurovascular injury. This study aimed to introduce and evaluate the safety and efficacy of a new CPS placement technique using intraoperative C-arm cone-beam CT (CBCT) and a pilot screw without navigation system. METHODS: This was a case-control study to compare the accuracy and safety of intraoperative C-arm CBCT-guided CPS placement with freehand CPS placement under lateral fluoroscopy using control data from a previous multicenter study. A total of 166 CPSs were inserted under intraoperative C-arm CBCT guidance in 48 consecutive patients (20 rheumatoid arthritis, 16 degenerative spinal disorders, 6 spinal tumor, 2 congenital deformity, 2 ossification of posterior longitudinal ligament, and 2 fracture dislocation). Accuracy and safety of CPS placement were assessed. RESULTS: The overall malposition rate was 2.4% (4 screws in grade 1: malposition by less than half-screw diameter, 0 in grade 2: malposition by more than half-screw diameter), which was significantly lower than the reported malposition rate of 14.8% in lateral fluoroscopy-guided freehand placement. There were no complications directly related to CPS insertion. The average estimated effective radiation dose per surgery was 14.7 mSv. CONCLUSIONS: The novel technique enables intraoperative adjustment of the trajectory of the CPS as well as confirmation of the CPS path before penetrating the isthmus of the pedicle, resulting in accurate and safe CPS placement, which outweighs the demerits of radiation exposure. These slides can be retrieved under Electronic Supplementary Material.
• Siglec-15-targeting therapy increases bone mass in rats without impairing skeletal growth.

  Sato D, Takahata M, Ota M, Fukuda C, Tsuda E, Shimizu T, Okada A, Hiruma Y, Hamano H, Hiratsuka S, Fujita R, Amizuka N, Hasegawa T, Iwasaki N

  Bone 116 172 - 180 8756-3282 2018/11 [Refereed][Not invited]
   

  The treatment of juvenile osteoporosis has not been established due to a lack of data regarding the efficacy and adverse effects of therapeutic agents. The possible adverse effects of the long-term use of antiresorptive therapies on skeletal growth in children is of particular concern. Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immunoreceptor that regulates osteoclast development and bone resorption, and its deficiency suppresses bone remodeling in the secondary spongiosa, but not in the primary spongiosa, due to a compensatory mechanism of osteoclastogenesis. This prompted us to develop an anti-Siglec-15 therapy for juvenile osteoporosis because most anti-resorptive drugs have potential adverse effects on skeletal growth. Using growing rats, we investigated the effects of an anti-Siglec-15 neutralizing antibody (Ab) on systemic bone metabolism and skeletal growth, comparing this drug to bisphosphonate, a first-line treatment for osteoporosis. Male 6-week-old F344/Jcl rats were randomized into six groups: control (PBS twice per week), anti-Siglec-15 Ab (0.25, 1, or 4 mg/kg every 3 weeks), and alendronate (ALN) (0.028 or 0.14 mg/kg twice per week). Treatment commenced at 6 weeks of age and continued for the next 6 weeks. Changes in bone mass, bone metabolism, bone strength, and skeletal growth during treatment were analyzed. Both anti-Siglec-15 therapy and ALN increased bone mass and the mechanical strength of both the femora and lumbar spines in a dose-dependent manner. Anti-Siglec-15 therapy did not have a significant effect on skeletal growth as evidenced by micro-CT-based measurements of femoral length and histology, whereas high-dose ALN resulted in growth retardation with histological abnormalities in the growth plates of femurs. This unique property of the anti-Siglec-15 Ab can probably be attributed to compensatory signaling for Siglec-15 inhibition in the primary spongiosa, but not in the secondary spongiosa. Thus, anti-Siglec-15 therapy could be a safe and effective for juvenile osteoporosis.
• Alteration in stress distribution patterns through the elbow joint in professional and college baseball pitchers: Using computed tomography osteoabsorptiometry.

  Daisuke Momma, Tadanao Funakoshi, Kaori Endo, Masashi Yokota, Kazuhiro Fujisaki, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 23 (6) 948 - 952 2018/11 

  BACKGROUND: Long-term pitching activities change the stress distribution across the elbow joint surface in living subjects, however the influence of the different strength of stress on the stress distribution patterns remain unclear. The aims of this study were to evaluate the distribution of subchondral bone density across the elbow joint in different levels of pitchers, and to reveal the influence of the strength of stress on the elbow joint surface under long-term loading conditions of baseball pitching. METHODS: The current analysis was performed using computed tomography (CT) image data obtained from the throwing side elbow of 12 nonthrowing athletes (controls), 15 college baseball pitchers (college group) and 13 professional baseball pitchers (professional group). The distribution patterns of subchondral bone density through the articular surface of the elbow joints were assessed using a CT osteoabsorptiometry method. The quantitative analysis was based on location and percentages of high-density area on the articular surface. RESULTS: High-density area in the college and professional groups were found in the anterior part of the captellum, posterior part of the trochlea and radial head. In the professional group, the percentages of high-density area in the anterior part of the capitellum, posterior part of the trochlea, radial head and olecranon were significantly greater than in the college group. CONCLUSIONS: Stress distribution on the articular surface of the elbow joint was affected by pitching abilities or competitive levels. Our analysis indicates that high strength of stress in professional baseball players produce potential risk of elbow injuries.
• Coordinated existence of multiple gangliosides is required for cartilage metabolism.

  Momma D, Onodera T, Homan K, Matsubara S, Sasazawa F, Furukawa J, Matsuoka M, Yamashita T, Iwasaki N

  Osteoarthritis and cartilage 1063-4584 2018/11 [Refereed][Not invited]
  
• An acellular bioresorbable ultra-purified alginate gel promotes intervertebral disc repair: A preclinical proof-of-concept study.

  Takeru Tsujimoto, Hideki Sudo, Masahiro Todoh, Katsuhisa Yamada, Koji Iwasaki, Takashi Ohnishi, Naoki Hirohama, Takayuki Nonoyama, Daisuke Ukeba, Katsuro Ura, Yoichi M Ito, Norimasa Iwasaki

  EBioMedicine 37 521 - 534 2018/11 [Refereed][Not invited]
   

  BACKGROUND: The current surgical procedure of choice for lumbar intervertebral disc (IVD) herniation is discectomy. However, defects within IVD produced upon discectomy may impair tissue healing and predispose patients to subsequent IVD degeneration. This study aimed to investigate whether the use of an acellular bioresorbable ultra-purified alginate (UPAL) gel implantation system is safe and effective as a reparative therapeutic strategy after lumbar discectomy. METHODS: Human IVD cells were cultured in a three-dimensional system in UPAL gel. In addition, lumbar spines of sheep were used for mechanical analysis. Finally, the gel was implanted into IVD after discectomy in rabbits and sheep in vivo. FINDINGS: The UPAL gel was biocompatible with human IVD cells and promoted extracellular matrix production after discectomy, demonstrating sufficient biomechanical characteristics without material protrusion. INTERPRETATION: The present results indicate the safety and efficacy of UPAL gels in a large animal model and suggest that these gels represent a novel therapeutic strategy after discectomy in cases of lumbar IVD herniation. FUND: Grant-in-Aid for the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.
• Morphological characteristics of the sigmoid notch of the distal radius affect the stress distribution patterns in the distal radioulnar joint.

  Tsukuda Y, Kawamura D, Matsui Y, Iwasaki N

  The Journal of hand surgery, European volume 44 (5) 1753193418803522 - 502 1753-1934 2018/10 [Refereed][Not invited]
   

  The aim of this study was to clarify the effects of morphological patterns of the sigmoid notch on the stress distribution across the articular surface of the distal radioulnar joint using a computed tomography osteoabsorptiometry method. Fourteen wrists from 13 patients were classified into two groups according to the type of sigmoid notch, namely the 'C' type and ski-slope sigmoids, and the percentages of high-density areas on the articular surface were quantitatively analysed. The percentage of the high-density area of the dorsal region in the ski-slope sigmoid group was significantly greater than that of the 'C' type sigmoid group (16% vs 4.1%) and of the volar region of the ski-slope sigmoid group (16% vs 2.4%). The results indicate that bony morphological differences in the radial sigmoid notch affect the stress distribution pattern through the distal radioulnar joint.
• Impact of Multilevel Facetectomy and Rod Curvature on Anatomical Spinal Reconstruction in Thoracic Adolescent Idiopathic Scoliosis.

  Sudo H, Abe Y, Kokabu T, Kuroki K, Iwata A, Iwasaki N

  Spine 43 (19) E1135 - E1142 0362-2436 2018/10 [Refereed][Not invited]
   

  STUDY DESIGN: A prospective, nonrandomized study. OBJECTIVE: The aim of this study was to assess surgical outcomes of multilevel facetectomy and rod curvature with simultaneous double-rod rotation technique for anatomical spinal reconstruction in thoracic adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Although some surgical techniques maintain or restore thoracic kyphosis (TK), next-generation strategies for thoracic AIS should include corrections in three anatomical planes. METHODS: The study included 39 consecutive patients with Lenke 1 or Lenke 2 thoracic AIS treated at our institution. After all-level facetectomy at instrumentation level, except for the lowest intervertebral segment, two rods were identically bent to guide postoperative anatomical TK without reference to the intraoperative coronal alignment of the AIS deformity. Outcome measures included patient demographics, radiographic measurements, and Scoliosis Research Society (SRS) questionnaire scores. RESULTS: After 2 years of follow-up, the average main thoracic Cobb angle correction rate was 83.5%, and the final correction loss was 2.2°. The average preoperative TK (T5-T12) significantly increased from 13.2° to 24.6° (P < 0.001) at final follow-up. The percentage of patients with a T6-T8 location of the TK apex significantly increased from 51.3% preoperatively to 87.2% at final follow-up. The average preoperative vertebral rotation angle significantly decreased from 18.7° to 12.8° postoperatively (P < 0.001). The average preoperative total SRS questionnaire score significantly increased from 3.5 to 4.5 (P < 0.001) at final follow-up. There was no implant breakage and vascular and neurologic complications, with all patients demonstrating solid fusion at final follow-up. CONCLUSION: Multilevel facetectomy and rod curvature play an important role in anatomical spinal reconstruction in patients with thoracic AIS. From the spatiotemporal point of view, four-dimensional correction could be actively performed by rod curvature under multilevel facetectomy and is expected to obtain an anatomical thoracic spine postoperatively, indicating that an anatomically designed rod could be supplied as a pre-bent rod. LEVEL OF EVIDENCE: 3.
• 経時的応力計測可能なラメラ構造二重膜ヒドロゲルを用いたヒト関節靱帯における内部応力解析

  門間 太輔, 黒川 孝幸, 河村 太介, 瓜田 淳, 松井 雄一郎, 本谷 和俊, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 37 (3) 256 - 256 1883-2873 2018/10
• Inverted V-Shaped High Tibial Osteotomy for Medial Osteoarthritic Knees With Severe Varus Deformity.

  Kondo E, Yasuda K, Yabuuchi K, Aoki Y, Inoue M, Iwasaki N, Yagi T

  Arthroscopy techniques 7 (10) e999 - e1012 2018/10 [Refereed][Not invited]
   

  A hemi-closing-wedge and hemi-opening-wedge, inverted V-shaped high tibial osteotomy with local bone graft has been reported to be an effective surgical procedure for medial osteoarthritis of the knee. In this procedure, an inverted V-shaped osteotomy is made and a thin wedged bone block is resected from the lateral side and implanted in the medial opening space created after valgus correction. This procedure can provide sufficient valgus correction of the knee with severe varus deformity more easily than can closing-wedge high tibial osteotomy. The inverted V-shaped osteotomy does not change the posterior tibial slope, the patellar height, or the length of the lower limb at all because the center of tibial alignment correction by the inverted V-shaped osteotomy is located near the center of rotation of angulation of the lower-limb deformity. We recently modified this procedure by performing biplanar osteotomy, developing useful cutting guides, and fixing the tibia with a lateral locking compression plate. The surgical technique is described to enable the reproducible creation of the hemi-closing-wedge and hemi-opening-wedge, inverted V-shaped osteotomy with the locking plate for medial osteoarthritic knees with moderate or severe varus deformity.
• Cervical nerve root anomaly: Report of a case and review of the literature.

  Takahata M, Iwasaki N

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 23 (5) 842 - 844 0949-2658 2018/09 [Refereed][Not invited]
  
• 第5腰椎骨腫瘍摘出術における腸骨稜切離飜転による椎骨側方アプローチの有用性

  岩田 玲, 高畑 雅彦, 須藤 英毅, 角家 健, 山田 勝久, 大西 貴士, 岩崎 倫政

  東日本整形災害外科学会雑誌 東日本整形災害外科学会 30 (3) 353 - 353 1342-7784 2018/08
• 椎間板再生治療における組織修復材の開発

  辻本 武尊, 山田 勝久, 岩崎 浩司, 大西 貴士, 岩崎 倫政, 須藤 英毅, 東藤 正浩

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 60 (1) 144 - 145 1343-3873 2018/08
• 遺伝子改変マウスを用いた椎間板変性におけるcaspase 3遺伝子の果たす機能解析

  大西 貴士, 岩崎 浩司, 辻本 武尊, 岩崎 倫政, 須藤 英毅

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 60 (1) 162 - 162 1343-3873 2018/08
• 経時的応力計測可能なラメラ構造二重膜ヒドロゲルを用いたヒト関節靱帯における内部応力解析

  門間 太輔, 黒川 孝幸, 河村 太介, 瓜田 淳, 松井 雄一郎, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 92 (8) S1921 - S1921 0021-5325 2018/08
• Molecular chaperone HSP70 prevents formation of inclusion bodies of the 25-kDa C-terminal fragment of TDP-43 by preventing aggregate accumulation.

  Kitamura A, Iwasaki N, Kinjo M

  Cell stress & chaperones 1355-8145 2018/08 [Refereed][Not invited]
  
• Blood Flow Changes in Subsynovial Connective Tissue on Contrast-Enhanced Ultrasonography in Patients With Carpal Tunnel Syndrome Before and After Surgical Decompression.

  Motomiya M, Funakoshi T, Ishizaka K, Nishida M, Matsui Y, Iwasaki N

  Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine 37 (7) 1597 - 1604 0278-4297 2018/07 [Refereed][Not invited]
   

  OBJECTIVES: Although qualitative alteration of the subsynovial connective tissue in the carpal tunnel is considered to be one of the most important factors in the pathophysiologic mechanisms of carpal tunnel syndrome (CTS), little information is available about the microcirculation in the subsynovial connective tissue in patients with CTS. The aims of this study were to use contrast-enhanced ultrasonography (US) to evaluate blood flow in the subsynovial connective tissue proximal to the carpal tunnel in patients with CTS before and after carpal tunnel release. METHODS: The study included 15 volunteers and 12 patients with CTS. The blood flow in the subsynovial connective tissue and the median nerve was evaluated preoperatively and at 1, 2, and 3 months postoperatively using contrast-enhanced US. RESULTS: The blood flow in the subsynovial connective tissue was higher in the patients with CTS than in the volunteers. In the patients with CTS, there was a significant correlation between the blood flow in the subsynovial connective tissue and the median nerve (P = .01). The blood flow in both the subsynovial connective tissue and the median nerve increased markedly after carpal tunnel release. CONCLUSIONS: Our results suggest that increased blood flow in the subsynovial connective tissue may play a role in the alteration of the microcirculation within the median nerve related to the pathophysiologic mechanisms of CTS. The increase in the blood flow in the subsynovial connective tissue during the early postoperative period may contribute to the changes in intraneural circulation, and these changes may lead to neural recovery.
• Identification of optimized rod shapes to guide anatomical spinal reconstruction for adolescent thoracic idiopathic scoliosis.

  Kokabu T, Kanai S, Abe Y, Iwasaki N, Sudo H

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society 36 (12) 3219 - 3224 0736-0266 2018/07 [Refereed][Not invited]
   

  Adolescent idiopathic scoliosis (AIS), the most common pediatric musculoskeletal disorder, causes a three-dimensional deformity of the spine. Although rod curvature could play an important role in anatomical spinal reconstruction in patients with thoracic AIS, intraoperative contouring of the straight rod induces notches into the rod, leading to decreased fatigue strength. Here, we analyzed pre-bent rod geometries from 46 intraoperative tracings of the rod geometry, which can provide anatomical spinal reconstruction in patients with thoracic AIS. The center point clouds of the rod shapes were extracted and approximated as arcs and straight lines. The difference between the center point clouds were evaluated using the iterative closest point methods. When the rod shapes were divided into six groups based on length followed by hierarchical cluster analysis, 10 representative rod shapes were obtained with a difference value of 5 mm. Thus, we identified optimized rod shapes to guide anatomical spinal reconstruction for thoracic AIS, which will reduce not only the risk of rod breakage but also operation time, leading to decreased patient burden. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3219-3224, 2018.
• Is There an Association Between Borderline-to-mild Dysplasia and Hip Osteoarthritis? Analysis of CT Osteoabsorptiometry.

  Tohru Irie, Daisuke Takahashi, Tsuyoshi Asano, Ryuta Arai, Muhammad Alaa Terkawi, Yoichi M Ito, Norimasa Iwasaki

  Clinical orthopaedics and related research 476 (7) 1455 - 1465 0009-921X 2018/07 [Refereed][Not invited]
   

  BACKGROUND: The definitive treatment of borderline-to-mild dysplasia remains controversial. A more comprehensive understanding of the etiology of osteoarthritis (OA) and clarification of any possible association between borderline-to-mild dysplasia and the pathogenesis of OA are essential. QUESTIONS/PURPOSES: (1) Does the distribution of acetabular subchondral bone density increase according to dysplasia severity? (2) Is there an association between borderline-to-mild dysplasia and OA pathogenesis? METHODS: We evaluated bilateral hips of patients with developmental dysplasia of the hip who underwent eccentric rotational acetabular osteotomy (ERAO) for inclusion in the dysplasia group and contralateral hips of patients with unilateral idiopathic osteonecrosis of the femoral head (ONFH) who underwent curved intertrochanteric varus osteotomy (CVO) for the control group. ERAO was performed in 46 patients and CVO was performed in 32 patients between January 2013 and August 2016 at our institution. All patients underwent bilateral hip CT. The study included 55 hips categorized according to dysplasia severity: (1) borderline-mild, 19 hips (15° ≤ lateral center-edge angle [LCEA] < 25°); (2) moderate, 20 hips (5° ≤ LCEA < 15°); (3) severe, 16 hips (LCEA < 5°); and (4) control, 15 hips. Thirty-seven dysplastic hips (age < 15 or > 50 years old, prior hip surgery, subluxation, aspherical femoral head, cam deformity, and radiographic OA) and 17 control hips (age < 15 or > 50 years old, bilateral ONFH, LCEA < 25° or ≥ 35°, cam deformity, and radiographic OA) were excluded. CT-osteoabsorptiometry (OAM) predicts physiologic biomechanical conditions in joints by evaluating subchondral bone density. We evaluated the distribution of subchondral bone densities in the acetabulum with CT-OAM, dividing the stress distribution map into six segments: anteromedial, anterolateral, centromedial, centrolateral, posteromedial, and posterolateral. We calculated the percentage of high-density area, which was defined as the upper 30% of Hounsfield units values in each region and compared least square means difference estimated by the random intercept model among the four groups. RESULTS: In all regions, the percentage of high-density area did not differ between the borderline-mild group and the control (eg, anterolateral, 16.2 ± 5.6 [95% CI, 13.4 to 18.9] versus 15.5 ± 5.7 [95% CI, 12.4 to 18.5, p = 0.984]; centrolateral, 39.1 ± 5.7 [95% CI, 36.4 to 41.8] versus 39.5 ± 4.7 [95% CI, 36.6 to 42.5, p = 0.995]; posterolateral, 10.9 ± 5.2 [95% CI, 8.0 to 13.8] versus 15.1 ± 6.8 [95% CI, 11.7 to 18.5, p = 0.389]). In the anterolateral region, a smaller percentage of high-density area was observed in the borderline-mild group than in both the moderate group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 28.2 ± 5.1 [95% CI, 25.5-30.9], p < 0.001) and the severe group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 22.2 ± 6.8 [95% CI, 19.2-25.2, p = 0.026). CONCLUSIONS: Our results suggest that the cumulative hip stress distribution in borderline-to-mild dysplasia was not concentrated on the lateral side of the acetabulum, unlike severe dysplasia. CLINICAL RELEVANCE: Based on the stress distribution pattern, our results may suggest that there is no association between borderline-to-mild dysplasia and the pathogenesis of OA. Further studies are needed to evaluate the association between borderline-to-mild dysplasia and instability of the hip.
• Autologous Osteochondral Mosaicplasty for Centrally and Laterally Located, Advanced Capitellar Osteochondritis Dissecans in Teenage Athletes: Clinical Outcomes, Radiography, and Magnetic Resonance Imaging Findings.

  Funakoshi T, Momma D, Matsui Y, Kamishima T, Matsui Y, Kawamura D, Nagano Y, Iwasaki N

  The American journal of sports medicine 46 (8) 1943 - 1951 0363-5465 2018/07 [Refereed][Not invited]
   

  BACKGROUND: Autologous osteochondral mosaicplasty (ie, mosaicplasty) results in satisfactory clinical outcomes and reliable return to play for patients with large or unstable lesions due to osteochondritis dissecans (OCD) of the humeral capitellum. However, the association between the healing of the reconstructed cartilage and clinical outcomes remains unclear. PURPOSE: To evaluate the efficacy of mosaicplasty in teenage athletes through use of clinical scores and imaging. The secondary purpose was to compare the clinical outcomes with images of centrally and laterally located lesions. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This study analyzed 22 elbows (all male patients; mean age, 13.5 ± 1.2 years) with capitellar OCD managed with mosaicplasty. Patients were divided into 2 groups according to the location of the lesions: central (10 patients) and lateral (12 patients). Evaluation was performed through use of the clinical rating system of Timmerman and Andrews, plain radiographs, and magnetic resonance imaging (MRI; the cartilage repair monitoring system of Roberts). The mean follow-up period was 27.5 months (range, 24-48 months). RESULTS: Lateral lesions were significantly larger than central lesions (147.1 ± 51.9 mm2 vs 95.5 ± 27.4 mm2, P = .01). No other significant differences were found between central and lateral lesions. Timmerman and Andrews scores for both central and lateral lesions improved significantly from 125.0 ± 30.1 points and 138.3 ± 34.5 points preoperatively to 193.5 ± 11.3 points and 186.7 ± 18.1 points, respectively, at final follow-up ( P < .0001, P < .0001). Radiography identified complete graft incorporation in all cases and the absence of severe osteoarthritic changes or displaced osteochondral fragments. In the lateral group, the radial head ratio at final follow-up (1.83 ± 0.23) was significantly larger than the preoperative findings (1.75 ± 0.14, P = .049). The quality of joint surface reconstruction was found to be acceptable for central and lateral lesions on MRI evaluation. CONCLUSION: Mosaicplasty resulted in satisfactory clinical outcomes and smooth cartilage surface integrity in teenage athletes with OCD on their return to competition-level sports activities irrespective of lesion location.
• Bone Marrow Stimulation Technique Augmented by an Ultrapurified Alginate Gel Enhances Cartilage Repair in a Canine Model.

  Rikiya Baba, Tomohiro Onodera, Masatake Matsuoka, Kazutoshi Hontani, Zenta Joutoku, Shinji Matsubara, Kentaro Homan, Norimasa Iwasaki

  The American journal of sports medicine 46 (8) 1970 - 1979 0363-5465 2018/07 [Refereed][Not invited]
   

  BACKGROUND: The optimal treatment for a medium- or large-sized cartilage lesion is still controversial. Since an ultrapurified alginate (UPAL) gel enhances cartilage repair in animal models, this material is expected to improve the efficacy of the current treatment strategies for cartilage lesions. HYPOTHESIS: The bone marrow stimulation technique (BMST) augmented by UPAL gel can induce hyaline-like cartilage repair. STUDY DESIGN: Controlled laboratory study. METHODS: Two cylindrical osteochondral defects were created in the patellar groove of 27 beagle dogs. A total of 108 defects were divided into 3 groups: defects without intervention (control group), defects with the BMST (microfracture group), and defects with the BMST augmented by implantation of UPAL gel (combined group). At 27 weeks postoperatively, macroscopic and histological evaluations, micro-computed tomography assessment, and mechanical testing were performed for each reparative tissue. RESULTS: The defects in the combined group were almost fully covered with translucent reparative tissues, which consisted of hyaline-like cartilage with well-organized collagen structures. The macroscopic score was significantly better in the combined group than in the control group ( P < .05). The histological scores in the combined group were significantly better than those in the control group ( P < .01) and microfracture group ( P < .05). Although the repaired subchondral bone volumes were not influenced by UPAL gel augmentation, the mechanical properties of the combined group were significantly better than those of the microfracture group ( P < .05). CONCLUSION: The BMST augmented by UPAL gel elicited hyaline-like cartilage repair that had characteristics of rich glycosaminoglycan and matrix immunostained by type II collagen antibody in a canine osteochondral defect model. The present results suggest that the current technique has the potential to be one of the autologous matrix-induced chondrogenesis techniques of the future and to expand the operative indications for the BMST without loss of its technical simplicity. CLINICAL RELEVANCE: The data support the clinical reality of 1-step minimally invasive cartilage-reparative medicine with UPAL gel without harvesting donor cells.
• Anatomic analysis of the whole articular capsule of the shoulder joint, with reference to the capsular attachment and thickness.

  Momma D, Nimura A, Muro S, Fujishiro H, Miyamoto T, Funakoshi T, Mochizuki T, Iwasaki N, Akita K

  Journal of experimental orthopaedics 5 (1) 16 - 16 2018/06 [Refereed][Not invited]
   

  BACKGROUND: Although conventional Bankart repair has been the accepted procedure for traumatic anterior glenohumeral instability, the humeral avulsion of the glenohumeral ligament or an elongation of the capsule remains challenging to decide the appropriate treatment. The anatomical knowledge regarding the whole capsule of glenohumeral joint is necessary to accurately treat for the capsular disorders. The aims of the current study were to investigate the anatomical features of capsular attachment and thickness in a whole capsule of glenohumeral joint. METHODS: We used 13 shoulders in the current study. In 9 shoulders, we macroscopically measured the attachment widths of the capsulolabrum complex on the scapular glenoid, and the attachment widths of the capsule on the humerus in reference to the scapular origin of the long head of triceps brachii, and the humeral insertion of the rotator cuff tendons. We additionally used 4 cadaveric shoulders, which were embalmed using Thiel's method, for the analysis of the thickness in a whole capsule by using micro-CT. RESULTS: The glenoidal attachment of the articular capsule appeared to have a consistent width except for the superior part of the origin of the long head of triceps brachii. On the humerus, the articular capsule was widely attached to areas without overlying rotator cuffs, with the widest width (17.3 ± 0.9 mm) attached to the axillary pouch. The inferior part of the capsule, which was consistently thicker than the superior part, continued to the superior part along the glenoid and humeral side edge. CONCLUSIONS: The current study showed that the inferior part of the glenohumeral capsule had a wide humeral attachment from the inferior edge of the subscapularis insertion to the inferior edge of the teres minor insertion via the anatomical neck of the humerus, and the thickness of it was thicker than the superior part of the capsule.
• Double-Bundle Anterior Cruciate Ligament Reconstruction Using Hamstring Tendon Hybrid Grafts in Patients Over 40 Years of Age: Comparisons Between Different Age Groups

  Yusuke Nishio, Eiji Kondo, Jun Onodera, Tomohiro Onodera, Tomonori Yagi, Norimasa Iwasaki, Kazunori Yasuda

  Orthopaedic Journal of Sports Medicine 6 (5) 2325967118773685 - 2325967118773685 2325-9671 2018/05/21 [Refereed][Not invited]
   

  Background: Several recent studies have reported that favorable clinical results and a high level of patient satisfaction can generally be obtained with no increased risk of complications after single-bundle anterior cruciate ligament (ACL) reconstruction performed in patients > 40 years of age. However, no studies have yet clarified the age-based differences in clinical outcomes after double-bundle reconstruction. Purpose: To compare clinical outcomes after double-bundle ACL reconstruction using hamstring tendon hybrid grafts between patients in 2 different age groups: ≥40 years and < 40 years. Study Design: Cohort study Level of evidence, 3. Methods: A retrospective study was conducted using 96 patients (48 men, 48 women mean age, 37 years) who underwent unilateral ACL reconstruction between 2008 and 2011. These patients were divided into 2 groups: group M included patients ≥40 years of age (n = 40 patients), and group Y included patients < 40 years of age (n = 56 patients). All patients underwent the same anatomic double-bundle ACL reconstruction procedure. Clinical outcomes were evaluated at 2 years after surgery. Tunnel enlargement was also evaluated by computed digital radiography at 1 week and 2 years after surgery. Results: Mean postoperative side-to-side differences in anterior laxity were 0.5 ± 1.9 mm and 1.2 ± 1.5 mm in groups M and Y, respectively there was a significant difference between the 2 groups (P =.039). There were no significant differences between the groups in Lysholm knee scores, International Knee Documentation Committee (IKDC) scores, or peak muscle torque of the hamstring. On the other hand, peak muscle torque of the quadriceps was significantly lower in group M (81%) than in group Y (89%) (P =.025). With respect to femoral tunnel enlargement, the posterolateral tunnel in group M was significantly larger than that in group Y on anteroposterior and lateral radiographs (P =.015 and P =.002, respectively). Conclusion: Equivalent clinical outcomes were seen between the 2 age groups after double-bundle ACL reconstruction. Postoperative anterior laxity was significantly less in older patients than in younger patients, however, older patients had significantly less quadriceps muscle strength than younger patients. Surgeons should be aware of residual muscle weakness and tunnel enlargement when performing double-bundle ACL reconstruction in older patients.
• Variation in stress distribution patterns across the radial head fovea in osteochondritis dissecans: predictive factors in radiographic findings

  Yuki Matsui, Tadanao Funakoshi, Daisuke Momma, Azusa Miyamoto, Kaori Endo, Kozo Furushima, Kazuhiro Fujisaki, Norimasa Iwasaki

  Journal of Shoulder and Elbow Surgery 27 (5) 923 - 930 1532-6500 2018/05/01 [Refereed][Not invited]
   

  Background: Predictive factors for the development of osteoarthritis in adolescent osteochondritis dissecans (OCD) of the humeral capitellum remain unclear. The objectives of this study were to assess subchondral bone density in the radial head fovea of patients with OCD and to evaluate stress distribution in the radiocapitellar joint. The relationship between radiologic classification and stress distribution, according to multivariate ordinal regression analysis, was also investigated. Methods: Computed tomography (CT) imaging data from 54 male patients with OCD (mean age, 13.1 years) were collected. Stress in the radial head fovea was measured using CT osteoabsorptiometry. A stress map was constructed and divided into 4 sections, and percentages of high-density regions in each section were quantitatively analyzed. Multivariate ordinal regression analyses were performed of bone density, incorporating the stage, location, and size of the OCD lesion and the presence of medial elbow disturbance in the radiographic images. Results: The percentage of high-density area in the anteromedial, posteromedial, and the anterolateral sections of the radial head fovea were significantly increased compared with the posterolateral section. Multivariate ordinal regression analysis revealed that the location and size of the lesion and a history of excessive valgus stress were associated with imbalances in the radial head fovea. Conclusions: When the OCD lesion is large and located laterally and a medial epicondyle disturbance is apparent on radiographs, the risk for developing advanced radiocapitellar osteoarthritis should be considered. These findings can be useful in the decision-making process for treating OCD.
• Optimal administration frequency and dose of teriparatide for acceleration of biomechanical healing of long-bone fracture in a mouse model.

  Ota M, Takahata M, Shimizu T, Momma D, Hamano H, Hiratsuka S, Amizuka N, Hasegawa T, Iwasaki N

  Journal of bone and mineral metabolism 37 (2) 256 - 263 0914-8779 2018/05 [Refereed][Not invited]
   

  Despite preclinical studies demonstrating the effectiveness of teriparatide for skeletal repair in small animals, inconclusive data from clinical trials have raised questions regarding the optimal teriparatide dosing regimen for bone repair. To address this, we assessed the effect of teriparatide frequency and dose on long-bone healing using a mouse femur osteotomy/fracture model. Eight-week-old male ICR mice were subjected to open femur osteotomies, then randomized into following five groups (n = 8 per group): vehicle; low dose/high frequency: 3 μg/kg/dose, 3 times/day; low dose/low frequency: 9 μg/kg/dose, 1 time/day; high dose/high frequency: 9 μg/kg/dose, 3 times/day; high dose/low frequency: 27 μg/kg/dose, 1 time/day. Skeletal repair was assessed by microcomputed tomography, mechanical testing, and histology 4 weeks after surgery. High-dose and/or high-frequency teriparatide treatment increased callus bone volume but failed to have a significant impact on the biomechanical recovery of fractured femurs, possibly because of impaired cortical shell formation in fracture calluses. Meanwhile, low-dose/low-frequency teriparatide therapy enhanced callus bone formation without interfering with cortical shell formation despite a lesser increase in callus bone volume, leading to significant two and fourfold increases in ultimate load and stiffness, respectively. Our findings demonstrate that administering teriparatide at higher doses and/or higher frequencies raises fracture callus volume but does not always accelerate the biomechanical recovery of fractured bone, which points to the importance of finding the optimal teriparatide dosing regimen for accelerating skeletal repair.
• Potential association with early changes in serum calcium level after starting or switching to denosumab combined with eldecalcitol.

  Asano T, Shimizu T, Takahashi D, Ota M, Sato D, Hamano H, Hiratsuka S, Takahata M, Iwasaki N

  Journal of bone and mineral metabolism 37 (2) 351 - 357 0914-8779 2018/05 [Refereed][Not invited]
   

  The aims of this study are to investigate changes in serum calcium (Ca) level after switching from either non-therapy, bisphosphonate, selective estrogen receptor modulators (SERM) or teriparatide treatments to a combination therapy of denosumab (DMAb), and eldecalcitol, and the association between early changes in serum calcium and changes in bone metabolic markers and bone mineral density (BMD). 129 patients with postmenopausal osteoporosis (32 non-pretreatment, 50 bisphosphonates, 18 SERM, and 29 teriparatide) were recruited and switched to DMAb plus eldecalcitol. Serum calcium levels, bone metabolism markers, and BMD measurements of the lumbar spine and femoral neck were evaluated. All groups showed an increase in BMD 6 months and 1 year after DMAb administration compared to baseline via suppression of bone metabolism markers. The TPD group showed a significant decrease in serum calcium level 1 week after the first injection of DMAb and eldecalcitol compared to baseline and the bisphosphonate group. Changes in serum calcium level from baseline to 1 week after the first injection of DMAb trended to correlate with changes in bone metabolism markers and lumbar BMD. The risks of DMAb-induced hypocalcemia are different between starting and switching from bone resorption inhibitors and bone formation promoters. Therefore, appropriate assessment before administration of DMAb, including pretreatment therapy as well as serum Ca and bone metabolic markers will help identify the risk of hypocalcemia following DMAb in combination with eldecalcitol. Our findings also showed that early change in serum Ca level after DMAb initiation could potentially predict the efficacy for therapy reaction.
• Absence of flexor carpi radialis identified during volar approach for fixation of distal radius fracture: A case report

  Tomoyo Irie, Makoto Motomiya, Norimasa Iwasaki

  BMC Research Notes 11 (1) 240 - 240 1756-0500 2018/04/11 [Refereed][Not invited]
   

  Background: Volar locking plate fixation of distal radius fractures is commonly performed because of its good clinical outcomes. The flexor carpi radialis (FCR) approach is one of the most popular approaches to dissecting the volar side of the distal radius because of its simplicity and safety. We describe an extremely rare case of an absent FCR identified during a volar approach for fixation of a distal radius fracture. Case presentation: A 59-year-old woman with distal radius fracture underwent surgery using the usual FCR approach and volar locking plate. We could not identify the absence of the FCR tendon preoperatively because of severe swelling of the distal forearm. At first, we wrongly identified the palmaris longus tendon as the FCR because it was the tendinous structure at the most radial location of the volar distal forearm. When we found the median nerve just radial to the palmaris longus tendon, we were then able to identify the anatomical abnormality in this case. To avoid iatrogenic neurovascular injuries, we changed the approach to the classic Henry's approach. Conclusions: Although the FCR approach is commonly used for fixation of distal radius fractures because of its simplicity and safety, this is the first report of complete absence of the FCR during the commonly performed volar approach for fixation of a distal radius fracture, to our knowledge. Because the FCR is designated as a favorable landmark because of its superficially palpable location, strong and thick structure, and rare anatomical variations, there is the possibility of iatrogenic complications in cases of the absence of the FCR. We suggest that surgeons should have a detailed knowledge of the range of possible anomalies to complete the fixation of a distal radius fracture safely.
• Drug therapy targeting pyrophosphate slows the ossification of spinal ligaments in twy mice

  Shigeto Hiratsuka, Masahiko Takahata, Tomohiro Shimizu, Hiroki Hamano, Masahiro Ota, Dai Sato, Norimasa Iwasaki

  Journal of Orthopaedic Research 36 (4) 1256 - 1261 1554-527X 2018/04/01 [Refereed][Not invited]
   

  The lack of an effective drug therapy against ossification of spinal ligament (OSL) warrants investigation into the therapeutic target of this disease. An endogenous inhibitor of biomineralization, pyrophosphate (PPi) is a potential therapy for ectopic ossification however, exogenous PPi is rapidly hydrolyzed by tissue non-specific alkaline phosphatase (TNAP) present in body fluids. In this study, we examined whether a drug therapy targeting PPi is efficacious for the treatment of OSL using the Enpp1ttw/ttw (twy) mouse model. Twenty male twy mice were randomized into four groups: (i) vehicle (Control) (ii) alkaline phosphatase inhibitor levamisole (5 mg/kg/day sc continuously) (iii) levamisole + exogenous PPi (160 µmol/kg/day sc continuously) and (iv) nuclear retinoic acid receptor-γ (RARγ) agonist (6 µg/kg sc daily). The RARγ agonist, which is a proven inhibitor of ectopic endochondral ossification, was used as a positive control. Treatments commenced when the mice were 5 weeks of age and continued for 4 weeks. Longitudinal micro-computed tomography and postmortem histological analysis were performed. Administration of levamisole alone and in combination with PPi increased serum PPi concentration by 17% and 52%, respectively, compared to that in vehicle-treated mice. The development of OSL in twy mice was suppressed by levamisole + PPi and RARγ agonist treatments, but not by levamisole alone. The levamisole + PPi therapy did not cause osteoporosis, whereas RARγ agonist-treated mice developed osteoporosis. Treatment of twy mice with levamisole in combination with exogenous PPi increased serum PPi level, which slowed the progression of OSL without producing adverse effect on bone. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1256–1261, 2018.
• Trigger wrist caused by avascular necrosis of the capitate: A case report

  Yuichiro Matsui, Daisuke Kawamura, Hiroaki Kida, Kanako C. Hatanaka, Norimasa Iwasaki

  BMC Musculoskeletal Disorders 19 (1) 90 - 90 1471-2474 2018/03/27 [Refereed][Not invited]
   

  Background: Trigger wrist is a rare condition first described by Marti in 1960, and various causes have been reported. The condition mostly occurs with finger flexion and extension, and rarely with flexion and extension of the wrist itself. Avascular necrosis of the capitate is also a rare condition, first described by Jönsson in 1942. While some reports of this condition have been published, little is known about its etiology. Therefore, no established treatment exists. We report a case of trigger wrist caused by avascular necrosis of the capitate. Case presentation: A 16-year-old right-handed male who was a high school handball player was referred to our department from a nearby hospital 5 months after the onset of pain in the dorsal aspect of the right wrist, with an unknown cause. At the previous hospital, imaging findings led to a diagnosis of avascular necrosis of the capitate, and conservative treatment with a wrist brace did not improve the pain. At the initial visit to our department, the patient was noted to have a painful trigger wrist that was brought on by wrist flexion and extension. Preoperative imaging findings led to a diagnosis of trigger wrist caused by capitolunate instability secondary to avascular necrosis of the capitate. We performed a partial excision of the proximal capitate with tendon ball interposition. Two years after surgery, the patient's clinical outcome was favorable, with no recurrence of wrist pain or triggering. Conclusions: Both trigger wrist and avascular necrosis of the capitate are rare disorders. When a patient presents with painful triggering at the wrist, surgeons must bear in mind that avascular necrosis of the capitate may result in this phenomenon. We recommend partial excision of the proximal capitate with tendon ball interposition for the treatment of this lesion.
• Failed Reconstruction of the Extensor Pollicis Longus in a Patient with a Major Variation of the Extensor Indicis Proprius Tendon: A Case Report.

  Matsumae G, Motomiya M, Iwasaki N

  The journal of hand surgery Asian-Pacific volume 23 (1) 132 - 136 2424-8355 2018/03 [Refereed][Not invited]
   

  Tendon transfer with extensor indicis proprius (EIP) has been performed widely for reconstructing ruptures of the extensor pollicis longus because of its simplicity and clinical outcome. We experienced a rerupture of the extensor pollicis longus restored by incorrect tendon transfer because of a major unrecognized variation in the anatomy of the EIP. Surgeons should perform such transfer with a detailed knowledge of the possible anatomical variations to avoid such serious complications.
• 椎間板再生治療における組織修復材の開発

  辻本 武尊, 須藤 英毅, 東藤 正浩, 山田 勝久, 大西 貴士, 岩崎 倫政

  Journal of Spine Research (一社)日本脊椎脊髄病学会 9 (3) 234 - 234 1884-7137 2018/03
• Quick and easy sample preparation without resin embedding for the bone quality assessment of fresh calcified bone using fourier transform infrared imaging

  Hiromi Kimura-Suda, Masahiko Takahata, Teppei Ito, Tomohiro Shimizu, Kyosuke Kanazawa, Masahiro Ota, Norimasa Iwasaki

  PLoS ONE 13 (2) e0189650  1932-6203 2018/02/01 [Refereed][Not invited]
   

  Fourier transform infrared (FTIR) imaging is a powerful tool for the assessment of bone quality however, it requires the preparation of thin bone sections. Conventional poly(methyl methacrylate) (PMMA) embedding for the preparation of sections takes more than two weeks and causes denaturation of the bone. Development of a quick and easy sample preparation technique without denaturation is needed for accurate clinical evaluation of fresh calcified bone using FTIR imaging. Frozen sectioning allows the quick and easy preparation of thin sections without denaturation, but it requires a substrate with good chemical resistance and improved heat shock resistance. Polypropylene (PP) film afforded both good chemical resistance and greater heat shock resistance, and the 4-μm-thick PP film coated with glue was thin enough for the IR beam to pass through it, while the optical anisotropy of infrared bands overlapping with PO4 3- band was negligible. The bone quality of femoral thin sections prepared by the conventional PMMA embedding and sectioning procedure (RESIN-S) or the newly developed frozen sectioning procedure (FROZEN-S) was evaluated by FTIR imaging. The mineral-to-matrix ratio and crystallinity in the RESIN-S sections were higher than those in the FROZEN-S sections, whereas the carbonate-to-phosphate ratio in the RESIN-S sections was lower than that in the FROZEN-S sections. In RESIN-S, the increased mineral-to-matrix ratio could be caused by dehydration, and the increased crystallinity and decreased carbonate-to-phosphate ratio might be consequence of dissolution of bone mineral during PMMA embedding. Therefore, the combined use of PP film coated with glue and the frozen sectioning procedure without denaturation appears well suited to the assessment of the bone quality of fresh calcified bone using FTIR imaging.
• Age-related spontaneous lumbar intervertebral disc degeneration in a mouse model

  Takashi Ohnishi, Hideki Sudo, Takeru Tsujimoto, Norimasa Iwasaki

  Journal of Orthopaedic Research 36 (1) 224 - 232 1554-527X 2018/01/01 [Refereed][Not invited]
   

  The pathogenesis of intervertebral disc degeneration is unclear, but it is a major cause of several spinal diseases. Animal models have historically provided an appropriate benchmark for understanding the human spine. However, there is little information about when intervertebral disc degeneration begins in the mouse or regarding the relationship between magnetic resonance imaging and histological findings. The aim for this study was to obtain information about age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine using magnetic resonance imaging and a histological score regarding when the intervertebral disc degeneration started and how rapidly it progressed, as well as how our histological score detected the degeneration. The magnetic resonance imaging index yielded a moderate correlation with our Age-related model score. The Pfirrmann grade and magnetic resonance imaging index had moderate correlations with age. However, our Age-related model score had a high correlation with age. Intervertebral disc level was not a significant variable for the severity of disc degeneration. Both Pfirrmann grade and the Age-related model score were higher in the ≥14-month-old group than in the 6-month-old group. The present results indicated that mild but significant intervertebral disc degeneration occurred in 14-month-old mice, and the degree of degeneration progressed slowly, reaching a moderate to severe condition for 22-month-old mice. At least a 14-month follow-up is mandatory for evaluating spontaneous age-related mouse intervertebral disc degeneration. The histological classification score can precisely detect the gradual progression of age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine, and is appropriate for evaluating it. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:224–232, 2018.
• Transcriptional profile of human macrophages stimulated by ultra-high molecular weight polyethylene particulate debris of orthopedic implants uncovers a common gene expression signature of rheumatoid arthritis

  Mohamad Alaa Terkawi, Masanari Hamasaki, Daisuke Takahashi, Masahiro Ota, Ken Kadoya, Tomoyo Yutani, Keita Uetsuki, Tsuyoshi Asano, Tohru Irie, Ryuta Arai, Tomohiro Onodera, Masahiko Takahata, Norimasa Iwasaki

  Acta Biomaterialia 65 417 - 425 1878-7568 2018/01/01 [Refereed][Not invited]
   

  Osteolysis is a serious postoperative complication of total joint arthroplasty that leads to aseptic loosening and surgical revision. Osteolysis is a chronic destructive process that occurs when host macrophages recognize implant particles and release inflammatory mediators that increase bone-resorbing osteoclastic activity and attenuate bone-formation osteoblastic activity. Although much progress has been made in understanding the molecular responses of macrophages to implant particles, the pathways/signals that initiate osteolysis remain poorly characterized. Transcriptomics and gene-expression profiling of these macrophages may unravel key mechanisms in the pathogenesis of osteolysis and aid the identification of molecular candidates for therapeutic intervention. To this end, we analyzed the transcriptional profiling of macrophages exposed to ultra-high molecular weight polyethylene (UHMWPE) particles, the most common components used in bearing materials of orthopedic implants. Regulated genes in stimulated macrophages were involved in cytokine, chemokine, growth factor and receptor activities. Gene enrichment analysis suggested that stimulated macrophages elicited common gene expression signatures for inflammation and rheumatoid arthritis. Among the regulated genes, tumor necrosis factor superfamily member 15 (TNFSF15) and chemokine ligand 20 (CCL20) were further characterized as molecular targets involved in the pathogenesis of osteolysis. Treatment of monocyte cultures with TNFSF15 and CCL20 resulted in an increase in osteoclastogenesis and bone-resorbing osteoclastic activity, suggesting their potential contribution to loosening between implants and bone tissues. Statement of Significance Implant loosening due to osteolysis is the most common mode of arthroplasty failure and represents a great challenge to orthopedic surgeons and a significant economic burden for patients and healthcare services worldwide. Bone loss secondary to a local inflammatory response initiated by particulate debris from implants is considered the principal feature of the pathogenesis of osteolysis. In the present study, we analyzed the transcriptional profiling of human macrophages exposed to UHMWPE particles and identified a large number of inflammatory genes that were not identified previously in macrophage responses to wear particles. Our data provide a new insight into the molecular pathogenesis of osteolysis and highlights a number of molecular targets with prognostic and therapeutic implications.
• 18F-FDG-PET/CT localizes intervertebral disc space infection following posterior lumbar interbody fusion surgery leading to successful retention of percutaneously inserted pedicle screws: a case report.

  Haraya K, Yamada K, Kokabu T, Iwata A, Endo T, Sudo H, Iwasaki N, Takahata M

  Spinal cord series and cases 4 81 - 81 2018 [Refereed][Not invited]
   

  Introduction: Postoperative infection is a potentially devastating complication of spine surgery and an appropriate strategy and timely decision-making are essential for successful treatment of deep surgical site infection (SSI) after spinal instrumentation surgeries. However, there is a lack of consensus on implant removal or retention. We report on a case of deep SSI after posterior lumbar interbody fusion (PLIF) surgery in which we achieved clinical cure by debridement and removal of the interbody fusion cage without removing the percutaneously inserted pedicle screws (PPS). Case presentation: A case was a 53-year-old woman with deep SSI after PLIF surgery using the PPS system at the L4-5 level. Computed tomography (CT) showed no clear radiolucent line around the screws and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT demonstrated abnormal FDG uptake around the cages and no uptake around the pedicle screws. Intervertebral cages were removed and iliac bone grafts were inserted between the vertebral bodies, without removing the pedicle screws. The infection was cleared and bone fusion was achieved after the revision surgery. Discussion: Targeting active infection using FDG-PET/CT is considered useful in narrowing the surgical margins and determining whether to preserve instrumentation in revision surgery after SSI. PLIF using the PPS system could be useful in preventing the easy spread of infection from the intervertebral space to the insertion point of PPS through the interstitial space.
• Two-stage corrective surgery for severe rigid cervical kyphotic deformity with unilateral vertebral artery occlusion after old blunt trauma: a case report.

  Konomi T, Suda K, Matsumoto S, Komatsu M, Takahata M, Iwasaki N, Minami A

  Spinal cord series and cases 4 18 - 18 2018 [Refereed][Not invited]
   

  INTRODUCTION: There are considerable risks for vertebral artery (VA) injury in case of corrective surgery for a severe and rigid cervical kyphotic deformity. This case report describes a rare case of surgical management for pre-existing traumatic rigid cervical kyphosis associated with unilateral VA occlusion. CASE PRESENTATION: A 73-year-old male fell down and injured his neck. He was referred to our hospital 10 months after injury because his degree of head drop progressed gradually to a chin-on-chest position such that he could not look straight forward. On plain X-ray, the C2-7 angles in the neutral, flexion, and extension positions were 61°, 71°, and 50°, respectively. CT revealed a collapse of the C5 vertebral body and bone fusion between C4 and C5 in the anterior vertebrae, and unilateral VA occlusion was confirmed by angiography. Two-stage surgery was planned to correct the kyphosis. In the first stage, anterior release of the C4/5 bone-spur fusion and dissection of the intervertebral disk were performed. After release, angiography confirmed neither occlusion nor rupture of the VA. In the second stage, anterior and posterior fixation was performed at correcting position while maintaining slight kyphosis in order to avoid excessive distortion of the VA. The postoperative C2-7 kyphosis angle improved to 16° without any VA injury, and the patient could look forward easily. DISCUSSION: The degree of correction as well as risk management of VAs should be considered carefully during corrective surgery for severe and rigid cervical kyphosis, especially with unilateral VA occlusion.
• Awareness of traumatic occult lateral mass fracture of the cervical spine triggered by the presence of unilateral vertebral artery occlusion: a case report.

  Konomi T, Suda K, Matsumoto S, Komatsu M, Takahata M, Iwasaki N, Minami A

  Spinal cord series and cases 4 20 - 20 2018 [Refereed][Not invited]
   

  INTRODUCTION: We present an unusual case of traumatic occult lateral mass fracture of the cervical spine with unilateral occlusion of the vertebral artery (VA), that was missed by plain X-ray and magnetic resonance imaging (MRI), but identified by computed tomography (CT) after suspecting high-energy trauma as the underlying cause. CASE PRESENTATION: A 67-year-old male was injured in a car accident and came to our institute on foot 4 days after injury with complaints of neck pain and numbness in the right hand. Although, no specific bone injury was visible on plain X-ray, the absence of flow voids in the right VA was confirmed on axial T2-weighted MRI. We suspected high-energy trauma of the cervical spine at that point and performed CT for a more detailed assessment. Consequently, a fracture was detected in the right lateral mass of C6 and we speculated that spontaneous reduction of the fracture-dislocation had occurred. One-stage surgery with posterior fixation was subsequently performed for instability. The patient's preoperative symptoms were improved and neither recanalization of the occlusion nor another VA occlusion was observed after surgery. DISCUSSION: VA injury occurs frequently as a complication of blunt cervical spine trauma. In the present case, however, the lateral mass fracture was not seen on MRI and missed until the unilateral VA injury was detected. When high-energy trauma of the cervical spine is suspected, it is important to evaluate damage to the spinal cord, bone, soft-tissue, and VA by MRI and CT.
• 腹臥位頸椎後方固定術後に舌腫脹による気道閉塞をきたした1例

  村上 俊文, 高畑 雅彦, 岩田 玲, 山田 勝久, 遠藤 努, 大西 貴士, 須藤 英毅, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 60 (135th suppl) 67 - 67 1343-3873 2018
• 脊柱靱帯骨化症を合併した環椎後頭骨癒合症の1例

  小池 良直, 高畑 雅彦, 山田 勝久, 岩田 玲, 遠藤 努, 大西 貴士, 須藤 英毅, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 60 (135th suppl) 68 - 68 1343-3873 2018
• 第5腰椎摘出術における脊柱起立筋付き腸骨 切離翻転による後方からの椎体側方剥離操作への有用性

  岩田 玲, 高畑 雅彦, 須藤 英毅, 角家 健, 山田 勝久, 遠藤 努, 大西 貴士, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 60 (135th suppl) 70 - 70 1343-3873 2018
• 脊椎および骨盤への悪性腫瘍の直接浸潤に対する腫瘍全摘出術の報告

  岩田 玲, 高畑 雅彦, 須藤 英毅, 角家 健, 山田 勝久, 遠藤 努, 大西 貴士, 岩崎 倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 60 (135th suppl) 70 - 70 1343-3873 2018
• A mathematical model for predicting postoperative leg shortening after curved intertrochanteric varus osteotomy for osteonecrosis of the femoral head.

  Tsuyoshi Asano, Daisuke Takahashi, Tomohiro Shimizu, Tohru Irie, Ryuta Arai, Mohamad Alaa Terkawi, Norimasa Iwasaki

  PloS one 13 (12) e0208818  2018 [Refereed][Not invited]
   

  Despite good clinical outcomes associated with curved intertrochanteric varus osteotomy for the treatment of osteonecrosis of the femoral head, post-operative leg-length discrepancy is frequently reported and might reduce patient satisfaction. Although previous report showed that varus angulation affected post-operative leg-length discrepancy, sufficient varus angulation is the most important factor for obtaining a lateral intact portion. Therefore, to ensure better postoperative outcomes, detection of other parameters associated with leg shortening may prove useful. This study aimed to detect other factors influencing post-operative leg-length discrepancy and to develop a theory for pre-operative planning. The study included 42 hips of 36 patients with osteonecrosis of the femoral head [25 men and 11 women; mean age at the time of surgery, 33.8 years (range, 17 to 53 years)]. Patients were assessed their clinical and radiological results bofore and after surgery. Additionally, a mathematical model was developed to predict leg shortening after curved intertrochanteric varus osteotomy based on the degree of varus angulation and the distance between the femoral head and osteotomy arc centers. Predicted and actual leg shortening in patients were compared to verify the accuracy of our model. Post-operatively, mean varus angle was 21.7° (range, 15 to 38°) and mean leg shortening was 1.7 mm (range, -5.1 to 11.4 mm). Univariate analysis showed that varus angulation and lateral shift of the osteotomy arc might influence the degree of leg shortening. Furthermore, mathematically predicted leg shortening significantly correlated with actual leg shortening (r = 0.905, p < 0.001), suggesting the usefulness of our model for predicting complications of curved intertrochanteric varus osteotomy. This study indicates the importance of not positioning the center of the osteotomy arc lateral from the center of the femoral head to minimize leg shortening after curved intertrochanteric osteotomy.
• Impact of spino-pelvic and global spinal alignment on the risk of osteoporotic vertebral collapse

  Takashi Ohnishi, Akira Iwata, Masahiro Kanayama, Fumihiro Oha, Tomoyuki Hashimoto, Norimasa Iwasaki

  SPINE SURGERY AND RELATED RESEARCH 2 (1) 72 - 76 2018 [Refereed][Not invited]
   

  INTRODUCTION: Numerous studies have reported the risk factors of osteoporotic vertebral collapse. However, whether spino-pelvic and global spinal alignments are associated with the occurrence of osteoporotic vertebral collapse remains unclear. This study aimed to investigate the association between spino-pelvic and global spinal alignments and the occurrence of osteoporotic vertebral collapse. METHODS: A total of 46 consecutive patients who underwent a nonoperative treatment for a single-level fresh osteoporotic thoracolumbar vertebral compression fracture (T10 to L3) were retrospectively reviewed. The parameters evaluated were the pelvic incidence, anterior deviation of the C7 plumb line, distance between the C7 plumb line and the center of the fractured vertebra, and kyphotic wedge angle of the fractured vertebra in a standing whole-spine radiograph at the beginning of the nonoperative treatment. As an outcome measure, the presence or absence of osteoporotic vertebral collapse was radiographically evaluated at the final follow-up. Multiple logistic regression analysis was used to determine significant risk factors of osteoporotic vertebral collapse. RESULTS: The mean values for each parameter were as follows: pelvic incidence, 58.0 degrees; anterior deviation of the C7 plumb line, 3.0 cm; distance between the C7 plumb line and the center of the fractured vertebra, 5.7 cm; and kyphotic wedge angle of the fractured vertebra, 14.6 degrees. Multiple logistic regression analysis revealed that the distance between the C7 plumb line and center of the fractured vertebra was a significant risk factor of osteoporotic vertebral collapse (p = 0.012; odds ratio, 1.025). The anterior deviation of the C7 plumb line (p = 0.214), pelvic incidence (p = 0.728), and kyphotic wedge angle of the fractured vertebra (p = 0.07) did not affect the occurrence of osteoporotic vertebral collapse. CONCLUSIONS: A large distance between the C7 plumb line and center of the fractured vertebra was a significant risk factor of osteoporotic vertebral collapse. The distance approximately represents that of between gravity center of trunk cranial to the fractured vertebra and the fractured vertebra. Accordingly, the large distance may cause larger flexion moment to the fractured site, leading to stress concentration that results in insufficient bone healing.
• Preoperative knee deformity and kinematics impact postoperative knee kinematics in total knee arthroplasty

  Naoki Seito, Tomohiro Onodera, Yasuhiko Kasahara, Eiji Kondo, Norimasa Iwasaki, Tokifumi Majima

  The Knee 24 (6) 1462 - 1468 0968-0160 2017/12 [Refereed][Not invited]
   

  BACKGROUND: The purpose of this study was to evaluate the relationship between the preoperative knee deformity/kinematic pattern and the postoperative knee kinematic pattern in posterior cruciate ligament substituting (PS)-total knee arthroplasty (TKA). METHODS: This study involved 39 patients with medial osteoarthritis who underwent a primary PS-TKA using a computed-tomography-based navigation system. All the operations were performed by a single surgeon using a subvastus approach, modified gap technique and the same PS type of prosthesis (Genesis II™ total knee system, Smith & Nephew, Memphis, TN, USA). Knee deformity, kinematic pattern after capsule incision (preoperative knee kinematics), and kinematic pattern after implantation (postoperative knee kinematics) in PS-TKA were measured. Kinematic patterns were divided into two groups: a medial pivot group and a non-medial pivot group. RESULTS: Preoperative varus knee deformity was significantly larger in the non-medial pivot group than in the medial pivot group (femorotibial angle: 184.7±6.4° vs. 180.8±3.9°, P<0.05). In addition, preoperative knee kinematics were conserved postoperatively, at a rate of 82% (P<0.01). CONCLUSIONS: The severity of varus knee deformity and the preoperative knee kinematic pattern might have affected the postoperative knee kinematics in PS-TKA. This must be confirmed with a randomized controlled trial on a large population study. LEVEL OF EVIDENCE: case control study, Level III.
• 椎間板再生治療における組織修復材の開発

  須藤 英毅, 辻本 武尊, 東藤 正浩, 山田 勝久, 大西 貴士, 岩崎 倫政

  日本バイオマテリアル学会大会予稿集 日本バイオマテリアル学会 39回 96 - 96 2017/11
• Effective Repair of Dural Tear Using Bioabsorbable Sheet With Fibrin Glue

  Akira Iwata, Masahiko Takahata, Ken Kadoya, Hideaki Sudo, Terufumi Kokabu, Katsuhisa Yamada, Norimasa Iwasaki

  SPINE 42 (18) 1362 - 1366 0362-2436 2017/09 [Refereed][Not invited]
   

  Study Design. Basic science. Objective. This study aimed to compare the techniques of surgical repair of dural tear using bioabsorbable material and fibrin glue. Summary of Background Data. Cerebrospinal fluid (CSF) leakage caused by dural tear can often be difficult to manage even after repair when the same materials are used in a similar manner. Methods. Burst pressure was measured for repaired porcine dura with holes of different diameters using spray of combined fibrinogen and thrombin solution (fibrin spray) alone as a control and the 5-mm hole following different methods using fibrinogen and thrombin solutions plus polyglactin 910 sheet (PGS). For group 1, fibrinogen was applied on the dura followed by PGS and thrombin. For group 2, thrombin was followed by PGS and fibrinogen. For group 3, fibrinogen was followed by PGS and fibrin spray. For group 4, thrombin was followed by PGS and fibrin spray. Microscopic observation was conducted for each specimen. Results. Repair using fibrin spray alone was successful for the 0.3-mm diameter pinhole (breakdown pressure: 27.8 +/- 8.6 mmHg), but was not able to cover the 2.7-and 5-mm holes. For a 5-mm diameter hole, the breakdown pressure was 54.4 +/- 38.8 mmHg in group 1, 26.3 +/- 19.4 mmHg in group 2, 147.7 +/- 65.0 mmHg in group 3, and 35.5 +/- 23.4 mmHg in group 4 (P< 0.001). There was little fibrin glue in the burst layer between the dural surface and PGS with thrombin on the dural surface (group 2 and group 4). Conclusion. Suppression of excessive CSF leakage could be successful by performing several cycles of the group 1 method (fibrinogen was applied on the dura followed by PGS and thrombin), followed by the group 3 method (fibrinogen was applied on the dura followed by PGS and fibrin spray), with thrombin solution wash each time.
• "Half-folded" pedicled scapular bone flap for nonunion after humeral neck fracture: A case report

  Gen Matsumae, Makoto Motomiya, Naoya Watanabe, Norimasa Iwasaki

  MICROSURGERY 37 (6) 689 - 693 0738-1085 2017/09 [Refereed][Not invited]
   

  Treatment of a nonunion of the proximal humerus remains a challenge because of the small proximal fragment and poor central cancellous bone stock of the humeral head. In this report, we describe our experience using a half-folded pedicled scapular bone flap with an anatomical locking plate to treat an atrophic nonunion of the proximal humerus in a 64-year-old right-handed woman. The patient had fallen and experienced a common humeral neck fracture 2.5 years previously. During the operation, we elevated the pedicled scapular bone flap, which measured 8.0 cm long and 1.5 cm wide, with a vascular pedicle about 10 cm long. We modified the bone flap to the half-folded type to fill the massive bone cavity in the humeral head. The proximal tip of the flap was divided into two segments while keeping the ventral soft tissue intact. The grafted bone bridging between the head and shaft of the humerus was rigidly fixed with a plate and screw. The operated shoulder was fixed with a sling and a chest belt for 3 weeks, after which the patient began active motion exercises of the shoulder joint. The flap survived without serious donor site morbidity, and good bone healing was obtained about 3.5 months after surgery. The patient was able to use the shoulder comfortably in daily activity without any serious donor site morbidity at 16 months after the surgery. This procedure may be effective in treating nonunion of the proximal humerus with a massive bone cavity in the humeral head.
• Long-term prognosis of hematogenous vertebral osteomyelitis: Mortality, quality of life, and pain

  Terufumi Kokabu, Masahiko Takahata, Nobuhisa Ishiguro, Norimasa Iwasaki

  JOURNAL OF ORTHOPAEDIC SCIENCE 22 (5) 822 - 827 0949-2658 2017/09 [Refereed][Not invited]
   

  Background: Hematogenous vertebral osteomyelitis (HVO) has a generally favorable prognosis if appropriate treatment is initiated in its early phase; however, some intractable cases with HVO can develop neurological impairment as well as spinal deformity during the course of treatment and these sequelae may lead to impaired quality of life (QOL). In this study, we aimed to evaluate the long-term relapse rate, mortality, and QOL of patients with HVO. Methods: In this retrospective case series study, medical records of 60 patients with HVO with a mean follow-up period of 8 years (5-23 years) were reviewed to assess demographic data, details of infection, and clinical course. Mortality rate was assessed using a Kaplan-Meier plot. QOL was measured using the EuroQol 5 Dimension (EQ-5D) questionnaire and residual pain using a numeric rating scale (NRS). Results: HVO relapsed in 4 of 60 patients (7%). Overall 5-year survival rate in 60 patients with HVO was 85%. The factors associated with increased mortality were malignant tumor, diabetes mellitus, chronic use of glucocorticoids, and drug-resistant strains of staphylococcus. Female-to-male ratio, NRS, prevalence of neurological impairment were significantly higher in patients with low EQ-5D score (poor health) compared to those with high EQ-5D score (good health). Conclusions: Patients with HVO have shorter life expectancy if they have malignancy, diabetes mellitus, chronic use of glucocorticoids, and a history of drug-resistant strains of staphylococcus infection. Female gender, residual neurological defects and persistent back pain are associated with impaired QOL in patients with HVO. (C) 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.
• 体操選手における手関節応力分布の解析 CT osteoabsorptiometry法を用いた手関節応力解析

  門間 太輔, 船越 忠直, 岩本 航, 遠藤 香織, 松井 雄一郎, 河村 太介, 松本 秀雄, 岩崎 倫政

  日本整形外科スポーツ医学会雑誌 (一社)日本整形外科スポーツ医学会 37 (4) 386 - 386 1340-8577 2017/08
• 体操選手における手関節応力分布の解析 CT osteoabsorptiometry法を用いた手関節応力解析

  門間 太輔, 船越 忠直, 岩本 航, 遠藤 香織, 河村 太介, 永野 裕介, 松井 雄一郎, 濱野 博基, 本谷 和俊, 岩崎 倫政, 松本 秀男

  日本整形外科学会雑誌 (公社)日本整形外科学会 91 (8) S1746 - S1746 0021-5325 2017/08
• 高純度硬化性ゲルによる無細胞移植椎間板組織自然再生誘導法の検討

  辻本 武尊, 須藤 英毅, 岩崎 浩司, 大西 貴士, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 91 (8) S1534 - S1534 0021-5325 2017/08
• 椎間板変性と再生医療 椎間板変性におけるcaspase 3の関与

  大西 貴士, 須藤 英毅, 岩崎 浩司, 辻本 武尊, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 91 (8) S1689 - S1689 0021-5325 2017/08
• 椎間板変性と再生医療 椎間板再生治療における組織修復材の開発

  須藤 英毅, 辻本 武尊, 東藤 正浩, 山田 勝久, 大西 貴士, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 91 (8) S1692 - S1692 0021-5325 2017/08
• Synergistic effect of ascorbic acid and collagen addition on the increase in type 2 collagen accumulation in cartilage-like MSC sheet

  Yasushi Sato, Hisashi Mera, Daisuke Takahashi, Tokifumi Majima, Norimasa Iwasaki, Shigeyuki Wakitani, Mutsumi Takagi

  CYTOTECHNOLOGY 69 (3) 405 - 416 0920-9069 2017/06 [Refereed][Not invited]
   

  Aiming to increase the content of type 2 collagen in scaffold-free cartilage-like cell sheets prepared using human bone marrow mesenchymal stem cells, the effect of several kinds of additives in a chondrogenic medium was investigated. Addition of ascorbic acid 2 phosphate (VCP) at a high concentration (250 A mu g/ml) and type 1 atelocollagen (5 A mu g/ml) increased the accumulation of type 2 collagen by fourfold and twofold, respectively. On the other hand, an antioxidant, glutathione showed no such effect. The synergistic effect of VCP and type 1 atelocollagen resulted in an eightfold increase in the accumulation level of type 2 collagen. Furthermore, the gene expression level of type 2 collagen increased and that of matrix metalloproteinase-13 (MMP-13) decreased to approximately one-third of the control. The increase in type 2 collagen accumulation in the scaffold-free cartilage-like cell sheet might be due to not only the enhancement of the synthesis but also the suppression of the degradation of type 2 collagen by MMP-13.
• Effect of teriparatide (rh-PTH 1-34) versus bisphosphonate on the healing of osteoporotic vertebral compression fracture: A retrospective comparative study

  Akira Iwata, Masahiro Kanayama, Fumihiro Oha, Tomoyuki Hashimoto, Norimasa Iwasaki

  BMC MUSCULOSKELETAL DISORDERS 18 (1) 148 - 148 1471-2474 2017/04 [Refereed][Not invited]
   

  Background: Teriparatide (recombinant human parathyroid hormone 1-34) is increasingly used for the treatment of severe osteoporosis because it stimulates bone formation and may potentially enhance fracture healing. The objective of this study was to investigate the effects of teriparatide versus a bisphosphonate on radiographic outcomes in the treatment of osteoporotic vertebral compression fractures (OVCF). Methods: A total of 98 patients undergoing non-operative treatment for recent single-level OVCF were reviewed retrospectively. Thirty-eight patients were treated by a once-daily subcutaneous injection of 20 micrograms of teriparatide (TPD group), whereas 60 patients received 35 mg of alendronate weekly (BP group). Except for these medications, the same treatment protocol was applied to both groups. The radiographic assessments included union status, vertebral kyphosis, and mid-vertebral body height. The rates of fracture site surgical intervention were also compared between the two groups. The mean follow-up period was 27 months (median 22.5, range 2 - 75 months). Results: Cox regression analysis showed that TPD reduced the time-to-union (adjusted relative hazard ratio: 1.86, 95% C.I.: 1.21 - 2.83). The union rate at six months after treatment was 89% in the TPD group and 68% in the BP group; the surgical intervention rate was significantly higher in the TPD group (p = 0.026, adjusted odds ratio: 8.15, 95% C.I.: 2.02 - 43.33). The change in local kyphosis was 4.6 degrees in the TPD group and 3.8 degrees in the BP group (p = 0.495, paired t-test). The change of mid-vertebral body height was 4.4 mm in the TPD group and 3.4 mm in the BP group (p = 0.228, paired t-test). Fracture site surgical interventions were not required in the TPD group; however, two patients in the BP group eventually underwent surgical treatment for symptomatic non-union or vertebral collapse. Conclusions: This retrospective study suggests that teriparatide may enhance fracture healing and improve the union rate in OVCF.
• Efficacy and safety of osteoporosis medications in a rat model of late-stage chronic kidney disease accompanied by secondary hyperparathyroidism and hyperphosphatemia

  M. Ota, M. Takahata, T. Shimizu, Y. Kanehira, H. Kimura-Suda, Y. Kameda, H. Hamano, S. Hiratsuka, D. Sato, N. Iwasaki

  OSTEOPOROSIS INTERNATIONAL 28 (4) 1481 - 1490 0937-941X 2017/04 [Refereed][Not invited]
   

  This study showed that bisphosphonate was safe and effective for the treatment of bone disorders in stage 4 chronic kidney disease (CKD) rats. Intermittent teriparatide therapy showed an anabolic action on bone even under secondary hyperparathyroidism conditions without having an adverse effect on mineral metabolism in late-stage CKD. Patients with late-stage CKD are at high risk for fragility fractures. However, there are no consensus on the efficacy and safety of osteoporosis medications for patients with late-stage CKD. In the present study, we aimed to examine the efficacy and safety of alendronate (ALN) and teriparatide (TPD) for treating bone disorder in late-stage CKD with pre-existing secondary hyperparathyroidism using a rat model of CKD. Male 10-week-old Sprague-Dawley rats were subjected to a 5/6 nephrectomy or sham surgery and randomized into the following four groups: sham, vehicle (saline subcutaneous (sc) daily), ALN (50 mu g/kg sc daily), and TPD (40 mu g/kg sc daily). Medications commenced at 24 weeks of age and continued for 4 weeks. Micro-computed tomography, histological analysis, infrared spectroscopic imaging, and serum assays were performed. Nephrectomized rats developed hyperphosphatemia, secondary hyperparathyroidism (SHPT), and high creatinine, equivalent to CKD stage 4 in humans. ALN suppressed the bone turnover and increased the degree of mineralization in cortical bone, resulting in an improvement in the mechanical properties. TPD further increased the bone turnover and significantly increased the degree of mineralization, micro-geometry, and bone volume, resulting in a significant improvement in the mechanical properties. Both ALN and TPD had no adverse effect on renal function and mineral metabolism. BP is safe and effective for the treatment of bone disorders in stage 4 CKD rats. Intermittent TPD therapy showed an anabolic action on bone even under SHPT conditions without having an adverse effect on mineral metabolism in late-stage CKD.
• Depletion of Gangliosides Enhances Articular Cartilage Repair in Mice

  Masatake Matsuoka, Tomohiro Onodera, Kentaro Homan, Fumio Sasazawa, Jun-ichi Furukawa, Daisuke Momma, Rikiya Baba, Kazutoshi Hontani, Zenta Joutoku, Shinji Matsubara, Tadashi Yamashita, Norimasa Iwasaki

  SCIENTIFIC REPORTS 7 43729 - 43729 2045-2322 2017/03 [Refereed][Not invited]
   

  Elucidation of the healing mechanisms in damaged tissues is a critical step for establishing breakthroughs in tissue engineering. Articular cartilage is clinically one of the most successful tissues to be repaired with regenerative medicine because of its homogeneous extracellular matrix and few cell types. However, we only poorly understand cartilage repair mechanisms, and hence, regenerated cartilage remains inferior to the native tissues. Here, we show that glycosylation is an important process for hypertrophic differentiation during articular cartilage repair. GM3, which is a precursor molecule for most gangliosides, was transiently expressed in surrounding damaged tissue, and depletion of GM3 synthase enhanced cartilage repair. Gangliosides also regulated chondrocyte hypertrophy via the Indian hedgehog pathway. These results identify a novel mechanism of cartilage healing through chondrocyte hypertrophy that is regulated by glycosylation. Manipulation of gangliosides and their synthases may have beneficial effects on articular cartilage repair.
• 無症候性野球選手における肩甲上腕関節の動作解析 四次元computed tomographyを用いて

  門間 太輔, 船越 忠直, 遠藤 香織, 庄野 康弘, 永野 裕介, 河村 太介, 松井 雄一郎, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 91 (2) S505 - S505 0021-5325 2017/03
• プロ野球選手における肘関節応力分布の解析 CT osteoabsorptiometry法を用いた肘応力解析

  門間 太輔, 船越 忠直, 横田 正司, 遠藤 香織, 永野 裕介, 河村 太介, 松井 雄一郎, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 91 (3) S698 - S698 0021-5325 2017/03
• 高純度硬化性ゲルによる無細胞移植椎間板組織自然再生誘導法

  辻本 武尊, 須藤 英毅, 岩崎 浩司, 大西 貴士, 岩崎 倫政

  Journal of Spine Research (一社)日本脊椎脊髄病学会 8 (3) 298 - 298 1884-7137 2017/03
• Viability of Cells From Displaced Fragments of the Elbow Osteochondritis Dissecans: Alternative Source of Autologous Chondrocyte Implantation

  Yusuke Kameda, Tadanao Funakoshi, Shunsuke Takeuchi, Katsura Sugawara, Norimasa Iwasaki

  ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY 33 (2) 291 - U550 0749-8063 2017/02 [Refereed][Not invited]
   

  Purpose: To assess the histological properties of cells from displaced fragments obtained from patients with advanced osteochondritis dissecans (OCD) of the elbow and to examine whether these displaced fragments could be used as cell sources for autologous chondrocyte implantation. Methods: We harvested 6 displaced fragments from 6 patients who underwent osteochondral mosaicplasty for OCD of the elbow. The displaced fragments were examined histologically and digested to obtain chondrocytes. The cells obtained from young patients and skeletally matured cadaveric donors were examined using quantitative reverse transcription polymerase chain reaction analysis to quantify the expression of chondrocyte marker genes. The cells were cultured in atelocollagen, and the properties of 3-dimensional cultured cartilage were examined. Results: All 6 displaced fragments contained hyaline cartilage tissue. Chondrocyte marker genes were examined using cells from only 4 patients, because we obtained enough cells in only 4 patients. The relative expression levels of aggrecan, type II, Sox 9 were 2.61, 4.03, and 1.71, respectively. Three-dimensional cultured cartilage from all 6 displaced fragments contained 62.0 pg/cell (range, 22.8-91.3 pg/cell) of glycosaminoglycan and expressed type II collagen in the superficial and middle layer. Conclusions: The chondrocytes obtained from the displaced fragments remained viable and exhibited chondrogenic features. These cells may potentially be a cell source of autologous chondrocytes implantation. Clinical Relevance: We have shown that displaced fragments from OCD of the elbow have potential for a cell source for generating 3-dimensional cultured cartilage.
• A rare case of multiple phosphaturic mesenchymal tumors along a tendon sheath inducing osteomalacia

  Ryuta Arai, Tomohiro Onodera, Mohamad Alaa Terkawi, Tomoko Mitsuhashi, Eiji Kondo, Norimasa Iwasaki

  BMC MUSCULOSKELETAL DISORDERS 18 (1) 79 - 79 1471-2474 2017/02 [Refereed][Not invited]
   

  Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia, reduction of 1,25-dihydroxyl vitamin D, and bone calcification disorders. Tumors associated with TIO are typically phosphaturic mesenchymal tumors that are bone and soft tissue origin and often present as a solitary tumor. The high production of fibroblast growth factor 23 (FGF23) by the tumor is believed to be the causative factor responsible for the impaired renal tubular phosphate reabsorption, hypophosphatemia and osteomalacia. Complete removal of the tumors by surgery is the most effective procedure for treatment. Identification of the tumors by advanced imaging techniques is difficult because TIO is small and exist within bone and soft tissue. However, systemic venous sampling has been frequently reported to be useful for diagnosing TIO patients. Case presentation: We experienced a case of 39-year-old male with diffuse bone pain and multiple fragility fractures caused by multiple FGF23-secreting tumors found in the hallux. Laboratory testing showed hypophosphatemia due to renal phosphate wasting and high levels of serum FGF23. Contrast-enhanced MRI showed three soft tissue tumors and an intraosseous tumor located in the right hallux. Systemic venous sampling of FGF23 revealed an elevation in the right common iliac vein and external iliac vein, which suggested that the tumors in the right hallux were responsible for overproduction of FGF23. Thereafter, these tumors were surgically removed and subjected to histopathological examinations. The three soft tissue tumors were diagnosed as phosphaturic mesenchymal tumors, which are known to be responsible for TIO. The fourth tumor had no tumor structure and was consisting of hyaline cartilage and bone tissue. Immediately after surgery, we noted a sharply decrease in serum level of FGF23, associated with an improved hypophosphatemia and a gradual relief of systematic pain that disappeared within two months of surgery. Conclusion: The authors reported an unusual case of osteomalacia induced by multiple phosphaturic mesenchymal tumors located in the hallux. Definition of tumors localization by systemic venous sampling led to successful treatment and cure this patient. The presence of osteochondral tissues in the intraosseous tumor might be developed from undifferentiated mesenchymal cells due to high level of FGF23 produced by phosphaturic mesenchymal tumors.
• Autoimmune arthritis deteriorates bone quantity and quality of periarticular bone in a mouse model of rheumatoid arthritis

  T. Shimizu, M. Takahata, H. Kimura-Suda, Y. Kameda, K. Endo, H. Hamano, S. Hiratsuka, M. Ota, D. Sato, T. Ito, M. Todoh, S. Tadano, N. Iwasaki

  OSTEOPOROSIS INTERNATIONAL 28 (2) 709 - 718 0937-941X 2017/02 [Refereed][Not invited]
   

  This study showed that autoimmune arthritis induces especially severe osteoporosis in the periarticular region adjacent to inflamed joints, suggesting that arthritis increases the fragility fracture risk near inflamed joints, which is frequently observed in patients with RA. Periarticular osteoporosis near inflamed joints is a hallmark of early rheumatoid arthritis (RA). Here we show that rheumatic inflammation deteriorates the bone quality and bone quantity of periarticular bone, thereby decreasing bone strength and toughness in a mouse model of RA. Female BALB/c mice and SKG mice, a mutant mouse model of autoimmune arthritis on the BALB/c background, were used. At 12 weeks of age, BALB/c mice underwent either Sham surgery or bilateral ovariectomy (OVX), and SKG mice underwent intraperitoneal injection of mannan to induce arthritis. Eight weeks later, the mice were killed and the femurs and tibias were subjected to micro-computed tomography, Fourier transform infrared (FTIR) spectroscopic imaging, X-ray diffraction, histology, and mechanical testing. SKG mice developed significant trabecular bone loss in both the distal metaphysis of the femur and the lumbar vertebral body, but the extent of the bone loss was more severe in the distal metaphysis. Neither SKG nor OVX mice exhibited changes in the geometry and matrix properties of the diaphysis of the femur, whereas SKG mice, but not OVX mice, did exhibit changes in these properties in the distal metaphysis of the femur. Bone strength and fracture toughness of the distal metaphysis of the tibia adjacent to the inflamed ankle joint were significantly decreased in SKG mice. Autoimmune arthritis induces periarticular osteoporosis, characterized by deterioration of cortical bone geometry and quality as well as by trabecular bone loss, leading to severe bone fragility in periarticular bone adjacent to inflamed joints.
• Cervical myelopathy due to atraumatic odontoid fracture in patients with rheumatoid arthritis: A case series

  Masahiko Takahata, Kuniyoshi Abumi, Hideki Sudo, Ken Nagahama, Norimasa Iwasaki

  MODERN RHEUMATOLOGY 27 (5) 901 - 904 1439-7595 2017 [Refereed][Not invited]
   

  To highlight the risk of cervical myelopathy due to occult, atraumatic odontoid fracture in patients with rheumatoid arthritis, we retrospectively reviewed radiographic findings and clinical observations for 7 patients with this disorder. This fracture tends to occur in patients with long-lasting rheumatoid arthritis and to be misdiagnosed as simple atlantoaxial dislocation. Since this fracture causes multidirectional instability between C1 and C2 and is expected to have poor healing potential due to bone erosion and inadequate blood supply, posterior spinal arthrodesis surgery is indicated upon identification of the fracture to prevent myelopathy.
• Difference in vascular patterns between transosseous-equivalent and transosseous rotator cuff repair

  Atsushi Urita, Tadanao Funakoshi, Tatsunori Horie, Mutsumi Nishida, Norimasa Iwasaki

  JOURNAL OF SHOULDER AND ELBOW SURGERY 26 (1) 149 - 156 1058-2746 2017/01 [Refereed][Not invited]
   

  Background: Vascularity is the important factor of biologic healing of the repaired tissue. The purpose of this study was to clarify sequential vascular patterns of repaired rotator cuff by suture techniques. Methods: We randomized 21 shoulders in 20 patients undergoing arthroscopic rotator cuff repair into 2 groups: transosseous-equivalent repair (TOE group, n = 10) and transosseous repair (TO group, n = 11). Blood flow in 4 regions inside the cuff (lateral articular, lateral bursal, medial articular, and medial bursal), in the knotless suture anchor in the TOE group, and in the bone tunnel in the TO group was measured using contrast-enhanced ultrasound at 1 month, 2 months, 3 months, and 6 months postoperatively. Results: The sequential vascular pattern inside the repaired rotator cuff was different between groups. The blood flow in the lateral articular area at 1 month, 2 months, and 3 months (P = .002, .005, and .025) and that in the lateral bursal area at 2 months (P = .031) in the TO group were significantly greater than those in the TOE group postoperatively. Blood flow was significantly greater for the bone tunnels in the TO group than for the knotless suture anchor in the TOE group at 1 month and 2 months postoperatively (P = .041 and .009). Conclusion: This study clarified that the sequential vascular pattern inside the repaired rotator cuff depends on the suture technique used. Bone tunnels through the footprint may contribute to biologic healing by increasing blood flow in the repaired rotator cuff. (C) 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.
• Does spinopelvic alignment affect the union status in thoracolumbar osteoporotic vertebral compression fracture?

  Akira Iwata, Masahiro Kanayama, Fumihiro Oha, Tomoyuki Hashimoto, Norimasa Iwasaki

  European Journal of Orthopaedic Surgery and Traumatology 27 (1) 87 - 92 1432-1068 2017/01/01 [Refereed][Not invited]
   

  Purpose: In the healing of osteoporotic vertebral fracture, global spinal mal-alignment might increase the load sharing at the fracture site and deteriorate the fracture healing. This study aimed to evaluate the effect of spinopelvic alignment on the union status of thoracolumbar osteoporosis-related vertebral compression fracture (OVCF). Methods: Consecutive 48 patients with a single-level thoracolumbar fresh OVCF were treated non-operatively. Union was judged by three independent observers at 6 months, and patients were divided into union group and non-union group. Spinopelvic alignment was measured using upright whole spine radiograph before treatment as follows: pelvic incidence (PI), pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis (TK), sagittal vertical axis (SVA), and DSVA, defined as the distance from a plumb line dropped from the center of the C7 body to the center of fractured vertebral body. Result: Global spinal alignment was different in union group and non-union group: SVA (4.7 ± 0.7 cm in union group vs. 8.9 ± 1.3 cm in non-union group, P = 0.007), DSVA (4.2 ± 0.6 cm in union group vs. 9.5 ± 1.0 cm in non-union group, P <  0.001), and PI–LL (18.9° ± 2.2° in union group vs. 30.3° ± 3.9° in non-union group, P = 0.014). Over 5 cm of DSVA [P = 0.022, adjusted odds 7.9 (95 % CI 1.3–77.0)] and/or over 30° of PI–LL [P = 0.026, adjusted odds 6.6 (95 % CI 1.5–44.2)] showed the significant risk factors for non-union using multivariate logistic regression analysis in the other background status. Conclusions: Global spinal mal-alignment, showing over 5 cm of DSVA and/or over 30° of PI–LL, affected the union status of OVCF.
• Comparison of femoral head translation following eccentric rotational acetabular osteotomy and rotational acetabular osteotomy

  Tohru Irie, Daisuke Takahashi, Tsuyoshi Asano, Ryuta Arai, Takuya Konno, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki

  HIP INTERNATIONAL 27 (1) 49 - 54 1120-7000 2017/01 [Refereed][Not invited]
   

  Purpose: Eccentric rotational acetabular osteotomy (ERAO) is a modification of rotational acetabular osteotomy (RAO); it has been reported that ERAO allows the femoral head to translate medially and distally. However, no study has compared femoral head translation following RAO or ERAO. The purpose of this study was to compare immediate postoperative translation of the femoral head after RAO and ERAO in comparison with the preoperative position by radiological methods. Methods: Patients treated by RAO or ERAO between 2006 and 2014 were retrospectively evaluated. 19 hips (17 patients) were treated with RAO, and 25 hips (22 patients) were treated with ERAO. The acetabular roof angle and the location of the femoral head were measured on anteroposterior pelvic radiographs. Results: The mean preoperative acetabular roof angle was 20.9 degrees in the RAO group and 22.0 degrees in the ERAO group, showing no significant difference. The mean acetabular roof angle immediately postoperatively was -0.5 degrees in the RAO group and -0.4 degrees in the ERAO group, again showing no significant difference. The mean femoral head translation immediately postoperatively was 3.1 mm (95% confidence interval (CI), 1.5-4.7 mm) laterally and 3.0 mm (95% CI, 1.3-4.7 mm) proximally in the RAO group and 0.8 mm (95% CI, -0.7-2.3 mm) medially and 2.8 mm (95% CI, 1.5-4.1 mm) distally in the ERAO group; this difference was very highly significant (p<0.001). Conclusions: In contrast with RAO, ERAO resulted in significant femoral head translation both medially and distally immediately postoperatively.
• Efficacy of teriparatide in the treatment of nontraumatic osteonecrosis of the femoral head: a retrospective comparative study with alendronate

  Ryuta Arai, Daisuke Takahashi, Masahiro Inoue, Tohru Irie, Tsuyoshi Asano, Takuya Konno, Mohamad Alaa Terkawi, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki

  BMC MUSCULOSKELETAL DISORDERS 18 (1) 24 - 24 1471-2474 2017/01 [Refereed][Not invited]
   

  Background: Collapse of the femoral head associated with nontraumatic osteonecrosis (NOFH) is one of the most common causes of disability in young adult patients. Excessive bone resorption by osteoclast coincident with the suppression of osteogenesis are believed to be responsible for collapse progression. Alendronate that inhibits bone resorption by inducing osteoclast apoptosis has been traditionally used for treating NOFH; however, several reports documented serious complications by the use of this drug. On the other hand, teriparatide activates osteoblasts leading to an overall increase in bone volume, and is expected to reduce the progression of femoral head collapse in NOFH. Therefore, the present study was undertaken to examine pharmacological effects of teriparatide on collapse progression of NOFH and to compare these effects with alendronate. Methods: We conducted a retrospective study in our facility for comparing the pharmacological effects of teriparatide and alendronate on 32 NOFH patients diagnosed with osteoporosis. Between 2007 and 2013, patients were treated with daily administration of 20 mu g teriparatide (15 patients: 18 hips), or with 35 mg of alendronate once a week (17 patients: 22 hips). The mean period of follow-up was 18.7 months. The progression of collapse was evaluated prior to the administration and later every three months by anteroposterior radiographs. Collapse progression with > 1 mm was defined as advanced collapse, while with < 1 mm was defined as stable radiologic disease. Student's t-test and the chi-square test was used to do compare the pharmacological effects of the two groups. Results: Treatment with terparatide had a tendency to reduce the rate of advanced collapse as compared to that with alendronate (p = 0.105). Kaplan-Meier curves related to stable radiologic disease showed that teriparatide-treated patients had better stable states than these treated with alendronate (p = 0.08, log-rank test). Moreover, treatment with teriparatide resulted in a significant reduction in collapse progression as compared to that with alendronate, noted at the end of follow-up period (p = 0.049). Conclusion: The present study suggests that teriparatide has greater pharmacological effects than alendronate for treating NOFH and preventing the collapse of femoral head.
• Dural penetration caused by a vertebral bone fragment in a lumbar burst fracture: a case report.

  Ushiku C, Suda K, Matsumoto S, Komatsu M, Takahata M, Iwasaki N, Minami A

  Spinal cord series and cases 3 16040 - 16040 2017 [Refereed][Not invited]
   

  INTRODUCTION: This case report describes an unusual case of lumbar burst fracture in which a bone fragment from the vertebral body penetrated into the dorsal dura through the ventral dura mater, requiring bone fragment extraction via an intradural approach. CASE PRESENTATION: A 23-year-old male involved in a motor vehicle accident was admitted to our hospital complaining of right leg paresis and bladder-bowel disorder. Computed tomography (CT) revealed an L5 burst fracture of type B by the Denis classification scheme, with a bone fragment from the vertebral body that had perforated the ventral aspect of the dura mater and penetrated dorsally. We abandoned attempts to extract the bone fragment via an epidural approach and instead resected the fragment via an intradural approach with a dorsal dural incision. We corrected L4/5 kyphosis as possible and performed L4/5 posterolateral fusion. The patient's leg paralysis and bladder-bowel disorder were relieved, and he was discharged 2 months after the surgery with the ability to walk without crutches. DISCUSSION: When bone fragments penetrate the dura mater, their extraction must be performed with particular care. For cases in which the dura mater cannot be pulled apart, the removal of bone fragments using an intradural approach is appropriate.
• Increased expression of v integrin as a regulator of fibrosis in Dupuytren's nodules

  Y. Matsui, S. Kon, T. Funakoshi, T. Miyashita, T. Matsuda, N. Iwasaki

  JOURNAL OF HAND SURGERY-EUROPEAN VOLUME 42 (1) 18 - 25 1753-1934 2017/01 [Refereed][Not invited]
   

  Although Dupuytren's contracture is characterized by increased transforming growth factor-1 (TGF-1) and fibrosis in the palmar fascia, the relationship between TGF-1 and integrins, which are considered to be related to fibrosis, remains unclear. We investigated the involvement of TGF-1 and integrins in the pathological palmar fascia of Dupuytren's contracture. Seven patients underwent partial fasciectomy for treatment of this disease. The nodule and cord were isolated from the fascial tissues of the patients. Control fasciae were obtained from seven patients with carpal tunnel syndrome. Immunohistochemical analysis was performed to detect the fibrosis marker -smooth muscle actin and integrins in the fascial tissues. The expression of TGF-1 and integrins was assessed by real-time polymerase chain reaction. The results suggest that nodules may be areas involved in activation of fibrosis in the fascia, associated with increased expression of TGF-1 and v integrin. Thus, v integrin may contribute to fibrosis in Dupuytren's contracture by activating TGF-1. Level of Evidence: IV
• Effects of Multiple Intra-articular Injections of 0.5% Bupivacaine on Normal and Osteoarthritic Joints in Rats

  Koji Iwasaki, Hideki Sudo, Yasuhiko Kasahara, Katsuhisa Yamada, Takashi Ohnishi, Takeru Tsujimoto, Norimasa Iwasaki

  ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY 32 (10) 2026 - 2036 0749-8063 2016/10 [Refereed][Not invited]
   

  Purpose: To determine the in vivo effects of multiple local anesthetic injections of 0.5% bupivacaine on normal and osteoarthritic articular cartilage. Methods: Rats with normal knee joints received an intra-articular injection of 0.9% saline solution or 0.5% bupivacaine in their right knees joint once a week for 5 consecutive weeks, starting 4 weeks after the beginning of the experiment. Rats were humanely killed at 8, 16, and 24 weeks. In a parallel experiment, rats underwent anterior cruciate ligament transection to induce osteoarthritic changes. These rats were subjected to the same protocol as those with normal knee joints, starting 4 weeks after the procedure. Static weight-bearing tests were performed on both hind limbs to evaluate changes in weight-bearing ability throughout the experiments. Rats were humanely killed at 8 and 16 weeks. Cell viability was assessed with confocal microscopy, using samples from the distal femur. Histologic assessment of osteoarthritis was performed using samples from the tibial plateau based on the Osteoarthritis Research Society International (OARSI) cartilage histopathology assessment system (i.e., OARSI score). Results: Static weight-bearing tests showed no significant changes after intra-articular injection of saline solution or bupivacaine, and bupivacaine injection did not increase weight bearing compared with saline solution injection, regardless of whether there were osteoarthritic changes. There were also no significant differences in cell viability, cell density, or OARSI scores between the saline solution and bupivacaine groups at each time point, regardless of whether osteoarthritic changes were induced. Conclusions: This study suggested that single or intermittent intra-articular bupivacaine injections might not have deleterious effects on either osteoarthritic or normal joints.
• Use of a pneumatic tourniquet in total knee arthroplasty increases the risk of distal deep vein thrombosis: A prospective, randomized study

  Noriaki Mori, Shoichi Kimura, Tomohiro Onodera, Norimasa Iwasaki, Izumi Nakagawa, Takeshi Masuda

  KNEE 23 (5) 887 - 889 0968-0160 2016/10 [Refereed][Not invited]
   

  Background: There has been controversy regarding the incidence of deep vein thrombosis (DVT) after total knee arthroplasty (TKA) with or without the use of a tourniquet. The aim of this randomized, prospective study was to clarify the effects of tourniquet use on DVT in TKA. Methods: The subjects were 109 patients scheduled to undergo TKA from April 2008 to March 2009 before the establishment of the American Association of Orthopedic Surgeons (AAOS) practice guidelines. They were randomized into two groups: 51 patients in the tourniquet group (group T) and 52 patients in the control group without a tourniquet (group C). We investigated the thrombotic presence using ultrasonography one week after surgery and compared both groups. Results: There was no difference in the rate of proximal DVTs (P = 0.63). However, the risk of distal DVT was significantly higher in group T than in group C (52.9% vs. 23.1%; P = 0.002). Conclusions: Use of the tourniquet in TKA increased the risk of distal DVT. (C) 2016 Elsevier B.V. All rights reserved.
• ビタミンK依存性グラ化オステオカルシンは副甲状腺ホルモン製剤の骨治癒効果に影響する

  清水智弘, 高畑雅彦, 亀田裕亮, 濱野博基, 伊藤哲平, 木村(須田)廣美, 東藤正浩, 但野茂, 岩崎倫政

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 58 (1) 9‐14 - 14 1343-3873 2016/10 [Refereed][Not invited]
   

  テリパラチド(PTH1-34)は骨治癒効果を促進し骨量増加効果を有する。ビタミンKはタンパクをグラ化するために必要なため骨器質の石灰化に重要な役割を果たす。それゆえ、低栄養状態によるビタミンK不足やビタミンK拮抗剤であるワーファリン投与を受けている場合にはPTH1-34の骨治癒効果に影響する可能性がある。そこで本研究ではラット大腿骨骨切りモデルを用いて、ビタミンKがPTH1-34の骨治癒効果に影響するかどうかを調査した。12週齢の雌のSDラットの大腿骨骨切りモデルを作成し、ランダムに以下の4群に分けた(n=10)。Vehicle、PTH1-34(30μg/kg/day連日皮下注射)と生理食塩水(週3回経口投与)、PTH1-34とワーファリン(0.4mg/kg/day週3回経口投与)、PTH1-34とビタミンK2(menatetrenone、30mg/kg/day週3回経口投与)。血清Gla化、Glu化オステオカルシン濃度と骨治癒の画像的評価を2週毎に評価し、8週後にマイクロCT評価と組織学的評価と力学試験を行った。PTH1-34投与により仮骨の骨密度増加だけでなく、骨治癒に伴うGla化オステオカルシン濃度の上昇と力学的特性の改善を認めた。ワーファリン追加投与することによりPTH1-34投与による骨治癒効果が減弱した。これはグラ化オステオカルシンの欠乏による石灰化障害による可能性が考えられた。PTH1-34とビタミンK2の併用は餌によって充足された状態でのPTH1-34単独投与と比較して有意な優位性はなかったが、ワーファリンやビタミンK2の使用に関わらず、グラ化オステオカルシン濃度がPTH1-34使用下の骨切り部の力学的強度は相関した。これらの結果はビタミンK依存性グラ化オステオカルシンの充足がPTH1-34の骨治癒効果に影響することを示唆している。(著者抄録)
• Pyogenic spondylodiscitis following anti-interleukin-6 therapy in a patient with rheumatoid arthritis (implication of hematogenous infection risk in degenerative intervertebral discs): A case report and review of the literature

  Takeru Tsujimoto, Masahiko Takahata, Terufumi Kokabu, Megumi Matsuhashi, Norimasa Iwasaki

  JOURNAL OF ORTHOPAEDIC SCIENCE 21 (5) 694 - 697 0949-2658 2016/09 [Refereed][Not invited]
  
• Correlation analysis between change in thoracic kyphosis and multilevel facetectomy and screw density in main thoracic adolescent idiopathic scoliosis surgery

  Hideki Sudo, Yuichiro Abe, Terufumi Kokabu, Manabu Ito, Kuniyoshi Abumi, Yoichi M. Ito, Norimasa Iwasaki

  SPINE JOURNAL 16 (9) 1049 - 1054 1529-9430 2016/09 [Refereed][Not invited]
   

  BACKGROUND CONTEXT: Controversy exists regarding the effects of multilevel facetectomy and screw density on deformity correction, especially thoracic kyphosis (TK) restoration in adolescent idiopathic scoliosis (AIS) surgery. PURPOSE: This study aimed to evaluate the effects of multilevel facetectomy and screw density on sagittal plane correction in patients with main thoracic (MT) AIS curve. STUDY DESIGN: A retrospective correlation and comparative analysis of prospectively collected, consecutive, non-randomized series of patients at a single institution was undertaken. PATIENT SAMPLE: Sixty-four consecutive patients with Lenke type 1 AIS treated with posterior correction and fusion surgery using simultaneous double-rod rotation technique were included. OUTCOME MEASURES: Patient demographics and preoperative and 2-year postoperative radiographic measurements were the outcome measures for this study. METHODS: Multiple stepwise linear regression analysis was conducted between change in TK (T5-T12) and the following factors: age at surgery, Risser sign, number of facetectomy level, screw density, preoperative main thoracic curve, flexibility in main thoracic curve, coronal correction rate, preoperative TK, and preoperative lumbar lordosis. Patients were classified into two groups: TK< 15 degrees group defined by preoperative TK below the mean degree of TK for the entire cohort (< 15 degrees) and the TK >= 15 degrees group, defined by preoperative TK above the mean degree of kyphosis (>= 15 degrees). Independent sample t tests were used to compare demographic data as well as radiographic outcomes between the two groups. There were no study-specific biases related to conflicts of interest. RESULTS: The average preoperative TK was 14.0 degrees, which improved significantly to 23.1 degrees (p<.0001) at the 2-year final follow-up. Greater change in TK was predicted by a low preoperative TK (p<.0001). The TK < 15 degrees group showed significant correlation between change in TK and number of facetectomy level (r=0.492, p=.002). Similarly, significant correlation was found between change in TK and screw density (r=0.333, p=.047). Conversely, in the TK >= 15 degrees group, correlation was found neither between change in TK and number of facetectomy level (r=0.047, p=.812), nor with screw density (r= 0.030, p=.880). Furthermore, in patients with preoperative TK< 15 degrees, change in TK was significantly correlated with screw density at the concave side (r=0.351, p=.036) but not at the convex side (r=0.144, p=.402). CONCLUSIONS: In patients with hypokyphotic thoracic spine, significant positive correlation was found between change in TK and multilevel facetectomy or screw density at the concave side. This indicates that in patients with AIS who have thoracic hypokyphosis as part of their deformity, the abovementioned factors must be considered in preoperative planning to correct hypokyphosis. (C) 2016 Elsevier Inc. All rights reserved.
• In Vivo Mouse Intervertebral Disc Degeneration Model Based on a New Histological Classification

  Takashi Ohnishi, Hideki Sudo, Koji Iwasaki, Takeru Tsujimoto, Yoichi M. Ito, Norimasa Iwasaki

  PLOS ONE 11 (8) e0160486  1932-6203 2016/08 [Refereed][Not invited]
   

  Although human intervertebral disc degeneration can lead to several spinal diseases, its pathogenesis remains unclear. This study aimed to create a new histological classification applicable to an in vivo mouse intervertebral disc degeneration model induced by needle puncture. One hundred six mice were operated and the L4/5 intervertebral disc was punctured with a 35- or 33-gauge needle. Micro-computed tomography scanning was performed, and the punctured region was confirmed. Evaluation was performed by using magnetic resonance imaging and histology by employing our classification scoring system. Our histological classification scores correlated well with the findings of magnetic resonance imaging and could detect degenerative progression, irrespective of the punctured region. However, the magnetic resonance imaging analysis revealed that there was no significant degenerative intervertebral disc change between the ventrally punctured and non-punctured control groups. To induce significant degeneration in the lumbar intervertebral discs, the central or dorsal region should be punctured instead of the ventral region.
• Effects of Multilevel Facetectomy and Screw Density on Postoperative Changes in Spinal Rod Contour in Thoracic Adolescent Idiopathic Scoliosis Surgery

  Terufumi Kokabu, Hideki Sudo, Yuichiro Abe, Manabu Ito, Yoichi M. Ito, Norimasa Iwasaki

  PLOS ONE 11 (8) e0161906  1932-6203 2016/08 [Refereed][Not invited]
   

  Flattening of the preimplantation rod contour in the sagittal plane influences thoracic kyphosis (TK) restoration in adolescent idiopathic scoliosis (AIS) surgery. The effects of multilevel facetectomy and screw density on postoperative changes in spinal rod contour have not been documented. This study aimed to evaluate the effects of multilevel facetectomy and screw density on changes in spinal rod contour from before implantation to after surgical correction of thoracic curves in patients with AIS prospectively. The concave and convex rod shapes from patients with thoracic AIS (n = 49) were traced prior to insertion. Postoperative sagittal rod shape was determined by computed tomography. The angle of intersection of the tangents to the rod end points was measured. Multiple stepwise linear regression analysis was used to identify variables independently predictive of change in rod contour (Delta theta). Average Delta theta at the concave and convex side were 13.6 degrees +/- 7.5 degrees and 4.3 degrees +/- 4.8 degrees, respectively. The Delta theta at the concave side was significantly greater than that of the convex side (P < 0.0001) and significantly correlated with Risser sign (P = 0.032), the preoperative main thoracic Cobb angle (P = 0.031), the preoperative TK angle (P = 0.012), and the number of facetectomy levels (P = 0.007). Furthermore, a Delta theta at the concave side +/- 14 degrees significantly correlated with the postoperative TK angle (P = 0.003), the number of facetectomy levels (P = 0.021), and screw density at the concave side (P = 0.008). Rod deformation at the concave side suggests that corrective forces acting on that side are greater than on the convex side. Multilevel facetectomy and/or screw density at the concave side have positive effects on reducing the rod deformation that can lead to a loss of TK angle postoperatively.
• 慢性腎臓病に伴う骨ミネラル代謝異常がもたらす骨質異常と骨代謝改善薬による治療効果と安全性 ラット前臨床モデルを用いた検討

  太田 昌博, 高畑 雅彦, 清水 智弘, 亀田 裕亮, 濱野 博基, 平塚 重人, 木村 廣美[須田], 岩崎 倫政

  日本骨代謝学会学術集会プログラム抄録集 (一社)日本骨代謝学会 34回 184 - 184 1349-0761 2016/07
• Venipuncture Nerve Injuries in the Upper Extremity From More Than 1 Million Procedures.

  Tsukuda Y, Funakoshi T, Nasuhara Y, Nagano Y, Shimizu C, Iwasaki N

  Journal of patient safety 15 (4) 299 - 301 1549-8417 2016/06 [Refereed][Not invited]
   

  OBJECTIVES: The purpose of this study was to investigate the nerve injury rate for 1 million venipunctures and the efficacy of attempts to avoid severe nerve injury. METHODS: We collected data for outpatients from whom a venipuncture blood sample was obtained in our hospital from 2005 to 2014. Every venipuncture procedure for outpatients was performed by a trained nurse or clinical technologist at the center for blood sampling in our hospital. In addition, a series of lectures by a specialist is held in our hospital at various times. All complaints related to venipuncture blood sampling were reported to our division of hospital safety management and were followed up using the guidelines for injuries related to the venipuncture. RESULTS: The number of venipuncture-related complications was 293 (0.027%, 1/3700) of 1,082,053 during the 10 years. A total of 40 of the 1,082,053 venipunctures were referred to the department of orthopedic surgery, and 16 (0.0015%, 1/67,000) were diagnosed with obvious nerve injuries. The average duration of the treatment was 46.4 days (range, 1-126 days); 69% of the patients recovered within 5 weeks, and all patients recovered within 18 weeks. CONCLUSIONS: Although it is impossible to completely prevent venipuncture-related complications, appropriate venipuncture skills and risk management decrease the incidence of chronic or permanent nerve injury risk after venipuncture.
• Alteration of Stress Distribution Patterns in Symptomatic Valgus Instability of the Elbow in Baseball Players: A Computed Tomography Osteoabsorptiometry Study

  Tadanao Funakoshi, Kozo Furushima, Daisuke Momma, Kaori Endo, Yuichiro Abe, Yoshiyasu Itoh, Kazuhiro Fujisaki, Shigeru Tadano, Norimasa Iwasaki

  AMERICAN JOURNAL OF SPORTS MEDICINE 44 (4) 989 - 994 0363-5465 2016/04 [Refereed][Not invited]
   

  Background: Repetitive valgus stress applied during a throwing motion can lead to various elbow disturbances, including ulnar collateral ligament (UCL) injury. Subchondral bone density reportedly reflects the cumulative force on a joint surface under actual loading conditions. Purpose: (1) To evaluate the distribution of subchondral bone density across the elbow joint in asymptomatic baseball pitchers and symptomatic valgus instability pitchers and (2) to clarify the alterations in stress distribution pattern associated with symptomatic UCL insufficiency pitching activities. Study Design: Controlled laboratory study. Methods: Computed tomography (CT) imaging data were collected from the dominant-side elbow of 7 nonathletic volunteers (controls), 12 asymptomatic pitchers (asymptomatic group), and 12 symptomatic valgus instability pitchers with UCL insufficiency (symptomatic group). Bone mineral density across the elbow joint was measured with CT osteoabsorptiometry. A 2-dimensional mapping model was divided into 4 areas of the distal end of the humerus and 5 areas of the ulna with the radial head. The locations and percentages of high-density areas on the articular surface were quantitatively analyzed. Results: High-density areas in the asymptomatic and symptomatic groups were found in the anterolateral and posteromedial parts of the humerus and in the radial head, posteromedial to the ulna. The high-density areas in the anterior and posteromedial of the humerus, the radial head, and the posteromedial part of the ulna in the controls were smaller than those in the baseball group. In the symptomatic group, the percentages of high-density areas in the anterolateral part of the humerus (mean, 36.3%; 95% CI, 31.9%-40.7%) and the anterolateral part of the ulna (mean, 31.7%; 95% CI, 24.3%-39.1) were significantly greater than those in the asymptomatic group (P = .047 and P < .0001, respectively). Conclusion: Symptomatic UCL insufficiency was associated with characteristic high-stress distribution patterns on the anterolateral part of the capitellum and the anterolateral part of the ulna. The current results indicate that symptomatic UCL insufficiency produces excessive and cumulative stress in the elbow joint. Clinical Relevance: The information obtained from the CT images can useful for early detection of overstress conditions of the elbow joint.
• 4次元computed tomographyを用いた野球選手における肩甲上腕関節の動作解析

  船越 忠直, 門間 太輔, 遠藤 香織, 瓜田 淳, 松井 雄一郎, 河村 太介, 佃 幸憲, 岩崎 倫政, 山口 隆義

  北海道整形災害外科学会雑誌 北海道整形災害外科学会 57 (2) 351 - 352 1343-3873 2016/04
• Selection of the upper vertebra to be instrumented in the treatment of thoracolumbar and lumbar adolescent idiopathic scoliosis by anterior correction and fusion surgery using dual-rod instrumentation: a minimum 12-year follow-up study

  Hideki Sudo, Kiyoshi Kaneda, Yasuhiro Shono, Norimasa Iwasaki

  SPINE JOURNAL 16 (3) 281 - 287 1529-9430 2016/03 [Refereed][Not invited]
   

  BACKGROUND CONTEXT: Consensus regarding the optimal upper vertebra to be instrumented during surgical treatment of Lenke 5C thoracolumbar and lumbar adolescent idiopathic scoliosis (AIS) remains limited. PURPOSE: This study aimed to assess whether a short fusion strategy is appropriate for correction of a Lenke 5C AIS curve by anterior correction and fusion surgery using dual-rod instrumentation. STUDY DESIGN: This study design used retrospective comparative analysis of a prospectively collected, consecutive, non-randomized series of patients at a single institution. PATIENT SAMPLE: Thirty consecutive patients with Lenke 5C AIS treated with anterior correction and fusion surgery using dual-rod instrumentation were included. OUTCOME MEASURES: Patient demographics, radiographic measurements, and Scoliosis Research Society-22 questionnaire (SRS-22) scores were the outcome measures for this study. METHODS: Thirty patients were treated surgically for AIS with a Lenke 5C curve (mean age, 14.4 years [11-19 years)]) and followed up for a mean period of 17.2 years (12-23 years). Radiographical parameters and clinical outcomes were compared between patients treatment with the end vertebra (EV) instrumented (n=14) and those treated by short fusion (S group) with instrumentation starting at the vertebra one level caudal to the EV (n=16 patients). There were no study-specific biases related to conflicts of interest. RESULTS: In the EV group, a mean preoperative Cobb angle of 56 degrees was corrected to 5 degrees after surgery and to 8 degrees at the final follow-up. In the S group, a mean preoperative Cobb angle of 55 degrees was corrected to 10 degrees after surgery and 14 degrees at the final follow-up. The mean correction rate at the final follow-up was significantly lower in the S group (74%) than in the EV group (86%; p=.020). The coronal and sagittal balance, thoracic kyphosis, lumbar lordosis, and clinical outcomes evaluated using SRS-22 did not differ between the two groups. CONCLUSIONS: The short fusion strategy, which involves instrumentation of the vertebra one level caudal to the upper EV, can be considered as an alternative to the conventional strategy, which includes instrumentation of the upper EV, for treating Lenke 5C curves via anterior spinal fusion. (C) 2016 Elsevier Inc. All rights reserved.
• Predictive factors of long head of the biceps tendon disorders-the bicipital groove morphology and subscapularis tendon tear

  Atsushi Urita, Tadanao Funakoshi, Toraji Amano, Yuichiro Matsui, Daisuke Kawamura, Yusuke Kameda, Norimasa Iwasaki

  JOURNAL OF SHOULDER AND ELBOW SURGERY 25 (3) 384 - 389 1058-2746 2016/03 [Refereed][Not invited]
   

  Background: Disorders of the long head of the biceps (LHB) tendon contribute to anterior shoulder pain. Although LHB tendon disorders are associated with rotator cuff disease, distinguishing between biceps and rotator cuff pathology is difficult. The objective was to identify the predictors of LHB tendon disorders associated with a supraspinatus tear. Methods: In 55 patients (average age, 65 years) undergoing arthroscopic rotator cuff repair, bicipital groove morphology were assessed using computed tomography, and subscapularis tear and bicipital groove effusion were assessed using magnetic resonance imaging, retrospectively. The LHB tendon was evaluated arthroscopically according to the Lafosse classification. Univariate and multivariate ordinal logistic regression analyses were conducted for injury grade with all covariates. Results: The arthroscopic evaluation of the LHB tendon showed that there were 23 shoulders classified as grade 0, 15 as grade 1, and 17 as grade 2. Univariate logistic regression analysis showed that the width and depth, a medial spur of the bicipital groove, and a subscapularis tear were significantly associated with LHB tendon disorders. Multivariate ordinal logistic regression analysis identified a medial spur and subscapularis tear as significant predictors of LHB tendon disorders. Conclusions: The preoperative computed tomography and magnetic resonance images, notably the presence of a spur on the bicipital groove or a subscapularis tear, were useful for identifying LHB tendon disorders. When these are found in preoperative images, the clinician should evaluate the patient for the presence of an LHB tendon disorder as a pain generator. (C) 2016 Journal of Shoulder and Elbow Surgery Board of Trustees
• Bizarre parosteal osteochondromatous proliferation (Nora's lesion) affecting the distal end of the ulna: a case report

  Yuichiro Matsui, Tadanao Funakoshi, Hideyuki Kobayashi, Tomoko Mitsuhashi, Tamotsu Kamishima, Norimasa Iwasaki

  BMC MUSCULOSKELETAL DISORDERS 17 130 - 130 1471-2474 2016/03 [Refereed][Not invited]
   

  Background: Bizarre parosteal osteochondromatous proliferation (BPOP), first described by Nora et al. in 1983 and therefore termed "Nora's lesion", is a rare lesion that occurs in the short bones of the hands and feet and eventually presents as a parosteal mass. Reports of BPOP in the long bones are very rare. A benign disease, BPOP does not become malignant, although a high rate of recurrence following surgical resection is reported. Because of its atypical imaging findings and histopathological appearance, a BPOP might be misdiagnosed as a malignant tumor such as an osteochondroma with malignant transformation, a parosteal osteosarcoma, or a periosteal osteosarcoma. Case presentation: A 58-year-old woman complained of left ulnar wrist pain at the time of her initial presentation. Plain x-rays showed ectopic calcifications in and around the distal radioulnar joint, which supported the diagnosis of subacute arthritis with hydroxyapatite crystal deposition. She was initially given a wrist brace and directed to follow-up, but her persistent pain required the administration of corticosteroid injections into the distal radioulnar joint. Increasing ulnar wrist joint pain and limited forearm pronation and wrist flexion necessitated computed tomography and contrast-enhanced magnetic resonance imaging. BPOP was diagnosed based on the preoperative imaging studies, and a resection of the lesion was performed along with the decortication of the underlying the cortical bone to reduce recurrence rates. The diagnosis of BPOP was confirmed by pathologic examination. Two years after surgery, the patient has no subsequent pain complaints and an improved range of motion. Conclusions: BPOP affecting the distal end of the ulna is exceedingly rare. Because BPOP was diagnosed primarily based upon preoperative imaging findings in our patient, decortication of the underlying cortical bone was performed to reduce recurrence rates. Further careful follow-up in these patients is essential, despite the non-recurrence of the lesion.
• Surgical treatment of double thoracic adolescent idiopathic scoliosis with a rigid proximal thoracic curve

  Hideki Sudo, Yuichiro Abe, Kuniyoshi Abumi, Norimasa Iwasaki, Manabu Ito

  EUROPEAN SPINE JOURNAL 25 (2) 569 - 577 0940-6719 2016/02 [Refereed][Not invited]
   

  There is limited consensus on the optimal surgical strategy for double thoracic adolescent idiopathic scoliosis (AIS). Recent studies have reported that pedicle screw constructs to maximize scoliosis correction cause further thoracic spine lordosis. The objective of this study was to apply a new surgical technique for double thoracic AIS with rigid proximal thoracic (PT) curves and assess its clinical outcomes. Twenty one consecutive patients with Lenke 2 AIS and a rigid PT curve (Cobb angle a parts per thousand yen30A(0) on side-bending radiographs, flexibility a parts per thousand currency sign30 %) treated with the simultaneous double-rod rotation technique (SDRRT) were included. In this technique, a temporary rod is placed at the concave side of the PT curve. Then, distraction force is applied to correct the PT curve, which reforms a sigmoid double thoracic curve into an approximate single thoracic curve. As a result, the PT curve is typically converted from an apex left to an apex right curve before applying the correction rod for PT and main thoracic curve. All patients were followed for at least 2 years (average 2.7 years). The average main thoracic and PT Cobb angle correction rate at the final follow-up was 74.7 and 58.0 %, respectively. The average preoperative T5-T12 thoracic kyphosis was 9.3A degrees, which improved significantly to 19.0A degrees (p < 0.0001) at the final follow-up. Although 71 % patients had preoperative level shoulders or a positive radiographic shoulder height, all patients had mildly imbalanced or balanced shoulders at the final follow-up. The average preoperative main thoracic apical vertebral rotation angle of 20.7A degrees improved significantly after surgery to 16.4A degrees (p = 0.0046), while the average preoperative total SRS questionnaire score of 3.7 improved significantly to 4.4 (p = 0.0012) at the final follow-up. Radiographic findings and patient outcomes were satisfactory. Thoracic kyphosis can be maintained or improved, while coronal and axial deformities can be corrected using SDRRT for Lenke 2 AIS with a rigid PT curve.
• Teriparatide Improves Trabecular Osteoporosis but Simultaneously Promotes Ankylosis of the Spine in the Twy Mouse Model for Diffuse Idiopathic Skeletal Hyperostosis

  Hiroki Hamano, Masahiko Takahata, Masahiro Ota, Shigeto Hiratsuka, Tomohiro Shimizu, Yusuke Kameda, Norimasa Iwasaki

  CALCIFIED TISSUE INTERNATIONAL 98 (2) 140 - 148 0171-967X 2016/02 [Refereed][Not invited]
   

  Diffuse idiopathic skeletal hyperostosis (DISH) is a common skeletal disorder in the elderly, which can develop into periosteal hyperostosis and paradoxically into immobilization-associated trabecular osteoporosis. The bone anabolic agent, teriparatide (TPD), seems to be a rational treatment for the immobilization-associated osteoporosis. However, it can lead to development of hyperostosis lesions in DISH patients. Here, we demonstrate TPD effectively treats trabecular osteoporosis while simultaneously promoting ankylosis of the spine in DISH model tiptoe-walking Yoshimura (twy) mice, compared with the ICR mice. Eighteen male twy mice were divided into three groups, and ICR mice were used as a normal control. Subcutaneous injections of TPD or phosphate-buffered saline (PBS) were performed according to three dosing regimens; 40 A mu g/kg once daily (TPD x 1 group), 40 A mu g/kg three times daily (TPD x 3 group), and PBS (control; Ctl group). Treatment was commenced at the age of 7 weeks and continued for 5 weeks. Micro-computed tomography (A mu CT) and histological analysis were performed. Longitudinal A mu CT study revealed that trabecular bone volume in both the vertebral body and distal femur decreased with time in the Ctl group, but increased dramatically in the TPD x 3 group. The twy mice developed ankylosis of the spine, the progression of which was accelerated with TPD therapy. We also confirmed that TPD therapy promoted ossification of spinal ligaments. Histomorphometrical study revealed that TPD treatment increased bone formation at the vertebrae enthesis region and in the trabecular bone. TPD therapy effectively treats trabecular osteoporosis, but potentially promotes ankylosis of the spine in patients with DISH.
• Effects of initial graft tension on clinical outcome after anatomic double-bundle anterior cruciate ligament reconstruction: comparison of two graft tension protocols

  Eiji Kondo, Kazunori Yasuda, Nobuto Kitamura, Jun Onodera, Masashi Yokota, Tomonori Yagi, Norimasa Iwasaki

  BMC MUSCULOSKELETAL DISORDERS 17 65 - 65 1471-2474 2016/02 [Refereed][Not invited]
   

  Background: In anatomic double-bundle anterior cruciate ligament (ACL) reconstruction, there are great controversies concerning the ideal graft tension protocols. The purpose of this study was to clarify differences in the effect of two graft tension protocols on the clinical outcome after anatomic double-bundle anterior cruciate ligament (ACL) reconstruction by comparing the minimum 2-year clinical results. Methods: Ninety-seven patients with unilateral anatomic double-bundle ACL reconstruction were divided into two groups. In the first 44 patients (Group I), a 40-N tension was applied to each of the two hamstring autografts at 30 degrees of knee flexion, and simultaneously fixed onto the tibia. In the remaining 53 patients (Group II), a 30-N tension was applied to each graft at 10 degrees of knee flexion, and simultaneously fixed onto the tibia. Each patient was examined 2 years after surgery. Results: There wasn't a significant difference in the background of the two groups. There was no significant difference in the postoperative anterior laxity between the two groups. The average was 1.1 mm and 0.9 mm in Groups I and II, respectively. There wasn't any differences between the two groups in Lysholm knee score, International Knee Documentation Committee (IKDC) evaluation and muscle strength. Four patients had loss of knee extension in a range of 5 degrees and 10 degrees in Group I and none of the patients in Group II exhibited any loss in knee extension; which was statistically significant (p = 0.025). Conclusion: The two initial graft tension protocols did not result in any significant differences in the Lysholm knee score and IKDC grade. However, it was noted that the 40-N tension applied to each graft at 30 degrees of knee flexion more significantly induced loss of knee extension in comparison to the 30-N tension applied to each graft at 10 degrees. From a clinical viewpoint, the loss of knee extension is one of the pathological conditions that should be absolutely avoided after ACL reconstruction. Therefore, the 30-N tension applied to each graft at 10 degrees is preferable to the other graft tension protocol.
• Structural strength of cancellous specimens from bovine femur under cyclic compression

  Kaori Endo, Satoshi Yamada, Masahiro Todoh, Masahiko Takahata, Norimasa Iwasaki, Shigeru Tadano

  PEERJ 4 e1562  2167-8359 2016/01 [Refereed][Not invited]
   

  The incidence of osteoporotic fractures was estimated as nine million worldwide in 2000, with particular occurrence at the proximity of joints rich in cancellous bone. Although most of these fractures spontaneously heal, some fractures progressively collapse during the early post-fracture period. Prediction of bone fragility during progressive collapse following initial fracture is clinically important. However, the mechanism of collapse, especially the gradual loss of the height in the cancellous bone region, is not clearly proved. The strength of cancellous bone after yield stress is difficult to predict since structural and mechanical strength cannot be determined a priori. The purpose of this study was to identify whether the baseline structure and volume of cancellous bone contributed to the change in cancellous bone strength under cyclic loading. A total of fifteen cubic cancellous bone specimens were obtained from two 2-year-old bovines and divided into three groups by collection regions: ferrioral head, neck, and proximal metaphysic. Structural indices of each 5-mm cubic specimen were determined using micro-computed tomography. Specimens were then subjected to five cycles of uniaxial compressive loading at 0.05 mm/min with initial 20 N loading, 0.3 min displacement, and then unloading to 0.2 mm with 0.1 mm displacement for five successive cycles. Elastic modulus and yield stress of cancellous bone decreased exponentially during five loading cycles. The decrease ratio of yield stress from baseline to fifth cycle was strongly correlated with bone volume fraction (BV/TV, r = 0.96, p < 0.01) and structural model index (SMI, r = 0.81, p < 0.01). The f decrease ratio of elastic modulus from baseline to cycle was also correlated with BV/TV (r = 0.80, p < 0.01) and SMI (r-= 0.78, p < 0.01). These data indicate that structural deterioration of cancellous bone is associated with bone strength after yield stress. This study suggests that baseline cancellous bone structure estimated from adjacent non-fractured bone contributes to the cancellous bone strength during collapse.
• Delayed bilateral vertebral artery occlusion after cervical spine injury: a case report.

  Miki Komatsu, Kota Suda, Masahiko Takahata, Satoko Matsumoto, Chikara Ushiku, Katsuhisa Yamada, Junichi Yamane, Tsutomu Endo, Norimasa Iwasaki, Akio Minami

  Spinal cord series and cases 2 16031 - 16031 2016 [Refereed][Not invited]
   

  INTRODUCTION: There are considerable risks for the secondary spinal cord injury and the initial and/or delayed vertebral artery occlusion in cases of cervical fracture dislocation. CASE PRESENTATION: An 86-year-old man was injured in a car accident and was diagnosed with no fracture or dislocation of the cervical spine by the emergency physician. However, he was transferred to our hospital 3 days later because he had motor weakness that was evaluated to be 32 points (out of 50 points) on the upper limb American Spinal Injury Association (ASIA) motor score and was diagnosed with spontaneously reduced fracture dislocation at C5/6. Magnetic resonance images revealed that the bilateral vertebral arteries were occluded, and there were some microinfarction lesions in the brain. On the first visit to his previous doctor, he was found to have a flow void in the right vertebral artery. This indicated that it was occluded during the waiting period at his previous doctor. On the day of his arrival at our hospital, the patient underwent a C5/6 posterior spinal fusion. Three months after surgery, he recovered to 46 points on the upper extremity ASIA motor score, and blood flow in the left vertebral artery was resumed. DISCUSSION: Early reduction and stabilization are necessary for cervical spine fracture dislocation; however, it is important not only for the prevention of the secondary injury but also for the reduction of the risk of vertebral artery occlusion.
• Short fusion strategy for thoracolumbar and lumbar adolescent idiopathic scoliosis using anterior dual-rod instrumentation

  Sudo H, Kaneda K, Shono Y, Iwasaki N

  Bone Joint J 98 402 - 409 2016 [Refereed][Not invited]
  
• Maintenance of spontaneous lumbar curve correction following thoracic fusion of main thoracic curves in adolescent idiopathic scoliosis

  Sudo H, Mayer M, Kaneda K, Pereira SN, Shono Y, Hitzl W, Iwasaki N, Koller H

  Bone Joint J 98 997 - 1002 2016 [Refereed][Not invited]
  
• PCSK5 mutation in a patient with the VACTERL association

  Yukio Nakamura, Shingo Kikugawa, Shoji Seki, Masahiko Takahata, Norimasa Iwasaki, Hidetomi Terai, Mitsuhiro Matsubara, Fumio Fujioka, Hidehito Inagaki, Tatsuya Kobayashi, Tomoatsu Kimura, Hiroki Kurahashi, Hiroyuki Kato

  BMC Research Notes 8 (1) 228 - 228 1756-0500 2015/12/14 [Refereed][Not invited]
   

  Background: The VACTERL association is a typically sporadic, non-random collection of congenital anomalies that includes vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, renal anomalies, and limb abnormalities. Although several chromosomal aberrations and gene muta tions have been reported as disease-causative, these findings have been sparsely replicated to date. Case presentation: In the present study, whole exome sequencing of a case with the VACTERL association uncovered a novel frameshift mutation in the PCSK5 gene, which has been reported as one of the causative genes for the VACTERL association. Although this mutation appears potentially pathogenic in its functional aspects, it was also carried by the healthy father. Furthermore, a database survey revealed several other deleterious variants in the PCSK5 gene in the general population. Conclusions: Further studies are necessary to clarify the etiological role of the PCSK5 mutation in the VACTERL association.
• A Novel Bone Marrow Stimulation Technique Augmented by Administration of Ultrapurified Alginate Gel Enhances Osteochondral Repair in a Rabbit Model

  Rikiya Baba, Tomohiro Onodera, Daisuke Momma, Masatake Matsuoka, Kazutoshi Hontani, Sameh Elmorsy, Kaori Endo, Masahiro Todoh, Shigeru Tadano, Norimasa Iwasaki

  TISSUE ENGINEERING PART C-METHODS 21 (12) 1263 - 1273 1937-3384 2015/12 [Refereed][Not invited]
   

  Cartilage injuries are a common health problem resulting in the loss of daily activities. Bone marrow stimulation technique, one of the surgical techniques for the cartilage injuries, is characterized by technical simplicity and less invasiveness. However, it has been shown to result in fibrous or fibrocartilaginous repair with inferior long-term results. This study focused on using ultrapurified alginate gel (UPAL gel) as an adjuvant scaffold in combination with a bone marrow stimulation technique. The objective of this study was to assess the efficacy of a bone marrow stimulation technique augmented by UPAL gel in a rabbit osteochondral defect model. To achieve this goal, three experimental groups were prepared as follows: defects without intervention, defects treated with a bone marrow stimulation technique, and defects treated with a bone marrow stimulation technique augmented by UPAL gel. The macroscopic and histological findings of the defects augmented by UPAL gel improved significantly more than those of the others at 16 weeks postoperatively. The combination technique elicited hyaline-like cartilage repair, unlike bone marrow stimulation technique alone. This combination procedure has the potential of improving clinical outcomes after use of a bone marrow stimulation technique for articular cartilage injuries.
• Therapeutic effects of intra-articular ultra-purified low endotoxin alginate administration on an experimental canine osteoarthritis model

  Yukinori Tsukuda, Tomohiro Onodera, Masayuki Ito, Yasuharu Izumisawa, Yasuhiko Kasahara, Tatsuya Igarashi, Nobuo Ohzawa, Masahiro Todoh, Shigeru Tadano, Norimasa Iwasaki

  JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 103 (11) 3441 - 3448 1549-3296 2015/11 [Refereed][Not invited]
   

  Objective: This study aimed to elucidate the therapeutic effects of intra-articular administration of ultra-purified low endotoxin alginate (UPLE-alginate) on osteoarthritis (OA) using a canine anterior cruciate ligament transection (ACLT) model. Design: We used 20 beagle dogs. ACLT was performed on the left knee of each dog and a sham operation was performed on the right knee as a control. All animals were randomly divided into the control (saline) and therapeutic (UPLE-alginate) groups. Animals in the control and therapeutic groups received weekly injections with 0.7 mL normal saline or 0.7 mL 0.5% UPLE-alginate, respectively, from 0 to 3 weeks after ACLT or sham operation. At 9 weeks after ACLT, the knee joints of all animals were observed using arthroscopy. All animals were euthanized at 14 weeks after ACLT and evaluated using morphologic assessment, histologic assessment, and biomechanical testing. Results: Arthroscopic findings showed intact cartilage surface in both groups. Morphologic findings in the therapeutic group showed milder degeneration compared with those of the control group, but there were no significant differences between groups. Histologic scores of the medial femoral condyle (MFC) and lateral femoral condyle (LFC) were better in the therapeutic group than the control group (MFC: p=0.009, LFC: p=0.009). Joint lubrication did not differ significantly between groups. Conclusion: Intra-articular administration of UPLE-alginate in the early stage of OA slowed disease progression in canines. UPLE-alginate may have potential as a therapeutic agent for OA patients and reduce the number of patients who need to undergo total joint arthroplasty. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3441-3448, 2015.
• A preclinical large animal study on a novel intervertebral fusion cage covered with high porosity titanium sheets with a triple pore structure used for spinal fusion

  Katsuhisa Yamada, Manabu Ito, Toshiyuki Akazawa, Masaru Murata, Toru Yamamoto, Norimasa Iwasaki

  EUROPEAN SPINE JOURNAL 24 (11) 2530 - 2537 0940-6719 2015/11 [Refereed][Not invited]
   

  To evaluate the osteoconductivity and the bonding strength of the newly developed interbody cage covered with the porous titanium sheet (porous Ti cage) to vertebral bodies in a sheep model. Twelve sheep underwent anterior lumbar interbody fusion at L2-3 and L4-5 using either the new porous Ti cages (Group-P) or conventional Ti cages with autogenous iliac bone (Group-C). The animals were euthanized at 2 or 4 months postoperatively and subjected to radiological, biomechanical, and histological examinations. Computed tomography analyses showed that the ratio of bone contact area in Group-P was significantly increased at 4 months compared with that at 2 months (p = 0.01). Although the ratio of bone contact area in Group-C was significantly higher than Group-P at 2 months (p < 0.001), there was no statistically significant difference between the two groups at 4 months. Biomechanical test showed that there was no significant difference in bonding strength between the two groups at either 2 or 4 months. Histological analyses revealed that the bone apposition ratio increased significantly with time in Group-P (p < 0.001). Although Group-C showed significantly higher bone apposition ratio than Group-P at 2 months (p = 0.001), there was no statistical difference between the two groups at 4 months. There was bone ingrowth into the porous Ti sheet, and bonding capacity of the porous Ti cage to the host bone increased with time. However, the speed of union to the bone with a porous Ti cage was marginally lower than a conventional cage along with an autogenous bone graft. Although it needs further experiment with a larger sample size, the results of the current study suggested that this material could achieve interbody fusion without the need for bone grafts.
• Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) mediates periarticular bone loss, but not joint destruction, in murine antigen-induced arthritis

  Tomohiro Shimizu, Masahiko Takahata, Yusuke Kameda, Tsutomu Endo, Hiroki Hamann, Shigeto Hiratsuka, Masahiro Ota, Norimasa Iwasaki

  BONE 79 65 - 70 8756-3282 2015/10 [Refereed][Not invited]
   

  Osteoclastogenesis requires immunoreceptor tyrosine-based activation motif signaling. Multiple immuno-receptors associated with immunoreceptor tyrosine-based activation motif adaptor proteins, including DNAX-activating protein 12 kDa (DAP12) and Fc receptor common gamma (FcR gamma), have been identified in osteoclast lineage cells, and some are involved in arthritis-induced bone destruction. Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immunoreceptor that regulates osteoclast development and bone resorption in association with DAP12. Whether Siglec-15 is involved in arthritis-induced bone lesions, however, remains unknown. Here we used a murine antigen-induced arthritis model to examine the role of Siglec-15 in the development of bone lesions induced by joint inflammation. Arthritis was unilaterally induced in the knee joints of 8-week-old female wild-type (WT) and Siglec-15(-/-) mice, and the contralateral knees were used as a control. The degree of joint inflammation, and cartilage and subchondral bone destruction in Siglec-15(-/-) mice was comparable to that in WT mice, indicating that Siglec-15 is not involved in the development of arthritis and concomitant cartilage and subchondral bone destruction. On the other hand, the degree of periarticular bone loss in the proximal tibia of the arthritic knee was significantly lower in Sig1ec-15(-/-) mice compared to WT mice. Although osteoclast formation in the metaphysis was enhanced in both WT and Siglec-15(-/-) mice after arthritis induction, mature multinucleated osteoclast formation was impaired in Siglec-15(-/-) mice, indicating impaired osteoclast bone resorptive function in the periarticular regions of the arthritic joint in Siglec-15(-/-) mice. Confirming this result, Siglec-15(-/-) primary unfractionated bone marrow cells harvested from arthritic femurs and tibiae failed to develop into mature multinuclear osteoclasts. Our findings suggest that Siglec-15 is a therapeutic target for periarticular bone loss, but not for joint destruction, in inflammatory arthritis, such as rheumatoid arthritis. (C) 2015 Elsevier Inc. All rights reserved.
• 4次元computed tomographyを用いた投球動作における肩甲上腕関節の動作解析

  門間 太輔, 船越 忠直, 遠藤 香織, 瓜田 淳, 松井 雄一郎, 河村 太介, 亀田 裕亮, 山口 隆義, 庄野 泰弘, 岩崎 倫政

  日本関節病学会誌 (一社)日本関節病学会 34 (3) 286 - 286 1883-2873 2015/10
• Syndecan 4 Regulation of the Development of Autoimmune Arthritis in Mice by Modulating B Cell Migration and Germinal Center Formation.

  Tsutomu Endo, Koyu Ito, Junko Morimoto, Masashi Kanayama, Daichi Ota, Masahiro Ikesue, Shigeyuki Kon, Daisuke Takahashi, Tomohiro Onodera, Norimasa Iwasaki, Toshimitsu Uede

  Arthritis & rheumatology (Hoboken, N.J.) 67 (9) 2512 - 22 2326-5191 2015/09 [Refereed][Not invited]
   

  OBJECTIVE: Syndecan 4 has been implicated as a critical mediator of inflammatory responses because of its functions as a coreceptor and reservoir for growth factors and chemokines. Although syndecan 4 is known to be expressed on B cells, its role in immune responses remains unclear. The purpose of this study was to investigate the contribution of syndecan 4 to the development of immune arthritis in murine models. METHODS: The clinical severity of 3 immunopathologically distinct models, collagen-induced arthritis (CIA), antigen-induced arthritis (AIA), and collagen antibody-induced arthritis (CAIA), was evaluated in wild-type (WT) mice and in syndecan 4-deficient (Sdc4(-/-) ) mice. Germinal center (GC) formation, B cell profiles, humoral immune responses, and B cell migration were analyzed during the course of CIA. RESULTS: Sdc4(-/-) mice were resistant to the induction of CIA, which is T cell and B cell dependent, but AIA and CAIA, which are T cell dependent and T cell independent, respectively, occurred with equal frequency in WT mice and Sdc4(-/-) mice. Furthermore, Sdc4(-/-) mice had reduced numbers of B cells and deficient GC formation in draining lymph nodes (DLNs) during the course of CIA, resulting in reduced production of collagen-specific autoantibodies. Compared with B cells from WT mice, B cells from Sdc4(-/-) mice showed reduced chemotactic migration toward stromal cell-derived factor 1 (SDF-1) and reduced SDF-1-mediated Akt phosphorylation. Consistent with these findings, in vivo transfer experiments showed that fewer Sdc4(-/-) B cells than WT B cells were found in and around the follicles in the DLNs. CONCLUSION: Our findings suggest that syndecan 4 contributes to the development of CIA by promoting GC formation and autoantibody production through its regulation of SDF-1-mediated B cell migration.
• APPLICATION OF FREE TEMPOROPARIETAL FASCIAL FLAP FOR RECURRENT NEURAL ADHESION OF SUPERFICIAL RADIAL NERVE-A CASE REPORT

  Reiji Yamamoto, Makoto Motomiya, Keisuke Sakurai, Hirotake Sekiguchi, Tadanao Funakoshi, Norimasa Iwasaki

  MICROSURGERY 35 (6) 489 - 493 0738-1085 2015/09 [Refereed][Not invited]
   

  Because of its anatomical location, the superficial radial nerve is vulnerable to trauma as well as injury during various surgical procedures. Once the nerve adheres to surrounding scar tissue, radiating pain often occurs due to nerve traction caused by loss of smooth gliding. Since it has been reported that the success rate with neurolysis only is lower, additional preventive procedures for recurrent neural readhesion are recommended. In the current report, we describe our experience performing neurolysis followed by nerve coverage using a free temporoparietal fascial flap for recurrent neural adhesion of the superficial radial nerve. A 45-year-old male complained of motion pain of the left wrist and thumb joints caused by recurrent neural adhesion of the superficial radial nerve after a chain saw trauma and following multiple reconstructive procedures. The radiating pain completely disappeared after neurolysis performed by a previous surgeon; however, it recurred 4 weeks later. Four months after the previous neurolysis the patient underwent external neurolysis and covering of the nerve with a free temporoparietal fascial flap to prevent neural readhesion because local soft tissue could not be used due to the massive scar tissues on the forearm. One year after the secondary neurolysis, the symptoms of radiating pain during wrist and thumb motion were drastically improved. A free adipofascial flap such as a temporoparietal flap may be an option for prevention of neural readhesion after neurolysis of the superficial radial nerve in cases where a local flap cannot be used on the forearm. (C) 2015 Wiley Periodicals, Inc.
• An Articular Cartilage Repair Model in Common C57Bl/6 Mice

  Masatake Matsuoka, Tomohiro Onodera, Fumio Sasazawa, Daisuke Momma, Rikiya Baba, Kazutoshi Hontani, Norimasa Iwasaki

  TISSUE ENGINEERING PART C-METHODS 21 (8) 767 - 772 1937-3384 2015/08 [Refereed][Not invited]
   

  To analyze the genetic and biomolecular mechanisms underlying cartilage repair, an optimized mouse model of osteochondral repair is required. Although several models of articular cartilage injury in mice have recently been established, the articular surface in adult C57Bl/6 mice heals poorly. Since C57Bl/6 mice are the most popular strain of genetically manipulated mice, an articular cartilage repair model using C57Bl/6 mice would be helpful for analysis of the mechanisms of cartilage repair. The purpose of this study was to establish a cartilage repair model in C57Bl/6 mice using immature animals. To achieve this goal, full-thickness injuries were generated in 3-week-old (young), 4-week-old (juvenile), and 8-week-old (adult) C57Bl/6 mice. To investigate the reproducibility and consistency of full-thickness injuries, mice were sacrificed immediately after operation, and cartilage thickness at the patellar groove, depth of the cartilage injury, cross-sectional width, and cross-sectional area were compared among the three age groups. The depth of cartilage injury/cartilage thickness ratio (%depth) and the coefficient of variation (CV) for each parameter were also calculated. At 8 weeks postoperatively, articular cartilage repair was assessed using a histological scoring system. With respect to the reproducibility and consistency of full-thickness injuries, cartilage thickness, depth of cartilage injury, and cross-sectional area were significantly larger in young and juvenile mice than in adult mice, whereas cross-sectional width and %depth were almost equal among the three age groups. CVs of %depths were less than 10% in all groups. With respect to articular cartilage repair, young and juvenile mice showed superior results. In conclusion, we established a novel cartilage repair model in C57Bl/6 mice. This model will be valuable in achieving mechanistic insights into the healing process of the joint surface, as it will facilitate the use of genetically modified mice, which are most commonly developed on a C57Bl/6 background.
• A combination of subscapularis tendon transfer and small-head hemiarthroplasty for cuff tear arthropathy: a pilot study.

  Urita A, Funakoshi T, Suenaga N, Oizumi N, Iwasaki N

  The bone & joint journal 97-B (8) 1090 - 1095 2049-4394 2015/08 [Refereed][Not invited]
  
• 18F-FDG-PET/CT better localizes active spinal infection than MRI for successful minimally invasive surgery

  Masayuki Nakahara, Manabu Ito, Naoya Hattori, Keiichi Magota, Masahiko Takahata, Ken Nagahama, Hideki Sudo, Tamotsu Kamishima, Nagara Tamaki, Norimasa Iwasaki

  ACTA RADIOLOGICA 56 (7) 829 - 836 0284-1851 2015/07 [Refereed][Not invited]
   

  Background: Surgical debridement is often required to treat spinal infections. Successful surgery requires accurate localization of the active infections, however, current imaging technique still requires surgeons' experience to narrow the surgical fields to achieve less invasive procedures. Purpose: To investigate the use of F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for successful surgical planning. Material and Methods: Nine patients with suspected spinal infection underwent magnetic resonance imaging (MRI) and FDG-PET/CT before surgery to locate active foci of infections. The spinal structures were divided into seven compartments at each intervertebral disc level for a total of 315 compartments investigated. The same classification system was used to design operating fields for histological correlation. Results: FDG-PET/CT diagnosed fewer compartments as active infection (34 compartments, 10.8%) than MRI (62 compartments, 19.7%, P = 0.002). Surgical exploration was performed in 49 compartments, and demonstrated active infection in 25 compartments. The sensitivity / specificity of FDG-PET/CT was 100% / 79%, respectively, which was superior to those of MRI, 76% / 42%. Foci of active infection showed hypermetabolic activity with a SUVmax of 7.1 +/- 2.6 (range, 3.0-12.7). Receiver operating characteristic (ROC) analysis indicated an optimal threshold for active spinal infection at a SUVmax of 4.2, corresponding to a sensitivity of 90.3% and specificity of 91.2%. Conclusion: FDG-PET/CT demonstrated limited areas of abnormality allowing accurate delineation, and is thus useful to narrow the surgical fields. Since overall diagnostic accuracy of FDG-PET/CT was superior to that of MRI, FDG-PET/CT is a useful technique to narrow the surgical field for successful less invasive surgery.
• A Comparative Study With In Vitro Ultrasonographic and Histologic Grading of Metatarsal Head Cartilage in Rheumatoid Arthritis

  Tomohiro Onodera, Yasuhiko Kasahara, Toshiyuki Kasemura, Yuki Suzuki, Eiji Kondo, Norimasa Iwasaki

  FOOT & ANKLE INTERNATIONAL 36 (7) 774 - 779 1071-1007 2015/07 [Refereed][Not invited]
   

  Background: Ultrasonography is among the valid methods to assess articular cartilage in the foot. This study aimed to evaluate the validity of ultrasonographic grading to assess metatarsal head articular cartilage for rheumatoid forefoot deformity in vivo and to compare the findings with in vitro ultrasonographic and histologic gradings. Methods: Participants were 15 patients scheduled to undergo resection arthroplasty of the metatarsal heads of the lesser toes because of rheumatoid arthritis of the metatarsophalangeal joints. Ultrasonographic examination was performed in vivo the day before surgery. Specimens of the second to fifth metatarsal heads taken intraoperatively were graded from in vitro ultrasonographic and histologic evaluations. Correlations among in vivo ultrasonographic, in vitro ultrasonographic, and histologic gradings were analyzed. Results: In 46 metatarsal heads, the distribution of grading ranged from grade 1 to 6 for in vivo ultrasonographic examinations and from grade 1 to 4 for histologic examinations. In vivo ultrasonographic grading showed significant correlation to both in vitro ultrasonographic grading (P < .001, R = 0.74) and histologic grading (P < .001, R = 0.67). Conclusions: The significant correlations between in vivo ultrasonographic and histologic gradings suggest that a semiquantitative in vivo ultrasonographic assessment of forefoot deformity in rheumatoid arthritis may be possible. Ultrasonographic grading may prove useful for pre- and postoperative evaluation of remaining joint function in rheumatoid forefoot deformity. An ultrasonographic grading system for remaining joint surfaces might be helpful in selecting surgical procedures such as joint-sparing osteotomy and metatarsal head resection. Level of Evidence: Level IV, case series.
• Right-convex thoracolumbar scoliosis

  Kei Kuroki, Hideki Sudo, Norimasa Iwasaki

  SPINE JOURNAL 15 (5) 1154 - 1155 1529-9430 2015/05 [Refereed][Not invited]
  
• 四次元computed tomographyを用いた野球選手における肩甲上腕関節の動作解析

  船越 忠直, 山口 隆義, 遠藤 香織, 門間 太輔, 瓜田 淳, 松井 雄一郎, 河村 太介, 佃 幸憲, 庄野 泰弘, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 89 (3) S1084 - S1084 0021-5325 2015/03
• BRACHIAL ARTERY PERFORATOR-BASED PROPELLER FLAP COVERAGE FOR PREVENTION OF READHESION AFTER ULNAR NERVE NEUROLYSIS

  Hirotake Sekiguchi, Makoto Motomiya, Keisuke Sakurai, Dai Matsumoto, Tadanao Funakoshi, Norimasa Iwasaki

  MICROSURGERY 35 (2) 158 - 162 0738-1085 2015/02 [Refereed][Not invited]
   

  It is difficult for most plastic and orthopaedic surgeons to treat nerve dysfunction related to neural adhesion because the pathophysiology and suitable treatment have not been clarified. In the current report, we describe our experience of surgical treatment for adhesive ulnar neuropathy. A 58-year-old male complained of pain radiating to the ulnar nerve-innervated area during elbow and wrist motion caused by adhesive ulnar neuropathy after complex open trauma of the elbow joint. The patient obtained a good clinical outcome by surgical neurolysis of the ulnar nerve combined with a brachial artery perforator-based propeller flap to cover the soft tissue defect after resection of the scar tissue and to prevent readhesion of the ulnar nerve. This flap may be a useful option for ulnar nerve coverage after neurolysis without microvascular anastomosis in specific cases. (c) 2014 Wiley Periodicals, Inc. Microsurgery 35:158-162, 2015.
• Siglec-15 is a potential therapeutic target for postmenopausal osteoporosis

  Yusuke Kameda, Masahiko Takahata, Shintaro Mikuni, Tomohiro Shimizu, Hiroki Hamano, Takashi Angata, Shigetsugu Hatakeyama, Masataka Kinjo, Norimasa Iwasaki

  BONE 71 217 - 226 8756-3282 2015/02 [Refereed][Not invited]
   

  Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immunoreceptor that regulates osteoclast development and bone resorption in association with an immunoreceptor tyrosine-based activation motif (ITAM) adaptor protein, DNAX-activating protein 12 kDa (DAP12). Although Siglec-15 has an important role in physiologic bone remodeling by modulating RANKL signaling, it is unclear whether it is involved in pathologic bone loss in which multiple osteoclastogenic factors participate in excessive osteoclastogenesis. Here we demonstrated that Siglec-15 is involved in estrogen deficiency-induced bone loss. WT and Siglec-15(-/-) mice were ovariectomized (Ovx) or sham-operated at 14 wk of age and their skeletal phenotype was evaluated at 18 and 22 wk of age. Siglec-15(-/-) mice showed resistance to estrogen deficiency-induced bone loss compared to WT mice. Although the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts increased after ovariectomy in both WT and Siglec-15(-/-) mice, the increase was lower in Siglec-15(-/-) mice than in WT mice. Importantly, osteoclasts in Siglec-15(-/-) mice were small and failed to spread on the bone surface, indicating impaired osteoclast differentiation. Because upregulated production of TNF-alpha as well as RANKL is mainly responsible for estrogen deficiency-induced development of osteoclasts, we examined whether Siglec-15 deficiency affects TNF-alpha-induced osteoclastogenesis in vitro. The TNF-alpha mediated induction of TRAP-positive multinucleated cells was impaired in Siglec-15(-/-) cells, suggesting that Siglec-15 is involved in TNF-alpha induced osteoclastogenesis. We also confirmed that signaling through osteoclast-associated receptor/Fc receptor common gamma chain, which is an alternative ITAM adaptor to DAP12, rescues multinucleation but not cytoskeletal organization of TNF-alpha and RANKL-induced Siglec-15(-/-) osteoclasts, indicating that the Siglec-15/DAP12 pathway is especially important for cytoskeletal organization of osteoclasts in both RANKL and TNF-alpha induced osteoclastogenesis. The present findings indicate that Siglec-15 is involved in estrogen deficiency-induced differentiation of osteoclasts and is thus a potential therapeutic target for postmenopausal osteoporosis. (C) 2014 Elsevier Inc. All rights reserved.
• Various Diagnostic and Treatment Pitfalls of Combined Fracture Dislocations of Trapezoid and Multiple Carpometacarpal Joints.

  Motomiya M, Tazaki Y, Iwasaki N

  Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 20 (2) 325 - 329 0218-8104 2015 [Refereed][Not invited]
   

  We report a rare case of combined fracture dislocations of the trapezoid and multiple carpometacarpal joints that became chronic due to inappropriate treatments. Although an acceptable clinical result was obtained with limited intercarpal fusion, correct diagnosis and initial treatments including anatomical reduction and fixation for obtaining a good clinical result, are important for complex trapezoid injury.
• Two-staged arthroscopy-assisted treatment of a large depression fracture in the lateral femoral condyle associated with an acute anterior cruciate ligament tear

  Masatake Matsuoka, Masayuki Inoue, Norimichi Shimamoto, Norimasa Iwasaki, Kazunori Yasuda

  European Orthopaedics and Traumatology 6 (1) 55 - 60 1867-4577 2015 [Refereed][Not invited]
   

  A 38-year-old man sustained a large depression fracture in the lateral femoral condyle associated with an acute anterior cruciate ligament (ACL) tear in the right knee, while snowboarding. Ten days after the injury, we started a two-staged operation plan. Because the depressed area in the lateral femoral condyle was very huge, we performed an arthroscopically assisted reduction of the depression fracture in the first operation. Under arthroscopic observations, we created a bone tunnel from the extra-articular wall of the lateral condyle towards the depressed subchondral area and anatomically reduced the subchondral bone using a bone impactor. Then, we grafted many cancellous bone chips harvested from the iliac crest. The computed tomography (CT) showed that the regular, convex shape of the lateral femoral condyle was almost restored. Postoperatively, we did not perform aggressive rehabilitation. CT taken at 12 weeks showed that the small impressed lesion of the lateral femoral condyle surface existed in a part of the area almost anatomically reduced in the first surgery. At 13 weeks after the first surgery, we carried out the second operation, which included anatomic double-bundle ACL reconstruction with the semitendinosus tendon and an additional osteochondral plug graft for the small defect using an 8-mm osteochondral plug. At 2 years after the second operation, the patient returned to his previous level of snowboard activity without any knee pain. The Lachman test was found to be negative, and a range of knee motion was between 0 and 130°.
• Correlation Between Knee Kinematics and Patellofemoral Contact Pressure in Total Knee Arthroplasty

  Takuya Konno, Tomohiro Onodera, Yusuke Nishio, Yasuhiko Kasahara, Norimasa Iwasaki, Tokifumi Majima

  JOURNAL OF ARTHROPLASTY 29 (12) 2305 - 2308 0883-5403 2014/12 [Refereed][Not invited]
   

  The aim of this study is to evaluate the relationship between patellofemoral contact stress and intraoperative knee kinematic patterns after mobile bearing total knee arthroplasty (TKA). Medial osteoarthritic knees of forty-six posterior-stabilized total knee prostheses were evaluated using a computed tomography-guided navigation system. Subjects were divided into two groups based on intraoperative knee kinematic patterns: the medial pivot group (n = 19) and the non-medial pivot group (n = 27). Mean intraoperative patellofemoral contact stress was significantly lower in the medial pivot group than in the non-medial pivot group (1.7 MPa vs. 3.2 MPa, P < 0.05). An intraoperative medial pivot pattern results in reduced patello-femoral contact stress. (C) 2014 Elsevier Inc. All rights reserved.
• Sulfation patterns of exogenous chondroitin sulfate affect chondrogenic differentiation of ATDC5 cells

  Daisuke Kawamura, Tadanao Funakoshi, Shuji Mizumoto, Kazuyuki Sugahara, Norimasa Iwasaki

  JOURNAL OF ORTHOPAEDIC SCIENCE 19 (6) 1028 - 1035 0949-2658 2014/11 [Refereed][Not invited]
   

  Background Chondroitin sulfate (CS) has been used in cartilage tissue engineering techniques as a positive modulator of scaffolds. CS is a linear polysaccharide consisting of variously sulfated repeating disaccharides. The sulfation patterns of CS are closely related to their biological functions, but only monosulfated CS has been applied to scaffolds. In this study, we investigated the effects of various sulfation patterns of CS on chondrogenic differentiation using ATDC5 chondroprogenitor cells. Methods Disaccharide composition analysis of CS produced by ATDC5 cells at various differentiation steps was performed using high-performance liquid chromatography. ATDC5 cells were cultured with exogenously added, variously sulfated CS. Cell proliferation was analyzed by the 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt (WST-8) assay. Extracellular matrix production was evaluated by Alcian blue staining. Alkaline phosphatase (ALP) activity was evaluated using an ALP assay kit. Expression of chondrogenic markers was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) or an enzyme-linked immunosorbent assay (ELISA) using a Type II Collagen Detection kit. Results The major components of CS produced by ATDC5 cells were 4-O-monosulfated disaccharides throughout chondrogenic differentiation. Low proportions of 4,6-O-disulfated disaccharides were also detected. Compared to the control group, which did not contain GAGs, the WST-8 assay indicated fewer viable cells when treated with CS-E, which are rich in 4,6-O-disulfated disaccharides. CS-E significantly enhanced Alcian blue staining in a dose-dependent manner and decreased ALP activity after 21 days of culture. Real-time RT-PCR showed that CS-E significantly enhanced all chondrogenic markers, col2a1, aggrecan, and sox9, either at day 4 or day 14 of culture. The results of ELISA analysis confirmed that CS-E significantly enhanced the production of type II collagen. Conclusions ATDC5 cells produced four different monosulfated or disulfated disaccharides in their extracellular matrices. The sulfation patterns of exogenously added CS affected chondrogenic differentiation of ATDC5 cells. In particular, CS-E rich in disulfated disaccharides significantly promoted chondrogenic differentiation of ATDC5 cells. Thus, CS containing this disulfated structure may be a useful scaffold component for enhancing chondrogenesis in cartilage tissue engineering.
• Quantitative glycomics monitoring of induced pluripotent- and embryonic stem cells during neuronal differentiation

  Michiyo Terashima, Maho Amano, Tomohiro Onodera, Shin-Ichiro Nishimura, Norimasa Iwasaki

  STEM CELL RESEARCH 13 (3) 454 - 464 1873-5061 2014/11 [Refereed][Not invited]
   

  Alterations in the structure of cell surface glycoforms occurring during the stages of stem cell differentiation remain unclear. We describe a rapid glycoblotting-based cellular glycomics method for quantitatively evaluating changes in glycoform expression and structure during neuronal differentiation of murine induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs). Our results show that changes in the expression of cellular N-glycans are comparable during the differentiation of iPSCs and ESCs. The expression of bisect-type N-glycans was significantly up-regulated in neurons that differentiated from both iPSCs and ESCs. From a glycobiological standpoint, iPSCs are an alternative neural cell source in addition to ESCs. (C) 2014 The Authors. Published by Elsevier B.V.
• Reliability of peripheral intraneural microhemodynamics evaluation by using contrast-enhanced ultrasonography

  Kinya Ishizaka, Mutsumi Nishida, Makoto Motomiya, Megumi Satoh, Mamiko Inoue, Yusuke Kudoh, Satomi Omotehara, Tatsunori Horie, Tadanao Funakoshi, Norimasa Iwasaki

  JOURNAL OF MEDICAL ULTRASONICS 41 (4) 481 - 486 1346-4523 2014/10 [Refereed][Not invited]
   

  Purpose The purpose of the study was to validate the reliability of quantitative intraneural enhancement patterns by using contrast-enhanced ultrasonography (CEUS). Methods Nine asymptomatic wrists underwent a total of three CEUS examinations each conducted at 1-month intervals. The CEUS enhancement pattern of median nerves was quantitatively evaluated. The area under the time-intensity curve was calculated by placing the regions of interest at the proximal, center, and distal regions of the median nerve. An intra-class correlation coefficient for intra-observer, inter-observer, and inter-examination reproducibility was calculated. Results The intra- and inter-observer reproducibility was almost perfect. Inter-examination reproducibility of the proximal, center, and distal regions was 0.891, 0.614, and 0.535, respectively. In this study, we found that the reproducibility of the distal and center regions of the median nerve in the carpal tunnel was lower than that of the proximal region. Conclusion High intra-observer, inter-observer, and inter-examination reproducibility of CEUS was obtained in the evaluation of the intraneural enhancement pattern when the region of interest was placed in the proximal region of the median nerve.
• Effects of Single Injection of Local Anesthetic Agents on Intervertebral Disc Degeneration: Ex Vivo and Long-Term In Vivo Experimental Study

  Koji Iwasaki, Hideki Sudo, Katsuhisa Yamada, Hideaki Higashi, Takashi Ohnishi, Takeru Tsujimoto, Norimasa Iwasaki

  PLOS ONE 9 (10) e109851  1932-6203 2014/10 [Refereed][Not invited]
   

  Background: Analgesic discography (discoblock) can be used to diagnose or treat discogenic low back pain by injecting a small amount of local anesthetics. However, recent in vitro studies have revealed cytotoxic effects of local anesthetics on intervertebral disc (IVD) cells. Here we aimed to investigate the deteriorative effects of lidocaine and bupivacaine on rabbit IVDs using an organotypic culture model and an in vivo long-term follow-up model. Methods: For the organotypic culture model, rabbit IVDs were harvested and cultured for 3 or 7 days after intradiscal injection of local anesthetics (1% lidocaine or 0.5% bupivacaine). Nucleus pulposus (NP) cell death was measured using confocal microscopy. Histological and TUNEL assays were performed. For in vivo study, each local anesthetic was injected into rabbit lumbar IVDs under a fluoroscope. Six or 12 months after the injection, each IVD was prepared for magnetic resonance imaging (MRI) and histological analysis. Results: In the organotypic culture model, both anesthetic agents induced time-dependent NP cell death; when compared with injected saline solution, significant effects were detected within 7 days. Compared with the saline group, TUNEL-positive NP cells were significantly increased in the bupivacaine group. In the in vivo study, MRI analysis did not show any significant difference. Histological analysis revealed that IVD degeneration occurred to a significantly level in the saline-and local anesthetics-injected groups compared with the untreated control or puncture-only groups. However, there was no significant difference between the saline and anesthetic agents groups. Conclusions/Significance: In the in vivo model using healthy IVDs, there was no strong evidence to suggest that discoblock with local anesthetics has the potential of inducing IVD degeneration other than the initial mechanical damage of the pressurized injection. Further studies should be performed to investigate the deteriorative effects of the local injection of analgesic agents on degenerated IVDs.
• SS18-SSX-regulated miR-17 promotes tumor growth of synovial sarcoma by inhibiting p21WAF1/CIP1

  Yusuke Minami, Shinji Kohsaka, Masumi Tsuda, Kazuhiro Yachi, Nobuaki Hatori, Mishie Tanino, Taichi Kimura, Hiroshi Nishihara, Akio Minami, Norimasa Iwasaki, Shinya Tanaka

  CANCER SCIENCE 105 (9) 1152 - 1159 1347-9032 2014/09 [Refereed][Not invited]
   

  MicroRNA (miRNA) can function as tumor suppressors or oncogenes, and also as potential specific cancer biomarkers; however, there are few published studies on miRNA in synovial sarcomas, and their function remains unclear. We transfected the OncomiR miRNA Precursor Virus Library into synovial sarcoma Fuji cells followed by a colony formation assay to identify miRNAs to confer an aggressive tumorigenicity, and identified miR-17-5p from the large colonies. MiR-17 was found to be induced by a chimeric oncoprotein SS18-SSX specific for synovial sarcoma, and all examined cases of human synovial sarcoma expressed miR-17, even at high levels in several cases. Overexpression of miR-17 in synovial sarcoma cells, Fuji and HS-SYII, increased colony forming ability in addition to cell growth, but not cell motility and invasion. Tumor volume formed in mice in vivo was significantly increased by miR-17 overexpression with a marked increase of MIB-1 index. According to PicTar and Miranda algorithms, which predicted CDKN1A (p21) as a putative target of miR-17, a luciferase assay was performed and revealed that miR-17 directly targets the 3-UTR of p21 mRNA. Indeed, p21 protein level was remarkably decreased by miR-17 overexpression in a p53-independent manner. It is noteworthy that miR-17 succeeded in suppressing doxorubicin-evoked higher expression of p21 and conferred the drug resistance. Meanwhile, introduction of anti-miR-17 in Fuji and HS-SYII cells significantly decreased cell growth, consistent with rescued expression of p21. Taken together, miR-17 promotes the tumor growth of synovial sarcomas by post-transcriptional suppression of p21, which may be amenable to innovative therapeutic targeting in synovial sarcoma.
• Development of cartilage tissue engineering techniques based on biomedical research

  Norimasa Iwasaki

  JOURNAL OF ORTHOPAEDIC SCIENCE 19 (5) 699 - 706 0949-2658 2014/09 [Refereed][Not invited]
  
• ウシ大腿骨海綿骨の異方性弾性率とハイドロキシアパタイト(HAp)結晶構造の関係

  遠藤 香織, 山田 悟史, 東藤 正浩, 但野 茂, 高畑 雅彦, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 88 (8) S1741 - S1741 0021-5325 2014/08
• Vitamin K-dependent carboxylation of osteocalcin affects the efficacy of teriparatide (PTH1-34) for skeletal repair

  Tomohiro Shimizu, Masahiko Takahata, Yusuke Kameda, Hiroki Hamano, Teppei Ito, Hiromi Kimura-Suda, Masahiro Todoh, Shigeru Tadano, Norimasa Iwasaki

  BONE 64 95 - 101 8756-3282 2014/07 [Refereed][Not invited]
   

  Teriparatide (PTH1-34) promotes skeletal repair and increases bone mass. Vitamin K is involved in bone mineralization as a coenzyme of gamma-carboxylase for Gla proteins, and therefore vitamin K insufficiency caused by malnutrition or therapeutic intake of the vitamin K antagonist warfarin could affect the efficacy of PTH1-34 therapy for bone repair. In the present study, we investigated whether vitamin K influences the efficacy of PTH1-34 therapy for bone repair in a rat osteotomy model. Female 12-week-old Sprague-Dawley rats were subjected to a closed midshaft osteotomy of the femur and randomized into four groups (n = 10 per group): vehicle, PTH1-34 (daily 30 mu g/kg/day subcutaneous injection) + solvent (orally, three times a week), PTh1-34 + warfarin (0.4 mg/kg/day orally, three times a week), and PTH1-34 + vitamin K-2 (menatetrenone, 30 mg/kg/day orally, three times a week). Serum gamma-carboxylated and uncarboxylated osteocalcin (Gla-OC and Glu-OC) levels and radiographic healing were monitored every 2 weeks. Skeletal repair was assessed by micro-computed tomography, mechanical testing, and histology at 8 weeks after surgery. PTH1-34 amplified the osteotomy-induced increase in Gla-OC and improved the mechanical properties as well as the volumetric bone mineral tissue density of the fracture callus. Concurrent use of warfarin decreased the response to PTH1-34 therapy in terms of mechanical recovery, probably by impairing mineralization due to the lack of Gla-OC. Although the effects of combination therapy with PTH1-34 and vitamin K-2 on bone repair did not significantly exceed those of PTH1-34 monotherapy in rats fed sufficient dietary vitamin K, postoperative Gla-OC levels were correlated with the mechanical properties of the osteotomized femur in PTH1-34-treated rats regardless of the use of warfarin or vitamin K-2. These findings suggest the importance of vitamin K dependent gamma-carboxylation of DC for realizing the full effects of PTH1-34 on skeletal repair. (C) 2014 Elsevier Inc. All rights reserved.
• Surgical Treatment of Lenke 1 Thoracic Adolescent Idiopathic Scoliosis With Maintenance of Kyphosis Using the Simultaneous Double-Rod Rotation Technique

  Hideki Sudo, Manabu Ito, Yuichiro Abe, Kuniyoshi Abumi, Masahiko Takahata, Ken Nagahama, Shigeto Hiratsuka, Kei Kuroki, Norimasa Iwasaki

  SPINE 39 (14) 1163 - 1169 0362-2436 2014/06 [Refereed][Not invited]
   

  Study Design. Retrospective analysis of a prospectively collected, consecutive, nonrandomized series of patients. Objective. To assess the surgical outcomes of the simultaneous double-rod rotation technique for treating Lenke 1 thoracic adolescent idiopathic scoliosis (AIS). Summary of Background Data. With the increasing popularity of segmental pedicle screw spinal reconstruction for treating AIS, concerns regarding the limited ability to correct hypokyphosis have also increased. Methods. A consecutive series of 32 patients with Lenke 1 main thoracic AIS treated with the simultaneous double-rod rotation technique at our institution was included. Outcome measures included patient demographics, radiographical measurements, and Scoliosis Research Society questionnaire scores. Results. All 32 patients were followed up for a minimum of 2 years (average, 3.6 yr). The average main thoracic Cobb angle correction rate and the correction loss at the final follow-up were 67.8% and 3.3 degrees, respectively. The average preoperative thoracic kyphosis (T5-T12) was 11.9, which improved significantly to 20.5 degrees (P < 0.0001) at the final follow-up. An increase in thoracic kyphosis was significantly correlated with an increase in lumbar lordosis at the final follow-up (r = 0.42). The average preoperative vertebral rotation angle was 19.7 degrees, which improved significantly after surgery to 14.9 degrees (P = 0.0001). There was no correlation between change in thoracic kyphosis and change in apical vertebral rotation (r = - 0.123). The average preoperative total Scoliosis Research Society questionnaire score was 3.0, which significantly improved to 4.4 (P < 0.0001) at the final follow-up. Throughout surgery and even after, there were no instrumentation failures, pseudarthrosis, infection of the surgical site, or clinically relevant neurovascular complications. Conclusion. The simultaneous double-rod rotation technique for treating Lenke 1 AIS provides significant sagittal correction of the main thoracic curve while maintaining sagittal profiles and correcting coronal and axial deformities.
• Intraoperative Medial Pivot Affects Deep Knee Flexion Angle and Patient-Reported Outcomes After Total Knee Arthroplasty

  Yusuke Nishio, Tomohiro Onodera, Yasuhiko Kasahara, Daisuke Takahashi, Norimasa Iwasaki, Tokifumi Majima

  JOURNAL OF ARTHROPLASTY 29 (4) 702 - 706 0883-5403 2014/04 [Refereed][Not invited]
   

  The aim of this study was to evaluate the relationship between clinical results including patient-reported outcomes and intraoperative knee kinematic patterns after total knee arthroplasty (TKA). A cross-sectional survey of forty consecutive medial osteoarthritis patients who had a primary TKA using a CT-based navigation system was conducted. Subjects were divided into two groups based on intraoperative kinematic patterns: a medial pivot group (n = 20) and a non-medial pivot group (n = 20). Subjective outcomes with the new Knee Society Score and clinical outcomes were evaluated. The functional activities, patient satisfaction and the knee flexion angle of the medial pivot group were significantly better than those of the non-medial pivot group. An intraoperative medial pivot pattern positively influences deep knee flexion and patient-reported outcomes. (C) 2014 Elsevier Inc. All rights reserved.
• Radial Shortening Osteotomy for Kienbock Disease: Minimum 10-Year Follow-Up

  Yuichiro Matsui, Tadanao Funakoshi, Makoto Motomiya, Atsushi Urita, Michio Minami, Norimasa Iwasaki

  JOURNAL OF HAND SURGERY-AMERICAN VOLUME 39 (4) 679 - 685 0363-5023 2014/04 [Refereed][Not invited]
   

  Purpose To clarify long-term clinical and radiological results more than 10 years after radial shortening osteotomy for Kienbock disease. Methods Eleven wrists of 10 patients that had been classified as Lichtman stages 3A (2 wrists), 3B (8 wrists), and 4 (1 wrist) underwent radial shortening for Kienbock disease. The mean follow-up period was 14.3 years (range, 10-21 y). Clinical outcomes were quantified using the Japanese version of the Disabilities of the Arm, Shoulder, and Hand questionnaire and the modified Mayo wrist score. Radiographic and magnetic resonance imaging studies were performed for 9 of the 10 patients preoperatively, and all 10 patients at follow-up. Results At follow-up, 6 wrists were asymptomatic and the remaining 5 had mild occasional pain. The mean range of extension and grip strength significantly improved. The mean modified Mayo wrist score and Disabilities of the Ann, Shoulder, and Hand scores were 92 (range, 80-100) and 5 (range, 0-18), respectively. At follow-up, no progression of the Lichtman stage was found in any patient. There was no significant progressive Innate collapse in any patient. The magnetic resonance imaging in 7 wrists showed increased signal intensity of the lunate; the remaining 3 wrists had no alteration in signal intensity of the bone. Conclusions Our study demonstrated satisfactory clinical results after 10 or more years in patients who underwent radial shortening for Kienbock disease. Although we found no improvement in signal intensity of the lunate in 3 wrists, unloading of the diseased lunate after radial shortening gives long-lasting symptom relief and may prevent lunate collapse. (Copyright (C) 2014 by the American Society for Surgery of the Hand. All rights reserved.)
• alpha 9 beta 1 integrin acts as a critical intrinsic regulator of human rheumatoid arthritis

  Tsuyoshi Asano, Norimasa Iwasaki, Shigeyuki Kon, Masashi Kanayama, Junko Morimoto, Akio Minami, Toshimitsu Uede

  RHEUMATOLOGY 53 (3) 415 - 424 1462-0324 2014/03 [Refereed][Not invited]
   

  Objective. The role of the joint tissue microenvironment in the pathogenesis of human RA has recently attracted much attention. The present study investigated the roles of alpha 9 beta 1 integrin and its ligands in synovial specimens of human RA patients in generating the unique human arthritic tissue microenvironment. Methods. Synovial fibroblasts and macrophages were isolated from the synovial tissue of patients with RA or OA. The expression of alpha 9 beta 1 integrin was analysed using FACS with multicolour staining. The production of MMPs and proinflammatory cytokines was analysed in cultures of synovial fibroblasts and macrophages with alpha 9 beta 1 integrin ligands. Results. Synovial fibroblasts and macrophages derived from arthritic joints spontaneously secreted tenascin-C and osteopontin. Synovial fibroblasts and macrophages obtained from patients with RA expressed alpha 9 beta 1 integrins, a common receptor for osteopontin and tenascin-C. In the synovial fibroblasts of RA, the amount of tenascin-C protein produced was much greater than that of osteopontin in synovial fibroblasts of RA. Importantly, autocrine and paracrine interactions of alpha 9 beta 1 integrin and tenascin-C induced the expression of MMPs and IL-6 in synovial fibroblasts, as well as TNF-alpha and IL-1 beta in synovial macrophages. Conclusion. These findings indicate that autocrine and paracrine interaction of alpha 9 beta 1integrin and tenascin-C in the joint tissue microenvironment contributes to the pathogenesis of RA. Therefore alpha 9 beta 1 integrin may become a potential therapeutic target for RA.
• Caspase 3 Silencing Inhibits Biomechanical Overload-Induced Intervertebral Disk Degeneration

  Katsuhisa Yamada, Hideki Sudo, Koji Iwasaki, Naoki Sasaki, Hideaki Higashi, Yusuke Kameda, Manabu Ito, Masahiko Takahata, Kuniyoshi Abumi, Akio Minami, Norimasa Iwasaki

  AMERICAN JOURNAL OF PATHOLOGY 184 (3) 753 - 764 0002-9440 2014/03 [Refereed][Not invited]
   

  Intervertebral disk (IVD) degeneration causes debilitating low back pain in much of the worldwide population. No efficient treatment exists because of an unclear pathogenesis. One characteristic event early in such degeneration is the apoptosis of nucleus pulposus (NP) cells embedded in IVDs. Excessive biomechanical loading may also be a major etiology of IVD degeneration. The present study used in vitro and in vivo models of compressive loading to elucidate the underlying mechanism of IVD degeneration. In addition, we investigated whether the inhibition of apoptosis is a potential clinical therapeutic strategy for the treatment of IVD degeneration induced by biomechanicaL stress. A TUNEL assay showed that NP cell agarose three-dimensional composite cultures subjected to uniaxiaL, unconfined, static, compressive loading exhibited a time-dependent increase in apoptosis. Western blot analysis revealed the upregulation of several extracellular matrix-degrading enzymes and down-regulation of tissue inhibitor of metaLloproteinase 1. These responses to compressive loading were all significantly inhibited by caspase 3 siRNA. In the in vivo model of compressive Loading-induced IVD degeneration, a single Localinjection of caspase 3 siRNA significantly inhibited IVD degeneration by magnetic resonance imaging, histological findings, IHC, and TUNEL assay. The present study suggests that caspase 3 siRNA attenuates overload-induced IVD degeneration by inhibiting NP cell apoptosis and the expression of matrix-degrading enzymes.
• Cytotoxic Effects of the Radiocontrast Agent Iotrolan and Anesthetic Agents Bupivacaine and Lidocaine in Three-Dimensional Cultures of Human Intervertebral Disc Nucleus Pulposus Cells: Identification of the Apoptotic Pathways

  Koji Iwasaki, Hideki Sudo, Katsuhisa Yamada, Manabu Ito, Norimasa Iwasaki

  PLOS ONE 9 (3) e92442  1932-6203 2014/03 [Refereed][Not invited]
   

  Background: Discography and discoblock are imaging procedures used to diagnose discogenic low back pain. Although needle puncture of the intervertebral disc (IVD) itself induces disc degeneration, the agents used in these procedures may also have harmful effects on IVD cells. The purpose of this study was to analyze whether radiocontrast agents and local anesthetic agents have detrimental effects on human nucleus pulposus (NP) cells. Methods: Healthy human NP cells were cultured for 7 days in three-dimensional (3D) cell-alginate bead composites, and were then exposed to clinically relevant doses of a radiocontrast agent (iotrolan) or local anesthetic (lidocaine or bupivacaine). Cell viability and apoptosis were measured by confocal microscopy and flow cytometry. On the basis of caspase expression profiles, the apoptotic pathways activated by the agents were identified by Western blot analysis. Results: The radiocontrast agent iotrolan did not affect NP cell viability or induce apoptosis. In contrast, both the anesthetic agents significantly decreased cell viability and increased the apoptotic cell number in a time-and dose-dependent manner. After 120 min, 2% lidocaine and 0.5% bupivacaine decreased percent live cells to 13% and 10%, respectively (p<0.05). The number of apoptotic cells was doubled by increasing lidocaine dosage from 1% to 2% (23% and 42%) and bupivacaine from 0.25% to 0.50% (25% and 48%) (p<0.05). Western blot analysis revealed that both anesthetic agents upregulated cleaved caspase-3 and caspase-8, whereas only bupivacaine upregulated cleaved caspase-9. Conclusions/Significance: The present study demonstrates that iotrolan does not affect the viability of healthy human NP cells. In contrast, the two anesthetic agents commonly used in discography or discoblock may cause extensive damage to IVDs by inducing apoptotic cell death.
• Cervical spondylotic myelopathy with subacute combined degeneration

  Takuji Miyazaki, Hideki Sudo, Shigeto Hiratsuka, Norimasa Iwasaki

  SPINE JOURNAL 14 (2) 381 - 382 1529-9430 2014/02 [Refereed][Not invited]
  
• Depletion of gangliosides enhances cartilage degradation in mice

  F. Sasazawa, T. Onodera, T. Yamashita, N. Seito, Y. Tsukuda, N. Fujitani, Y. Shinohara, N. Iwasaki

  OSTEOARTHRITIS AND CARTILAGE 22 (2) 313 - 322 1063-4584 2014/02 [Refereed][Not invited]
   

  Objective: Glycosphingolipids (GSLs) are ubiquitous membrane components that play a functional role in maintaining chondrocyte homeostasis. We investigated the potential role of gangliosides, one of the major components of GSLs, in osteoarthritis (OA) pathogenesis. Design: Both age-associated and instability-induced OA models were generated using GM3 synthase knockout (GM3.5(-/-)) mice. A cartilage degradation model and transiently GM3S-transfected chondrocytes were analyzed to evaluate the function of gangliosides in OA development. The amount of each series of GSLs in chondrocytes after IL-1 alpha stimulation was profiled using mass spectrometry (MS). Results: OA changes in GM3.5(-/-) mice were dramatically enhanced with aging compared to those in wildtype (WT) mice. GM3.5(-/-) mice showed more severe instability-induced pathologic OA in vivo. Ganglioside deficiency also led to the induction of matrix metalloproteinase (MMP)-13 and ADAMTS-5 secretion and chondrocyte apoptosis in vitro. In contrast, transientGM3.5(-/-) transfection of chondrocytes suppressed MMP-13 and ADAMTS-5 expression after interleukin (IL)-1 alpha stimulation. GSL profiling revealed the presence of abundant gangliosides in chondrocytes after IL-1 alpha stimulation. Conclusion: Gangliosides play a critical role in OA pathogenesis by regulating the expression of MMP-13 and ADAMTS-5 and chondrocyte apoptosis. Based on the obtained results, we propose that gangliosides are potential target molecules for the development of novel OA treatments. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
• Discovery of novel differentiation markers in the early stage of chondrogenesis by glycoform-focused reverse proteomics and genomics.

  Ishihara T, Kakiya K, Takahashi K, Miwa H, Rokushima M, Yoshinaga T, Tanaka Y, Ito T, Togame H, Takemoto H, Amano M, Iwasaki N, Minami A, Nishimura S

  Biochimica et biophysica acta 1840 (1) 645 - 655 0006-3002 2014/01 [Refereed][Not invited]
   

  BACKGROUND: Osteoarthritis (OA) is one of the most common chronic diseases among adults, especially the elderly, which is characterized by destruction of the articular cartilage. Despite affecting more than 100 million individuals all over the world, therapy is currently limited to treating pain, which is a principal symptom of OA. New approaches to the treatment of OA that induce regeneration and repair of cartilage are strongly needed. METHODS: To discover potent markers for chondrogenic differentiation, glycoform-focused reverse proteomics and genomics were performed on the basis of glycoblotting-based comprehensive approach. RESULTS: Expression levels of high-mannose type N-glycans were up-regulated significantly at the late stage of differentiation of the mouse chondroprogenitor cells. Among 246 glycoproteins carrying this glycotype identified by ConA affinity chromatography and LC/MS, it was demonstrated that 52% are classified as cell surface glycoproteins. Gene expression levels indicated that mRNAs for 15 glycoproteins increased distinctly in the earlier stages during differentiation compared with Type II collagen. The feasibility of mouse chondrocyte markers in human chondrogenesis model was demonstrated by testing gene expression levels of these 15 glycoproteins during differentiation in human mesenchymal stem cells. CONCLUSION: The results showed clearly an evidence of up-regulation of 5 genes, ectonucleotide pyrophosphatase/phosphodiesterase family member 1, collagen alpha-1(III) chain, collagen alpha-1(XI) chain, aquaporin-1, and netrin receptor UNC5B, in the early stages of differentiation. GENERAL SIGNIFICANCE: These cell surface 5 glycoproteins become highly sensitive differentiation markers of human chondrocytes that contribute to regenerative therapies, and development of novel therapeutic reagents.
• Extensor tendon dislocation after end-to-side transfer in a rheumatoid patient.

  Matsubara S, Motomiya M, Iwasaki N

  Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 19 (1) 119 - 122 0218-8104 2014 [Refereed][Not invited]
   

  We report a case of extensor tendon dislocation at the metacarpophalangeal joint of the middle finger in which it appeared that an ulnar translation force created by an end-to-side transfer contributed to the dislocation. We recommend alterations in technique or alternative method of extensor tendon reconstruction to avoid this complication if unfavorable factors for end-to-side transfer exist.
• Anomalous vertebral and posterior communicating arteries as a risk factor in instrumentation of the posterior cervical spine

  K. Nagahama, H. Sudo, K. Abumi, M. Ito, M. Takahata, S. Hiratsuka, K. Kuroki, N. Iwasaki

  Bone and Joint Journal 96 (4) 535 - 540 2049-4408 2014 [Refereed][Not invited]
   

  We investigated the incidence of anomalies in the vertebral arteries and Circle of Willis with three-dimensional CT angiography in 55 consecutive patients who had undergone an instrumented posterior fusion of the cervical spine. We recorded any peri-operative and post-operative complications. The frequency of congenital anomalies was 30.9%, abnormal vertebral artery blood flow was 58.2% and vertebral artery dominance 40%. The posterior communicating artery was occluded on one side in 41.8% of patients and bilaterally in 38.2%. Variations in the vertebral arteries and Circle of Willis were not significantly related to the presence or absence of posterior communicating arteries. Importantly, 18.2% of patients showed characteristic variations in the Circle of Willis with unilateral vertebral artery stenosis or a dominant vertebral artery, indicating that injury may cause lethal complications. One patient had post-operative cerebellar symptoms due to intra-operative injury of the vertebral artery, and one underwent a different surgical procedure because of insufficient collateral circulation. Pre-operative assessment of the vertebral arteries and Circle of Willis is essential if a posterior spinal fusion with instrumentation is to be carried out safely.
• Chondroprotective effects of high-molecular-weight cross-linked hyaluronic acid in a rabbit knee osteoarthritis model

  S. Elmorsy, T. Funakoshi, F. Sasazawa, M. Todoh, S. Tadano, N. Iwasaki

  OSTEOARTHRITIS AND CARTILAGE 22 (1) 121 - 127 1063-4584 2014/01 [Refereed][Not invited]
   

  Objectives: We hypothesized that high-molecular-weight (MW) cross-linked (CL) hyaluronic acid (HA) improves joint lubrication and has an enhanced chondroprotective effect. We examined the histopathological changes and friction coefficients in osteoarthritic knee joints after injecting high-MW CL HA. Design: A bilateral anterior cruciate ligament transection (ACLT) model in 20 Japanese white rabbits was used. From week 5 after transection, low-MW HA (0.8 x 10(6) Da; HA80) or high-MW CL HA (6 x 10(6) Da; HA600) was injected weekly into 10 right knee for 3 weeks; normal saline (NS) was injected into the 10 left knee. A sham operation was undertaken to exclude spontaneous osteoarthritis (OA) in five knees. Results were evaluated with macroscopy, histopathology (Kikuchi's score), biomechanical testing, and rheological assessment of the joint fluid viscoelasticity. Statistical analysis was performed using one-way analysis of variance with a 95% confidence interval (CI) (P < 0.05). Results: The macroscopic findings showed severely damaged cartilage in 30% of the NS group and 20% of the HA80 and HA600 groups and intact cartilage in 100% of the sham group. The histological scores and friction coefficients of the HA600 group were significantly lower than those of the NS group (P = 0.007 and P = 0.002, respectively). Viscoelasticity measurements of the joint fluid showed no significant differences between the three treatment groups. Conclusion: High-MW CL HA exerts potential chondroprotective effects and produces superior friction coefficients. Our results suggest that HA600 delays the progression of OA effectively and improves joint lubrication significantly. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
• Siglec-15 Regulates Osteoclast Differentiation by Modulating RANKL-Induced Phosphatidylinositol 3-Kinase/Akt and Erk Pathways in Association With Signaling Adaptor DAP12

  Yusuke Kameda, Masahiko Takahata, Miki Komatsu, Shintaro Mikuni, Shigetsugu Hatakeyama, Tomohiro Shimizu, Takashi Angata, Masataka Kinjo, Akio Minami, Norimasa Iwasaki

  JOURNAL OF BONE AND MINERAL RESEARCH 28 (12) 2463 - 2475 0884-0431 2013/12 [Refereed][Not invited]
   

  Siglecs are a family of sialic acid-binding immunoglobulin-like lectins that regulate the functions of cells in the innate and adaptive immune systems through glycan recognition. Here we show that Siglec-15 regulates osteoclast development and bone resorption by modulating receptor activator of nuclear factor B ligand (RANKL) signaling in association with DNAX-activating protein 12kDa (DAP12), an adaptor protein bearing an immunoreceptor tyrosine-based activation motif (ITAM). Among the known Siglecs expressed in myeloid lineage cells, only Siglec-15 was upregulated by RANKL in mouse primary bone marrow macrophages. Siglec-15-deficient mice exhibit mild osteopetrosis resulting from impaired osteoclast development. Consistently, cells lacking Siglec-15 exhibit defective osteoclast development and resorptive activity in vitro. RANKL-induced activation of phosphatidylinositol 3-kinase (PI3K)/Akt and Erk pathways were impaired in Siglec-15-deficient cells. Retroviral transduction of Siglec-15-null osteoclast precursors with wild-type Siglec-15 or mutant Siglec-15 revealed that the association of Siglec-15 with DAP12 is involved in the downstream signal transduction of RANK. Furthermore, we found that the ability of osteoclast formation is preserved in the region adjacent to the growth plate in Siglec-15-deficient mice, indicating that there is a compensatory mechanism for Siglec-15-mediated osteoclastogenesis in the primary spongiosa. To clarify the mechanism of this compensation, we examined whether osteoclast-associated receptor (OSCAR)/Fc receptor common (FcR) signaling, an alternative ITAM-mediated signaling pathway to DAP12, rescues impaired osteoclastogenesis in Siglec-15-deficient cells. The ligands in type II collagen activate OSCAR and rescue impaired osteoclastogenesis in Siglec-15-deficient cells when cultured on bone slices, indicating that Siglec-15-mediated signaling can be compensated for by signaling activated by type II collagen and other bone matrix components in the primary spongiosa. Our findings indicate that Siglec-15 plays an important role in physiologic bone remodeling by modulating RANKL signaling, especially in the secondary spongiosa. (c) 2013 American Society for Bone and Mineral Research.
• Anterior decompression and strut graft versus posterior decompression and pedicle screw fixation with vertebroplasty for osteoporotic thoracolumbar vertebral collapse with neurologic deficits

  Hideki Sudo, Manabu Ito, Kiyoshi Kaneda, Kuniyoshi Abumi, Yoshihisa Kotani, Ken Nagahama, Akio Minami, Norimasa Iwasaki

  Spine Journal 13 (12) 1726 - 1732 1529-9430 2013/12/01 [Refereed][Not invited]
   

  Background context With the increase of the elderly population, osteoporotic vertebral fractures have been frequently reported. Surgical intervention is usually recommended in osteoporotic vertebral collapse with neurologic deficits. However, very few reports on surgical interventions exist. Purpose To compare surgical results of anterior and posterior procedures for treating osteoporotic thoracolumbar vertebral collapse with sustained neurologic deficits. Study design Retrospective comparative study. Patient sample Fifty patients who sustained osteoporotic thoracolumbar vertebral collapse with neurologic deficits were treated either by anterior decompression and strut graft (n=32) or by posterior decompression and pedicle screw fixation with vertebroplasty (n=18). Outcome measures Incidence of complications, sagittal Cobb angle, spinal canal encroachment, and Japanese Orthopedic Association score. Methods The authors retrospectively reviewed the results of a consecutive series of patients undergoing anterior decompression and strut graft or posterior decompression and pedicle screw fixation with vertebroplasty for osteoporotic thoracolumbar vertebral collapse with neurologic deficits. Operative notes, clinical charts, and radiographs were analyzed. Results Operative time was similar between the groups, but intraoperative blood loss was significantly lower in the posterior group. All patients showed neurologic recovery. No significant difference was observed in the neurologic improvement, kyphosis correction angle, and loss of correction. Perioperative respiratory complications were found in 11 patients (34%) in the anterior group. In the anterior group, early posterior reinforcement was required in patients with very low bone density below 0.60 g/cm2 and/or in those with three segments of instrumentation for two vertebral collapses. Posterior group patients did not undergo additional surgery. Conclusions Anterior reconstruction for osteoporotic vertebral collapse is significant because anterior elements, particularly those at the thoracolumbar junction, play a major role in load bearing. However, difficulties arise when anterior reconstruction is performed in cases with very low bone density and in those with multiple vertebral collapse.
• Clinical and Radiological Results of Radiolunate Arthrodesis for Rheumatoid Arthritis: 22 Wrists Followed for an Average of 7 Years

  Makoto Motomiya, Norimasa Iwasaki, Akio Minami, Yuichiro Matsui, Atsushi Urita, Tadanao Funakoshi

  JOURNAL OF HAND SURGERY-AMERICAN VOLUME 38A (8) 1484 - 1491 0363-5023 2013/08 [Refereed][Not invited]
   

  Purpose To evaluate the clinical and radiological results of radiolunate (RL) arthrodesis for rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs and/or biologicals with an average of 7 years of follow-up. In addition, we compared the results in advanced stages with those in less advanced stages in patients with comparatively low disease activity of RA. Methods This study included RL arthrodesis for 22 wrists in 19 patients with comparatively low disease activity of RA. The mean follow-up period was 7 years (range, 2-16 y). Fourteen wrists with Larsen classification grade III and 8 wrists with grade IV were included in this study. The range of motion was calculated, and clinical scores were graded using the Mayo wrist score and the Stanley classification. The carpal height ratio (CHR) and ulnar translation (UT) were determined from the radiographs. Results All wrists achieved radiographic fusion. Clinical scores were markedly improved, although there was a decrease in flexion. The Larsen grade did not deteriorate during follow-up. CHR and UT improved immediately after operation and remained good through the final follow-up. Although the flexion/extension range of motion of the grade IV wrists was smaller than that of the grade In wrists at follow-up, both groups obtained good clinical results. Conclusions Our results for RL arthrodesis were clinically and radiologically better than those of previous reports. Control of the disease activity of RA could theoretically be a factor in obtaining good long-term clinical and radiographic outcomes. RL arthrodesis is our recommended procedure for the RA wrist even in the advanced stage. (Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.)
• Depth cameraを用いた術中3次元画像操作システムiKINESYSの開発

  高橋 大介, 遠藤 香織, 木村 晋宏, 眞島 任史, 岩崎 倫政

  東日本整形災害外科学会雑誌 東日本整形災害外科学会 25 (3) 311 - 311 1342-7784 2013/08
• 偏心性寛骨臼回転骨切り術における荷重分布の変化:有限要素法を用いた解析

  高橋 大介, 眞島 任史, 遠藤 香織, 佐野 正樹, 不破 崇行, 加藤 浩仁, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 87 (8) S1448 - S1448 0021-5325 2013/08
• Depth cameraを用いた術中三次元画像操作システムの開発

  遠藤 香織, 高橋 大介, 木村 晋宏, 眞島 任史, 岩崎 倫政

  日本整形外科学会雑誌 (公社)日本整形外科学会 87 (8) S1623 - S1623 0021-5325 2013/08
• Effect of low-intensity pulsed ultrasound on bone healing at osteotomy sites after forearm bone shortening

  Atsushi Urita, Norimasa Iwasaki, Makoto Kondo, Yasuhiko Nishio, Tamotsu Kamishima, Akio Minami

  Journal of Hand Surgery 38 (3) 498 - 503 0363-5023 2013/03 [Refereed][Not invited]
   

  Purpose: To test the hypothesis that low-intensity pulsed ultrasound (LIPUS) may accelerate healing at osteotomy sites after forearm bone shortening osteotomies. Methods: In this prospective study, we enrolled 27 patients who underwent ulnar shortening osteotomy for ulnar impaction syndrome or radial shortening osteotomy for Kienböck disease. We randomized limbs to be treated with LIPUS (14 osteotomies, LIPUS group) or without LIPUS (13 osteotomies, control group). At 1 week postoperatively, patients in the LIPUS group received once-daily 20-minute LIPUS treatments that continued until at least 12 weeks postoperatively. At 2, 4, 6, 8, 12, 16, and 24 weeks postoperatively, we assessed union of the osteotomy site to determine the time to union using 4 projections of x-rays. Results: In this study, all osteotomies achieved complete union. The mean times to complete cortical union were 57 days in the LIPUS group and 76 days in the control group. Regarding endosteal union, the mean times were 121 days in the LIPUS group and 148 days in the control group. The LIPUS group had significantly reduced times for both types of union. Conclusions: Application of LIPUS shortened the time to cortical union by 27%, and to endosteal union by 18%. Our results indicate that LIPUS accelerated bone healing after we performed forearm bone shortening osteotomies. This may provide earlier return to activity and work for patients undergoing forearm osteotomies. Type of study/level of evidence: Therapeutic I. © 2013 American Society for Surgery of the Hand.
• Correction in Malrotation of the Scapula and Muscle Transfer for the Management of Severe Sprengel Deformity: Static and Dynamic Evaluation Using 3-Dimensional Computed Tomography

  Katsuhisa Yamada, Naoki Suenaga, Norimasa Iwasaki, Naomi Oizumi, Akio Minami, Tadanao Funakoshi

  JOURNAL OF PEDIATRIC ORTHOPAEDICS 33 (2) 205 - 211 0271-6798 2013/03 [Refereed][Not invited]
   

  Background: The clinical results of surgical procedures for severe Sprengel deformity have been uncertain. To obtain improved elevation, we consider that it is necessary to realign the lateral border of the scapula for upward rotation. The purposes of the current study were to evaluate the clinical results and range of motion of the scapula after such realignment. Methods: Seven cases of Sprengel deformity of Cavendish grade 3 or 4 were treated surgically and then clinically evaluated and examined using 3-dimensional computed tomography (3D CT). (Two boys and 5 girls aged 50.9 +/- 15.4mo, mean +/- SD at the time of operation.) The mean follow-up was 53.1 months (range, 12 to 92mo). After the omovertebral bone and the superomedial side of the scapula were removed, the levator scapulae and rhomboids were reattached to wrap around the scapula at maximum upward rotation to assist in maintaining this position. Cavendish and Rigault grades were used for evaluation of postoperative appearance. The superior displacement and rotation of the scapula were measured on the trunk posterior view using 3D CT. The relationship between improvement in the range of motion and radiologic change were analyzed statistically. Results: The postoperative flexion (97.9 +/- 12.9 to 160 +/- 11.5 degrees) and abduction (99.3 +/- 13.0 to 161.4 +/- 15.7 degrees) were significantly improved compared with the mean preoperative values (P<0.0001). 3D CT revealed that in all patients the malrotation of the scapula was improved postoperatively. The current study shows that successful realignment of the scapula led to these improved clinical results. Conclusions: Our procedure has advantages not only for recovery of the range of motion but also for reducing the characteristic lump in the web of the neck. However, our procedure has an inherent limitation related to asymmetric shoulder level and width. 3D CT may be useful for preoperative planning and postoperative evaluation.
• Global Identification of Genes Related to Nutrient Deficiency in Intervertebral Disc Cells in an Experimental Nutrient Deprivation Model

  Hideki Sudo, Katsuhisa Yamada, Koji Iwasaki, Hideaki Higashi, Manabu Ito, Akio Minami, Norimasa Iwasaki

  PLOS ONE 8 (3) e58806  1932-6203 2013/03 [Refereed][Not invited]
   

  Background: Intervertebral disc degeneration is a significant cause of degenerative spinal diseases. Nucleus pulposus (NP) cells reportedly fail to survive in large degenerated discs with limited nutrient availability. Therefore, understanding the regulatory mechanism of the molecular response of NP cells to nutrient deprivation may reveal a new strategy to treat disc degeneration. This study aimed to identify genes related to nutrient deprivation in NP cells on a global scale in an experimental nutrient deprivation model. Methodology/Principal Findings: Rat NP cells were subjected to serum starvation. Global gene expression was profiled by microarray analysis. Confirmation of the selected genes was obtained by real-time polymerase chain reaction array analysis. Western blotting was used to confirm the expression of selected genes. Functional interactions between p21(Cip1) and caspase 3 were examined. Finally, flow cytometric analyses of NP cells were performed. Microarray analysis revealed 2922 differentially expressed probe sets with >= 1.5-fold changes in expression. Serum starvation of NP cells significantly affected the expression of several genes involved in DNA damage checkpoints of the cell cycle, including Atm, Brca1, Cdc25, Gadd45, Hus1, Ppm1D, Rad 9, Tp53, and Cyclin D1. Both p27(Kip1) and p53 protein expression was upregulated in serum-starved cells. p21(Cip1) expression remained in NP cells transfected with short interfering RNA targeting caspase 3 (caspase 3 siRNA). Both G1 arrest and apoptosis induced by serum starvation were inhibited in cells transfected with caspase 3 siRNA. Conclusions/Significance: Nutrient deprivation in NP cells results in the activation of a signaling response including DNA damage checkpoint genes regulating the cell cycle. These results provide novel possibilities to improve the success of intervertebral disc regenerative techniques.
• Finger flexion contracture due to muscular involvement of sarcoidosis.

  Motomiya M, Iwasaki N, Kawamura D

  Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 18 (1) 85 - 87 0218-8104 2013 [Refereed][Not invited]
   

  We describe a rare experience with the treatment of a patient with finger flexion contracture caused by muscular involvement of sarcoidosis, who had been misdiagnosed as having a trigger finger and underwent surgical release of the A1 pulley of her little finger. This report serves as a reminder that muscular involvement of sarcoidosis can cause finger flexion contractures.
• An unusual complication after suspensionplasty with the abductor pollicis longus tendon for osteoarthritis at the carpometacarpal joint of the thumb.

  Minami A, Suda K, Iwasaki N, Motomiya M

  Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 18 (1) 99 - 102 0218-8104 2013 [Refereed][Not invited]
   

  Suspensionplasty was performed using the abductor pollicis longus tendon for osteoarthritis at the carpometacarpal joint of the thumb. The operated wrist had a full range of motion four months after operation; however, there was swelling on the dorsoradial aspect of the wrist and, upon terminal wrist extension, pain was present at the maximum dorsiflexion. Suddenly, one year after operation the patient could not extend the interphalangeal joint of the thumb. Surgical exploration revealed rupture of the extensor pollicis longus tendon. Tenosynovitis at the extensor carpi radialis brevis tendon, where the abductor pollicis longus tendon is sutured, might cause extensor pollicis longus tendon rupture. Late postoperative complications such as this extensor pollicis longus tendon rupture after suspensionplasty using the abductor pollicis longus tendon are extremely rare and this is the first case in the literature.
• Transfer of teres minor with bone pedicle for irreparable posterior-superior rotator cuff tears

  Tomoya Matsuhashi, Naoki Suenaga, Naomi Oizumi, Tadanao Funakoshi, Norimasa Iwasaki, Akio Minami

  JOURNAL OF ORTHOPAEDIC SCIENCE 17 (5) 538 - 544 0949-2658 2012/09 [Refereed][Not invited]
   

  The objectives of this study are to evaluate the clinical and radiographic mid- to long-term outcomes of patients treated by teres minor with bone pedicle transfer for irreparable massive rotator cuff tear and to investigate the limitations of this procedure. Clinical outcomes were assessed by quantifying: the range of shoulder motion; a visual analog pain scale; the University of California, Los Angeles Shoulder Score (UCLA score); and the Disability of the Arm, Shoulder, and Hand (DASH) score. Radiographs were assessed for deterioration of the glenohumeral joint and upper migration of the humeral head. Eighteen patients with mean age of 66.9 years and mean follow-up of 74.4 months were included. The technique resulted in significant decrease in shoulder pain. The mean UCLA score improved from 10.3 points initially to 24.1 points at time of final follow-up. However, the postoperative results were classified as poor in 11 shoulders. The mean postoperative DASH score was 27.6 points. The mean active forward elevation significantly improved from 75.9A degrees initially to 121.6A degrees at time of final follow-up. In radiographic assessment, osteoarthritis of the glenohumeral joint progressed in 15 shoulders, and the upper migration of humeral head progressed in 14 shoulders. Aggravation of the glenohumeral joint and upper migration of the humeral head both progressed postoperatively at a high rate. Therefore, we conclude that this procedure should no longer be performed despite its relative simplicity.
• Long-term stress distribution patterns of the ankle joint in varus knee alignment assessed by computed tomography osteoabsorptiometry

  Tomohiro Onodera, Tokifumi Majima, Norimasa Iwasaki, Tamotsu Kamishima, Yasuhiko Kasahara, Akio Minami

  INTERNATIONAL ORTHOPAEDICS 36 (9) 1871 - 1876 0341-2695 2012/09 [Refereed][Not invited]
   

  The stress distribution of an ankle under various physiological conditions is important for long-term survival of total ankle arthroplasty. The aim of this study was to measure subchondral bone density across the distal tibial joint surface in patients with malalignment/instability of the lower limb. We evaluated subchondral bone density across the distal tibial joint in patients with malalignment/instability of the knee by computed tomography (CT) osteoabsorptiometry from ten ankles as controls and from 27 ankles with varus deformity/instability of the knee. The quantitative analysis focused on the location of the high-density area at the articular surface, to determine the resultant long-term stress on the ankle joint. The area of maximum density of subchondral bone was located in the medial part in all subjects. The pattern of maximum density in the anterolateral area showed stepwise increases with the development of varus deformity/instability of the knee. Our results should prove helpful for designing new prostheses and determining clinical indications for total ankle arthroplasty.
• Interruption of glycosphingolipid synthesis enhances osteoarthritis development in mice

  Naoki Seito, Tadashi Yamashita, Yukinori Tsukuda, Yuichiro Matsui, Atsushi Urita, Tomohiro Onodera, Takeomi Mizutani, Hisashi Haga, Naoki Fujitani, Yasuro Shinohara, Akio Minami, Norimasa Iwasaki

  ARTHRITIS AND RHEUMATISM 64 (8) 2579 - 2588 0004-3591 2012/08 [Refereed][Not invited]
   

  Objective Glycosphingolipids (GSLs) are ubiquitous membrane components that modulate transmembrane signaling and mediate cell-to-cell and cell-to-matrix interactions. GSL expression is decreased in the articular cartilage of humans with osteoarthritis (OA). This study was undertaken to determine the functional role of GSLs in cartilage metabolism related to OA pathogenesis in mice. Methods We generated mice with knockout of the chondrocyte-specific Ugcg gene, which encodes an initial enzyme of major GSL synthesis, using the Cre/loxP system (Col2-Ugcg-/- mice). In vivo OA and in vitro cartilage degradation models were used to evaluate the effect of GSLs on the cartilage degradation process. Results Although Col2-Ugcg-/- mice developed and grew normally, OA changes in these mice were dramatically enhanced with aging, through the overexpression of matrix metalloproteinase 13 and chondrocyte apoptosis, compared to their wild-type (WT) littermates. Col2-Ugcg-/- mice showed more severe instability-induced pathologic OA in vivo and interleukin-1a (IL-1a)induced cartilage degradation in vitro. IL-1a stimulation of chondrocytes from WT mice significantly increased Ugcg messenger RNA expression and up-regulated GSL metabolism. Conclusion Our results indicate that GSL deficiency in mouse chondrocytes enhances the development of OA. However, this deficiency does not affect the development and organization of cartilage tissue in mice at a young age. These findings indicate that GSLs maintain cartilage molecular metabolism and prevent disease progression, although GSLs are not essential for chondrogenesis of progenitor and stem cells and cartilage development in young mice. GSL metabolism in the cartilage is a potential target for developing a novel treatment for OA.
• Glenoid Stress Distribution in Baseball Players Using Computed Tomography Osteoabsorptiometry: A Pilot Study

  Tomohiro Shimizu, Norimasa Iwasaki, Kinya Nishida, Akio Minami, Tadanao Funakoshi

  CLINICAL ORTHOPAEDICS AND RELATED RESEARCH 470 (6) 1534 - 1539 0009-921X 2012/06 [Refereed][Not invited]
   

  It is important to understand the loading conditions when considering the pathology of shoulder disorders in overhead athletes. However, because throwing is a complicated motion and methods to directly determine stress distribution are complex, direct measurement of the stress distribution across the glenohumeral joint has not been attempted. Subchondral bone density reportedly reflects the cumulative stress acting on a joint surface under actual loading conditions. To assess alterations in stress distribution across the glenoid cavity caused by pitching, we investigated the distribution of subchondral bone density in nonathletic volunteers and asymptomatic baseball players, including fielders and pitchers. We collected CT imaging data from the dominant-side shoulder of 10 nonathletic volunteers (controls), 10 fielders, and 10 pitchers in a competitive college baseball league (all men aged 19-24 years, mean 20.7 years). We measured the distribution of subchondral bone density of the glenoid cavity using CT osteoabsorptiometry. The obtained stress distribution map was divided into four segments: anterosuperior, anteroinferior, posteroinferior, and posterosuperior regions. We quantitatively analyzed the location and percentages of high-density regions on the articular surface. The percentages of high-density regions, including the anteroinferior and posterior segments, were greater in pitchers and fielders than in controls. The percentages of high-density regions did not differ between pitchers and fielders. The bicentric density patterns indicated that the cumulative force of pitching activity affected the long-term stress distribution across the glenoid cavity. Our data should be useful for analyzing pitching activity and clarifying the pathology of shoulder disorders associated with throwing.
• Comparison of Splinting Versus Nonsplinting in the Treatment of Pediatric Trigger Finger

  Ritsu Shiozawa, Shigeharu Uchiyama, Yoshihiro Sugimoto, Shota Ikegami, Norimasa Iwasaki, Hiroyuki Kato

  JOURNAL OF HAND SURGERY-AMERICAN VOLUME 37A (6) 1211 - 1216 0363-5023 2012/06 [Refereed][Not invited]
   

  Purpose Because pediatric trigger finger is much less common than pediatric trigger thumb, there is no consensus on the efficacy of splinting, owing to both the rarity of the condition and a lack of natural history and comparative therapeutic data. We performed the present retrospective study on 47 fingers to compare pediatric trigger finger treatment by splinting and nonsplinting. Methods We included 24 children with a total of 47 trigger fingers. Affected fingers included 4 index, 28 middle, 11 ring, and 4 little fingers. Patient age at initial examination ranged from 1 month to 9 years (mean, 2 y). We observed 24 fingers treated with a static splint and 23 fingers treated without it. The time from initial examination to follow-up ranged from 2 to 18 years. Results In the splinting group, 16 fingers (67%) resolved, 4 fingers (17%) improved, and 4 fingers (17%) remained unchanged. Seven fingers (29%) ultimately required surgery. In the nonsplinting group, 7 fingers (30%) resolved spontaneously, 1 (4%) improved, and 15 (65%) remained unchanged. Fifteen fingers (65%) later underwent surgical release. The rate of resolution in the splinting group was significantly higher than that in the nonsplinting group. The proportion of fingers needing surgical treatment in the splinting group was significantly lower than that in the nonsplinting group. Conclusions For treatment of pediatric trigger finger, it is advisable to fit a static splint at the first visit. (J Hand Surg 2012;37A:1211-1216. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.)
• Ganglioside GM3 Has an Essential Role in the Pathogenesis and Progression of Rheumatoid Arthritis

  Yukinori Tsukuda, Norimasa Iwasaki, Naoki Seito, Masashi Kanayama, Naoki Fujitani, Yasuro Shinohara, Yasuhiko Kasahara, Tomohiro Onodera, Koji Suzuki, Tsuyoshi Asano, Akio Minami, Tadashi Yamashita

  PLOS ONE 7 (6) e40136  1932-6203 2012/06 [Refereed][Not invited]
   

  Rheumatoid arthritis (RA), a chronic systemic inflammatory disorder that principally attacks synovial joints, afflicts over 2 million people in the United States. Interleukin (IL)-17 is considered to be a master cytokine in chronic, destructive arthritis. Levels of the ganglioside GM3, one of the most primitive glycosphingolipids containing a sialic acid in the structure, are remarkably decreased in the synovium of patients with RA. Based on the increased cytokine secretions observed in in vitro experiments, GM3 might have an immunologic role. Here, to clarify the association between RA and GM3, we established a collagen-induced arthritis mouse model using the null mutation of the ganglioside GM3 synthase gene. GM3 deficiency exacerbated inflammatory arthritis in the mouse model of RA. In addition, disrupting GM3 induced T cell activation in vivo and promoted overproduction of the cytokines involved in RA. In contrast, the amount of the GM3 synthase gene transcript in the synovium was higher in patients with RA than in those with osteoarthritis. These findings indicate a crucial role for GM3 in the pathogenesis and progression of RA. Control of glycosphingolipids such as GM3 might therefore provide a novel therapeutic strategy for RA.
• Repair of Rabbit Osteochondral Defects by an Acellular Technique with an Ultrapurified Alginate Gel Containing Stromal Cell-Derived Factor-1

  Atsushi Sukegawa, Norimasa Iwasaki, Yasuhiko Kasahara, Tomohiro Onodera, Tatsuya Igarashi, Akio Minami

  TISSUE ENGINEERING PART A 18 (9-10) 934 - 945 1937-3341 2012/05 [Refereed][Not invited]
   

  The objective of this study was to determine whether the local administration of stromal cell-derived factor-1 (SDF-1) using ultrapurified alginate gel (UPAL gel) could improve reparative tissues of osteochondral defects compared with those without treatment. For the investigation, a full-thickness osteochondral defect 4.5mm in diameter and 3mm in depth was created in the patella groove of the distal femur in rabbits. Local expression of SDF-1 protein was temporarily upregulated at 1 week after creating the osteochondral defect. The local administration of SDF-1 enhanced the migration of host cells, mainly bone marrow stromal cells (BMSCs), to the site of the osteochondral defect. In vitro cell migration assay supported this result. In the SDF-1 (UPAL gel containing SDF-1) treatment group, the histological scores and the compressive modulus of reparative tissues were significantly improved compared with the no-treatment and vehicle (UPAL gel without SDF-1) groups. On the other hand, SDF-1 did not influence the cellular proliferation and chondrogenesis of BMSCs. Based on the results obtained here, we speculate that SDF-1 enhances the reparative process of osteochondral injuries not through direct effects on the behavior of host cells, but through increased migration of host cells to the injured site. UPAL gel, as a vehicle material, may play an important role in chondrogenesis of recruited cells, mainly BMSCs. The cell-free approach with local administration of SDF-1 may be an effective strategy for developing a minimally invasive technique for cartilage tissue regeneration.
• Alterations in stress distribution patterns through the forearm joint surface of the elbow in baseball players assessed using computed tomography osteoabsorptiometry

  Daisuke Momma, Norimasa Iwasaki, Naomi Oizumi, Kazuhiro Fujisaki, Tadanao Funakoshi, Yuichiro Abe, Tamotsu Kamishima, Shigeru Tadano, Akio Minami

  JOURNAL OF ORTHOPAEDIC SCIENCE 17 (3) 253 - 260 0949-2658 2012/05 [Refereed][Not invited]
   

  The distribution of subchondral bone density well reflects long-term resultant stress acting on an articular surface in living joints. Consequently, a measurement of the distribution pattern can determine the stress distribution across the elbow joint surface under long-term loading conditions of baseball pitching. Our purpose was to elucidate the characteristic alterations in the distribution pattern of subchondral bone density across the forearm bones of the elbow with pitching activities. The hypothesis is that pitching activities would change the stress distribution in living subjects. The analysis was performed using computed tomography (CT) images obtained from the dominant elbow of ten nonthrowing athletes (control group), ten college baseball fielders (fielder group), and ten college baseball pitchers (pitcher group). The distribution pattern of subchondral bone density through the articular surface of the proximal radius and ulna bones was assessed using CT osteoabsorptiometry. The maximum density area was located in the posterior part of the trochlea notch in all study participants. This maximum density area was significantly increased in the baseball groups compared with that in the control group. The pitcher group also showed a significant distribution of the maximum density area in the anterior part of the radial head. Our analysis indicates that pitching activities increase actual stress on the articular surface not only in the posterior part of the trochlea notch but also in the anterior part of the radial head. The stress across the elbow may be expanded from the ulnohumeral to the radiohumeral joint by repetitive pitching activities in living subjects.
• Distribution of Bone Mineral Density at Osteochondral Donor Sites in the Patellofemoral Joint Among Baseball Players and Controls

  Kinya Nishida, Norimasa Iwasaki, Kazuhiro Fujisaki, Tadanao Funakoshi, Tamotsu Kamishima, Shigeru Tadano, Akio Minami

  AMERICAN JOURNAL OF SPORTS MEDICINE 40 (4) 909 - 914 0363-5465 2012/04 [Refereed][Not invited]
   

  Background: To theoretically minimize complications of osteochondral graft harvest from the knee, grafts should be obtained from the site of lowest stress distribution across the joint. Hypothesis: Long-term stress distribution over the patellofemoral (PF) joint surface is not equal in athletes. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Measurement of subchondral bone density can determine long-term resultant stress acting on an articular surface in living joints. Our analysis was performed using computed tomography (CT) image data obtained from bilateral knees of 10 college baseball fielders (fielder group) and 10 college baseball pitchers (pitcher group) and 2 control groups, including 10 college soccer players (soccer group) and 10 nonathletes (nonathlete group). The distribution pattern of subchondral bone density throughout the articular surface of the PF joint was assessed using the CT osteoabsorptiometry method. The quantitative analysis focused on the location of the low-density area at the articular surface to assess potential osteochondral donor sites. Results: All participants in the pitcher and fielder groups demonstrated a low-density area widely distributed in the proximal part of the lateral trochlea. On the other hand, a high-density area was located in the distal part of the lateral notch, of the medial notch, and of the medial trochlea. No apparent differences in the distribution pattern were found between the baseball groups and the control groups. Conclusion: Our analysis, based on CT osteoabsorptiometry, indicates that the proximal lateral trochlea of the distal femur has the highest percentage area of low bone density at the PF joint level in donor knees of baseball players, soccer players, and nonathlete controls. Clinical Relevance: From a biomechanical viewpoint, the proximal lateral trochlea is the optimal site for harvesting osteochondral grafts in performing mosaicplasty for baseball players. This selection for the donor site may minimize postoperative PF joint symptoms.
• A Retrospective Evaluation of Magnetic Resonance Imaging Effectiveness on Capitellar Osteochondritis Dissecans Among Overhead Athletes

  Norimasa Iwasaki, Tamotsu Kamishima, Hiroyuki Kato, Tadanao Funakoshi, Akio Minami

  AMERICAN JOURNAL OF SPORTS MEDICINE 40 (3) 624 - 630 0363-5465 2012/03 [Refereed][Not invited]
   

  Background: Magnetic resonance imaging (MRI) has been widely used to characterize osteochondritis dissecans (OCD) lesions. However, the usefulness of MRI for predicting fragment stability in OCD of the humeral capitellum (capitellar OCD) remains unclear. Hypothesis: Preoperative MRI cannot accurately diagnose fragment instability of capitellar OCD in overhead athletes. Study Design: Cohort study (diagnosis); Level of evidence, 1. Methods: Twenty-seven male overhead athletes who had undergone surgery for capitellar OCD were included in the study. A single senior musculoskeletal radiologist blindly reviewed preoperative MRI of these OCD lesions. The radiologist reported the presence or absence of each of the 4 MRI signs indicating fragment instability as described by De Smet et al. The lesions were also classified according to the MRI staging system of Dipaola et al for characterizing the lesions. Intraoperative assessment of fragment stability was used as the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for fragment instability as assessed by MRI. Results: According to the MRI criteria by De Smet et al and the Dipaola et al staging system, 21 (78%) and 20 (74%) lesions were defined as unstable, respectively. The obtained results yielded a sensitivity of 89% and a specificity of 44% for diagnosing fragment instability using the De Smet et al MRI criteria and a sensitivity of 83% and a specificity of 44% using the Dipaola et al MRI staging system. The PPV and NPV for fragment instability were 76% and 67% using the De Smet et al criteria and 75% and 57% according to the Dipaola et al staging system, respectively. The overall correlation rate of Dipaola et al MRI and intraoperative stages was 41%. Conclusion: Preoperative MRI cannot precisely diagnose fragment instability of capitellar OCD that requires operative treatments in overhead athletes. Especially, MRI indicating stable lesions is considered not to be useful in predicting intraoperative instability of capitellar OCD in this study population.
• Repair of articular cartilage defects with a novel injectable in situ forming material in a canine model

  Tatsuya Igarashi, Norimasa Iwasaki, Daisuke Kawamura, Yasuhiko Kasahara, Yukinori Tsukuda, Nobuo Ohzawa, Masayuki Ito, Yasuharu Izumisawa, Akio Minami

  JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 100A (1) 180 - 187 1549-3296 2012/01 [Refereed][Not invited]
   

  We developed an ultra-purified in situ forming gel as an injectable delivery vehicle of bone marrow stromal cells (BMSCs). Our objective was to assess reparative tissues treated with autologous BMSCs implanted using the injectable implantation system into osteochondral defects in a canine model. Forty-eight osteochondral defects in the patella groove of the knee joint were created in 12 adult beagle dogs (two defects in each knee). The defects were divided into a defect group (n = 16), an acellular novel material implantation (material) group (n = 16), and a BMSCs implantation using the current vehicle system (material with BMSCs) group (n = 16). The reparative tissues at 16 weeks postoperatively were assessed through gross, histological, and mechanical analyses. The reparative tissues of the material with BMSCs group were substituted with firm and smooth hyaline-like cartilage tissue that was perfectly integrated into the host tissues. This treatment group obviously enhanced the subchondral bone reconstruction. The compressive modulus of the reparative tissues was significantly higher in the material with BMSCs group than the other groups. This study demonstrated that the implantation of BMSCs using our novel in situ forming material induced a mature hyaline-like cartilage repair of osteochondral defects in a canine model. (C) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 180-187, 2012.
• Therapeutic Effects of Intra-Articular Ultrapurified Low Endotoxin Alginate Administration on Experimental Osteoarthritis in Rabbits

  Tatsuya Igarashi, Norimasa Iwasaki, Daisuke Kawamura, Yukinori Tsukuda, Yasuhiko Kasahara, Masahiro Todoh, Shigeru Tadano, Akio Minami

  CARTILAGE 3 (1) 70 - 78 1947-6035 2012/01 [Refereed][Not invited]
   

  Objective: We have developed an ultrapurified low endotoxin alginate (UPLE alginate), which can drastically reduce endotoxin levels. Our purposes were to examine the effects of UPLE alginate administration on osteoarthritis (OA) progression and to determine the adequate molecular weight of the UPLE alginate for therapeutic effects. Design: To induce knee OA, 35 Japanese White rabbits underwent anterior cruciate ligament transection. Intra-articular injections of 0.3 mL solution of each material were started at 4 weeks postoperatively for a total of 5 weekly injections. Seventy knees were divided into the following groups: AL430 (430 kDa molecular weight UPLE alginate), AL1000 (1,000 kDa), AL1700 (1,700 kDa), HA (hyaluronan), and NS (normal saline). At 9 weeks postoperatively, all knees were assessed macroscopically, histologically, and mechanically. Results: Macroscopically, the UPLE alginate groups exhibited milder cartilage degradation compared to that of the NS and HA groups. Histological findings of the UPLE alginate groups showed an obvious reduction in the severity of OA. The histological scores of Kikuchi et al. were superior in the alginate treatment groups compared to the NS group. The friction coefficient of the AL1000 group was significantly lower than that of the NS and HA groups. Conclusion: This study indicates that our UPLE alginates, especially AL1000, have promising potential as an effective agent in preventing OA progression.
• Prevention of instability of the proximal end of the radius after radial head resection using an anconeus muscle flap.

  Nishida K, Iwasaki N, Funakoshi T, Motomiya M, Minami A

  Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 17 (1) 25 - 31 0218-8104 2012 [Refereed][Not invited]
   

  Resection of the radial head frequently causes instability of the proximal end of the radius. To prevent this instability, we performed a stabilization technique using an anconeus muscle flap. Since 2003, six patients with radiocapitellar joint dysfunction have been treated with radial head resection combined with stabilizing its proximal end using an anconeus muscle flap. At a mean follow-up of 51 months, all patients were free from elbow pain and the mean Mayo Elbow Performance Score and the Disabilities of the Arm, Shoulder and Hand score significantly improved. Radiographic findings showed no apparent instability of the proximal radius. The anconeus is useful as a reliable muscle flap for preventing instability of the proximal radius after a radial head resection. This procedure does not require any microvascular techniques and makes it possible to apply a pedicled muscle flap using a relatively simple technique without any considerable risks of elbow dysfunction.
• Cubital tunnel syndrome associated with arthrogryposis: a case report.

  Motomiya M, Iwasaki N, Minami A

  Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 17 (1) 85 - 87 0218-8104 2012 [Refereed][Not invited]
   

  Arthrogryposis is a syndrome of multiple joint contracture and subluxation that is present at birth and is characterized by a nonprogressive disorder. Patients with lack of active elbow motion show the typical elbow motion with passive assistance, such as the trunk-sway and cross-arm techniques. We describe our experience with the treatment of an arthrogryposis patient with cubital tunnel syndrome caused by the passive elbow motion. The ulnar nerve was entrapped by a thick fibrous band at the cubital tunnel, and simple decompression of the ulnar nerve brought the patient a good recovery from the palsy.
• In Vivo Vascularity Alterations in Repaired Rotator Cuffs Determined by Contrast-Enhanced Ultrasound

  Tadanao Funakoshi, Norimasa Iwasaki, Tamotsu Kamishima, Mutsumi Nishida, Yoichi Ito, Kinya Nishida, Makoto Motomiya, Naoki Suenaga, Akio Minami

  AMERICAN JOURNAL OF SPORTS MEDICINE 39 (12) 2640 - 2646 0363-5465 2011/12 [Refereed][Not invited]
   

  Background: The alterations in blood flow after rotator cuff repair remain unclear. Visualization of vascular patterns could clarify basic and clinical investigations. Purpose: To assess longitudinal blood flow inside the repaired cuff and the surrounding tissue after rotator cuff repair, using contrast-enhanced ultrasonography. Study Design: Descriptive laboratory study. Methods: Fifteen patients (7 men and 8 women; mean age, 65.0 +/- 9.8 years) consented to participate. The patients underwent an ultrasound scan before and 1, 2, and 3 months after surgery. Enhanced ultrasound images were recorded for 1 minute after intravenous injection of contrast reagent. Four regions of interest inside the cuff and 2 regions in the anchor hole and subacromial bursa were superimposed on the obtained images. Calculated areas under the time-intensity curves were expressed in acoustic units (AU). Results: We found area-dependent differences in patterns of alteration and magnitude of blood flow inside the repaired cuff and peritendinous tissues. Vascularity in the articular distal and bursal distal region of the repaired cuff at 1 month postoperatively increased significantly compared with that at the preoperative baseline (76 vs 5 AU, P = .0037; 92 vs 7 AU, P = .043). The vascularity peaked at 1 month after surgery in the bursal area within the cuff but at 2 months in the articular area. The vascularity in the articular proximal region of the repaired cuff was significantly lower than that in the bursal proximal (P = .0046), bursal distal (P = .0183), and articular distal regions (P = .0163) 1 month after surgery. Conclusion: Enhancement patterns in intratendinous tissue increased at 1 or 2 months postoperatively and decreased at 3 months. We found area-dependent differences in enhancement patterns inside the repaired cuff and peritendinous tissue. Clinical Relevance: Visualization of vascularization using contrast-enhanced ultrasound could help in deciding on an appropriate repair technique or on the form of postoperative rehabilitation after rotator cuff repair.
• Alterations of High-Mannose Type N-Glycosylation in Human and Mouse Osteoarthritis Cartilage

  Atsushi Urita, Tomoya Matsuhashi, Tomohiro Onodera, Hiroaki Nakagawa, Megumi Hato, Maho Amano, Naoki Seito, Akio Minami, Shin-Ichiro Nishimura, Norimasa Iwasaki

  ARTHRITIS AND RHEUMATISM 63 (11) 3428 - 3438 0004-3591 2011/11 [Refereed][Not invited]
   

  Objective. The process of N-glycosylation is involved in the pathogenesis of various diseases. However, little is known about the contribution of changes in N-glycans in osteoarthritis (OA). The aim of this study was to identify the alterations in N-glycans in human OA cartilage, to characterize the messenger RNA (mRNA) expression of N-glycan biosynthesis enzyme genes (N-glycogenes) in mouse articular chondrocytes during cartilage degradation, and to analyze the relationship between altered N-glycan patterns and mechanisms of cartilage degradation. Methods. Alterations in N-glycans were analyzed in human OA cartilage and degraded mouse cartilage by high-performance liquid chromatography and mass spectrometry. N-glycogene mRNA expression in mouse chondrocytes was measured using reverse transcription-polymerase chain reaction. To assess the relationship between the altered N-glycans and degradation of mouse cartilage, experiments involving either knockdown or overexpression of N-glycogenes were performed in mouse articular chondrocytes. Results. Alterations in high-mannose type N-glycans were observed in both human OA cartilage and degraded mouse cartilage. The expression of beta 1,2N-acetylglucosaminyltransferase I (GlcNAc-TI) mRNA, which converts high-mannose type N-glycans, was significantly increased in degraded mouse cartilage. Mouse chondrocytes with suppressed GlcNAc-TI expression had reduced levels of matrix metalloproteinase 13 (MMP-13) and ADAMTS-5 (aggrecanase 2) mRNA following stimulation with interleukin-1 alpha (IL-1 alpha). In contrast, mouse chondrocytes overexpressing GlcNAc-TI had increased levels of MMP-13 and ADAMTS-5 mRNA following stimulation with IL-1 alpha. Conclusion. These findings indicate that alterations in high-mannose type N-glycans and N-glycogenes in chondrocytes correlate with the release of MMP-13 and ADAMTS-5 during cartilage degradation. These findings suggest that N-glycans play a crucial role in the initiation and progression of OA.
• Non-vascularized bone graft with Herbert-type screw fixation for proximal pole scaphoid nonunion

  Hiroyuki Matsuki, Junichi Ishikawa, Norimasa Iwasaki, Shigeharu Uchiyama, Akio Minami, Hiroyuki Kato

  JOURNAL OF ORTHOPAEDIC SCIENCE 16 (6) 749 - 755 0949-2658 2011/11 [Refereed][Not invited]
   

  Since proximal pole fractures of the scaphoid are frequently overlooked, the poor vascularity in the proximal pole fragment often leads to nonunion. Vascularized bone grafts have been recently tested in cases with scaphoid proximal pole nonunion, but the indication for this treatment has not been well established. Alternatively, we have been treating such patients with a non-vascularized iliac bone graft and Herbert-type screw fixation with considerable success. The purpose of this investigation is to evaluate these cases retrospectively and clarify the surgical efficacy of our procedure. Between 1996 and 2009, 11 consecutive patients with proximal pole scaphoid nonunion were treated with a non-vascularized corticocancellous iliac bone graft and Herbert-type screw fixation. They were all male aged from 12 to 26 years. In two patients, avascular changes were recognized in the proximal pole in preoperative radiographs or MRI. Follow-up ranged from 12 to 76 months. Bone union was radiographically confirmed in all patients, who returned to their former activities without any complications. The period from operation to union ranged from 12 to 24 weeks. The mean Mayo modified wrist score was 76.4 points preoperatively and 91.4 points postoperatively, and was improved in all cases. A non-vascularized iliac bone graft with Herbert-type screw fixation obtained satisfactory clinical and radiographic results in cases with scaphoid proximal pole nonunion, regardless of the vascularity in the proximal fragment.
• Arthroscopic-Assisted Repair of Avulsed Triangular Fibrocartilage Complex to the Fovea of the Ulnar Head: A 2-to 4-Year Follow-up Study

  Norimasa Iwasaki, Kinya Nishida, Makoto Motomiya, Tadanao Funakoshi, Akio Minami

  ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY 27 (10) 1371 - 1378 0749-8063 2011/10 [Refereed][Not invited]
   

  Purpose: The objective of this study was to conduct a follow-up evaluation of an arthroscopic reattachment technique using an avulsed deep component of the triangular fibrocartilage complex (dc-TFCC) from the fovea of the distal ulna (ulnar fovea). Methods: A retrospective study was performed on a consecutive cohort of 12 patients who underwent arthroscopic reattachment of the avulsed dc-TFCC into the ulnar fovea over a 24-month period. The mean age was 31 years (range, 20 to 50 years). There were 6 men and 6 women. This technique anchors the avulsed portion of the dc-TFCC to the ulnar fovea by means of a repair suture passed through the created osseous tunnel from the ulnar neck to the foveal surface. Postoperative clinical and functional outcomes were quantitatively evaluated with the Modified Mayo Wrist Score. The Disabilities of the Arm, Shoulder and Hand questionnaire served to assess each patient's subjective outcome. A questionnaire regarding each patient's return to his or her previous job was also completed. Radiographic evaluation was based on computed tomography and magnetic resonance imaging examinations. Results: At the mean follow-up of 30 months, all patients had significant reduction of wrist pain. The mean Modified Mayo Wrist Score was 92.5 +/- 7.5, and all patients were rated as having excellent or good clinical results. The Disabilities of the Arm, Shoulder and Hand score significantly improved from 59.5 +/- 18.5 to 7.7 +/- 11.9 postoperatively (P < .0001). Of the 9 working patients, 7 returned to their previous work. Two patients had occasional extensor carpi ulnaris tendinitis after surgery. Magnetic resonance images at 12 weeks postoperatively showed findings indicating attachment of the triangular fibrocartilage complex (TFCC) to the fovea. Conclusions: Arthroscopic reattachment of the avulsed TFCC to the ulnar fovea by the described technique is a valid alternative for treating avulsion of the foveal TFCC insertion. Level of Evidence: Level IV, therapeutic case series.
• Computed Tomography Osteoabsorptiometry Alterations in Stress Distribution Patterns Through the Wrist After Radial Shortening Osteotomy for Kienbock Disease

  Hikaru Makabe, Norimasa Iwasaki, Tamotsu Kamishima, Naomi Oizumi, Shigeru Tadano, Akio Minami

  JOURNAL OF HAND SURGERY-AMERICAN VOLUME 36A (7) 1158 - 1164 0363-5023 2011/07 [Refereed][Not invited]
   

  Purpose The distribution pattern of subchondral bone density is considered to closely reflect the stress distribution across a joint under physiological loading conditions. Our purpose was to determine alterations in the distribution pattern of subchondral bone density across the distal articular surfaces of the radius and the ulna in patients with Kienbock disease after radial shortening. Methods We collected preoperative and postoperative computed tomography (CT) image data from 7 wrists of 7 patients who had undergone radial shortening for Kienbock disease. We measured the distribution of subchondral bone density through the distal articular surface of the radius and the ulna using a CT osteoabsorptiometry method. The obtained data were quantitatively assessed by calculating the high-density area ratio of the entire radiocarpal joint surface, scaphoid fossa, lunate fossa, and distal ulnar surface. Results At the mean postoperative period of 27 months, the mean high-density area ratio in the entire distal articular surface of the radius significantly decreased from 0.413 preoperatively to 0.141 postoperatively. The postoperative value in each fossa demonstrated a significant reduction from 0.253 to 0.096 in the scaphoid fossa and from 0.160 to 0.045 in the lunate fossa. No significant alteration in the value was found in the distal ulna at follow-up. Conclusions Our CT osteoabsorptiometry analysis suggests that the distribution of subchondral bone density in both scaphoid and lunate fossae notably decreases after radial shortening. This indicates that radial shortening unloads the lunate by reducing the actual stress across the distal articular surface of the radius in subjects with Kienbock disease. (J Hand Surg 2011;36A:1158-1164. Copyright (C) 2011 by the American Society for Surgery of the Hand. All rights reserved.)
• Long term results of early active extension and passive flexion mobilization following one-stage tendon grafting for neglected injuries of the flexor digitorum profundus in children

  Hiroshi Yamazaki, Hiroyuki Kato, Shigeharu Uchiyama, Norimasa Iwasaki, Hisamitsu Ishikura, Akio Minami

  JOURNAL OF HAND SURGERY-EUROPEAN VOLUME 36E (4) 303 - 307 1753-1934 2011/05 [Refereed][Not invited]
   

  We retrospectively reviewed the long-term clinical outcomes of one-stage flexor tendon grafting for seven paediatric patients with isolated flexor digitorum profundus (FDP) tendon injuries in Zones 1 or 2. Free tendon grafts (one palmaris longus tendons and six plantaris tendons) were used for reconstruction by Pulvertaft's procedure. The ages of the patients at reconstruction ranged from 7 to 15 (mean 11) years. The time from injury to surgery ranged from three to 78 (mean 25) months. These patients were followed up from 2.5 to 21 years after surgery (mean 8.5 years). All cases were started on early active extension and passive flexion according to the modified Kleinert mobilization for postoperative rehabilitation. The mean active motion after surgery was 49 degrees (range 20-80 degrees) for the DIP joints and 106 degrees (range 95-110 degrees) for the PIP joints. The total active range of motion was on average 237 degrees (range 195-275 degrees). Excellent results were achieved in five patients, good in one, and fair in one. Growth arrest of the distal phalanx was seen in one patient. One-stage flexor tendon grafting in paediatric patients combined with early controlled mobilization can be used to reconstruct neglected isolated ruptures of the FDP tendon with satisfactory results.
• Improved bioabsorbability of synthetic hydroxyapatite through partial dissolution-precipitation of its surface

  Xianjun Ding, Masahiko Takahata, Toshiyuki Akazawa, Norimasa Iwasaki, Yuichiro Abe, Miki Komatsu, Masaru Murata, Manabu Ito, Kuniyoshi Abumi, Akio Minami

  JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE 22 (5) 1247 - 1255 0957-4530 2011/05 [Refereed][Not invited]
   

  Even though synthetic hydroxyapatite (HAp) has a chemical composition similar to the mineral phase of bone, it is minimally absorbed and replaced by bone tissue. This could be because HAp is composed of compactly arranged apatite crystals with homogenously large grains. In this study, the surface and non-stoichiometry of the synthetic HAp crystals was modified by partial dissolution and precipitation (PDP) to improve bioabsorbability of HAp. In vitro cell culture demonstrated that more osteoclasts were activated on PDP-HAp compared with HAp. In vivo implantation using a rabbit bone defect model revealed that PDP-HAp was gradually degraded and was replaced by bone tissue. Consistent with the in vitro results, more osteoclasts were activated in PDP-HAp than in HAp, indicating that the former was absorbed through the stimulation of osteoclastic activity. These results suggest that the PDP technique may have clinical utility for modifying synthetic HAp for use as superior bone graft substitutes.
• Long-Term Stress Distribution Patterns Across the Elbow Joint in Baseball Players Assessed by Computed Tomography Osteoabsorptiometry

  Daisuke Mommma, Norimasa Iwasaki, Naomi Oizumi, Hiroki Nakatsuchi, Tadanao Funakoshi, Tamotsu Kamishima, Shigeru Tadano, Akio Minami

  AMERICAN JOURNAL OF SPORTS MEDICINE 39 (2) 336 - 341 0363-5465 2011/02 [Refereed][Not invited]
   

  Background: The distribution pattern of subchondral bone density is considered to highly reflect the stress distribution across a joint under long-term physiologic loading conditions. Therefore, the biomechanical characteristics over the elbow joint surface under long-term loading conditions of baseball pitching can be determined by a measurement of the distribution pattern. Hypothesis: Stress distribution over the elbow joint surface alters with long-term pitching activities. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Computed tomography (CT) imaging data from the dominant elbow of 10 nonthrowing athletes, 10 college baseball fielders, and 10 college baseball pitchers were collected for the current analysis. The distribution of subchondral bone density through the distal articular surface of the humerus was measured using a CT osteoabsorptiometry method. The quantitative analysis of the obtained data focused on location and size of the maximum density area at the articular surface. Results: The maximum density area of subchondral bone across the articular surface of the distal humerus was located in the posterior part of the trochlea in all subjects. This maximum density area was significantly increased in the pitcher group, compared with that in other groups. Additionally, the pitcher group demonstrated a significant distribution of the maximum density area in the anterior part of the capitellum. Conclusion: The results indicate that actual stress across the elbow is concentrated in the posterior part of the trochlea in humans. Baseball pitching may produce excessive or repetitive stress against not only this part, but also the anterior part of the capitellum. The majority of osteochondritis dissecans lesions affecting the elbow are found in the anterior part of the capitellum in throwing athletes. The results may support an important role of mechanical conditions in the cause of elbow osteochondritis dissecans.
• Rupture of the flexor digitorum profundus tendon after injections of insoluble steroid for a trigger finger

  Katsuhisa Yamada, Tatsuya Masuko, Norimasa Iwasaki

  JOURNAL OF HAND SURGERY-EUROPEAN VOLUME 36E (1) 77 - 78 1753-1934 2011/01 [Refereed][Not invited]
  
• COVERING THE BELOW-KNEE AMPUTATION STUMP WITH THE PEDICLED DORSALIS PEDIS FLAP FROM THE IPSILATERAL FOOT: A CASE REPORT

  Makoto Motomiya, Norimasa Iwasaki, Yasushi Tazaki, Kinya Nishida, Tadanao Funakoshi, Akio Minami

  MICROSURGERY 31 (2) 155 - 158 0738-1085 2011 [Refereed][Not invited]
   

  It is important to preserve the length, appropriate durable skin, and sensation of the stump when performing below-knee amputation to achieve functional ambulation with a prosthesis. There are many reports of reconstruction procedures using microvascular surgery to preserve the optimum length of the amputation stump for prosthesis; however, free tissue reconstruction is necessary to accompany with the donor site morbidity. In this report, we describe our experience with a below-knee amputation and stump covering using the pedicled dorsalis pedis flap from the no longer usable foot in the case of a severe osteomyelitis of a lower extremity after highly contaminated Gustilo type IIIB fracture. We achieved a well-healed amputated stump with enough length for a prosthesis and for protective sensation. The pedicled dorsalis pedis flap is easily elevated without microvascular anastomosis and is one useful option for the reconstruction of the below-knee amputated stump in the specific case. (C) 2010 Wiley-Liss, Inc. Microsurgery 31:155-158, 2011.
• Clinical outcomes of excision arthroplasty for Kienbock's disease.

  Matsuhashi T, Iwasaki N, Kato H, Minami M, Minami A

  Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 16 (3) 277 - 282 0218-8104 2011 [Refereed][Not invited]
   

  We have carried out a replacement of the lunate in 12 patients with advanced Kienböck's disease, with excision of the lunate and insertion of an iliac bone flap wrapped into palmaris longus. The aims of this study were to determine the effect of this procedure for advanced Kienböck's disease. At a mean follow-up period of 45.3 months, the mean clinical score was excellent in all cases. Radiographically, progression of osteoarthritis (OA) in the radiocarpal joint was found in two patients. At follow-up, the X-ray findings indicated a reduced of osseous core in four patients. On the other hand, carpal height ratio showed no significant change at follow-up. Excision arthroplasty using a tendon ball with osseous core for advanced Kienböck's disease leads to OA progression in some cases. However, clinical results were excellent in all cases. Therefore, this current study provides effective therapeutic procedure for advanced Kienböck's disease.
• Arthroscopic debridement with continuous irrigation for septic arthritis of the shoulder joint

  Tomoya Matsuhashi, Naoki Suenaga, Naomi Oizumi, Norimasa Iwasaki, Akio Minami

  European Orthopaedics and Traumatology 2 (3-4) 87 - 92 1867-4569 2011 [Refereed][Not invited]
   

  Purpose: The purpose of this study was to investigate the outcome of arthroscopic debridement with continuous irrigation in patients with septic arthritis of the shoulder joint. Methods: Ten patients (four men, six women) with septic arthritis of the shoulder joint were treated with a combination of arthroscopic debridement and continuous irrigation. All patients were followed for a minimum of 4 years. The average age was 61. 7 years with a range of 25 to 86. The etiology of infection was determined to be a subacromial injection in six cases, EMG needle puncture in one, hematogenous in two, and unknown in one case. Causative bacteria, follow-up period, recurrence, shoulder pain, University of California, Los Angeles (UCLA) shoulder score, and radiographic findings were evaluated. Result: Staphylococcus aureus was cultured in six cases, and Staphylococcus epidermidis, in four cases. The average follow-up period was 103.3 months with a range of 48 to 199. The infection was eradicated completely with a single arthroscopic debridement with continuous irrigation in nine patients. One patient required a second operation. In all patients, severe pain before operation improved. The average UCLA shoulder score increased from 5.7 points prior to the operation to a post-operation score of 26.4 points. In standard radiographic findings, five cases had aggravated osteoarthritis in the affected joint. Conclusion: This study shows that arthroscopic debridement with continuous irrigation for septic arthritis of the shoulder joint improves shoulder pain, functional scores, and subjective outcome and prevents recurrence in many cases. © 2011 EFORT.
• Penetration of linezolid into rabbit intervertebral discs and surrounding tissues

  Miki Komatsu, Masahiko Takahata, Mitsuru Sugawara, Yoh Takekuma, Takashi Kato, Manabu Ito, Yuichiro Abe, Tohru Irie, Norimasa Iwasaki, Akio Minami

  EUROPEAN SPINE JOURNAL 19 (12) 2149 - 2155 0940-6719 2010/12 [Refereed][Not invited]
   

  Linezolid belongs to a new class of synthetic antimicrobial agent that is effective for a variety of methicillin-resistant Staphylococcus aureus (MRSA) infections including bone and joint MRSA infections, but the effectiveness of linezolid for the treatment of MRSA spine infection remains controversial. In this study, we investigated the diffusion of linezolid or vancomycin into normal rabbit spinal tissues to determine the adequacy of linezolid for the treatment of spinal infection. The penetration efficacy of linezolid into the annulus fibrosus, nucleus pulposus, and vertebral bone (10, 8, and 10%, respectively) was lower than that of vancomycin (27, 11, and 14%, respectively). The penetration efficacy of linezolid into the bone marrow and iliopsoas muscle (88 and 84%, respectively), however, was higher than that of vancomycin (67 and 9%, respectively). These results suggest that linezolid is inadequate for the treatment of spine infection limited to the intervertebral disc, but may be effective for the treatment of infection extending into the muscle and bone marrow, such as in vertebral osteomyelitis, iliopsoas abscess, and postsurgical infection.
• In Vivo Visualization of Vascular Patterns of Rotator Cuff Tears Using Contrast-Enhanced Ultrasound

  Tadanao Funakoshi, Norimasa Iwasaki, Tamotsu Kamishima, Mutsumi Nishida, Yoichi Ito, Makoto Kondo, Akio Minami

  AMERICAN JOURNAL OF SPORTS MEDICINE 38 (12) 2464 - 2471 0363-5465 2010/12 [Refereed][Not invited]
   

  Background: Hypoxia and decreased blood supply have been proposed as risks for tendon rupture. Visualization of the vascularity of intact and torn rotator cuffs would be useful for improving treatments for rotator cuff tear. Purpose: To assess vascularity inside a tendon or an adjacent rotator cuff insertion point in patients differing in age and extent of damage to the tendon. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Ten volunteers (all men) and 15 patients (10 men, 5 women) consented to participate in the study. Contrast agent for enhanced ultrasound was injected intravenously. Enhanced ultrasound images of the torn cuff and the contralateral shoulder were recorded for 1 minute. Four small regions of interest, the articular and bursal sides of the tendon and the medial and lateral sides of the bursa, were studied in all shoulders. Results: There was a significant decrease in blood flow in the intratendinous region in elderly subjects compared with young subjects, but age had no effect on blood flow in bursal tissue. Blood flow in ruptured rotator cuffs did not differ from that in intact rotator cuffs. The intraclass correlation coefficient for intraobserver reproducibility was 0.82 (95% confidence interval: 0.77-0.86). Conclusions: The findings of this investigation were the hypovascular pattern in intratendinous tissue compared with the subacromial bursa, the age-related decrease in intratendinous vascularity, and the hypovascular pattern in the tendon, regardless of rupture of the tendon. Clarification of vascular patterns inside or around the torn ends of a rotator cuff will assist in the development of successful treatments for torn rotator cuffs.
• Transplantation of tissue-engineered cartilage for the treatment of osteochondritis dissecans in the elbow: Outcomes over a four-year follow-up in two patients

  Norimasa Iwasaki, Shintarou Yamane, Kinya Nishida, Tatsuya Masuko, Tadanao Funakoshi, Tamotsu Kamishima, Akio Minami

  JOURNAL OF SHOULDER AND ELBOW SURGERY 19 (8) E1 - E6 1058-2746 2010/12 [Refereed][Not invited]
  
• A cellular implantation system using an injectable ultra-purified alginate gel for repair of osteochondral defects in a rabbit model

  Tatsuya Igarashi, Norimasa Iwasaki, Yasuhiko Kasahara, Akio Minami

  JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 94A (3) 844 - 855 1549-3296 2010/09 [Refereed][Not invited]
   

  We developed a novel cellular implantation system using an in situ forming ultra-purified alginate gel with quite low endotoxity. The aims of this study were to determine the superiority of chondrogenic potential of bone marrow stromal cells (BMSCs) cultured in the purified alginate gel compared with a commercial grade gel, and to assess reparative tissues treated with BMSCs implanted using the developed system into cartilage defects in rabbit knees. The effects of each alginate gel on cellular proliferation and chondrogenesis of rabbit BMSCs were determined by in vitro assessments. Using our purified alginate gel, a novel vehicle system for injecting BMSCs into osteochondral defects without periosteal patch was successfully established in this animal models. The in vitro analyses demonstrated that the purification of alginate significantly enhanced the cellular proliferation and chondrogenic differentiation of BMSCs. The in vivo assessments suggested that the implantation of BMSCs with the developed system using the purified alginate gel histologically and mechanically improved the reparative tissue of osteochondral defects. This system using the purified alginate gel shows the clinical potential for arthroscopically injectable implantation of BMSCs for the treatment of cartilaginous lesions. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 94A: 844-855, 2010
• Congenital Dorsally Curving Deformity of the Distal Phalanx of the Little Finger: Case Report

  Norimasa Iwasaki, Takashi Terashima, Akio Minami, Hiroyuki Kato

  JOURNAL OF HAND SURGERY-AMERICAN VOLUME 35A (9) 1502 - 1505 0363-5023 2010/09 [Refereed][Not invited]
   

  A deformity of the distal phalanx of the little finger with a curvature in the dorsal direction, referred to as a reverse Kirner's deformity, is extremely rare. We present a case of such a deformity found in a 6-year-old girl. A successful result was obtained after double corrective osteotomy of the distal phalanx at 12 years of age. (J Hand Surg 2010;35A:1502-1505. (C) 2010 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.)
• Autologous Osteochondral Mosaicplasty for Osteochondritis Dissecans of the Elbow in Teenage Athletes Surgical Technique

  Norimasa Iwasaki, Hiroyuki Kato, Jyunichi Ishikawa, Tatsuya Masuko, Tadanao Funakoshi, Akio Minami

  JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME 92A 208 - 216 0021-9355 2010/09 [Refereed][Not invited]
   

  BACKGROUND: Although autologous osteochondral mosaicplasty is widely used as a procedure for osteochondritis dissecans lesions, the effectiveness of this procedure in elbow lesions remains unclear. Our aim was to clarify the surgical efficacy of mosaicplasty for teenage athletes with advanced lesions of capitellar osteochondritis dissecans. METHODS: From 2001 to 2006, nineteen teenage male patients who were competitive athletes and had advanced lesions of capitellar osteochondritis dissecans underwent mosaicplasties. The mean age of the patients was 14.2 years. The surgical technique involved obtaining small-sized cylindrical osteochondral grafts with a mean diameter of 3.5 mm from the lateral periphery of the femoral condyle at the level of the patellofemoral joint and transplanting the grafts (mean, 3.3 grafts) to prepared osteochondral defects. The patients were evaluated clinically and radiographically at a mean of forty-five months after surgery. RESULTS: Eighteen patients were free from elbow pain, and one had mild pain occasionally. The mean total arc of elbow motion and standard deviation increased significantly from 112 degrees +/- 17 degrees preoperatively to 128 degrees +/- 12 degrees postoperatively (p < 0.005). The mean clinical score described by Timmerman and Andrews (with a maximum of 200 points) improved significantly from 131 +/- 23 points preoperatively to 191 +/- 15 points postoperatively (p < 0.0001). All patients except one had an excellent or good clinical result. All donor knees were graded as excellent on the basis of the Lysholm knee scoring system. All patients except two returned to a competitive level of the sport they had previously played. Neither loose-body formation nor secondary osteoarthritic changes were found in any patient. CONCLUSIONS: The current midterm results indicate that mosaicplasty can provide satisfactory clinical outcomes for teenage athletes with advanced capitellar osteochondritis dissecans lesions. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. ORIGINAL ABSTRACT CITATION: "Autologous Osteochondral Mosaicplasty for Osteochondritis Dissecans of the Elbow in Teenage Athletes" (2009;91:2359-66).
• Effect of Selective Estrogen Receptor Modulator/Raloxifene Analogue on Proliferation and Collagen Metabolism of Tendon Fibroblast

  Toru Irie, Masahiko Takahata, Tokifumi Majima, Yuichiro Abe, Miki Komatsu, Norimasa Iwasaki, Akio Minami

  CONNECTIVE TISSUE RESEARCH 51 (3) 179 - 187 0300-8207 2010/06 [Refereed][Not invited]
   

  The selective estrogen receptor modulator raloxifene is therapeutically beneficial for postmenopausal connective tissue degradation, such as osteoporosis, vascular sclerosis, and dermal degradation; however, the effects of raloxifene on postmenopausal tendon metabolism have not been clarified. In this study, we investigated the effects of raloxifene analogue (LY117018) on cell proliferation and collagen metabolism using cultured rat Achilles tendon fibroblasts. 17 beta-Estradiol (E(2); 10<SU-11</SU-10<SU-9</SU M) and LY117018 (10<SU-9</SU-10<SU-7</SU M) had no significant effects on tendon fibroblast proliferation, based on a BrdU (5-bromo-2'-deoxyuridine) incorporation assay (24 hr) and a WST-8 colorimetric assay (2 or 6 days). Neither E(2) nor LY117018 significantly altered the expression of type I collagen, which is a main component of the tendon extracellular matrix (ECM), whereas both E(2) and LY117018 significantly increased the expression of matrix metalloproteinase (MMP)-13, which is responsible for tendon collagen degradation in rat. Also, both E(2) and LY117018 increased the expression of type III collagen and elastin, which are minor components of tendon ECM, but are considered to govern the elastic properties of tendons. These changes in collagen and MMP induced by either E(2) or LY117018 were attenuated by the estrogen receptor alpha blocker ICI 182,780. The results of this study suggest that postmenopausal estrogen deficiency might downregulate tendon collagen turnover and decrease tendon elasticity. Further, raloxifene treatment might restore these changes to premenopausal levels.</.
• Bone induction of human tooth and bone crushed by newly developed automatic mill

  Murata Masaru, Akazawa Toshiyuki, Takahata Masahiko, Ito Manabu, Tazaki Junichi, Hino Jun, Nakamura Katsuo, Iwasaki Norimasa, Shibata Takanori, Arisue Makoto

  JOURNAL OF THE CERAMIC SOCIETY OF JAPAN 118 (1378) 434 - 437 1882-0743 2010/06 [Refereed][Not invited]
  
• Characterization of microstructure and bio-absorption of the hydroxyapatite ceramics modified by a partial dissolution-precipitation technique using supersonic treatment

  Akazawa Toshiyuki, Murata Masaru, Takahata Masahiko, Ding Xianjun, Abe Yuichiro, Nakamura Katsuo, Hino Jun, Tazaki Junichi, Ito Katsutoshi, Ito Manabu, Iwasaki Norimasa, Minami Akio, Nakajima Takehiko, Sakamoto Michiko

  JOURNAL OF THE CERAMIC SOCIETY OF JAPAN 118 (1378) 535 - 540 1882-0743 2010/06 [Refereed][Not invited]
  
• Analysis of the Expression and Function of BRINP Family Genes During Neuronal Differentiation in Mouse Embryonic Stem Cell-Derived Neural Stem Cells

  Michiyo Terashima, Miwako Kobayashi, Makoto Motomiya, Nobuo Inoue, Tetsu Yoshida, Hideyuki Okano, Norimasa Iwasaki, Akio Minami, Ichiro Matsuoka

  JOURNAL OF NEUROSCIENCE RESEARCH 88 (7) 1387 - 1393 0360-4012 2010/05 [Refereed][Not invited]
   

  We previously identified a novel family of genes, BRINP1, 2, and 3, that are predominantly and widely expressed in both the central nervous system (CNS) and peripheral nervous system (PNS). In the present study, we analyzed the expression pattern of three BRINP genes during differentiation of mouse embryonic stem (ES) cell-derived neural stem cells (NSCs) and their effects on the cell-cycle regulation of NSCs. While there was no significant expression of any BRINP-mRNA expressed in mouse ES cells, BRINP 1 and 2-mRNAs was expressed at high levels in the ES cell-derived neural stem cells. Upon differentiation into neuronal cells in the presence of retinoic acid and BDNF, all three types of BRINP-mRNA were induced with a similar time course peaking at day three of treatment. Upon differentiation into astroglial cells in the presence of serum, BRINP1-mRNA was slightly up-regulated, while BRINP2- and BRINP3-mRNAs were almost abolished in the astrocytes. While 69.2, 26.1, and 7.7% of cells in a population of NSCs in the exponentially growing phase were in the G1, S and G2 phases, respectively, over-expression of any one of the three BRINP genes completely abolished cells in the G2 phase and significantly reduced the cells in S phase to 11.8-13.8%. Based on these results, the physiological roles of induced BRINP genes in the cell-cycle suppression of terminally differentiated post-mitotic neurons are discussed. (C) 2009 Wiley-Liss, Inc.
• Threshold in Stage-specific Embryonic Glycotypes Uncovered by a Full Portrait of Dynamic N-Glycan Expression during Cell Differentiation

  Maho Amano, Misa Yamaguchi, Yasuhiro Takegawa, Tadashi Yamashita, Michiyo Terashima, Jun-ichi Furukawa, Yoshiaki Miura, Yasuro Shinohara, Norimasa Iwasaki, Akio Minami, Shin-ichiro Nishimura

  MOLECULAR & CELLULAR PROTEOMICS 9 (3) 523 - 537 1535-9476 2010/03 [Refereed][Not invited]
   

  Although various glycoforms appear to participate independently in multiple molecular interactions in cellular adhesion that contribute to embryogenesis and organogenesis, a full portrait of the glycome diversity and the effect of the structural variations of cellular glycoforms on individual cell stages in proliferation and differentiation remain unclear. Here we describe a novel concept for the characterization of dynamic glycoform alteration during cell differentiation by means of "glycoblotting-based cellular glycomics," the only method allowing for rapid and quantitative glycan analysis. We demonstrated that processes of dynamic cellular differentiation of mouse embryonic carcinoma cells, P19CL6 and P19C6, and mouse embryonic stem cells into cardiomyocytes or neural cells can be monitored and characterized quantitatively by profiling entire N-glycan structures of total cell glycoproteins. Whole N-glycans enriched and identified by the glycoblotting method (67 glycans for P19CL6, 75 glycans for P19C6, and 72 glycans for embryonic stem cells) were profiled and bar-coded quantitatively with respect to the ratio of subgroups composed of characteristic glycoforms, namely glycotypes. Molecular & Cellular Proteomics 9: 523-537, 2010.
• Brown tumour of the wrist with primary hyperparathyroidism

  Norimasa Iwasaki, Akio Minami

  JOURNAL OF HAND SURGERY-EUROPEAN VOLUME 35E (1) 71 - 72 1753-1934 2010/01 [Refereed][Not invited]
  
• Elderly kendo (Japanese fencing) player with Kienböck's disease in one wrist and Preiser's disease in the other wrist: a case report.

  Iwasaki N, Masuko T, Funakoshi T, Minami A

  Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 15 (1) 47 - 51 0218-8104 2010 [Refereed][Not invited]
   

  Elderly patients suffering from avascular necrosis of a carpal bone in both wrists are extremely rare. We report a case of an elderly kendo (Japanese fencing) competitor who sustained Preiser's disease in the left hand following the occurrence of Kienböck's disease in the right hand. The current case demonstrates the importance of raising awareness of these diseases as potential sports-related problems in the elderly.
• Palmar subluxation of the thumb carpometacarpal joint following the median nerve recurrent branch injury.

  Matsuhashi T, Iwasaki N, Nishida K, Motomiya M, Minami A

  Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 15 (1) 53 - 55 0218-8104 2010 [Refereed][Not invited]
   

  To our knowledge, the combination of a palmar subluxation of the thumb carpometacarpal (CMC) joint with low median nerve deficit followed by the recurrent branch injury is extremely rare. We present a case of the subluxation of the thumb CMC joint with low median nerve deficit.
• Giant-cell tumor of the distal ulna treated by wide resection and ulnar support reconstruction: A case report

  Akio Minami, Norimasa Iwasaki, Kinya Nishida, Makoto Motomiya, Katsuhisa Yamada, Daisuke Momma

  Case Reports in Medicine 2010 871278 - 871278 1687-9635 2010 [Refereed][Not invited]
   

  Giant-cell tumor of bone occurred in the distal end of the ulna is extremely uncommon. A 23-year-old male had a giant-cell tumor occurred in the distal end of the ulna. After wide resection of the distal segment of the ulna including giant-cell tumor, ulnar components of the wrist joint were reconstructed with modified Sauvé-Kapandji procedure using the iliac bone graft, preserving the triangular fibrocartilage complex and ulnar collateral ligament in order to maintain ulnar support of the wrist, and the proximal stump of the resected ulna was stabilized by tenodesis using the extensor carpi ulnaris tendon. One year after operation, the patient's wrist was pain-free and had a full range of motion. Postoperative X-rays showed no abnormal findings including recurrence of the giant-cell tumor and ulnar translation of the entire carpus. The stability of the proximal stump of the distal ulna was also maintained. Copyright © 2010 Akio Minami et al.
• Sequential Alterations in Magnetic Resonance Imaging Findings After Autologous Osteochondral Mosaicplasty for Young Athletes With Osteochondritis Dissecans of the Humeral Capitellum

  Norimasa Iwasaki, Hiroyuki Kato, Tamotsu Kamishima, Akio Minami

  AMERICAN JOURNAL OF SPORTS MEDICINE 37 (12) 2349 - 2354 0363-5465 2009/12 [Refereed][Not invited]
   

  Background: The goal of osteochondral mosaicplasty (mosaicplasty) against osteochondritis dissecans of the humeral capitellum (capitellar OCD) is to allow patients to return to their sports activities without functional disturbance of the affected elbow. Consequently, the rehabilitation protocol and the interval before returning to sports activities must be established. Although surgeons need this type of data for establishing sequential alterations of grafts in the elbow, no such data have been published. Hypothesis: The findings of magnetic resonance imaging (MRI) improve with increasing time after mosaicplasty for capitellar OCD. Study Design: Case series; Level of evidence, 4. Methods: Ten young male athletes with advanced lesions of capitellar OCD, treated with mosaicplasties, underwent MRI scans at 3, 6, and 12 months, postoperatively. The surgical technique involved obtaining small-sized cylindrical osteochondral grafts from the lateral periphery of the femoral condyle at the level of the patellofemoral joint and transplanting them to the capitellar lesion. The MRI findings were semiquantitatively assessed according to the scoring system of Henderson et al (4, normal; 16, no repair). Results: At 12 months, all patients returned to their competitive level of sports without any disturbances of the operated elbow. Fluid surrounding the graft was found in all patients at 3 months and 4 patients at 6 months. The grafts were all well seated within the recipient sites, with no MRI evidence of graft loosening at 12 months. The overall MRI scores significantly improved from 3 to 12 months. Conclusion: The MRI findings indicate that the graft incorporation to the surrounding tissues occurs around or after 6 months, postoperatively. This finding suggests that rehabilitation precautions be taken for up to 6 months after mosaicplasty for young athletes with capitellar OCD.
• Autologous Osteochondral Mosaicplasty for Osteochondritis Dissecans of the Elbow in Teenage Athletes

  Norimasa Iwasaki, Hiroyuki Kato, Jyunichi Ishikawa, Tatsuya Masuko, Tadanao Funakoshi, Akio Minami

  JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME 91A (10) 2359 - 2366 0021-9355 2009/10 [Refereed][Not invited]
   

  Background: Although autologous osteochondral mosaicplasty is widely used as a procedure for osteochondritis dissecans lesions, the effectiveness of this procedure in elbow lesions remains unclear. Our aim was to clarify the surgical efficacy of mosaicplasty for teenage athletes with advanced lesions of capitellar osteochondritis dissecans. Methods: From 2001 to 2006, nineteen teenage male patients who were competitive athletes and had advanced lesions of capitellar osteochondritis dissecans underwent mosaicplasties. The mean age of the patients was 14.2 years. The surgical technique involved obtaining small-sized cylindrical osteochondral grafts with a mean diameter of 3.5 mm from the lateral periphery of the femoral condyle at the level of the patellofemoral joint and transplanting the grafts (mean, 3.3 grafts) to prepared osteochondral defects. The patients were evaluated clinically and radiographically at a mean of forty-five months after surgery. Results: Eighteen patients were free from elbow pain, and one had mild pain occasionally. The mean total arc of elbow motion and standard deviation increased significantly from 112 degrees +/- 17 degrees preoperatively to 128 degrees +/- 12 degrees postoperatively (p < 0.005). The mean clinical score described by Timmerman and Andrews (with a maximum of 200 points) improved significantly from 131 +/- 23 points preoperatively to 191 +/- 15 points postoperatively (p < 0.0001). All patients except one had an excellent or good clinical result. All donor knees were graded as excellent on the basis of the Lysholm knee scoring system. All patients except two returned to a competitive level of the sport they had previously played. Neither loose-body formation nor secondary osteoarthritic changes were found in any patient. Conclusions: The current midterm results indicate that mosaicplasty can provide satisfactory clinical outcomes for teenage athletes with advanced capitellar osteochondritis dissecans lesions.
• Intravenous pyogenic granuloma of the finger

  Tamotsu Kamishima, Akiko Hasegawa, Kanako C. Kubota, Naomi Oizumi, Norimasa Iwasaki, Akio Minami, Satoru Sasaki, Yuhei Yamamoto, Tokuhiko Omatsu, Yuya Onodera, Satoshi Terae, Hiroki Shirato

  JAPANESE JOURNAL OF RADIOLOGY 27 (8) 328 - 332 1867-1071 2009/10 [Refereed][Not invited]
   

  Intravenous pyogenic granuloma is a rare solitary form of lobular capillary hemangioma that usually occurs in the veins of the neck and upper extremities. We report two cases of intravenous pyogenic granuloma localized in the finger, giving details of the magnetic resonance imaging (MRI) findings. These two cases had similar locations in fingers and identical MRI findings. The differential diagnoses of this rare entity are also discussed.
• Arthroscopically Assisted Reattachment of Avulsed Triangular Fibrocartilage Complex to the Fovea of the Ulnar Head

  Norimasa Iwasaki, Akio Minami

  JOURNAL OF HAND SURGERY-AMERICAN VOLUME 34A (7) 1323 - 1326 0363-5023 2009/09 [Refereed][Not invited]
   

  Triangular fibrocartilage complex (TFCC) insertion into the fovea of the distal ulna plays a crucial role in stabilizing the distal radioulnar joint. Consequently, surgical reattachment against avulsion of the foveal TFCC insertion is required to stabilize the distal radioulnar joint. However, because of technical difficulties, no arthroscopic procedure for such a lesion has currently been established. We present a new technique for arthroscopic reattachment of the avulsed TFCC into the fovea. An osseous tunnel 2.9 mm in diameter is created from the ulnar neck to the foveal surface. Under arthroscopic guidance, a nonabsorbable suture passed into a 21-gauge needle is placed into the TFCC through the osseous tunnel. The avulsed portion of the TFCC is anchored to the fovea by means of a repair suture passed through the TFCC. To achieve normal tension of the TFCC, the suture is tied onto the periosteum around the proximal entrance of the osseous tunnel. Our arthroscopic technique is relatively simple and has great advantages for progressive healing at the attachment site between the TFCC and the fovea. (J Hand Surg 2009;34A:1323-1326. Copyright (C) 2009 by the American Society for Surgery of the Hand. All rights reserved.)
• Radial Overgrowth After Radial Shortening Osteotomies for Skeletally Immature Patients With Kienbock's Disease

  Tomoya Matsuhashi, Norimasa Iwasaki, Naomi Oizumi, Hiroyuki Kato, Michio Minami, Akio Minami

  JOURNAL OF HAND SURGERY-AMERICAN VOLUME 34A (7) 1242 - 1247 0363-5023 2009/09 [Refereed][Not invited]
   

  Purpose We hypothesized that radial shortening osteotomy (radial shortening) for skeletally immature patients with Kienbock's disease would induce overgrowth of the radius. The purpose of this study was to determine the effect of radial shortening on radial growth in skeletally immature patients with Kienbock's disease and to clarify the relationship between the postoperative growth alterations and the clinical results. Methods Eight wrists of 8 skeletally immature patients with Kienbock's disease were treated with radial shortening. There were 3 boys and 5 girls, ranging in age from 11 to 18 (mean, 14) years old. All patients presented with open physis and negative ulnar variance. The length of the radial shortening equaled the amount of negative ulnar variance. Clinical assessment was based on the modified Nakamura scoring system. Radiographic assessment, including Lichtman's stages, ulnar variance, carpal height ratio, radial inclination, and volar tilt, was performed before surgery, immediately after surgery, and at follow-up. A difference in ulnar variance of more than 2 mm between these 3 measurements was considered to be overgrowth. Statistical comparisons were performed using paired t-tests. Results At a mean follow-up period of 69 months, the mean clinical score was 19.7 of 21. maximum points, with all wrists rated as excellent. Radiographically, no progression of Lichtman stage was found in any patient. At follow-up, the x-ray and magnetic resonance imaging findings indicated lunate revascularization in all patients. Four of the 8 had overgrowth in the operated radius. On the other hand, other radiographic parameters showed no significant changes at follow-up. The occurrence of postoperative radial overgrowth did not notably affect the clinical scores. Conclusions The current results suggest the probability of overgrowth of the radius in skeletally immature patients with Kienbock's disease treated with radial shortening. The postoperative radial overgrowth after this osteotomy had no effect on clinical and other radiographic outcomes. (J Hand Surg 2009;34A:1242-1247. (C) 2009 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.)
• Local Upregulation of Stromal Cell-Derived Factor-1 After Ligament Injuries Enhances Homing Rate of Bone Marrow Stromal Cells in Rats

  Kazumi Shimode, Norimasa Iwasaki, Tokifumi Majima, Tadanao Funakoshi, Naohiro Sawaguchi, Tomohiro Onodera, Akio Minami

  TISSUE ENGINEERING PART A 15 (8) 2277 - 2284 1937-3341 2009/08 [Refereed][Not invited]
   

  In the present study the local expression of stromal cell-derived factor-1 (SDF-1) after ligament injury and correlated change in the homing rate of systemically induced bone marrow stromal cells (BMSCs) to the injured site were clarified using a rat medial collateral ligament (MCL) injury model. SDF-1 was temporarily upregulated peaking at 2 weeks after injury. Correlated with the alteration in SDF-1 expression, the homing rate of systemically induced BMSCs was temporarily upregulated peaking at 2-4 weeks after injury. The SDF-1 expression in the MCL seems to play a crucial role in cell homing. In addition, SDF-1 did not influence the BMSCs behavior in vitro in terms of the proliferation, adhesivity, and expression of ligament fibroblast markers. The cell-based therapy for ligament and tendon injury with reference to local expression of SDF-1 may be one of the available applications.
• Down-Regulation of Cathepsin K in Synovium Leads to Progression of Osteoarthritis in Rabbits

  Daisuke Takahashi, Norimasa Iwasaki, Shigeyuki Kon, Yuichiro Matsui, Tokifumi Majima, Akio Minami, Toshimitsu Uede

  ARTHRITIS AND RHEUMATISM 60 (8) 2372 - 2380 0004-3591 2009/08 [Refereed][Not invited]
   

  Objective. The hypothesis of this study was that synovial factors playing a pivotal role in the pathogenesis of osteoarthritis (OA) and thus gene expression in the synovium would be altered at the initial stage of OA. The aims of this study were to identify the candidate genes in synovium related to OA initiation, to evaluate cartilage degeneration after knockdown of the gene using small interfering RNA (siRNA) gene silencing in the knee joints at the initial stage of OA, and to determine the potential role of the knocked-down gene in OA initiation. Methods. Genes overexpressed in synovium at the initial stage of disease in a rabbit model of anterior cruciate ligament transection (ACLT)-induced OA were identified using the suppression subtractive hybridization technique and differential screening. Candidate gene expression in the synovium of the knees of rabbits with OA was manipulated with electroporation-assisted siRNA transduction 4 times before and after operation. Four weeks after surgery, histologic analysis was performed. Results. Cathepsin K gene and protein expression was significantly up-regulated in synovium at the initial stage of OA in rabbits. Down-regulation of cathepsin K in synovium at the initial stage of OA significantly accelerated cartilage degeneration. Conclusion. These results indicate that cathepsin K plays a protective role in cartilage degeneration at the initial stage of OA. We believe that the current results obtained from models of the early phase of OA will provide useful information for developing a novel strategy to prevent disease progression.
• Accelerated Development of Aging-Associated and Instability-Induced Osteoarthritis in Osteopontin-Deficient Mice

  Yuichiro Matsui, Norimasa Iwasaki, Shigeyuki Kon, Daisuke Takahashi, Junko Morimoto, Yutaka Matsui, David T. Denhardt, Susan Rittling, Akio Minami, Toshimitsu Uede

  ARTHRITIS AND RHEUMATISM 60 (8) 2362 - 2371 0004-3591 2009/08 [Refereed][Not invited]
   

  Objective. To investigate the role of osteopontin (OPN) in the development of osteoarthritis (OA) under in vivo and in vitro conditions. Methods. Both instability-induced and aging-associated OA models were generated using OPN-deficient (OPN(-/-)) and control wild-type (WT) mice. An in vitro cartilage degradation model was also used, to evaluate the effect of OPN on proteoglycan loss from joint cartilage. Results. OPN deficiency exacerbated both aging-associated and instability-induced OA. Both structural changes and an increased loss of proteoglycan from cartilage tissue were augmented in the absence of OPN. OPN deficiency also led to the induction of matrix metalloproteinase 13 (MMP-13), which degrades a major component of the cartilage matrix protein type II collagen. Both the loss of proteoglycan and the induction of the collagen-degrading enzyme MMP-13 facilitated the development of OA. Conclusion. OPN plays a pivotal role in the progression of both instability-induced and aging-associated spontaneous OA. OPN is a critical intrinsic regulator of cartilage degradation via its effects on MMP-13 expression and proteoglycan loss.
• Anconeus muscle flap for the treatment of soft tissue defects over the olecranon after total elbow arthroplasty

  Kinya Nishida, Norimasa Iwasaki, Akio Minami

  JOURNAL OF HAND SURGERY-EUROPEAN VOLUME 34E (4) 538 - 539 1753-1934 2009/08 [Refereed][Not invited]
  
• Alpha9 integrin and its ligands constitute critical joint microenvironments for development of autoimmune arthritis.

  Masashi Kanayama, Daisuke Kurotaki, Junko Morimoto, Tsuyoshi Asano, Yutaka Matsui, Yosuke Nakayama, Yoshinari Saito, Koyu Ito, Chiemi Kimura, Norimasa Iwasaki, Koji Suzuki, Tanenobu Harada, Hong Mei Li, Jun Uehara, Tadaaki Miyazaki, Akio Minami, Shigeyuki Kon, Toshimitsu Uede

  Journal of immunology (Baltimore, Md. : 1950) 182 (12) 8015 - 25 0022-1767 2009/06/15 [Refereed][Not invited]
   

  Osteopontin is critically involved in rheumatoid arthritis; however, the molecular cross-talk between osteopontin and joint cell components that leads to the inflammatory joint destruction is largely unknown. We found that not only osteopontin but also tenascin-C and their common receptor, alpha(9) integrin, are expressed at arthritic joints. The local production of osteopontin and tenascin-C is mainly due to synovial fibroblasts and, to a lesser extent, synovial macrophages. Synovial fibroblasts and macrophages express alpha(9) integrin, and autocrine and paracrine interactions of alpha(9) integrin on synovial fibroblasts and macrophages and its ligands contribute differently to the production of proinflammatory cytokines and chemokines. alpha(9) integrin is also involved in the recruitment and accumulation of inflammatory cells. Inhibition of alpha(9) integrin function with an anti-alpha(9) integrin Ab significantly reduces the production of arthrogenic cytokines and chemokines and ameliorates ongoing arthritis. Thus, we identified alpha(9) integrin as a critical intrinsic regulator that controls the development of autoimmune arthritis.
• Radiolunate fusion with distraction using corticocancellous bone graft for minimizing decrease of wrist motion in rheumatoid wrists.

  Masuko T, Iwasaki N, Ishikawa J, Kato H, Minami A

  Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 14 (1) 15 - 21 0218-8104 2009 [Refereed][Not invited]
   

  Radiolunate fusion is a limited carpal fusion procedure used for patients with rheumatoid arthritis. However, this procedure inevitably causes decreases in range of motion, especially wrist flexion. Linscheid and Dobyns described the possibility of minimizing the decrease in motion at the radiocarpal joint by slight distraction of the joint. We hypothesized for our modified procedure that a corticocancellous bone graft was inserted between the radius and the lunate with a small amount of over-correction could provide slight distraction of radioscaphoid joint and protect the joint from decreased range of motion after arthrodesis. Twelve wrists in ten patients with rheumatoid arthritis underwent radiolunate fusion. Mean age at operation was 53 years old and mean follow-up period was 5.7 years. Clinical evaluation and radiological assessment showed that decrease in range of motion was minimized compared with other procedures. Because our modified procedure can minimize decrease in motion, it is recommended.
• Atelocollagen-associated autologous chondrocyte implantation for the repair of chondral defects of the knee: a prospective multicenter clinical trial in Japan.

  Tohyama H, Yasuda K, Minami A, Majima T, Iwasaki N, Muneta T, Sekiya I, Yagishita K, Takahashi S, Kurokouchi K, Uchio Y, Iwasa J, Deie M, Adachi N, Sugawara K, Ochi M

  J Orthop Sci. 2009 Sep;14(5):579-88. doi: 10.1007/s00776-009-1384-1. Epub 2009 Oct 3. 14 (5) 579 - 588 0949-2658 2009 [Refereed][Not invited]
  
• Patterned Immobilization of Unprotected Carbohydrates on an Aminooxy Polymer-Grafted Solid Surface

  Ryosuke Kamitani, Kenichi Niikura, Tomohiro Onodera, Norimasa Iwasaki, Hideyuki Shimaoka, Kuniharu Ijiro

  Bulletin of the Chemical Society of Japan 80 (9) 433 - 439 0009-2673 2007/08 [Refereed][Not invited]
  
• Identification of CLUAP1 as a human osteosarcoma tumor-associated antigen recognized by the humoral immune system

  Hisamitsu Ishikura, Hiroaki Ikeda, Hiroyuki Abe, Takayuki Ohkuri, Hiroaki Hiraga, Kazuo Isu, Tomohide Tsukahara, Noriyuki Sato, Hidemitsu Kitamura, Norimasa Iwasaki, Naoki Takeda, Akio Minami, Takashi Nishimura

  INTERNATIONAL JOURNAL OF ONCOLOGY 30 (2) 461 - 467 1019-6439 2007/02 [Refereed][Not invited]
   

  Since the prognosis of human osteosarcoma in advanced stage remains poor, the development of new and effective therapies including immunotherapy is required. To identify tumor-associated antigens of osteosarcoma applicable to the immunotherapy of this malignancy, we employed the serological analysis of recombinant cDNA expression library (SEREX) technique that defines tumor antigens recognized by the humoral immune system. Screening a cDNA library derived from an osteosarcoma cell line MG63 with sera from osteosarcoma patients identified 43 positive clones, representing 14 distinct antigens. Among them, CLUAP1 (clusterin-associated protein 1) was highly expressed in osteosarcoma tissue samples and cell lines. Overexpression of CLUAP1 was observed in other malignancies including ovarian, colon, and lung cancers. Our results suggest that CLUAP1 may be useful as a prognostic/diagnostic marker and/or for a target of immunotherapy of osteosarcoma.
• Bone marrow stromal cells act as feeder cells for tendon fibroblasts through soluble factors

  Kazumi Shimode, Norimasa Iwasaki, Tokifumi Majima, Tadanao Funakoshi, Naohiro Sawaguchi, Tomohiro Onodera, Akio Minami

  TISSUE ENGINEERING 13 (2) 333 - 341 1076-3279 2007/02 [Refereed][Not invited]
   

  Feeder effects of bone marrow stromal cells (BMSCs) on tendon fibroblasts were investigated using a coculture method for the application of ligament or tendon tissue engineering and cell therapy. BMSCs had significant effects on enhancing cell proliferation, the ability of cells to migrate, and cell adhesivity but little effect on the extracellular matrix (ECM) synthesis of tendon fibroblasts without cell-cell contact. Furthermore, the conditioned medium from BMSCs, despite the existence of fibroblasts, significantly increased the number of fibroblasts. Based on these results, the mechanism of the feeder effects is considered to be a certain signal of soluble factors from BMSCs to the fibroblasts. Comparative proteome analysis of the conditioned medium from co-culture of fibroblasts and BMSCs revealed less expression of plasminogen, which showed inhibitory effects on fibroblast proliferation. With regard to the relationships between plasminogen and BMSCs in the co-culture system, we speculate that BMSCs allow resolution of plasminogen or its cleavage activity in the medium via some mechanism.
• Specific cell behavior of human fibroblast onto carbohydrate surface detected by glycoblotting films

  Tomohiro Onodera, Kenichi Niikura, Norimasa Iwasaki, Noriko Nagahori, Hideyuki Shimaoka, Ryusuke Kamitani, Tokifumi Majima, Akio Minami, Shin-Ichiro Nishimura

  BIOMACROMOLECULES 7 (11) 2949 - 2955 1525-7797 2006/11 [Refereed][Not invited]
   

  We synthesized an aminooxyl polymer that is reactive with the reduced end of carbohydrates using our sugar-displaying approach. The carbohydrates were easily immobilized on the polymer film (glycoblotting film) by simple immersion in a in sugar solution through stable oxime bond. The in vitro behaviors of human fibroblasts on the carbohydrate-coated surface were investigated. The adhesion of human fibroblasts on the cellobiose- and cellotriose-coated surfaces was much greater than on the other coated surfaces and the noncoated surface. This result indicated that simple structural differences in carbohydrates induced biological changes in human cells, especially cell adhesion. Our approach provides a high-throughput assay system for carbohydrate-related cell adhesion and proliferation.
• Autologous osteochondral mosaicplasty for capitellar osteochondritis dissecans in teenaged patients

  Norimasa Iwasaki, Hiroyuki Kato, Jyunichi Ishikawa, Satoru Saitoh, Akio Minami

  AMERICAN JOURNAL OF SPORTS MEDICINE 34 (8) 1233 - 1239 0363-5465 2006/08 [Refereed][Not invited]
   

  Background: Autologous osteochondral mosaiciplasty is a new technique to provide hyaline repair for articular defects. Although recent studies have reported the successful treatment of articular defects in the knee and ankle joints with this surgical procedure, little attention has been given to the surgical efficacy of mosaicplasty in the treatment of osteochondritis dissecans of the humeral capitellum. Purpose: To clarify the clinical outcomes of mosaiciplasty for teenaged patients with advanced lesions of capitellar osteochondritis dissecans. Study Design: Case series; Level of evidence, 4. Methods: Eight teenaged patients with advanced lesions of capitellar osteochondritis dissecans underwent mosaicplasties. All patients were baseball players who were affected on the right side, which was also their throwing side. The surgical technique involves obtaining small-sized cylindrical osteochondral grafts from the lateral periphery of the femoral condyles and transplanting them to prepared osteochondral defects. At a mean follow-up of 24 months, all patients were evaluated clinically and radiographically. Results: Seven of the 8 patients were free from elbow pain, and the remaining patient had mild pain occasionally. The mean clinical score described by Timmerman and Andrews (a maximum of 200 points) significantly improved from 140 points to 183 points postoperatively. All patients except one had excellent or good clinical results. Radiographically, the graft incorporation and a normal contour of the subchondral cortex were found in all patients. Magnetic resonance imaging showed that the preoperative heterogeneity of the lesion had disappeared and the signal intensity returned to normal. Six of the 8 patients, including all 3 pitchers, returned to competitive-level baseball. Conclusion: Mosaicplasty for advanced lesions of capitellar osteochondritis dissecans in teenaged baseball players can provide satisfactory clinical and radiographic results.
• Numerical analysis of cooperative abduction muscle forces in a human shoulder joint

  N Oizumi, S Tadano, Y Narita, N Suenaga, N Iwasaki, A Minami

  JOURNAL OF SHOULDER AND ELBOW SURGERY 15 (3) 331 - 338 1058-2746 2006/05 [Refereed][Not invited]
   

  Because some shoulder muscles originate from a wide area, the modeling of such muscles has been a significant problem in a computer simulation. We demonstrated a new method of determining a vector for each of the muscles originating from a wide area. A 3-dimensional musculoskeletal model of a human shoulder was constructed from computed tomography data of a normal volunteer. Numerical analysis of I I muscle forces and the joint reaction force during shoulder abduction from 10 degrees to 150 degrees was performed from the static equilibrium equations. An optimal origin point for the vector of the muscle with a wide origin area was determined in every analyzed position. Electromyography was carried out to validate the results of the simulation, and a significant correlation with the analyzed force was obtained in each muscle. The anatomic biomechanical model with the new muscle modeling method led to the results reflecting the actual muscle activities in a living body.
• Extracellular matrix modulates expression of cell-surface proteoglycan genes in fibroblasts

  N Sawaguchi, T Majima, N Iwasaki, T Funakoshi, K Shimode, T Onodera, A Minami

  CONNECTIVE TISSUE RESEARCH 47 (3) 141 - 148 0300-8207 2006/05 [Refereed][Not invited]
   

  Cell-surface proteoglycans are involved in many functions, including interactions with components of the extracellular microenvironment. They also act as coreceptors that bind and modify the actions of various growth factors, cytokines, and the extracellular matrix (ECM). This study investigated the regulation by the ECM of the expression of cell-surface proteoglycans (CD44, syndecan-1-4, betaglycan, glypican-1). We examined the changes in the expression levels of cell-surface proteoglycan genes in intact tendon, monolayer culture, and under various culture conditions. There was a significant increase in the expression of CD44 and syndecan-4 mRNAs during cell isolation from the tendon. With the switch to a 3D culture environment, there was a significant increase in the expression of CD44 at each passage point relative to its expression in 2D at those passage points. Syndecan-4 mRNA also increased steadily at each passage point in 3D culture environment. This influence on cell surface proteoglycans gene expression may indicate that collagen gel culture mimics in vivo tendon environment. This study provides further insight into the regulation of cell-surface proteoglycans in ligament and tendon fibroblasts by the ECM and 3D culture conditions.
• Stabilization of the proximal ulnar stump in the Sauve-Kapandji procedure by using the extensor carpi ulnaris tendon: Long-term follow-up studies

  A Minami, N Iwasaki, J Ishikawa, N Suenaga, H Kato

  JOURNAL OF HAND SURGERY-AMERICAN VOLUME 31A (3) 440 - 444 0363-5023 2006/03 [Refereed][Not invited]
   

  Purpose: The Sauve-Kapandji procedure is considered a useful treatment option for distal radioulnar disorders. Postoperative instability of the proximal ulnar stump and radioulnar convergence, however, may be symptomatic. We modified the Sauve-Kapandji procedure by stabilizing the proximal ulnar stump with a half-slip of the extensor carpi ulnaris tendon. We previously reported on 13 patients with this procedure at an average follow-up period of 35 months; the patients had satisfactory clinical results and improved stability of the proximal ulnar stump as shown by x-ray examination. In this article we address the question of whether those clinical and radiographic results noted at an average follow-up period of 35 months after surgery were maintained at later follow-up examinations. Methods: We re-examined 12 of the 13 original patients and compared their initial follow-up results with their current results after an average follow-up period of 95 months. Results: The results of this series after 95 months of follow-up evaluation were similar to the results at 35 months. Conclusions: The results presented in this article suggest that the clinical radiographic results at the 35-month follow-up examination were maintained in the long-term 95-month follow-up evaluation despite the finding that the hole in the proximal ulnar stump had broken in 3 wrists at follow-up examination.
• Rotator cuff regeneration using chitin fabric as an acellular matrix

  T Funakoshi, T Majima, N Suenaga, N Iwasaki, S Yamane, A Minami

  JOURNAL OF SHOULDER AND ELBOW SURGERY 15 (1) 112 - 118 1058-2746 2006/01 [Refereed][Not invited]
   

  Twenty-one rabbits were used to investigate the feasibility of using nonwoven chitin fabric as an acellular matrix for rotator cuff regeneration. Infraspinatus tendons were cut bilaterally to create 10 x 10-mm defects. The defect in the right shoulder was covered with chitin fabric. The contralateral defect was left free as a control. The specimens were evaluated histologically and immunohistochemically at 2, 4, 8, and 12 weeks and biomechanically at 12 weeks after surgery. The acellular matrix increased cell numbers and improved collagen fiber alignment. The regenerated tissues were composed of type III collagen. The structural properties of the grafted shoulder were significantly greater than those of the control. This study revealed that using chitin fabric as an acellular matrix has advantages in enhancing both biologic and mechanical regeneration of rotator cuff tendons.
• High density sugar-displaying materials using the glycoblotting methods for cell patterning

  Ryosuke Kamitani, Kenichi Niikura, Tomohiro Onodera, Norimasa Iwasaki, Masataka Fumoto, Hideyuki Shimaoka, Kuniharu Ijiro, Shin-Ichiro Nishimura

  Polymer Preprints, Japan 55 (1) 1895  2006 

  Synthetic sugar-based materials have been interested in important tools, because cell surface carbohydrates are involved in numerous biological functions, including cellular recognition, adhesion, cell growth regulation. In this study, we present novel sugar-displaying materials by using the glycoblotting method combined with photo-patterning. The glycoblotting method is based on the chemoselective ligation of carbohydrates with reactive aminooxyl groups attached to the polymer side chains. Cell patternings were created on the sugar-displaying substrate by the specific cell-carbohydrate interactions.
• Surgical efficacy of carpal tunnel release for carpal tunnel syndrome in acromegaly: Report of four patients

  N Iwasaki, T Masuko, J Ishikawa, A Minami

  JOURNAL OF HAND SURGERY-BRITISH AND EUROPEAN VOLUME 30B (6) 605 - 606 0266-7681 2005/12 [Refereed][Not invited]
   

  Although carpal tunnel syndrome is frequent in acromegaly, few acromegalics will be encountered by most hand surgeons. This paper considers the treatment of four cases of acromegaly in whom carpal tunnel syndrome arose, to discuss aspects of management of carpal tunnel syndrome in this patient group.
• Influence of distal radioulnar joint subluxation on restricted forearm rotation after distal radius fracture

  J Ishikawa, N Iwasaki, A Minami

  JOURNAL OF HAND SURGERY-AMERICAN VOLUME 30A (6) 1178 - 1184 0363-5023 2005/11 [Refereed][Not invited]
   

  Purpose: To analyze the influence of subluxation of the distal radioulnar joint (DRUJ) on restricted forearm rotation after distal radius fracture. Methods: Twenty-two cases of healed unilateral distal radial fracture with restricted forearm rotation were included in the study. The subluxation of the DRUJ was evaluated using helical computed tomography scan at neutral, maximum pronation, and maximum supination and presented as the percent displacement of the ulnar head in both the injured and uninjured sides. The radiographic parameters of palmar tilt, radial inclination, dorsal shift, radial shift, and ulnar variance were measured on plain x-ray films and the rotational deformity of the distal radius was evaluated from the computed tomography scan. The differences of each radiographic parameter from the uninjured side were calculated. The relationships between the restricted forearm rotation and the percent displacement of the ulnar head and each of the radiographic parameters were analyzed statistically. Results: When forearm pronation was restricted the ulnar head was located palmarly at neutral, maximum supination, and maximum pronation with severe dorsal tilt of the distal radius. When supination was restricted the u1nar head was located dorsally at maximum supination with severe ulnar-positive variance. Conclusions: The subluxation of the DRUJ was related to restricted forearm rotation. The radiographic parameters of palmar tilt and ulnar variance showed an adverse influence on the position of the ulnar head at the DRUJ, which might lead to restricted forearm rotation after distal radial fracture.
• Radial osteotomies for teenage patients with Kienbock disease

  N Iwasaki, A Minami, J Ishikawa, H Kato, M Minami

  CLINICAL ORTHOPAEDICS AND RELATED RESEARCH 439 (439) 116 - 122 0009-921X 2005/10 [Refereed][Not invited]
   

  Age seems to affect the efficacy of radial osteotomies for Kienbock disease. We questioned whether an osteotomy would produce acceptable results in teenagers. We retrospectively identified II patients (six males and five females) between 11-19 years of age who were treated with radial osteotomies for Kienbock disease. Preoperatively, three patients had Lichtman Stage II disease, two patients had Stage IIIA disease, and six patients had Stage IIIB disease. Two patients with zero or positive ulnar variance had lateral closing wedge osteotomies, and nine patients with negative ulnar variance had radial shortenings. All patients were evaluated clinically and radiographically. At a mean followup of 50 months, 10 of 11 patients were free from pain, and the remaining one patient had moderate wrist pain during strenuous activity. All patients except one, who had Stage IIIB disease, had an excellent clinical outcome. Radiographic improvement, indicating lunate revascularization, was seen for eight patients. Despite Stage IIIB disease, radial osteotomies produced excellent clinical results in five of six teenage patients. The current results indicate that radial osteotomies are effective in improving not only short-term clinical outcomes, but also radiographic findings in teenage patients with Kienbock disease.
• Chitosan-RGDSGGC conjugate as a scaffold material for musculoskeletal tissue engineering

  T Masuko, N Iwasaki, S Yamane, T Funakoshi, T Majima, A Minami, N Ohsuga, T Ohta, SI Nishimura

  BIOMATERIALS 26 (26) 5339 - 5347 0142-9612 2005/09 [Refereed][Not invited]
   

  In the present study, we have developed a novel and versatile method for the preparation of chitosan-peptide complex based on the selective reaction of chitosan with 2-iminothiolane. The new type of SH-chitosan derivative showed an excellent solubility to aqueous solution even in the alkaline conditions. This characteristic greatly facilitated further modification study of chifosan with a variety of bioactive substances. A synthetic peptide, RGDSGGC containing RGDS moiety that is known as one of the most important cell adhesive peptides, was readily coupled by disulfide bonds formation with sulfhydryl groups of SH-chitosan in the presence of dimethyl sulfoxide. Next, the effect of the introduction of RGDSGGC moiety to chitosan on cell adhesion and proliferation activity of chondrocytes and fibroblasts were evaluated. As a result, it was suggested that this polysaccharide-peptide conjugate exhibited excellent capacities for both cell adhesion and cell proliferation of chondrocytes and fibroblasts. Considering the growing importance of the biocompatible scaffolds in the recent tailored tissue engineering technique, these results indicate that the present strategy of 2-iminothiolane-based conjugation of polysaccharides with biologically active peptides will become a key and potential technology to develop desirable scaffold materials for the tissue regenerations. (c) 2005 Elsevier Ltd. All rights reserved.
• Novel chitosan-based hyaluronan hybrid polymer fibers as a scaffold in ligament tissue engineering

  T Funakoshi, T Majima, N Iwasaki, S Yamane, T Masuko, A Minami, K Harada, H Tamura, S Tokura, SI Nishimura

  JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 74A (3) 338 - 346 1549-3296 2005/09 [Refereed][Not invited]
   

  To clarify the feasibility of using novel chitosan-based hyaluronan hybrid polymer fibers as a scaffold in ligament tissue engineering, their mechanical properties and ability to promote cellular adhesion, proliferation, and extracellular matrix production were studied in vitro. Chitosan fibers and chitosan-based 0.05% and 0.1% hyaluronan hybrid fibers were developed by the wet spinning method. Hyaluronan coating significantly increased mechanical properties, compared to the chitosan fibers. Rabbit fibroblasts adhesion onto hybrid fibers was significantly greater than for the control and chitosan fibers. For analysis of cell proliferation and extracellular matrix production, a three-dimensional scaffold was created by simply piling up each fiber. At I day after cultivation, the DNA content in the hybrid scaffolds was higher than that in the chitosan scaffold. Scanning electron microscopy showed that the fibroblasts had produced collagen fibers after 14 days of culture. Immunostaining for type I collagen was clearly predominant in the hybrid scaffolds, and the mRNA level of type I collagen in the hybrid scaffolds were significantly greater than that in the chitosan scaffold. The present study revealed that hyaluronan hybridization with chitosan fibers enhanced fiber mechanical properties and in vitro biological effects on the cultured fibroblasts. (c) 2005 Wiley Periodicals, Inc.
• Application of tissue engineering techniques for rotator cuff regeneration using a chitosan-based hyaluronan hybrid fiber scaffold

  T Funakoshi, T Majima, N Iwasaki, N Suenaga, N Sawaguchi, K Shimode, A Minami, K Harada, S Nishimura

  AMERICAN JOURNAL OF SPORTS MEDICINE 33 (8) 1193 - 1201 0363-5465 2005/08 [Refereed][Not invited]
   

  Background: The current surgical procedures for irreparable rotator cuff tears have considerable limitations. Tissue engineering techniques using novel scaffold materials offer potential alternatives for managing these conditions. Hypothesis: A chitosan-based hyaluronan hybrid scaffold could enhance type I collagen products with seeded fibroblasts and thereby increase the mechanical strength of regenerated tendon in vivo. Study Design: Controlled laboratory study. Methods: The scaffolds were created from chitosan-based hyaluronan hybrid polymer fibers. Forty-eight rabbit infraspinatus tendons and their humeral insertions were removed to create defects. Each defect was covered with a fibroblast-seeded scaffold (n = 16) or a non-fibroblast-seeded scaffold (n = 16). In the other 16 shoulders, the rotator cuff defect was left free as the control. At 4 and 12 weeks after surgery, the engineered tendons were assessed by histological, immunohistochemical (n = 2), and biomechanical (n = 6) analyses. Results: Type I collagen was only seen in the fibroblast-seeded scaffold and increased in the regenerated tissue. The tensile strength and tangent modulus in the fibroblast-seeded scaffold were significantly improved from 4 to 12 weeks postoperatively. The fibroblast-seeded scaffold had a significantly greater tangent modulus than did the non-fibroblast-seeded scaffold and the control at 12 weeks. Conclusion: This scaffold material enhanced the production of type I collagen and led to improved mechanical strength in the regenerated tissues of the rotator cuff in vivo. Clinical Relevance: Rotator cuff regeneration is feasible using this tissue engineering technique.
• A long-term follow-up of silicone-rubber interposition arthroplasty for osteoarthritis of the thumb carpometacarpal joint.

  Minami A, Iwasaki N, Kutsumi K, Suenaga N, Yasuda K

  Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 10 (1) 77 - 82 0218-8104 2005/07 [Refereed][Not invited]
   

  There are several surgical options for osteoarthritis (OA) of the thumb carpometacarpal (CMC) joint. This paper presents our long-term clinical and radiographic review of 12 thumbs in ten patients treated by partial trapezial excision and silicone-rubber interposition arthroplasty. The follow-up period averaged 15; three years with a ten-year minimum. Although the procedure provided early pain relief in most thumbs, all but two had mild to severe pain at follow-up. The average range of post-operative palmar abduction was 23 degrees. The average post-operative grip strength was 9.5 kg. Both tip and key pinch between thumb and index finger averaged about 50% that of normal subjects. Dislocation of the implant occurred in two joints and breakages in five. Bony erosions around the implant, which we attributed silicone synovitis, were found in four thumbs. The indications for silicone-rubber interposition arthroplasty for OA of the thumb CMC joint should be severely restricted as these produced unsatisfactory long-term results.
• Alginate and chitosan polyion complex hybrid fibers for scaffolds in ligament and tendon tissue engineering

  T Majima, T Funakosi, N Iwasaki, ST Yamane, K Harada, S Nonaka, A Minami, SI Nishimura

  JOURNAL OF ORTHOPAEDIC SCIENCE 10 (3) 302 - 307 0949-2658 2005/05 [Refereed][Not invited]
   

  Selecting the material for a scaffold is critically important for the success of tissue engineering. To simplify complicated biosynthetic matrices and achieve a novel class of potential materials, a model of polyion complex fibers was prepared from alginate and chitosan. In the current in vitro study, we thought that alginate-based chitosan hybrid biomaterials could provide excellent supports for fibroblast adhesion. In the current study, alginate polymer fiber (alginate group) and alginate-based chitosan hybrid polymer fibers (alginate with 0.05% chitosan, alginate-chitosan 0.05% group; alginate with 0.1% chitosan, alginate-chitosan 0.1% group) were originally prepared. We investigated the adhesion behavior of rabbit tendon fibroblast onto alginate polymer fibers versus the adhesion of the fibroblast onto alginate-based chitosan hybrid polymer fibers. Furthermore, mechanical properties and synthesis of the extracellular matrix were investigated. Mechanically, the novel fiber has considerable tensile strength of more than 200MPa. We demonstrated that the alginate-based chitosan hybrid polymer fibers showed much improved adhesion capacity with fibroblast compared with alginate polymer fiber. Additionally, morphologic studies revealed the dense fiber of the type I collagen produced by the fibroblast in the hybrid polymer fibers. We concluded that an alginate-based chitosan hybrid polymer fiber has considerable potential as a desirable biomaterial scaffold for tendon and ligament tissue engineering.
• Carbohydrate analysis by a phenol-sulfuric acid method in microplate format

  T Masuko, A Minami, N Iwasaki, T Majima, SI Nishimura, YC Lee

  ANALYTICAL BIOCHEMISTRY 339 (1) 69 - 72 0003-2697 2005/04 [Refereed][Not invited]
   

  Among many colorimetric methods for carbohydrate analysis, the phenol-sulfuric acid method is the easiest and most reliable method. It has been used for measuring neutral sugars in oligosaccharides, proteoglycans, glycoproteins, and glycolipids. This method is used widely because of its sensitivity and simplicity. In its original form, it required 50-450 nmol of monosaccharides or equivalent for analysis and thus is inadequate for precious samples. A scaled-down version requiring only 10-80 nmol of sugars was reported previously. We have now modified and optimized this method to use 96-well microplates for high throughput, to gain greater sensitivity, and to economize the reagents. This modified and optimized method allows longer linear range (1-150 nmol for Man) and excellent sensitivity. Moreover, our method is more convenient, requiring neither shaking nor covering, and takes less than 15 min to complete. The speed and simplicity of this method would make it most suitable for analyses of large numbers of samples such as chromatographic fractions. (c) 2004 Elsevier Inc. All rights reserved.
• Thiolation of chitosan. Attachment of proteins via thioether formation

  T Masuko, A Minami, N Iwasaki, T Majima, SI Nishimura, YC Lee

  BIOMACROMOLECULES 6 (2) 880 - 884 1525-7797 2005/03 [Refereed][Not invited]
   

  Chitosan has a variety of biological functions through conjugating of other compounds to their amino and hydroxyl groups. To further expand applicability of chitosan, we have modified the amino group of chitosan with 2-iminothiolane to bestow thiol groups and obtained about 20% yield, which is equivalent to 913 mu equiv SH/g chitosan or 457 nequiv SH/nmol chitosan. Bovine serum albumin (BSA) was reacted with N-(c-maleimidocaproyloxy)sulfosuccinimide ester (sulfo-EMCS), and maleimide-modified BSA (MaINBSA) was obtained. The yield of sulfo-EMCS addition was 12.8-36.8 mol MaIN/mol BSA. When the chitosan-SH was reacted with MalN-BSA via thioether, 97.8% of the maleimide group was reacted, and 37.2% of the SH group was consumed. The remaining SH group was quenched by bromoacetamide. This is the first report of covalent conjugation of a protein to chitosan. Our method should find many applications in developing new chitosan-based biomedical materials containing other components such as growth factors and cell adhesion molecules, known to be crucial to cells. Our thiolated chitosan will facilitate conjugation of such biomedical components to provide new types of materials for tissue engineering.
• Feasibility of chitosan-based hyaluronic acid hybrid biomaterial for a novel scaffold in cartilage tissue engineering

  S Yamane, N Iwasaki, T Majima, T Funakoshi, T Masuko, K Harada, A Minami, K Monde, S Nishimura

  BIOMATERIALS 26 (6) 611 - 619 0142-9612 2005/02 [Refereed][Not invited]
   

  In this study, we hypothesized that hyaluronic acid could provide superior biological effects on the chondrocytes in a three-dimensional culture system. To test this hypothesis, we investigated the in vitro behavior of rabbit chondrocytes oil a novel chitosan-based hyaluronic acid hybrid polymer fiber. The goal of the current study was to show the Superiority of this novel fiber as a scaffold biomaterial for cartilage tissue engineering. Chitosan polymer fibers (chitosan group) and chitosan-based hyaluronic acid hybrid polymer fibers (HA 0.04% and HA 0.07% groups, chitosan coated with hyaluronic acid 0.04% and 0.07%, respectively) were originally developed by the wetspinning method. Articular chondrocytes were isolated from Japanese white rabbits and cultured in the sheets consisting of each polymer fiber. The effects of each polymer fiber oil cell adhesivity, proliferation, morphological changes. and synthesis of the extracellular matrix were analyzed by quantitative a cell attachment test, DNA quantification, light and scanning electron microscopy, semi-quantitative RT-PCR, and immunohistochemical analysis. Cell adhesivity, proliferation and the synthesis of agrecan were significantly higher in the hybrid fiber (HA 0.04% and 0.07%) groups than in the chitosan group. On the cultured hybrid polymer materials, scanning electron microscopic observation showed that chondrocytes proliferated while maintaining their morphological phenotype and with a rich extracellular matrix synthesis around the cells. Immunohistochemical staining with an anti-type II collagen antibody demonstrated rich production of the type II collagen in the pericellular matrix from the chondrocytes. The chitosan-based hyaluronic acid hybrid polymer fibers show great potential as a desirable biomaterial for cartilaginous tissue scaffolds. (C) 2004 Elsevier Ltd. All rights reserved.
• Treatments of osteoarthritis of the distal radioulnar joint: long-term results of three procedures.

  Minami A, Iwasaki N, Ishikawa J, Suenaga N, Yasuda K, Kato H

  Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 10 (2-3) 243 - 248 0218-8104 2005 [Refereed][Not invited]
  
• Feasibility of polysaccharide hybrid materials for scaffolds in cartilage tissue engineering: Evaluation of chondrocyte adhesion to polyion complex fibers prepared from alginate and chitosan

  N Iwasaki, ST Yamane, T Majima, Y Kasahara, A Minami, K Harada, S Nonaka, N Maekawa, H Tamura, S Tokura, M Shiono, K Monde, SI Nishimura

  BIOMACROMOLECULES 5 (3) 828 - 833 1525-7797 2004/05 [Refereed][Not invited]
   

  The ideal cell-carrier material for cartilage regeneration should be one that closely mimics the natural environment in a living articular cartilage matrix. In the current study, we considered that alginate-based chitosan hybrid biomaterials could provide excellent supports for chondrocyte adhesion. To test this hypothesis, we investigated the adhesion behavior of rabbit chondrocytes onto an alginate polymer versus the adhesion of the chondrocytes onto some alginate-based chitosan hybrid polymer fibers in vitro. We demonstrated that the alginate-based chitosan hybrid polymer fibers showed much improved adhesion capacity with chondrocytes in comparison with alginate polymer fiber. Additionally, morphologic studies revealed maintenance of the characteristic round morphology of the chondrocyte and the dense fiber of the type II collagen produced by the chondrocytes in the hybrid polymer. On the basis of these results, we conclude that an alginate-based chitosan hybrid polymer fiber has considerable potential as a desirable biomaterial for cartilage tissue scaffolds.
• The use of pedicled posterior interosseous fat graft for mobilization of congenital radioulnar synostosis: A case report

  T Funakoshi, H Kato, A Minami, N Suenaga, N Iwasaki

  JOURNAL OF SHOULDER AND ELBOW SURGERY 13 (2) 230 - 234 1058-2746 2004/03 [Refereed][Not invited]
  
• Fluorescent glyconanoparticles as a sensitive device to monitor sugar-involving molecular events

  K Niikura, N Osuga, N Nagahori, R Sadamoto, M Shiono, N Iwasaki, K Monde, A Minami, SI Nishimura

  POLYMER JOURNAL 36 (3) 209 - 218 0032-3896 2004 [Not refereed][Not invited]
   

  We prepared sugar-displayed fluorescent nanoparticles using photopolyinerization of the vesicles of diacetylene-containing glycolipids. After photopolymerization, the nanoparticles exhibited fluorescent emission at 400-600 nm upon excitation at 380 nm. The binding of sugar-recognizing proteins (lectins) onto the fluorecent nanoparticles induced changes in fluorescence. The fluorescent intensity of the nanoparticles decreased with an increase in lectin concentration. On the contrary, the enzymatic release of oligosaccharides from the glyconanoparticles gave an increase in fluorescence. Using a phosphatidylcholine-type lipid as the matrix lipid of the nanoparticles, the non-specific adsorption of lectins on the surface was drastically restricted, leading to the generation of a specific response to the target proteins.
• Predictors of clinical results of radial osteotomies for Kienbock's disease

  N Iwasaki, A Minami, N Oizumi, S Yamane, N Suenaga, H Kato

  CLINICAL ORTHOPAEDICS AND RELATED RESEARCH (415) 157 - 162 0009-921X 2003/10 [Refereed][Not invited]
   

  The factors affecting the clinical results after radial osteotomies for Kienbock's disease are unknown. In the current study, we reviewed the data of 41 patients treated with radial osteotomies for Kienbock's disease and analyzed which preoperative factors significantly affected the clinical results of these procedures. Lateral closing wedge osteotomies of the radius were done for 22 patients (six patients with Lichtman Stage II disease, three patients with Lichtman Stage IIIA disease, 12 patients with Lichtman Stage IIIB disease, and one patient with Lichtman Stage IV disease) with zero or positive ulnar variance, and radial shortenings were done for 19 patients (four patients with Stage II disease, two patients with Stage IIIA disease, 12 patients with Stage IIIB disease, and one patient with Stage IV disease) with negative ulnar variance. The mean age of the patients at surgery was 36 years and the average followup was 38 months. To statistically assess the prognostic factors, multiple regression analysis focused on the postoperative clinical score as a dependent variable and preoperative patient data as independent variables. In the current analysis, patient age was the preoperative factor most clearly predictive of clinical results after radial osteotomies for Kienbock's disease. We think that the lower effectiveness of radial osteotomies must be considered in doing these procedures for elderly patients.
• Treatment of scapholunate dissociation: ligamentous repair associated with modified dorsal capsulodesis.

  Minami A, Kato H, Iwasaki N

  Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 8 (1) 1 - 6 0218-8104 2003/07 [Refereed][Not invited]
   

  We previously reported that our repair and/or reconstruction of the scapholunate interosseous ligament reduced the scapholunate dissociation and improved the clinical results. Re-evaluation of these patients after three years revealed that malrotation of the scaphoid advanced significantly although the clinical results declined only slightly. To prevent progression of scaphoid malrotation, a modified dorsal capsulodesis was subsequently added to the ligamentous repair of scapholunate dissociation. The records of 17 patients were available for this study. The time lapse from injury to surgical treatment ranged from four days to one year and six months. All but three patients were operated less than two months after the injury. All patients were followed for more than one year, with an average of 49 months. Clinical results were expressed by a modification of the point score method of Green and O'Brien. Scapholunate angles were measured on lateral X-ray films with the wrist in neutral position. Overall clinical results averaged 83 points (range: 25-100). The scapholunate angles averaged 49 degrees (range: 45-60). In the three patients, in whom the operation was performed more than 11 months after the injury, the clinical results averaged 38 points and scapholunate angles averaged 54 degrees, respectively. These clinical and X-ray results suggest that early repair of the scapholunate interosseous ligament along with a modified dorsal capsulodesis is a useful procedure in the treatment of scapholunate dissociation.
• Stress distribution patterns at the coracoacromial arch in rotator cuff tear measured by computed tomography osteoabsorptiometry

  N Oizumi, N Suenaga, A Minami, N Iwasaki, T Miyazawa

  JOURNAL OF ORTHOPAEDIC RESEARCH 21 (3) 393 - 398 0736-0266 2003/05 [Refereed][Not invited]
   

  When a rotator cuff tear occurs, forces compressing the humeral head toward the glenoid are disturbed, and the kinematics of the glenohumeral joint change. Therefore, stress distributions at the coracoacromial arch in cuff tear shoulders should differ from those in normal shoulders. To investigate this hypothesis, we studied stress distribution patterns at the coracoacromial arch in normal and cuff tear shoulders using a computed tomography (CT) osteoabsorptiometry method, in which bone density correlates directly with long-term physiologic loading. Eight normal subjects and 11 patients with cuff tear were examined. The stress distributions at the undersurface of the acromion and the posterolateral surface of the coracoid process differed markedly between normal and cuff tear shoulders. In cuff tear shoulders, a high-density area was located at the anterior or the anterolateral part of the undersurface of the acromion, while it was located at the posterior part in all but one normal shoulder. Additionally, a high-density area was located at the superior or the lateral part of the coracoid process in most of the cuff tear shoulders; on the other hand, it was located at the base in all but one normal shoulder. We believe that the differences in stress distribution patterns are due to impingement at the coracoacromial arch in cuff tear shoulders. CT osteoabsorptiometry can provide useful information in performing coracoacromial arch decompression for cuff tear shoulders. (C) 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
• Effect of single-dose administration of FK-506 on allogeneic limb transplantation in rats: Is there an optimal timing of its administration?

  T Gohda, N Iwasaki, C Yoshioka, A Minani

  PLASTIC AND RECONSTRUCTIVE SURGERY 111 (5) 1653 - 1658 0032-1052 2003/04 [Refereed][Not invited]
   

  Although a number of experimental studies have demonstrated that high-dose administration of FK-506 induces the success of limb allogeneic transplantation in rats, some of them have reported occurrences of lethal side effects. Therefore, a more effective regimen with lower-dose administration of this agent must be developed. The objective of this study was to determine an optimal timing of a single-dose administration of FK-506 in rat limb allografts. In the current study, orthotopic hindlimb transplantations were performed using major histocompatibility mismatched pairs of inbred rats. The rats were classified into five groups on the basis of the different time schedules of FK-506 administration as follows: syngeneic group, Lewis-to-Lewis transplantation; control group, ACI-to-Lewis without any immunotherapy; day 0 group, recipients treated with a single-dose administration of FK-506 (5 mg/kg of body weight, intramuscular injection) at day 0 postoperatively; day 1 group, with a single-dose administration of FK-506 at day 1 postoperatively; and day 2 group, with a single-dose administration of FK-506 at day 2 postoperatively. The median graft survival time in each group (n = 5) was 9 days in the control group, 19 days in the day 0 group, 49 days in the day 1 group, and 42 days in the day 2 group. The values in the day 1 and the day 2 groups significantly increased compared with those in other groups. For prolonged survival of a grafted limb, a single-dose administration of FK-506 is more effective at 24 to 48 hours after transplantation.
• Acute posterior interosseous nerve palsy caused by septic arthritis of the elbow: A case report

  H Kato, N Iwasaki, A Minami, T Kamishima

  JOURNAL OF HAND SURGERY-AMERICAN VOLUME 28A (1) 44 - 47 0363-5023 2003/01 [Refereed][Not invited]
   

  A rare case of acute posterior interosseous nerve palsy caused by septic elbow arthritis is reported. The nerve was compressed beneath the arcade of Frohse by hypertrophied synovium and joint fluid at the anterior aspect of the radial neck. Decompression of the nerve, synovectomy, and irrigation of the elbow joint were done. effective. Six months after the surgery the nerve palsy had recovered completely. Two years after surgery there was no recurrence of the infection or nerve palsy.
• Telescoping vascularized fibular graft: A new method

  A Minami, H Kato, N Suenaga, N Iwasaki

  JOURNAL OF RECONSTRUCTIVE MICROSURGERY 19 (1) 11 - 15 0743-684X 2003/01 [Refereed][Not invited]
   

  The authors describe a case of congenital pseudarthrosis of the tibia treated with a telescoping vascularized fibular graft. The advantages of this new method are that bone union and leg-length discrepancy may be corrected simultaneously.
• Scaphotrapeziotrapezoid fusion: Long-term follow-up study

  Akio Minami, Hiroyuki Kato, Naoki Suenaga, Norimasa Iwasaki

  Journal of Orthopaedic Science 8 (3) 319 - 322 0949-2658 2003 [Refereed][Not invited]
   

  The long-term effectiveness of scaphotrapeziotrapezoid (STT) fusion is still controversial. We evaluated our clinical and radiological results of 30 STT fusions in 30 patients (average age 41 years 23 males, 7 females). The follow-up period averaged 84 months. The indications were Kienböck's disease (n = 23), isolated STT arthrosis (n = 6), and dislocation of the trapezium (n = 1). A total of 26 simultaneous associated procedures were performed. Excisional arthroplasty of the lunate was done in all 23 patients with Kienböck's disease. Of the 30 total patients, 5 had post-operative pain ranging from mild to severe 4 patients were dissatisfied with the results. Postoperative ranges of motion of the wrist were 84% of extension and 91% of flexion compared with preoperative motion. The postoperative grip strength improved to 27 kgf from the preoperative value of 18 kgf. Altogether, 26 patients returned to their previous activities. All patients obtained uneventful STT fusion in an average of 11.2 weeks. Eight patients (27%) experienced postoperative complications seven had radioscaphoid arthroses, five had trapeziometacarpal arthrodeses, and one had a flexor pollicis longus tendon rupture. Although radioscaphoid arthrosis occurred in 23% of this series after STT fusion, the results suggest that it is an effective procedure for Kienböck's disease and isolated STT arthrosis.
• Long-term results after primary repairs of zone 2 flexor tendon lacerations in children younger than age 6

  H Kato, A Minami, N Suenaga, N Iwasaki, T Kimura

  JOURNAL OF PEDIATRIC ORTHOPAEDICS 22 (6) 732 - 735 0271-6798 2002/11 [Refereed][Not invited]
   

  In young children, methods of primary flexor tendon repair in the digital canal are controversial. The authors reviewed 12 children younger than age 6 years with zone 2 flexor tendon repairs. The mean follow-up period was 8 years. In all cases, the flexor digitorum profundus tendons were repaired according to the Kessler modified technique and the hands were immobilized by an above-elbow cast. As for postoperative complications, there were no fingers with tendon rupture and two fingers with tendon adhesion. One finger needed tenolysis. The total active motion (TAM) in the interphalangeal joints evaluated with the Strickland formula averaged 155degrees, and the TAM percentage averaged 89% (range 74%-100%). Eleven patients had an excellent result and one had a good result. The percentage phalangeal length averaged 99% (range 96%-100%). Functional motion and nearly normal growth of the finger can be expected after primary zone 2 flexor tendon repairs in children younger than age 6 years.
• Cubital tunnel syndrome associated with medial elbow ganglia and osteoarthritis of the elbow

  H Kato, T Hirayama, A Minami, N Iwasaki, K Hirachi

  JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME 84A (8) 1413 - 1419 0021-9355 2002/08 [Refereed][Not invited]
   

  Background: Medial elbow ganglia have been reported in association with cubital tunnel syndrome. This lesion is thought to occur rarely and has not been emphasized in the literature. The purposes of the present study are to report our experience with this lesion in order to elucidate its prevalence as well as its clinical and radiographic features, to describe our operative findings, and to present the results of surgical treatment. Methods: Four hundred and eighty-seven elbows in 472 patients were treated for cubital tunnel syndrome between 1980 and 1999. We performed a retrospective study of the thirty-eight patients who had a medial ganglion. All of the ganglia were excised, and the ulnar nerve was translocated subcutaneously. Thirty-two patients were followed for a mean of thirty-seven months. Results: Medial elbow ganglion was the third most common causative factor associated with cubital tunnel syndrome, with an overall prevalence of 8%. Resting pain in the medial aspect of the elbow was reported by twenty-five of the thirty-eight patients, and a sudden onset of numbness in the ring and little fingers or of medial elbow pain without prior symptoms was reported by twenty-nine patients. The symptoms lasted two months or less in thirty-one patients. All ganglia originated from the medial aspect of the ulnohumeral joint, and radiographs of that joint showed degenerative changes in thirty-seven patients. At the time of follow-up, all measurements of sensory and motor function of the u1nar nerve had improved and no recurrence of nerve palsy was found. Conclusions: Although, uncommon, medial elbow ganglia have a strong association with osteoarthritis of the elbow and can cause a relatively acute onset of cubital tunnel syndrome. A patient with cubital tunnel syndrome associated with elbow osteoarthritis who complains of medial elbow pain or severe numbness within two months after the onset of the syndrome should be strongly suspected of having a ganglion. Most ganglia are occult, and ultrasonography and magnetic resonance imaging can assist in the preoperative diagnosis. Careful excision of the ganglion performed concurrently with subcutaneous anterior transposition of the ulnar nerve can produce satisfactory results.
• Vascularized fibular graft after excision of giant-cell tumor of the distal radius: Wrist arthroplasty versus partial wrist arthrodesis

  A Minami, H Kato, N Iwasaki

  PLASTIC AND RECONSTRUCTIVE SURGERY 110 (1) 112 - 117 0032-1052 2002/07 [Refereed][Not invited]
   

  Several reconstructive procedures have been described for the complete defect of the distal radius that is created after a wide excision of a giant-cell tumor of bone, including hemiarthroplasty using the vascularized fibular head and partial wrist arthrodesis between a vascularized fibula and the scapholunate portion of the proximal carpal row. The objectives of this study are to compare clinical and radiographic results between the partial wrist arthrodesis and the wrist arthroplasty, and to discuss which procedure is superior. Four patients with giant-cell tumors involving the distal end of the radius were treated with en bloc resection and reconstruction with a free vascularized fibular graft. The wrists in two patients were reconstructed with an articular fibular head graft and the remaining two patients underwent partial wrist arthrodesis using a fibular shaft transfer. There was radiographic evidence of bone union at the host-graft junctions in all cases. In the newly reconstructed wrist joint, there was palmar subluxation of the carpal bones and degenerative changes in both patients. Local recurrence was seen in one patient. According to the functional results described by Enneking et al., the mean functional score was 67 percent. The functional scores including wrist/forearm range of motion in the cases with partial wrist arthrodesis were superior to those with wrist arthroplasty. A partial wrist arthrodesis using a vascularized fibular shaft graft appears a more useful and reliable procedure for reconstruction of the wrist after excision of the giant-cell tumor of the distal end of the radius than a wrist arthroplasty using the vascularized fibular head, although our study includes only a small number of patients.
• Radial osteotomy for late-stage Kienbock's disease - Wedge osteotomy versus radial shortening

  N Iwasaki, A Minami, N Oizumi, N Suenaga, H Kato, M Minami

  JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME 84B (5) 673 - 677 0301-620X 2002/07 [Refereed][Not invited]
   

  We have reviewed 20 patients with stage-IIIB and stage-IV Kienbock's disease in order to examine the efficacy of two forms of radial osteotomy, namely radial wedge osteotomy and radial shortening. Lateral closing wedge osteotomies and radial shortenings were carried out on 11 and nine patients, respectively. There were no preoperative differences with respect to age, gender, and radiological stage. After a mean follow-up of 29 months, all patients, in both groups, had either a good or an excellent outcome. After the lateral closing wedge osteotomy, the radioscaphoid angle significantly increased and the Stahl index significantly decreased. Progression of the degenerative changes at the radioscaphoid joint was found in two patients in this group. By contrast, there were no significant changes in any radiological parameters after radial shortening. Both procedures gave acceptable clinical results in stage-IIIB and stage-IV Kienbock's disease.
• Feasibility of immunosuppression in composite tissue allografts by systemic administration of CTLA4Ig

  N Iwasaki, T Gohda, C Yoshioka, A Murakami, M Inobe, A Minami, T Uede

  TRANSPLANTATION 73 (3) 334 - 340 0041-1337 2002/02 [Refereed][Not invited]
   

  Background. Although recent experimental studies have demonstrated CTLA4Ig to be a potent immunosuppressant in vascularized solid organ allografts, little attention has been given to the effect of this soluble recombinant fusion protein on immunosuppression in composite tissue allografts (CTAs). Using a rat hind limb allograft model, we examined the efficacy of CTLA4Ig against the allograft rejection of composite tissue. Methods. The hind limbs of ACI rats (RT1(a)) were heterotopically transplanted to Lewis rats (RT1(1)). Controls received no immunotherapy. Experimental recipients were treated with a single i.p. injection of either human immunoglobulin (Ig)G (0.5 mg/body) or CTLA4Ig (0.5 mg/body) according to different time schedules. Graft survival time and histopathological changes for each experimental group were evaluated and statistically compared. Results. Graft survival times were prolonged significantly in rats treated with CTLA4Ig on day 1 and day 2 after transplantation, compared with survival times of controls. In particular, the most significant prolongation was found in rats treated on day 2. At 7 days after transplantation, moderate-to-severe histological rejection occurred in all tissues in control rats. On the other hand, in rats treated with CTLA4Ig, all tissues showed significantly better preservation. Among these treated rats, the rats treated on day 2 showed excellent histopathological conditions in each tissue. Conclusions. This study supports the feasibility of using CTLA4Ig for preventing acute rejection in CTA. On the basis of the current results, the administration of CTLA4Ig for CTA is more effective at 24-48 hr after transplantation, after the initial immune response has been allowed to begin.
• Modification of the Sauve-Kapandji procedure with extensor carpi ulnaris tenodesis

  A Minami, H Kato, N Iwasaki

  JOURNAL OF HAND SURGERY-AMERICAN VOLUME 25A (6) 1080 - 1084 0363-5023 2000/11 [Refereed][Not invited]
   

  The Sauve-Kapandji procedure is a useful treatment option for osteoarthritis of the distal radioulnar joint. Recent reports of a painful unstable proximal ulnar stump prompted us to develop a method of stabilizing the proximal stump of the ulna during the Sauve-Kapandji procedure by using a half-slip of the extensor carpi ulnaris. Thirteen osteoarthritic wrists (8 primary and 5 traumatic) in 8 men and 5 women with an average age of 50 years were treated by this method. The length of the follow-up periods averaged 36 months. Pain improved in all patients after surgery but pain was elicited over 1 ulnar stump by direct pressure. Both pronation/supination and flexion/extension had statistically significant improvement with the exception of flexion. Grip strength improved in all wrists after surgery. Postoperative x-rays improved alignment in both corona[ and lateral planes. Stabilization of the proximal ulnar stump associated with Sauve-Kapandji procedure is a useful procedure to prevent an unstable ulnar stump in the treatment of osteoarthritis of the distal radioulnar joint. Copyright (C) 2000 by the American Society for Surgery of the Hand.
• Vascularised fibular grafts - An experience of 102 patients

  A Minami, T Kasashima, N Iwasaki, H Kato, K Kaneda

  JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME 82B (7) 1022 - 1025 0301-620X 2000/09 [Refereed][Not invited]
   

  The results and complications of 104 vascularised I fibular grafts in 102 patients are presented. Bony union was ultimately achieved in 97 patients, with primary union in 84 (84%), The mean time to union was 15.5 weeks (8 to 40), In 13 patients, primary union was achieved at one end of the fibula and secondary union at the other end. In these patients, the mean time to union was 31.1 weeks (24 to 40), Five patients failed to achieve union, with a resultant pseudarthrosis (3 patients) or amputation (2 patients). There were various complications. Immediate thrombosis occurred in 14 cases. In two of 23 patients with osteomyelitis, infection recurred at two and six months after surgery, respectively. Both patients had active osteomyelitis less than one month before the operation, Bony infection occurred in a patient with a synovial sarcoma of the forearm one year after surgery. In 15 patients, 19 fractures of the fibular graft occurred after bony union, all except one within one year after union. In patients in whom an external fixator had been used, fracture occurred soon after its removal. Union was difficult to achieve in cases of congenital pseudarthrosis of the tibia, Appropriate alignment of the fibular graft is an important factor in preventing stress fracture. The vascularised fibula should be protected during the first year after union. Postoperative complications at the donor site included transient palsy of the superficial peroneal nerve in three patients, contracture of flexor hallucis longus in two and valgus deformity of the ankle in three. Vascularised fibular grafts are useful in the reconstruction of massive bony defects. We believe that meticulous preoperative planning, including choosing which vessels to select in the recipient and the type of fixation devices to use, and care in the introduction of the vascularised fibula, can improve the results and prevent complications.
• Force distribution through the wrist joint in patients with different stages of Kienbock's disease: Using computed tomography osteoabsorptiometry

  N Iwasaki, A Minami, T Miyazawa, K Kaneda

  JOURNAL OF HAND SURGERY-AMERICAN VOLUME 25A (5) 870 - 876 0363-5023 2000/09 [Refereed][Not invited]
   

  The pattern of subchondral bone density has been considered to reflect the stress distribution that occurs under physiologic loading conditions. To determine the force distribution through the wrist joint with Kienbock's disease in living subjects, we applied a computed tomography osteoabsorptiometry and investigated the subchondral bone density pattern across the radiocarpal joint of 6 normal subjects and 10 patients suffering from Kienbock's disease (Lichtman's stage IIIA, 5 patients; stage IIIB, 5 patients). A single density maximum was found in Each scaphoid and lunate fossa in all normal subjects. Among the subjects with Kienbock's disease, the current analysis demonstrated that the density maximum area significantly increased in the scaphoid fossa and decreased in the lunate fossa from stage IIIA to IIIB group. These findings indicate that the load is shifted away from the lunate to the scaphoid with the progression of Kienbock's disease in living subjects. (J Hand Surg 2000;25A:870-876. Copyright (C) 2000 by the American Society for Surgery of the Hand.).
• Coracoacromial arch decompression in rotator cuff surgery

  N Suenaga, A Minami, N Iwasaki, K Kaneda

  INTERNATIONAL ORTHOPAEDICS 24 (4) 212 - 216 0341-2695 2000/09 [Refereed][Not invited]
   

  In rotator cuff surgery it is important to obtain adequate decompression of the coracoacromial arch. However, it is difficult to localize the impingement site preoperatively. Based on histological and morphological studies and the clinical findings in 45 patients and 15 cadavers, we have tried to determine the impingement site. In addition, as a part of these investigations, we assessed the clinical outcome for 100 patients. Soft tissue decompression was indicated in 12 shoulders, anterior acromioplasty in 67 and anterior acromioplasty with coracoplasty in 21. According to Neer's criteria there were 92 satisfactory and 8 unsatisfactory results. The mean postoperative UCLA scorn was 33.4 points and the results were rated excellent in 78, good in 18 and fair in 4.
• Distally-based free vascularized tissue grafts in the lower leg

  A Minami, H Kato, N Suenaga, N Iwasaki

  JOURNAL OF RECONSTRUCTIVE MICROSURGERY 15 (7) 495 - 499 0743-684X 1999/10 [Refereed][Not invited]
   

  In the field of orthopaedic surgery, the lower leg is often treated by free vascularized tissue grafts. In performing these grafts for reconstruction of the lower leg, the anterior tibial artery and its venae comitantes are frequently selected as anastomosing recipient vessels. However, due to the deep location of the anterior tibial vessels, it is extremely difficult to accomplish antegrade microsurgical anastomoses between the donor vessels and the anterior tibial vessels. This technical difficulty often leads to the possibility of immediate postoperative arterial and venous occlusion. To resolve this problem, the idea of a reverse-flow island flap has been applied to the free vascularized tissue grafts for reconstruction of the lower leg, based on both artery and vein reconstructed with retrograde blood flow. To evaluate clinical outcomes of the procedure mentioned, the postoperative results of 14 patients were reviewed. The free vascularized grafts consisted of seven vascularized fibular grafts with peroneal flaps, six vascularized latissimus dorsi myocutaneous flaps, and one vascularized groin flap. Venous congestion of the flap was not observed and all flaps survived. Bone union was obtained in seven patients treated with vascularized fibular grafts. There were no serious postoperative complications. Distally-based free vascularized tissue grafts in the lower leg are useful procedures in reconstruction of massive bone defects and osteomyelitis of the tibia, and for skin defects on the anterior aspect of the lower leg.
• Total wrist arthrodesis using bowed crossed K-wires

  A Minami, H Kato, N Iwasaki

  JOURNAL OF HAND SURGERY-BRITISH AND EUROPEAN VOLUME 24B (4) 410 - 415 0266-7681 1999/08 [Refereed][Not invited]
   

  A method of total mist arthrodesis using a combination of autogenous iliac crest bone graft and "bowed" crossed Kirschner sires is described. The method of bowing the K-wires results in a compressive force on the iliac bone graft. This technique resulted in bony union of 22 wrists in 20 patients. The mean time to union was 12 seeks (range, 8-14 weeks). There were no major postoperative complications. The advantages of this technique are its simplicity, versatility; and reliability which mean that special internal fixation devices are not needed.
• Limited wrist fusions: Comparison of results 22 and 89 months after surgery

  A Minami, H Kato, N Iwasaki, M Minami

  JOURNAL OF HAND SURGERY-AMERICAN VOLUME 24A (1) 133 - 137 0363-5023 1999/01 [Refereed][Not invited]
   

  Limited wrist arthrodeses were performed to treat wrist diseases other than rheumatoid arthritis. The purpose of this study was to evaluate whether clinical and radiographic results noted 22 months after the procedure were maintained on re-examination an average of 89 months (range, 66-148 months) after the procedure. The study comprised 17 wrists. The average patient age was 42 years (range, 11-65 years). Two patients, both with Kienbock's disease, were lost to follow-up. Four radiocarpal and 11 intercarpal arthrodeses were performed. The range of motion between the first and second follow-up examination showed no significant difference. Grip strength likewise was nearly identical at both visits. At the last follow-up visit, progression of osteoarthrosis about the fusion area was noted in only 1 patient. These results suggest that the clinical and radiographic results at 22 months were maintained at the final follow-up visit and that the effect of limited wrist fusion does not deteriorate. (J Hand Surg 1999;24A:133-137. Copyright (C) 1999 by the American Society for Surgery of the Hand.)

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  松岡正剛, 小野寺智洋, 岩崎倫政  整形・災害外科  66-  (12)  2023
• 高純度アルギン酸ゲルを用いた運動器再生医療開発

  小野寺智洋, 門間太輔, 馬場力哉, 松岡正剛, 岩崎浩司, 山口純, 斎藤充, 長濱宏治, 岩崎倫政  日本整形外科学会雑誌  97-  (8)  2023
• 肘軟骨損傷に対する再生治療アプローチ-硝子様軟骨による修復・再生を目指して-

  門間太輔, 近藤英司, 小野寺智洋, 岩崎倫政  日本整形外科学会雑誌  97-  (8)  2023
• 三次元動作解析による内側型変形性膝関節症患者におけるVarus Thrustの運動学的特徴の検討

  岩崎浩司, 大越康充, 館山唯, 三浦浩太, 浮城健吾, 川上健作, 鈴木昭二, 小野寺智洋, 近藤英司, 岩崎倫政  日本整形外科学会雑誌  97-  (8)  2023
• 高位脛骨骨切り術後の非術側膝の生体工学的変化

  岩崎浩司, 大越康充, 笹谷一輝, 櫻井茂幸, 浮城健吾, 川上健作, 鈴木昭二, 前田龍智, 小野寺智洋, 近藤英司, 岩崎倫政  日本整形外科学会雑誌  97-  (8)  2023
• 脛骨関節面の軟骨下骨の骨密度分布に関わる半月板逸脱の評価方法の検討

  岩崎浩司, 佐藤知哉, 濱崎雅成, 鈴木裕貴, 小野寺智洋, 近藤英司, 岩崎倫政  日本整形外科学会雑誌  97-  (8)  2023
• 内側閉鎖式大腿骨遠位内反骨切り術が大腿脛骨関節の応力分布に与える効果-CT osteoabsorptiometry法を用いた検討-

  濱崎雅成, 近藤英司, 鈴木裕貴, 松岡正剛, 岩崎浩司, 小野寺智洋, 井上雅之, 安田和則, 八木知徳, 岩崎倫政  日本整形外科学会雑誌  97-  (8)  2023
• 高純度アルギン酸ゲル移植術後3年の臨床成績の検討

  小野寺智洋, 門間太輔, 松岡正剛, 岩崎浩司, 近藤英司, 鈴木孝治, 井上雅之, 岩崎倫政  日本整形外科学会雑誌  97-  (8)  2023
• 脛骨関節面の骨密度分布に半月板逸脱と下肢アライメントが与える影響

  岩崎浩司, 佐藤知哉, 濱崎雅成, 鈴木裕貴, 松岡正剛, 小野寺智洋, 近藤英司, 岩崎倫政  日本整形外科学会雑誌  97-  (8)  2023
• 診断時遠隔転移を有する四肢発生原発性悪性骨腫瘍の原発巣切除が生存に与える影響-米国SEERデータベースを用いた研究-

  福田龍一, 松岡正剛, 小野寺智洋, 岩崎浩司, 鈴木裕貴, 濱崎雅成, 近藤英司, 岩崎倫政  日本整形外科学会雑誌  97-  (8)  2023
• 四肢原発悪性骨腫瘍症例における患肢温存術と切断術の比較-米国SEERデータベースを用いた研究-

  柳澤那由他, 松岡正剛, 小野寺智洋, 岩崎浩司, 鈴木裕貴, 濱崎雅成, 近藤英司, 岩崎倫政  日本整形外科学会雑誌  97-  (8)  2023
• 変形性膝関節症の重症度別外的膝関節モーメント成分の寄与率変化の検討

  鈴木裕貴, 鈴木裕貴, 小野寺智洋, 岩崎倫政, 大越康充, 前田龍智, 川上健作, 清水健太, 千田周也, 浮城健吾, 岩崎浩司, 鈴木昭二, 近藤英司  日本関節病学会誌(Web)  42-  (4)  2023
• 踵骨を含めた下肢アライメントX線画像評価と膝関節内反モーメントの関係

  塩田惇喜, 塩田惇喜, 大越康充, 井上貴博, 浮城健吾, 川上健作, 前田龍智, 岩崎浩司, 岩崎浩司, 小野寺智洋, 近藤英司, 岩崎倫政  日本足の外科学会雑誌  44-  (Supplement)  2023
• 重度外反母趾変形に対してParallel cut deviceを用いたLapidus変法の臨床成績の検討

  小野寺智洋, 松岡正剛, 岩崎浩司, 甲斐原拓真, 濱崎雅成, 江畑拓, 原健人, 近藤英司, 岩崎倫政  日本足の外科学会雑誌  44-  (Supplement)  2023
• 広範な膝軟骨損傷に対するアテロコラーゲンを用いた自家培養軟骨移植術後の活動レベルの変化

  甲斐原拓真, 甲斐原拓真, 近藤英司, 小野寺智洋, 門間太輔, 岩崎倫政  日本臨床スポーツ医学会誌  31-  (4)  2023
• 変形性膝関節症患者における歩行中の膝関節内側荷重量とKinematicsの関連

  佐橋健人, 渡邊謙太郎, 千徳風真, 千葉健, 岩崎浩司, 小野寺智洋, 岩崎倫政, 近藤英司, 遠山晴一  北海道整形災害外科学会  142nd-  2023
• Mechanisms of tendon tissue repair using alginate-cell cross-linked gel

  山口純, 山口純, 小野寺智洋, 宝満健太郎, 松岡正剛, 長濱宏冶, 上田菜摘, 澤田志穂, 斎藤充, 岩崎倫政  日本バイオマテリアル学会大会予稿集(Web)  45th-  2023
• 足部ウェアラブルデバイスによる歩行解析の妥当性と臨床研究の実際

  角家健, 宝満健太郎, 岩崎倫政  日本臨床スポーツ医学会誌  31-  (4)  2023
• アルギン酸-細胞間架橋ゲルによる腱組織修復機序の解明

  山口純, 山口純, 小野寺智洋, 宝満健太郎, 松岡正剛, 長濱宏治, 上田菜摘美, 澤田志穂, 斎藤充, 岩崎倫政  日本整形外科学会雑誌  97-  (8)  2023
• 深度カメラと機械学習の応用による全身を対象とした歩行解析-前十字靱帯再建術後の歩行識別の試み-

  宝満健太郎, 角家健, 三宅賢稔, 三宅賢稔, 浮城健吾, 福井大輔, 中川弘充, 田中毅, 片岸誠, 大越康充, 禰寝義人, 岩崎倫政  日本整形外科学会雑誌  97-  (8)  2023
• ケモカイン受容体CCR7欠損は小児骨端線損傷後における成長抑制を予防する

  松岡正剛, 金佑泳, 坂井裕子, 福田龍一, 松ヶ崎圭純, 宝満健太郎, 小野寺智洋, 岩崎倫政  日本整形外科学会雑誌  97-  (8)  2023
• 全身を対象とした動作解析によるACL再建者の歩行識別:深度カメラと機械学習の応用

  宝満健太郎, 岩崎倫政, 角家健, 三宅賢稔, 三宅賢稔, 片岸誠, 禰寝義人, 浮城健吾, 井上貴博, 大越康充, 福井大輔, 中川弘充, 田中毅  北海道整形災害外科学会  142nd-  2023
• Mechanisms of tendon tissue repair using alginate-cell cross-linked gel

  山口純, 山口純, 小野寺智洋, 宝満健太郎, 松岡正剛, 長濱宏冶, 上田菜摘美, 澤田志穂, 斎藤充, 岩崎倫政  日本軟骨代謝学会プログラム・抄録集  35th-  2023
• Intercomparison of all glycans expressed in osteoarthritic cartilage

  宝満健太郎, 小野寺智洋, 花松久寿, 古川潤一, 松ヶ崎圭純, LIU Yue, KIM WooYoung, 松岡正剛, 岩崎倫政  日本軟骨代謝学会プログラム・抄録集  35th-  2023
• 広範な膝軟骨欠損に対するアテロコラーゲンを用いた自家培養軟骨移植の中期臨床成績

  甲斐原拓真, 濱崎雅成, 鈴木裕貴, 松岡正剛, 小野寺智洋, 岩崎倫政, 近藤英司, 岩崎浩司, 小田義崇, 種井善一, 田中伸哉  北海道整形災害外科学会  142nd-  2023
• 歩行時下垂足の客観的指標としてのウェアラブルセンサーの活用

  佐伯拓馬, 斉藤貴志, 林達也, 石田直樹, 角谷健, 岩崎倫政, 宝満健太郎  運動器理学療法学(Web)  3-  (Supplement)  2023
• 歩行撮影とAIを使用した変形性膝関節症の新規診断方法の開発

  角家健, 宝満健太郎, 三宅賢稔, 三宅賢稔, 浮城健吾, 福井大輔, 中川弘充, 田中毅, 深水竜介, 大越康充, 禰寝義人, 岩崎倫政  日本整形外科学会雑誌  97-  (2)  2023
• VCP化合物による脊髄損傷後血液脊髄関門機能保護作用

  鈴木 裕貴, 角家 健, 五月女 慧人, 遠藤 健, 船木 智, 周東 智, 前仲 勝実, 岩崎 倫政  日本整形外科学会雑誌  96-  (8)  S1631  -S1631  2022/09
• 次硝酸ビスマスの急性期脊髄損傷に対する神経保護効果とその機序の解明

  五月女 慧人, 角家 健, 鈴木 裕貴, 遠藤 健, 中川 慎介, 前仲 勝実, 岩崎 倫政  日本整形外科学会雑誌  96-  (8)  S1691  -S1691  2022/09
• DXAで診測した閉経後骨粗鬆症患者の下肢、体幹筋量の推移 COVID-19パンデミック下での調査

  田中 将, 金山 雅弘, 大羽 文博, 嶋村 之利, 辻本 武尊, 長谷川 裕一, 橋本 友幸, 野尻 英俊, 岩崎 倫政, 石島 旨章  日本整形外科学会雑誌  96-  (3)  S918  -S918  2022/03
• 初診時遠隔転移を有する椎体発生悪性骨腫瘍において原発巣切除は生存を改善するか 米国SEERデータベースを用いた研究

  松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 菱村 亮介, 鈴木 裕貴, 岩田 玲, 近藤 英司, 岩崎 倫政  日本整形外科学会雑誌  96-  (3)  S1157  -S1157  2022/03
• 大菱形骨の骨形態の違いが母指CM関節における応力に及ぼす影響-CTOAM法を用いた解析-

  佃幸憲, 松井雄一郎, 遠藤香織, 松居祐樹, 平塚重人, 濱崎雅成, 宮野真博, 河村太介, 岩崎倫政  日本整形外科学会雑誌  96-  (3)  2022
• 膝軟骨欠損に対するアテロコラーゲンを用いた自家培養軟骨移植の臨床成績-3年以上経過例について

  甲斐原拓真, 近藤英司, 濱崎雅成, 鈴木裕貴, 岩崎浩司, 松岡正剛, 小野寺智洋, 小田義崇, 種井善一, 田中伸哉, 岩崎倫政  整形外科バイオマテリアル研究会プログラム・抄録集  41st-  2022
• 歩行撮影と機械学習を使用した変形性膝関節症の新規診断方法の開発

  角家健, 宝満健太郎, 三宅賢稔, 三宅賢稔, 浮城健吾, 福井大輔, 中川弘充, 田中毅, 深水竜介, 大越康充, 禰寝義人, 岩崎倫政  日本整形外科学会雑誌  96-  (8)  2022
• アルギン酸-細胞間架橋ゲルによる腱組織修復効果の検討

  山口純, 山口純, 小野寺智洋, 宝満健太郎, 松岡正剛, 細川吉暁, 岩崎倫政, 斎藤充, 長濱宏治, 上田菜摘美, 澤田志穂  日本整形外科学会雑誌  96-  (8)  2022
• 酸素-17安定同位体標識水を水トレーサーとして用いたMRIによる関節軟骨病変評価法の確立

  細川吉暁, 小野寺智洋, 亀田浩之, 宝満健太郎, 山口純, 工藤與亮, 杉森博之, 岩崎倫政  日本整形外科学会雑誌  96-  (8)  2022
• 総合グライコミクスアプローチによる変形性関節症標的分子の探索

  宝満健太郎, 小野寺智洋, 花松久寿, 古川潤一, 山口純, 細川吉暁, 金佑泳, 松岡正剛, 岩崎倫政  日本整形外科学会雑誌  96-  (8)  2022
• Gait analysis by foot wearable device: its validity and application for clinical study

  角家健, 宝満健太郎, 岩崎倫政  日本関節病学会誌(Web)  41-  (3)  2022
• 歩行撮影とAIを使用した運動器疾患診断方法の開発

  角家健, 宝満健太郎, 三宅賢稔, 三宅賢稔, 浮城健吾, 福井大輔, 中川弘充, 田中毅, 深水竜介, 大越康充, 禰寝義人, 岩崎倫政  日本骨代謝学会学術集会プログラム抄録集(CD-ROM)  40th-  2022
• 軟骨統合グライコミクスによる変形性関節症標的因子の探索

  宝満健太郎, 小野寺智洋, 花松久寿, 古川潤一, 山口純, 細川吉暁, 松ヶ崎圭純, 金佑泳, 松岡正剛, 岩崎倫政  北海道整形災害外科学会  141st-  2022
• 歩行撮影とAIを使用した変形性膝関節症の新規診断方法の開発

  角家健, 三宅賢稔, 宝満健太郎, 岩崎倫政, 三宅賢稔, 深水竜介, 禰寝義人, 浮城健吾, 大越康充, 福井大輔, 中川弘, 田中毅  北海道整形災害外科学会  141st-  2022
• 平滑筋弛緩薬パパベリンの新規効能:血液脊髄関門保護を介した脊髄損傷に対する神経保護効果

  鈴木裕貴, 角家健, 五月女慧人, 遠藤健, 浅野毅, 前仲勝実, 中川慎介, 岩崎倫政  日本整形外科学会雑誌  96-  (2)  2022
• O-17標識水を水トレーサーとして用いたMRIによる関節軟骨病変評価法の確立

  細川吉暁, 小野寺智洋, 宝満健太郎, 工藤與亮, 亀田浩之, 杉森博之, 岩崎倫政  日本整形外科学会雑誌  96-  (2)  2022
• 変形性膝関節症の新規スクリーニング方法の開発-歩行撮影による歩行解析-

  角家健, 宝満健太郎, 浮城健吾, 三宅賢稔, 三宅賢稔, 深水竜介, 禰寝義人, 大越康充, 岩崎倫政  日本整形外科学会雑誌  96-  (2)  2022
• アルギン酸-細胞間架橋ゲルを用いた腱組織修復の検討

  山口純, 山口純, 小野寺智洋, 宝満健太郎, 長濱宏冶, 上田菜摘美, 澤田志穂, 斎藤充, 岩崎倫政  日本整形外科学会雑誌  96-  (3)  2022
• Tendon tissue repair using alginate-cell cross-linked gel

  山口純, 山口純, 小野寺智洋, 宝満健太郎, 細川吉暁, 長濱宏冶, 上田菜摘美, 澤田志穂, 斎藤充, 岩崎倫政  日本軟骨代謝学会プログラム・抄録集  34th-  2022
• Deficiency of fucosylated glycan in articular cartilage inhibits recovery from damage and promotes cartilage degeneration

  宝満健太郎, 小野寺智洋, 花松久寿, 古川潤一, 宮崎拓自, 山口純, 細川吉暁, LIANG Dawei, KIM Woo Young, 江畑拓, 木村洋介, 松岡正剛, 岩崎倫政  日本軟骨代謝学会プログラム・抄録集  34th-  2022
• 大腿四頭筋腱浅層を用いた内側膝蓋大腿靱帯(MPFL)再建術の術後短期臨床成績

  井上 千春, 青木 喜満, 金子 知, 安田 和則, 八木 知徳, 井上 雅之, 近藤 英司, 遠山 晴一, 岩崎 倫政  日本整形外科学会雑誌  95-  (3)  S812  -S812  2021/03
• 大腿骨顆間窩外側壁における骨密度分布:前十字靱帯の大腿骨付着部に関する考察

  菅原悠太郎, 遠藤香織, 菱村亮介, 松原新史, 松岡正剛, 小野寺智洋, 岩崎倫政, 岩崎浩司, 門間大輔, 近藤英司  北海道整形災害外科学会  139th-  2021
• 大腿骨顆間外側壁における骨密度分布:前十字靱帯の大腿骨付着部についての考察

  菅原悠太郎, 岩崎浩司, 遠藤香織, 菱村亮介, 松原新史, 松岡正剛, 門間太輔, 小野寺智洋, 近藤英司, 岩崎倫政  日本整形外科学会雑誌  95-  (8)  2021
• アキレス腱縫合術20年後に発症した腱縫合糸に対する感染性異物性肉芽腫の1例

  糸賀 稜, 松岡 正剛, 小野寺 智洋, 松原 新史, 菱村 亮介, 岩崎 倫政, 清水 亜衣, 岩崎 浩司, 近藤 英司  北海道整形災害外科学会雑誌  63-  (139th suppl)  79  -79  2021
• 変形性膝関節症症例におけるウェアラブルセンサーを用いた歩行評価時の最適なセンサー貼付位置の検討

  佐橋 健人, 千葉 健, 岩崎 浩司, 小野寺 智洋, 岩崎 倫政, 近藤 英司, 遠山 晴一  北海道整形災害外科学会雑誌  63-  (139th suppl)  35  -35  2021
• Analysis of ground reaction force passing point on the proximal tibial surface.

  井上貴博, 岩崎浩司, 大越康充, 川上健作, 鈴木昭二, 浮城健吾, 櫻井茂幸, 大森啓司, 井野拓実, 井野拓実, 前田龍智, 鈴木裕貴, 鈴木裕貴, 近藤英司, 岩崎倫政  臨床バイオメカニクス  42-  2021
• 歩行動画によるロコモ評価システムの開発

  角家健, 山本強, 宝満健太郎, 岩崎倫政  医科学応用研究財団研究報告(CD-ROM)  38-  2021
• 細胞特異的糖鎖解析による定量評価を応用した未分化iPS細胞除去条件の最適化

  宮崎拓自, 小野寺智洋, 花松久寿, 古川潤一, 宝満健太郎, 川嵜敏祐, 岩崎倫政  日本整形外科学会雑誌  95-  (8)  2021
• マウス成長板軟骨損傷後にb-seriesガングリオシドが果たす役割

  細川吉暁, 松岡正剛, 小野寺智洋, 宝満健太郎, 金佑泳, 岩崎倫政  日本整形外科学会雑誌  95-  (8)  2021
• アルギン酸-細胞間架橋ゲルを用いた腱組織修復の検討

  山口純, 山口純, 小野寺智洋, 宝満健太郎, 長濱宏治, 上田菜摘美, 澤田志穂, 斎藤充, 岩崎倫政  日本整形外科学会雑誌  95-  (8)  2021
• Tendon tissue repair using alginate-cell cross-linked gel

  山口純, 山口純, 小野寺智洋, 宝満健太郎, 細川吉暁, 長濱宏治, 上田菜摘美, 澤田志穂, 斎藤充, 岩崎倫政  整形外科バイオマテリアル研究会プログラム・抄録集  40th-  2021
• マウス成長板軟骨損傷後に糖脂質ガングリオシドが果たす役割

  細川吉暁, 松岡正剛, 小野寺智洋, 宝満健太郎, 金佑泳, 岩崎倫政  北海道整形災害外科学会  140th-  2021
• 歩行解析研究に汎用される10m直線歩行は普段の歩行を代表しているか-足部時空間パラメーターによる検討-

  角家健, 種田健二, 宝満健太郎, 須田浩太, 松本聡子, 石田直樹, 武田直樹, 大越康充, 大野和則, 菅原誠, 三浪明男, 岩崎倫政  日本整形外科学会雑誌  95-  (2)  2021
• 免疫受容体Siglec-15は生理的骨吸収制御する主要調節因子である

  小林英之, 高畑雅彦, 太田昌博, 清水智弘, 佐藤大, 藤田諒, 岩崎倫政, 長谷川智香, 網塚憲生  北海道整形災害外科学会  140th-  2021
• 歩行解析研究に汎用される10m直線歩行は普段の歩行を代表しているか?:足部時空間パラメータによる検討

  角家健, 宝満健太郎, 岩崎倫政, 種田健二, 須田浩太, 松本聡子, 三浪明男, 石田直樹, 武田直樹, 大越康充, 大野和則, 菅原誠  北海道整形災害外科学会  139th-  2021
• 細胞特異的糖鎖解析の手法を用いた残存未分化iPS細胞の定量的評価法の確立

  宮崎拓自, 小野寺智洋, 徐亮, 宝満健太郎, 岩崎倫政, 花松久寿, 古川潤一  北海道整形災害外科学会  139th-  2021
• 平滑筋弛緩薬パパベリンの新規効能:血液脊髄関門保護を介した脊髄損傷に対する神経保護効果

  鈴木裕貴, 角家健, 五月女慧人, 遠藤健, 浅野毅, 岩崎倫政, 中川慎介, 前仲勝実  北海道整形災害外科学会  139th-  2021
• Glycolipid Expression Analysis Of Chondrocyte-like Cells Derived From Human Induced Pluripotent Stem Cells (hipsc).

  Liang Xu, Tomohiro Onodera, Jun-ichi Furukawa, Hisatoshi Hanamatsu, Kentaro Homan, Kazutoshi Hontani, Takuji Miyazaki, Yuan Tian, Norimasa Iwasaki  The 66th Annual Meeting of Orthopaedic Research Society (ORS)  45-  (PS2-2263)  2020/02  [Not refereed][Not invited]
  
• 四次元CTを用いた肩甲上腕関節の解析

  門間太輔, 井上望, 遠藤香織, 河村太介, 瓜田淳, 松井雄一郎, 岩崎倫政  日本整形外科学会雑誌  94-  (8)  2020
• 4次元CTを用いた肩甲上腕関節接触面の解析

  門間太輔, 井上望, 遠藤香織, 河村太介, 瓜田淳, 松井雄一郎, 岩崎倫政  日本肩関節学会抄録集  47th-  2020
• Stress distribution patterns through the subchondral bone density of the proximal tibia in anterior cruciate ligament injured knee assessed using computed tomography osteoabsorptiometry.

  三浦宗也, 岩崎浩司, 近藤英司, 岩崎倫政  臨床バイオメカニクス  41-  2020
• 胸椎後縦靱帯骨化症の骨化進展に関与する補酵素(ビタミン)の血清学的評価

  遠藤 努, 高畑 雅彦, 小池 良直, 久田 雄一郎, 岩崎 倫政, 今釜 史郎, 安藤 圭, 小林 和克, 加藤 仁志, 海渡 貴司, 金山 雅弘, 川口 善治, 坂井 宏旭, 池川 志郎  北海道整形災害外科学会雑誌  62-  (138th suppl)  10  -10  2020
• Serological evaluation of coenzymes (Vitamin) involved in the progress of ossification of the posterior longitudinal ligament in thoracic spine

  遠藤努, 高畑雅彦, 小池良直, 久田雄一郎, 今釜史郎, 安藤圭, 小林和克, 加藤仁志, 海渡貴司, 金山雅弘, 川口善治, 坂井宏旭, 岩崎倫政, 池川志郎  Journal of Spine Research (Web)  11-  (3)  2020
• ウサギ椎間板ヘルニアモデルにおける高純度硬化性ゲルの椎間板内炎症抑制効果についての検討

  浦勝郎, 筌場大介, 辻本武尊, 岩崎倫政, 須藤英毅  北海道整形災害外科学会  138th-  2020
• ウサギ髄核摘出モデルにおける高純度硬化性ゲルと自家骨髄濃縮液による組織修復効果

  筌場大介, 浦勝郎, 辻本武尊, 岩崎倫政, 須藤英毅  北海道整形災害外科学会  138th-  2020
• 骨髄由来間葉系幹細胞による椎間板細胞治療

  須藤英毅, 須藤英毅, 筌場大介, 岩崎倫政  日本再生医療学会総会(Web)  19th-  2020
• ウェアラブルシステムを使用した慢性期片麻痺患者の歩行解析(第2報):足部クリアランスと転倒の関連に関する検討

  佐伯拓馬, 斉藤貴志, 林達也, 石田直樹, 宝満健太郎, 角家健, 岩崎倫政  北海道整形災害外科学会  138th-  2020
• OCT(光干渉断層計)を用いたゲル内細胞分布の三次元解析

  山口純, 山口純, 小野寺智洋, 宝満健太郎, 岩崎倫政, 丸毛啓史, 斎藤充  日本整形外科学会雑誌  94-  (8)  2020
• 骨軟骨欠損に対する高純度アルギン酸ゲルと骨髄穿刺濃縮細胞併用移植の検討

  徐 亮, 瓜田 淳, 小野寺 智洋, 菱村 亮介, 宝満 健太郎, 岩崎 倫政  整形外科バイオマテリアル研究会  39th-  15  2019/12  [Not refereed][Not invited]
  
• OCT（光干渉断層計）を用いたゲル内細胞分布の3次元解析

  山口 純, 小野寺 智洋, 宝満 健太郎, 岩崎 倫政  整形外科バイオマテリアル研究会  39th-  5  2019/12  [Not refereed][Not invited]
  
• 半月板修復に寄与する細胞種の探求

  宝満 健太郎, 小野寺 智洋, 金 佑泳, 近藤 英司, 岩崎 倫政  整形外科バイオマテリアル研究会  39th-  17  2019/12  [Not refereed][Not invited]
  
• 半月板の再生を司るのは半月板か、滑膜か? －凍結解凍法を用いた家兎半月板損傷モデルの研究 －

  宝満 健太郎, 小野寺 智洋, 金 佑泳, 近藤英司, 岩崎 倫政  第41回日本バイオマテリアル学会大会  筑波-  2019/11  [Not refereed][Not invited]
  
• The Selective Removal Method of Undifferentiated iPS Cells Using Specifi c Antibody for Cartilage Regenerative Medicine.

  T. Miyazaki, T. Onodera, L. Xu, H. Hanamatsu, J. Furukawa, K. Homan, M. Hamasaki, R. Hishimura, T. Kawasaki, N. Iwasaki  World Congress of International Chemical Reference Substances (ICRS)  15-  (P174)  2019/10  [Not refereed][Not invited]
  
• 骨軟骨欠損に対する骨髄穿刺濃縮細胞と高純度アルギン酸ゲル併用移植の検討

  XU L, 瓜田淳, 小野寺智洋, 菱村亮介, 濱崎雅成, 梁大偉, 宝満健太郎, 岩崎倫政  日本整形外科学会雑誌  93-  (8)  S1665  2019/09/09  [Not refereed][Not invited]
  
• 側弯検診システムの研究開発

  須藤英毅, 小甲晃史, 小甲晃史, 安倍雄一郎, 岩崎倫政, 金井理  臨床整形外科  54-  (3)  306‐310  2019/03  [Not refereed][Not invited]
  
• 半月板と滑膜の半月板組織再生への寄与度の比較研究

  KIM WooYoung, 小野寺智洋, 近藤英司, 宝満健太郎, 菱村亮介, 岩崎倫政  日本軟骨代謝学会プログラム・抄録集  32nd-  88  2019/03  [Not refereed][Not invited]
  
• 脊椎脊髄疾患診療における費用対効果について 脊髄損傷に対する手術治療の費用対効果 QALY・ICERのシミュレーション

  須田 浩太, 松本 聡子, 小松 幹, 太田 昌博, 辻本 武尊, 東條 泰明, 宇都宮 祥弘, 高畑 雅彦, 岩崎 倫政  日本整形外科学会雑誌  93-  (2)  S316  -S316  2019/03  [Not refereed][Not invited]
  
• Which Contributes To Meniscal Regeneration, Synovium Or Meniscus? -in Vivo Rabbit Model Study With Ultrapurified Low Endotoxin Alginate (upal) Gel And Freeze-thaw Method-.

  WooYoung Kim, Tomohiro Onodera, Eiji Kondo, Mohamad A. Terkawi, Kentaro Homan, Ryosuku Hishimura, Norimasa Iwasaki  The 65th Annual Meeting of Orthopaedic Research Society (ORS)(New Investigator Recognition Award (NIRA) finalist)  44-  (27-154)  2019/02  [Not refereed][Not invited]
  
• Validation of the Wearable Sensor System Estimating Spatiotemporal Gait Parameters by Simultaneous 3D Optical Motion Analysis.

  Kentaro Homan, Ken Kadoya, Keizo Yamamoto, Norimasa Iwasaki  The 65th Annual Meeting of Orthopaedic Research Society (ORS)  44-  (PS1-054)  2019/02  [Not refereed][Not invited]
  
• 骨粗鬆症性椎体骨折後早期に生じるドミノ骨折および椎体圧潰の病態

  高畑雅彦, 岩田玲, 遠藤香織, 浦勝郎, 岩崎倫政  日本骨形態計測学会雑誌  29-  (1)  2019
• 無症候性野球選手における肩甲上腕関節の動作解析-4次元computed tomographyを用いて-

  門間太輔, 遠藤香織, 河村太介, 瓜田淳, 松井雄一郎, 濱野博基, 本谷和俊, 岩崎倫政  日本臨床スポーツ医学会誌  27-  (3)  2019
• ウサギ椎間板ヘルニアモデルにおける高純度硬化性ゲルの椎間板内炎症抑制効果についての検討

  浦勝郎, 須藤英毅, 辻本武尊, 筌場大介, 岩崎倫政  整形外科バイオマテリアル研究会プログラム・抄録集  39th-  2019
• 高純度硬化性ゲルを併用した椎間板細胞治療における各種骨髄由来間葉系幹細胞の効果

  筌場大介, 浦勝郎, 辻本武尊, 岩崎倫政, 須藤英毅  北海道整形災害外科学会  137th-  2019
• 軟骨再生医療への応用を標的とした未分化iPS細胞特異的除去法の検討

  宮崎拓自, 小野寺智洋, 徐亮, 花松久寿, 古川潤一, 宝満健太郎, 川嵜敏祐, 岩崎倫政  移植(Web)  54-  (4-5)  2019
• 造影超音波を用いた腱板大・広範囲断裂と小・中断裂における修復腱板内の血流パターンの違い

  瓜田 淳, 船越 忠直, 堀江 達則, 西田 睦, 岩崎 倫政  日本整形外科学会雑誌  92-  (8)  S1906  -S1906  2018/08
• 特発性側弯症手術に対して使用したロッドに対する形状類似分析手法の開発

  小甲晃史, 金井理, 安倍雄一郎, 岩崎倫政, 須藤英毅  Journal of Spine Research  9-  (3)  239  2018/03/25  [Not refereed][Not invited]
  
• 高純度アルギン酸ゲルを併用した骨髄刺激法の効果 ビーグル犬骨軟骨欠損モデルを用いて

  馬場 力哉, 小野寺 智洋, 本谷 和俊, 上徳 善太, 松原 新史, 宝満 健太郎, 岩崎 倫政  北海道整形災害外科学会雑誌  59-  (2)  250  -251  2018/03  [Not refereed][Not invited]
  
• CCL21/CCR7 Axis Regulating Juvenile Cartilage Repair Can Enhance Cartilage Healing In Adult.

  Zenta Joutoku, Tomohiro Onodera, Daisuke Momma, Masatake Matsuoka, Rikiya Baba, Kazutoshi Hontani, Shinji Matsubara, Ryosuke Hishimura, Norimasa Iwasaki  The 64th Annual Meeting of Orthopaedic Research Society (ORS)  43-  (12)  2018/03  [Not refereed][Not invited]
  
• 無症候性野球選手における肩甲上腕関節の動作解析-4次元computed tomographyを用いて-

  門間太輔, 遠藤香織, 河村太介, 瓜田淳, 松井雄一郎, 濱野博基, 本谷和俊, 岩崎倫政  日本臨床スポーツ医学会誌  26-  (4)  2018
• 骨軟骨柱移植術に高純度アルギン酸ゲル(UPALゲル)移植を併用した治療効果の検討

  菱村亮介, 小野寺智洋, 宝満健太郎, KIM Woo Yong, 濱崎雅成, XU Liang, 岩崎倫政  日本バイオマテリアル学会大会予稿集(Web)  40th-  166 (WEB ONLY)  -166  2018  [Not refereed][Not invited]
  
• 椎間板ブロックが変性椎間板細胞・組織に与える影響

  浦勝郎, 須藤英毅, 筌場大介, 辻本武尊, 岩崎倫政  日本整形外科学会雑誌  92-  (8)  2018
• 医工連携による椎間板再生治療用組織修復材の開発

  須藤英毅, 辻本武尊, 東藤正浩, 筌場大介, 浦勝郎, 岩崎倫政  日本整形外科学会雑誌  92-  (8)  2018
• 思春期特発性側弯症におけるロッド曲線形状の類似分析手法の開発

  小甲晃史, 金井理, 安倍雄一郎, 岩崎倫政, 須藤英毅  北海道整形災害外科学会  134th-  41  2018  [Not refereed][Not invited]
  
• 医工連携による次世代型脊柱変形矯正用インプラントの開発戦略

  須藤英毅, 金井理, 小甲晃史, 青柳健太, WANG Hao, 岩崎倫政, 千葉晶彦  日本バイオマテリアル学会大会予稿集(Web)  40th-  165 (WEB ONLY)  2018  [Not refereed][Not invited]
  
• ケモカインCCL21を用いた軟骨再生のためのインテリジェントマテリアルの開発

  上徳 善太, 小野寺 智洋, 松岡 正剛, 馬場 力哉, 本谷 和俊, 宝満 健太郎, 岩崎 倫政  日本バイオマテリアル学会大会予稿集  39回-  96  -96  2017/11/13  [Not refereed][Not invited]
  
• ケモカインCCL21を用いた軟骨再生のためのインテリジェントマテリアルの開発

  上徳 善太, 小野寺 智洋, 松岡 正剛, 馬場 力哉, 本谷 和俊, 宝満 健太郎, 岩崎 倫政  日本バイオマテリアル学会大会予稿集  39回-  96  -96  2017/11  [Not refereed][Not invited]
  
• 腱板大・広範囲断裂は修復腱板内の血行動態が小・中断裂と異なる

  瓜田 淳, 船越 忠直, 堀江 達則, 西田 睦, 岩崎 倫政  日本肩関節学会抄録集  44回-  75  -75  2017/10
• 自家骨軟骨柱移植術に高純度アルギン酸ゲルを併用した治療効果の検証

  菱村亮介, 小野寺智洋, 馬場力哉, 本谷和俊, 宝満健太郎, 松原新史, 上徳善太, 金佑泳, 岩崎倫政  日本整形外科学会雑誌  91-  (8)  S1727  -S1727  2017/08/31  [Not refereed][Not invited]
  
• 関節軟骨の再生医療 CCL21/CCR7は幼若個体での軟骨修復に重要である

  上徳 善太, 小野寺 智洋, 門間 太輔, 松岡 正剛, 馬場 力哉, 本谷 和俊, 松原 新史, 宝満 健太郎, 菱村 亮介, 金 佑泳, 濱崎 雅成, 徐 亮, 岩崎 倫政  日本整形外科学会雑誌  91-  (8)  S1467  -S1467  2017/08  [Not refereed][Not invited]
  
• Depletion Of Gangliosides Enhances Articular Cartilage Repair By Suppressing The Chondrocyte Hypertrophy.

  Masatake Matsuoka, Tomohiro Onodera, Kentaro Homan, Fumio Sasazawa, Daisuke Momma, Rikiya Baba, Kazutoshi Hontani, Zenta Joutoku, Shinji Matsubara, Ryosuke Hishimura, Norimasa Iwasaki  The 63th Annual Meeting of Orthopaedic Research Society (ORS)  2017/03  [Not refereed][Not invited]
  
• Effects Of Autologous Osteochondral Transplantation Augmented By Ultrapurified Alginate Gel In Rabbit Model.

  Ryosuke Hishimura, Tomohiro Onodera, Kazutoshi Hontani, Rikiya Baba, Kentaro Homan, Shinji Matsubara, Zenta Joutoku, WooYoung Kim, Norimasa Iwasaki  The 63th Annual Meeting of Orthopaedic Research Society (ORS)  2017/03  [Not refereed][Not invited]
  
• CCL21 Expressed in Cartilage Repair Process in Immature Mice and Accelerated Cartilage Repair.

  Zenta Joutoku, Tomohiro Onodera, Daisuke Momma, Masatake Matsuoka, Rikiya Baba, Kazutoshi Hontani, Shinji Matsubara, Kentaro Homan, Ryosuke Hishimura, Norimasa Iwasaki  The 63th Annual Meeting of Orthopaedic Research Society (ORS)  2017/03  [Not refereed][Not invited]
  
• The enzymatic cleavage of high-mannose type N-glycan induces recoverable cartilage degradation.

  Kentaro Homan, Tomohiro Onodera, Jun-ichi Furukawa, Daisuke Momma, Masatake Matsuoka, Rikiya Baba, Kazutoshi Hontani, Zenta Joutoku, Shinji Matsubara, Ryosuke Hishimura, Kim WooYoung, Masanari Hamasaki, Liang Xu, Norimasa Iwasaki  The 63th Annual Meeting of Orthopaedic Research Society (ORS)  2017/03  [Not refereed][Not invited]
  
• 無症候性野球選手における肩甲上腕関節の動作解析-四次元computed tomographyを用いて-

  門間太輔, 船越忠直, 遠藤香織, 庄野康弘, 永野裕介, 河村太介, 松井雄一郎, 岩崎倫政  日本整形外科学会雑誌  91-  (2)  2017
• プロ野球選手における肘関節応力分布の解析-CT osteoabsorptiometry法を用いた肘応力解析-

  門間太輔, 船越忠直, 横田正司, 遠藤香織, 永野裕介, 河村太介, 松井雄一郎, 岩崎倫政  日本整形外科学会雑誌  91-  (3)  2017
• 体操選手における手関節応力分布の解析-CT osteoabsorptiometry法を用いた手関節応力解析-

  門間太輔, 船越忠直, 岩本航, 遠藤香織, 松井雄一郎, 河村太介, 松本秀雄, 岩崎倫政  日本整形外科スポーツ医学会雑誌  37-  (4)  2017
• 3D-CTを用いた無症候性野球選手における肘尺側側副靭帯距離と関節裂隙の開大に関する評価

  門間太輔, 船越忠直, 遠藤香織, 松井雄一郎, 河村太介, 永野祐介, 岩崎倫政  日本整形外科スポーツ医学会雑誌  37-  (4)  2017
• 体操選手における手関節応力分布の解析-CT osteoabsorptiometry法を用いた手関節応力解析-

  門間太輔, 船越忠直, 岩本航, 遠藤香織, 河村太介, 永野裕介, 松井雄一郎, 濱野博基, 本谷和俊, 岩崎倫政, 松本秀男  日本整形外科学会雑誌  91-  (8)  2017
• マウスiPS細胞からの軟骨分化誘導と糖鎖解析を用いた新規バイオマーカーの探索

  本谷和俊, 小野寺智洋, 寺島理代, 門間太輔, 松岡正剛, 馬場力哉, 上徳善太, 松原新史, 宝満健太郎, 菱村亮介, 金佑泳, 濱崎雅成, 徐亮, 岩崎倫政  北海道整形災害外科学会  133rd-  (1)  145  -145  2017  [Not refereed][Not invited]
  
• 高純度アルギン酸gelを併用した骨髄刺激法の効果 ーbeagle犬骨軟骨欠損モデルを用いてー

  馬場力哉, 小野寺智洋, 本谷和俊, 上徳善太, 松原新史, 宝満健太郎, 岩崎倫政  日本バイオマテリアル学会シンポジウム2016  25  2016/10  [Not refereed][Not invited]
  
• ultra-purified alginate gel (UPAL gel) を用いたマウスiPS細胞からの軟骨分化誘導

  本谷和俊, 小野寺智洋, 寺島理代, 門間太輔, 松岡正剛, 馬場力哉, 上徳善太, 松原新史, 宝満健太郎, 菱村亮介, 金佑泳, 徐亮, 岩崎倫政  日本バイオマテリアル学会シンポジウム  13  2016/10  [Not refereed][Not invited]
  
• 骨軟骨再生に特異的に作用するケモカインの網羅的解析

  上徳善太, 小野寺智洋, 門間太輔, 松岡正剛, 馬場力哉, 本谷和俊, 松原新史, 宝満健太郎, 岩崎倫政  北海道整形災害外科学会雑誌  58-  (1)  82  -83  2016/10  [Not refereed][Not invited]
  
• 高マンノース型糖鎖構造変化に伴う軟骨変性へのアプローチ

  宝満 健太郎, 小野寺 智洋, 門間 太輔, 松岡 正剛, 馬場 力哉, 本谷 和俊, 松原 新史, 上徳 善太, 岩崎 倫政  北海道整形災害外科学会雑誌  58-  (1)  83  -83  2016/10  [Not refereed][Not invited]
  
• 骨髄MRI T1 map値は海綿骨強度予測のための間接的骨質指標となる

  遠藤香織, 高畑雅彦, 杉森博行, Wang Jeffrey, 山田悟史, 伊藤陽一, 高橋大介, 清水智弘, 東藤正浩, 但野茂, 工藤與亮, 岩崎倫政  日本整形外科学会雑誌  90-  (8)  S1732  -S1732  2016/08  [Not refereed][Not invited]
  
• 最新基礎科学 知っておきたい 脊椎骨増殖性病変と骨粗鬆症を併存するびまん性特発性骨増殖症に対するテリパラチドの治療効果 靱帯骨化石灰化症自然発症モデルマウス(twy/twy)を用いた検討

  濱野 博基, 高畑 雅彦, 太田 昌博, 平塚 重人, 清水 智弘, 亀田 裕亮, 岩崎 倫政  臨床整形外科  51-  (5)  458  -465  2016/05  [Not refereed][Not invited]
   

  脊椎骨増殖性病変と骨粗鬆症を併存するび漫性特発性骨増殖症(DISH)に対するテリパラチド(TPD)の治療効果について、靱帯骨化石灰化症自然発症モデルマウス(twy/twy)を用いて検討した。DISHにおける応力遮断性骨粗鬆症に対して、TPDが強力な骨同化作用を発揮することが示唆された。強力な骨形成促進作用をもつTPDがtwyマウスの異所性靱帯骨化/石灰化を促進し、脊椎強直進行を助長し、DISA患者においても同様の副次作用が発現しうることが示唆された。
• 関節リウマチでは皮質骨の骨質劣化により早期から骨脆弱性が生じる

  清水智弘, 高畑雅彦, 亀田裕亮, 濱野博基, 遠藤香織, 平塚重人, 太田昌博, 岩崎倫政, 伊藤哲平, 木村廣美, 須田, 東藤正浩, 但野茂  北海道整形災害外科学会雑誌  57-  (2)  311  -312  2016/04  [Not refereed][Not invited]
  
• Comprehensive Screening of Chemokines Related to Articular Cartilage Repair.

  Zenta Joutoku, Tomohiro Onodera, Daisuke Momma, Masatake Matsuoka, Rikiya Baba, Kazutoshi Hontani, Shinji Matsubara, Kentaro Homan, Ryosuke Hishimura, WooYoung Kim, Norimasa Iwasaki  The 62th Annual Meeting of Orthopaedic Research Society (ORS)  2016/03  [Not refereed][Not invited]
  
• 高純度アルギン酸ゲルを併用した骨髄刺激法による家兎骨軟骨欠損の修復効果-コラーゲンの配向性と力学強度に着目して-

  馬場力哉, 小野寺智洋, 門間太輔, 松岡正剛, 本谷和俊, 遠藤香織, 東藤正浩, 但野茂, 岩崎倫政  日本軟骨代謝学会プログラム・抄録集  29th-  2016
• 骨軟骨修復に関連するケモカインの網羅的解析

  上徳善太, 小野寺智洋, 門間太輔, 松岡正剛, 馬場力哉, 本谷和俊, 松原新史, 宝満健太郎, 岩崎倫政  北海道整形災害外科学会  131st-  (8)  26  -S1491  2016  [Not refereed][Not invited]
  
• 高純度アルギン酸ゲルを併用した骨髄刺激法の効果 家兎骨軟骨欠損モデルを用いて

  馬場 力哉, 小野寺 智洋, 門間 太輔, 松岡 正剛, 本谷 和俊, 遠藤 香織, 東藤 正浩, 但野 茂, 岩崎 倫政  日本整形外科学会雑誌  89-  (8)  S1592  -S1592  2015/09  [Not refereed][Not invited]
  
• 関節リウマチでは早期から関節近傍皮質骨の骨質異常と骨脆弱性が生じる

  清水 智弘, 高畑 雅彦, 亀田 裕亮, 遠藤 香織, 濱野 博基, 平塚 重人, 太田 昌博, 伊藤 哲平, 木村 廣美, 田, 東藤 正浩, 但野 茂, 岩崎 倫政  日本整形外科学会雑誌  89-  (8)  S1602  -S1602  2015/09  [Not refereed][Not invited]
  
• 脆弱性骨折後圧潰進行リスクの予測因子 ウシ海綿骨試験片を用いた繰返し圧縮破壊試験による検討

  遠藤 香織, 山田 悟史, 高畑 雅彦, 東藤 正浩, 但野 茂, 岩崎 倫政  日本整形外科学会雑誌  89-  (8)  S1693  -S1693  2015/09  [Not refereed][Not invited]
  
• 離断性骨軟骨炎に対する超音波定量評価の信頼性

  船越 忠直, 瓜田 淳, 岩崎 倫政, 西田 睦, 堀江 達則, 天野 虎次  北海道整形災害外科学会雑誌  56-  (2)  274  -275  2015/07
• 糖鎖受容体Siglec-15を介した生体内骨吸収制御機構

  亀田 裕亮, 高畑 雅彦, 清水 智弘, 濱野 博基, 平塚 重人, 太田 昌博, 岩崎 倫政  THE BONE  29-  (2)  101  -105  2015/07  [Not refereed][Not invited]
  
• 関節リウマチでは早期から関節近傍皮質骨の骨質異常と骨脆弱性が生じる

  清水 智弘, 高畑 雅彦, 亀田 裕亮, 遠藤 香織, 濱野 博基, 平塚 重人, 太田 昌博, 伊藤 哲平, 木村 廣美, 田, 東藤 正浩, 但野 茂, 岩崎 倫政  日本骨代謝学会学術集会プログラム抄録集  33回-  159  -159  2015/07  [Not refereed][Not invited]
  
• 副甲状腺ホルモン製剤による骨治癒促進効果にはビタミンK依存性Gla化蛋白オステオカルシンの充足が必要である

  清水 智弘, 高畑 雅彦, 亀田 裕亮, 濱野 博基, 岩崎 倫政, 伊藤 哲平, 木村 廣美, 田, 東藤 正浩, 但野 茂  北海道整形災害外科学会雑誌  56-  (2)  297  -297  2015/07  [Not refereed][Not invited]
  
• MRI T2 mappingによる移植骨の骨強度評価の可能性

  遠藤 香織, 高畑 雅彦, 高橋 大介, 岩崎 倫政, 杉森 博行, Wang Jeffery Kuo-Chen, 山田 悟史, 東藤 正浩, 但野 茂  北海道外科雑誌  60-  (1)  98  -98  2015/06  [Not refereed][Not invited]
  
• 投球動作が与える肩甲上腕関節の前方不安定性および後方拘縮-CT osteoabsorptiometry法を用いて-

  門間太輔, 船越忠直, 遠藤香織, 藤崎和弘, 瓜田淳, 松井雄一郎, 河村太介, 佃幸憲, 大泉尚美, 岩崎倫政  日本整形外科学会雑誌  89-  (3)  2015
• 4次元computed tomographyを用いた野球選手における肩甲上腕関節の動作解析

  船越忠直, 門間太輔, 遠藤香織, 瓜田淳, 松井雄一郎, 河村太介, 佃幸憲, 岩崎倫政, 山口隆義  北海道整形災害外科学会  128th-  2015
• ウシ海綿骨立方体試験片の繰返し圧縮時における強度特性

  遠藤香織, 山田悟史, 東藤正浩, 高畑雅彦, 岩崎倫政, 但野茂  日本機械学会年次大会講演論文集(CD-ROM)  2015-  2015
• 異なる腱板断裂修復法における微小血行動態の変化 造影超音波を用いて

  瓜田 淳, 船越 忠直, 堀江 達則, 西田 睦, 岩崎 倫政  超音波医学  42-  (1)  93  -93  2015/01
• 強皮症に合併した頚椎calcinosisの1例

  高橋要, 新井隆太, 校條祐輔, 高畑雅彦, 須藤英毅, 長濱賢, 黒木圭, 小甲晃史, 岩崎倫政  北海道整形災害外科学会  128th-  107  2015  [Not refereed][Not invited]
  
• ガングリオシド欠損は軟骨の肥大化を抑制することにより関節軟骨修復を促進する

  松岡正剛, 小野寺智洋, 笹沢史生, 門間太輔, 馬場力哉, 本谷和俊, 上徳善太, 松原新史, 宝満健太郎, 岩崎倫政  J. Jpn. Orthop. Assoc.  89-  (8)  S1710  2015  [Not refereed][Not invited]
  
• 軟骨細胞上の高マンノース型糖鎖構造の減少は軟骨変性を促進する

  宝満健太郎, 小野寺智洋, 門間太輔, 松岡正剛, 馬場力哉, 本谷和俊, 松原新史, 上徳善太, 岩崎倫政  J. Jpn. Orthop. Assoc.  89-  (8)  S1533  2015  [Not refereed][Not invited]
  
• ウシ海綿骨立方体試験片の繰返し圧縮時における強度特性

  遠藤 香織, 山田 悟史, 東藤 正浩, 但野 茂, 高畑 雅彦, 岩崎 倫政  生活生命支援医療福祉工学系学会連合大会講演要旨集  2014-  GS1  -6  2014/09  [Not refereed][Not invited]
  
• 破骨細胞誘導因子Siglec‐15は閉経後骨粗鬆症の治療ターゲットとなりうるか

  KAMEDA YUSUKE, TAKAHATA MASAHIKO, MIKUNI SHINTARO, HATAKEYAMA SHIGETSUGU, SHIMIZU TOMOHIRO, HAMANO HIROKI, ANGATA TAKASHI, KINJO MASATAKA, IWASAKI NORIMASA  日本整形外科学会雑誌  88-  (8)  S1477  2014/08/29  [Not refereed][Not invited]
  
• 破骨細胞誘導因子Siglec‐15は閉経後骨粗鬆症の治療ターゲットとなり得るか?

  KAMEDA YUSUKE, TAKAHATA MASAHIKO, MIKUNI SHINTARO, HATAKEYAMA SHIGETSUGU, SHIMIZU TOMOHIRO, HAMANO HIROKI, ANGATA TAKASHI, KINJO MASATAKA, IWASAKI NORIMASA  日本骨形態計測学会雑誌  24-  (2)  S116  2014/05/19  [Not refereed][Not invited]
  
• 離断性骨軟骨炎に対する超音波定量評価の信頼性

  船越 忠直, 瓜田 淳, 西田 睦, 堀江 達則, 岩崎 倫政  日本手外科学会雑誌  31-  (1)  1  -27  2014/04
• ウシ大腿骨海綿骨の異方性弾性率とハイドロキシアパタイト(HAp)結晶構造の関係

  遠藤香織, 山田悟史, 東藤正浩, 但野茂, 高畑雅彦, 岩崎倫政  日本整形外科学会雑誌  88-  (8)  2014
• 離断性骨軟骨炎に対する超音波定量評価の信頼性

  船越 忠直, 瓜田 淳, 西田 睦, 堀江 達則, 岩崎 倫政  日本肘関節学会雑誌  21-  (1)  S103  -S103  2014/01
• The role of syndecan-4 in the development of rheumatoid arthritis

  Tsutomu Endo, Junko Morimoto, Koyu Ito, Norimasa Iwasaki, Toshimitsu Uede  JOURNAL OF IMMUNOLOGY  190-  2013/05  [Not refereed][Not invited]
  
• J022021 Frictional and Viscoelastic Properties of Knee Joint Cartilage by Pendulum Test

  KASHIWA Shintaro, TODOH Hiroyuki, TADANO Shigeru, IWASAKI Masanori  Mechanical Engineering Congress, Japan  2012-  "J022021  -1"-"J022021-3"  2012/09/09  [Not refereed][Not invited]
   

  Osteoarthritis (OA) is the most common degenerative joint disease in the field of orthopaedics. In advanced stages of OA, the patients suffer from severe pain, functional limitations in the affected joints, and restriction of mobility. For detecting early OA and the prevention of progression in OA by novel therapeutic strategies, they are important to understand the functional properties of synovial joint and to establish the precise measurement technique. Pendulum friction test is one of the mechanical evaluations for lubrication properties of joints. The advantages of this method are the natural motion without the constraints of joint and also preservation of the joint capsule, the synovial fluid in it and the tendons and ligaments around the knee. In this study, in addition to the friction properties, the viscous and elastic effects were evaluated. The equation of motion of joint cartilage were proposed including the friction, viscous and elastic effect. The each mechanical parameters were identified by fitting the damping oscillation curve measured by pendulum terster with two laser displacement sensors and an accelerometer.
• The role of Syndecan-4 in the development of rheumatoid arthritis

  Tsutomu Endo, Junko Morimoto, Koyu Ito, Masashi Kanayama, Norimasa Iwasaki, Akio Minami, Toshimitsu Uede  JOURNAL OF IMMUNOLOGY  188-  2012/05  [Not refereed][Not invited]
  
• 高純度低エンドトキシンアルギン酸ゲルの膝関節内投与による変形性関節症の治療効果

  佃幸憲, 岩崎倫政, 五十嵐達弥, 河村太介, 笠原靖彦, 大澤伸雄, 東藤正浩, 但野茂, 三浪明男  再生医療  10-  247  2011/02/01  [Not refereed][Not invited]
  
• 造影超音波を用いた断裂および非断裂棘上筋の血行動態

  船越 忠直, 岩崎 倫政, 三浪 明男, 神島 保, 西田 睦, 近藤 真  日本整形外科学会雑誌  84-  (3)  S68  -S68  2010/03
• 【ますます重要になる細胞周辺環境(細胞ニッチ)の最新科学技術 細胞の生存、増殖、機能のコントロールから創薬研究、再生医療まで】細胞周辺環境のための材料科学技術 高分子 糖鎖による軟骨細胞機能制御の可能性 軟骨変性に伴うN-結合型糖鎖の変化より

  岩崎 倫政, 松橋 智弥, 瓜田 淳, 高畑 雅彦, 三浪 明男, 西村 紳一郎  遺伝子医学MOOK  別冊-  (ますます重要になる細胞周辺環境(細胞ニッチ)の最新科学技術)  55  -59  2009/08  [Not refereed][Not invited]
   

  軟骨組織変性を基本病態とする変形性関節症の発症早期よりN-結合型糖鎖に変化が生じた。この変化は,本疾患の発症病因である軟骨細胞のアポトーシスや細胞外マトリクス分解酵素の分泌に関与していると考えられる。更なる研究により,糖鎖による軟骨細胞の機能制御や関節疾患への関与などが明らかになっていくものと考えられる。これらが明らかになると,糖鎖生物学および糖鎖工学的アプローチによる新たな治療法の開発や,再生医療用マテリアルの開発が可能になるであろう。(著者抄録)
• Osteopontinによる変形性関節症の発症及び進行抑制効果

  松井雄一郎, 岩崎倫政, 高橋大介, 三浪明男, 今重之, 上出利光  北海道整形災害外科学会  116th-  2009
• Osteochondritis dissecans of the elbow

  Norimasa Iwasaki, Akio Minami  Current Orthopaedic Practice  19-  (6)  608  -611  2008/11  [Not refereed][Not invited]
   

  Purpose of review Treatment of osteochondritis dissecans of the elbow remains challenging. Recently, several techniques for resurfacing a cartilaginous lesion with hyaline cartilage have been developed and applied to osteochondritis dissecans lesions. In this review, we mainly focus on the development of surgical management for osteochondritis dissecans of the elbow over the past year. Recent findings The surgical strategy for osteochondritis dissecans of the humeral capitellum (capitellar osteochondritis dissecans) has tended to shift from marrow-stimulating techniques to autologous osteochondral grafts as a cartilage-resurfacing technique. Osteochondral grafts for capitellar osteochondritis dissecans provide better outcomes than simple excision. Regarding the postoperative morbidity of the donor knee, no adverse effect on the donor site is found in young athletes with capitellar osteochondritis dissecans. Additionally, arthroscopic surgery for osteochondritis dissecans lesions has been expanded as well as for other elbow disorders. However, there has been no evidence that arthroscopic surgery for osteochondritis dissecans lesions results in any better prognosis for the patient. Summary The goal of treatment for capitellar osteochondritis dissecans is to return patients to their previous level of sport activities and to regenerate long-lasting hyaline cartilage tissue to replace cartilaginous lesions. For this treatment goal, an arthroscopic cartilage-resurfacing procedure may be an ideal treatment for capitellar osteochondritis dissecans. © 2008 Wolters Kluwer Health|Lippincott Williams & Wilkins.
• Alteration of N-glycans related to articular cartilage deterioration after anterior cruciate ligament transection in rabbits

  T. Matsuhashi, N. Iwasaki, H. Nakagawa, M. Hato, M. Kurogochi, T. Majima, A. Minami, S. I. Nishimura  OSTEOARTHRITIS AND CARTILAGE  16-  (7)  772  -778  2008/07  [Not refereed][Not invited]
   

  Objective: Osteoarthritis (OA) is the most common of all joint diseases, but the molecular basis of its onset and progression is controversial. Several studies have shown that modifications of N-glycans contribute to pathogenesis. However, little attention has been paid to N-glycan modifications seen in articular cartilage. The goal of this study was to identify disease specific N-glycan expression profiles in degenerated cartilage in a rabbit OA model induced by anterior cruciate ligament transection (ACLT). Methods: Cartilage samples were harvested at 7, 10, 14, and 28 days after ACLT and assessed for cartilage degeneration and alteration in N-glycans. N-Glycans from cartilage were analyzed by high performance liquid chromatography and mass spectrometry. Results: Histological analysis showed that osteoarthritic changes in cartilage occurred 10 days after ACLT. Apparent alterations in the N-glycan peak pattern in cartilage samples were observed 7 days after ACLT, and overall N-glycan changes in CA reflected alterations in both sialylation and fucosylation. These changes apparently preceded histological changes in cartilage. Conclusion: These results indicate that changes in the expression of N-glycans are correlated with OA in an animal model. Understanding mechanisms underlying changes in N-glycans seen in CA may be of therapeutic value in treating cartilage deterioration. (C) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
• Crystallization and preliminary crystallographic analysis of the Tob-hCaf1 complex

  Kinya Nishida, Masataka Horiuchi, Nobuo N. Noda, Kiyohiro Takahasi, Norimasa Iwasaki, Akio Minami, Fuyuhiko Inagaki  ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS  63-  (63)  1061  -1063  2007/12  [Not refereed][Not invited]
   

  The Tob/BTG family is a group of antiproliferative proteins that contain two highly homologous regions named Box A and Box B. These proteins all associate with CCR4-associated factor 1 (Caf1), which belongs to the ribonuclease D family of deadenylases. The antiproliferative region of human Tob (residues 1-138) and intact hCaf1 were co-expressed in Escherichia coli, purified and successfully cocrystallized. The crystal belongs to the tetragonal space group I422, with unit-cell parameters a = b = 150.9, c = 113.9 angstrom, and is estimated to contain one heterodimer per asymmetric unit. The crystal diffracted to around 2.6 angstrom resolution.
• Donor site evaluation after autologous osteochondral mosaicplasty for cartilaginous lesions of the elbow joint

  Norimasa Iwasaki, Hiroyuki Kato, Tamotsu Kamishima, Naoki Suenaga, Akio Minami  AMERICAN JOURNAL OF SPORTS MEDICINE  35-  (12)  2096  -2100  2007/12  [Not refereed][Not invited]
   

  Background: One significant disadvantage of autologous osteochondral mosaicplasty (mosaicplasty) is the harvesting of osteochondral grafts from the normal articular area of the knee joint. However, the effect of harvesting grafts on knee function remains unclear. Purpose: To clarify the functional effects on the donor knee of harvesting osteochondral grafts and to perform magnetic resonance imaging evaluation of donor site repair after mosaicplasty for capitellar osteochondritis dissecans in young athletes. Study Design: Case series; Level of evidence, 4. Methods: Eleven, male competitive athletes with advanced lesions of capitellar osteochondritis dissecans underwent mosaicplasties. The surgical technique involves obtaining small-sized cylindrical osteochondral grafts from the lateral periphery of the femoral condyle at the level of the patellofemoral joint and transplanting them to osteochondral defects in the capitellum. Assessment at a mean follow-up of 26 months included local findings of the donor knees, a Lysholm knee scoring scale, International Knee Documentation Committee standard evaluation form, and magnetic resonance imaging evaluation. Results: All patients returned to a competitive level of their previous sports without any donor site disturbances. Based on the Lysholm knee score and International Knee Documentation Committee evaluation form, all knees were graded as excellent and normal, respectively. The magnetic resonance imaging showed 50% to 100% defect fill in 6 of 9 patients and normal or nearly normal signals in 4 patients at the donor sites. Conclusion: No adverse effects of osteochondral graft harvest on donor knee function were found after mosaicplasty for capitellar osteochondritis dissecans in young athletes. However, magnetic resonance imaging indicates that the donor site is resurfaced with fibrous tissue.
• Letter to the Editor

  N. Iwasaki, J. Ishikawa, A. Minami  Journal of Hand Surgery: European Volume  32-  (4)  472  -473  2007/08  [Not refereed][Not invited]
  
• Chitosan-based hyaluronan hybrid polymer fibre scaffold for ligament and tendon tissue engineering

  T. Majima, T. Irie, N. Sawaguchi, T. Funakoshi, N. Iwasaki, K. Harada, A. Minami, S-I Nishimura  PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART H-JOURNAL OF ENGINEERING IN MEDICINE  221-  (H5)  537  -546  2007/07  [Not refereed][Not invited]
   

  To establish medical use of tissue engineering technology for ligament and tendon injuries, a scaffold was developed which has sufficient ability for cell growth, cell differentiation, and mechanical properties. The scaffold made from chitosan and 0.1 per cent hyaluronic acid has adequate biodegradability and biocompatibility. An animal experiment showed that the scaffold has less toxicity and less inflammation induction. Furthermore, in-vivo animal experiments showed that the mechanical properties of the engineered ligament or tendon had the possibility to stabilize the joint. It was shown that newly developed hybrid-polymer fibre scaffold has feasibility for joint tissue engineering.
• Sialylation of cell surface glycoconjugates is essential for osteoclastogenesis

  Masahiko Takahata, Norimasa Iwasaki, Hiroaki Nakagawa, Yuichiro Abe, Takuya Watanabe, Manabu Ito, Tokifumi Majima, Akio Minami  BONE  41-  (1)  77  -86  2007/07  [Not refereed][Not invited]
   

  Sialic acid. which is located at the end of the carbohydrate moiety of cell surface glycoconjugates, is involved in many biologic responses, such as intercellular reactions and virus-cell fusion, especially in hematopoietic cells. Here we provide experimental evidence that the sialic acid of cell surface glycoconjugates has a role in osteoclast differentiation. Lectin histochemical study demonstrated the existence of both alpha (2,3)-linked-sialic acid and alpha (2,6)-linked-sialic acid in mouse bone marrow-derived macrophages and in the RAW264.7 macrophage cell line, which are osteoclast precursors. Flow cytometric analysis of surface lectin staining revealed the kinetics of these sialic acids during osteoclastogenesis: alpha (2,3)-linked-sialic acid was abundantly expressed throughout osteoclastogenesis, whereas alpha (2,6)-linked-sialic acid levels declined at the terminal stage of osteoclast differentiation. To investigate the role of sialic acid in osteoclast differentiation, we performed an osteoclastogenesis assay with or without exogenous sialidase treatment. Desialylated cells formed TRAP-positive mononuclear cells, but did not become multinuclear cells despite the normal expression of osteoclast markers such as cathepsin K, integrin 3, and nuclear factor-ATc1. Flow cytometric analysis also demonstrated that exogenous sialidase effectively removed alpha (2,6)-linked-sialic acid, but only slightly changed the alpha (2,3)-linked-sialic acid content, suggesting that alpha (2,6)-linked-sialic acid might be involved in osteoclast differentiation. Findings from knockdown analysis using small interfering RNA oligonucleotides against alpha 2,6-sialyttransferase support this idea: alpha (2,6)-linked-sialic acid-deficient cells markedly inhibit the formation of multinuclear osteoclasts. Our findings suggest that alpha (2,6)- linked-sialic acid of cell surface glycoconjugates has a role in osteoclast differentiation, possibly via its role in the cell-cell fusion process. (c) 2007 Elsevier Inc. All rights reserved.
• Detection of altered N-glycan profiles in whole serum from rheumatoid arthritis patients

  Hiroaki Nakagawa, Megumi Hato, Yasuhiro Takegawa, Kisaburo Deguchi, Hiroki Ito, Masahiko Takahata, Norimasa Iwasaki, Akio Minami, Shin-Ichiro Nishimura  JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES  853-  (1-2)  133  -137  2007/06  [Not refereed][Not invited]
   

  Altered N-glycosylation occurs in many diseases. In rheumatoid arthritis (RA), for example, reduction in galactose residues in IgG and an increase in fucose residues in alpha 1-acid glycoprotein have been observed. To further analyse N-glycans in disease, we show N-glycan profiling from whole serum employing reversed phase high performance liquid chromatography/negative-ion mode by sonic spray ionization ion trap mass spectrometry with pyridylamination. Profiles from female 15 RA patients and 18 aged-matched healthy women were compared. The most significant change seen in RA was decreased levels of mono-galactosyl bi-antennary N-glycans, in agreement with the previous reports regarding IgG. We also show previously unreported differences between isomers and increased tri-antennary oligosaccharides. These results indicate that LC-MS analysis of whole serum N-glycans can identify N-glycan alterations in RA and that this is a promising method both for studies of RA mechanisms and diagnosis. (c) 2007 Elsevier B.V. All rights reserved.
• Results of surgical treatment for proximal scaphoid nonunions

  ISHIKAWA Jun-ichi, MINAMI Akio, IWASAKI Norimasa, SUENAGA Naoki, KATO Hiroyuki  東日本整災会誌  19-  (4)  419  -422  2007  [Not refereed][Not invited]
  
• Trigger wrist caused by tendon adhesion between the flexor pollicis longus and flexor digitorum superficialis tendons: A case report.（共著）

  J Hand Surg Eur  32-  472  -473  2007  [Not refereed][Not invited]
  
• Factors affecting results of ulnar shortening for ulnar impaction syndrome.（共著）

  Clin Orthop Relat Res  465-  215  -219  2007  [Not refereed][Not invited]
  
• Magnetic nanoparticles for improving cell invasion in tissue engineering.（共著）

  J Biomed. Mater. Res. A,  2007  [Not refereed][Not invited]
  
• Tumor location affects the results of simple excision for multiple osteochondromas in the forearm.（共著）

  J Bone Joint Surg Am  89-  1238  -1247  2007  [Not refereed][Not invited]
  
• Identification of CLUAP1 as a human osteosarcoma tumor-associated antigen recognized by the humoral immune system.（共著）

  Int J Oncol  30-  461  -467  2007  [Not refereed][Not invited]
  
• Development of mature cartilage constructs using novel three-dimensional porous scaffolds for enhanced repair of osteochondral defects.（共著）

  J Biomed. Mater. Res. A  2007  [Not refereed][Not invited]
  
• Activity-dependent regulation of BRINP family genes

  Makoto Motomiya, Miwako Kobayashi, Norimasa Iwasaki, Akio Minami, Ichiro Matsuoka  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS  352-  (3)  623  -629  2007/01  [Not refereed][Not invited]
   

  We previously identified a family of novel developmentally regulated genes: BRINP1, 2, and 3, which are predominantly and widely expressed in the CNS from earlier developmental stages to adulthood. In the present study, we investigated the activity-dependent regulation of BRINP expression in the CNS. Among the three BRINP genes, BRINP1-mRNA was specifically up-regulated in the dentate gyrus of mouse hippocampus by kainic acid treatment. In cultured hippocampal neurons, the induction of BRINP1-mRNA was also observed by the activation of glutamate receptors. Although BDNF-mRNA is up-regulated in a similar activity-dependent manner, BDNF itself did not induce BRINP1-mRNA. From these results, the physiological roles of the activity-dependent induction of BRINP1-mRNA are discussed. (c) 2006 Elsevier Inc. All rights reserved.
• The role of osteopontin in tendon tissue remodeling after denervation-induced mechanical stress deprivation

  Noriaki Mori, Tokifumi Majima, Norimasa Iwasaki, Shigeyuki Kon, Kiyoshi Miyakawa, Chiemi Kimura, Kunio Tanaka, David T. Denhardt, Susan Rittling, Akio Minami, Toshimitsu Uede  MATRIX BIOLOGY  26-  (1)  42  -53  2007/01  [Not refereed][Not invited]
   

  It has been shown that musculoskeletal tissues undergo dynamic tissue remodeling by a process that is quite sensitive to the mechanical environment. However, the detailed molecular mechanism underlying this process remains unclear. We demonstrate here that after denervation-induced mechanical stress deprivation, tendons undergo dynamic tissue remodeling as evidenced by a significant reduction of the collagen fibril diameter. Importantly, the transient up-regulation of osteopontin (OPN) expression was characteristic during the early phase of tendon tissue remodeling. Following this dynamic change of OPN expression, matrix metalloproteinase (MMP)-13 expression was induced, which presumably accounts for the morphological changes of tendon by degrading tendon collagen fibrils. The modulation of MMP-13 expression by OPN was specific, since the expression of MMP-2, which is also known to be involved in tissue remodeling, did not alter in the tendons under the absence or presence of OPN. We also demonstrate that the modulation of MMP-13 expression by OPN is due to the signaling through cell surface receptors for OPN. Thus, we conclude that OPN plays a crucial role in conveying the effect of denervation-induced mechanical stress deprivation to the tendon fibroblasts to degrade the extracellular matrices by regulating MMP-13 expression in tendon fibroblasts. (c) 2006 Elsevier B.V./International Society of Matrix Biology. All rights reserved.
• Effect of pore size on in vitro cartilage formation using chitosan-based hyaluronic acid hybrid polymer fibers.（共著）

  J Biomed Mater Res.A  81-  586  -93  2007  [Not refereed][Not invited]
  
• Is there a role for radial osteotomy in advanced Kienböck's disease?

  Akio Minami, Norimasa Iwasaki  Current Opinion in Orthopaedics  13-  (4)  246  -250  2002  [Not refereed][Not invited]
   

  Roles of radial osteotomies in the treatment of advanced Kienböck's diseases remain unsolved problems. Eighteen patients with Lichtman's stage IIIB Kienböck's disease were treated with radial osteotomies consisting of both methods of radial shortening and lateral closing radial wedge osteotomy. There were radial shortenings in 8 patients, and lateral closing radial wedge osteotomies in 10. There were no preoperative differences with respect to age and gender between both osteotomy groups. The period of follow-up ranged from 36 to 108 months with an average of 48 months. All patients in both groups had either good or excellent, clinically. Radiographically, the radioscaphoid angle significantly increased and the Ståhl index significantly decreased in the lateral closing radial wedge osteotomy group. The progression of degenerative changes at the radioscaphoid joint was observed in two of ten patients in this osteotomy group. On the contrary, progression of any radiographic parameters and occurrence of degenerative changes were not observed in the radial shortening group. Although radiographic progression occurred after the lateral closing radial wedge osteotomy, both osteotomy procedures provided satisfactory clinical results in the treatment of stage IIIB Kienböck's disease. © 2002 Lippincott Williams & Wilkins, Inc.
• Effects of major histocompatibility complex matching on graft survival in allogeneic rat limb transplantation

  N Iwasaki, T Gohda, H Itoga, A Minami, K Kaneda  JOURNAL OF HAND SURGERY-AMERICAN VOLUME  26A-  (3)  540  -545  2001/05  [Not refereed][Not invited]
   

  Differences in the major histocompatibility complex (MHC) between recipients and donors present a problem because of immunologic responses in graft rejection. The purpose of this study is to clarify the efficacy of MHC matching against acute graft rejection of allogeneic limb transplants in rats. Right hindlimb transplantations were performed using various MHC-mismatched pairs of inbred rats. The rats were classified into 5 groups according to the differences in subregions of the RT1 (rat MHC) between the recipient and the donor: group 1, RT1-A,B,D barrier (the differences of RT1-A,B,D subregions); group 2, RT1-A barrier; group 3, RT1-B,D barrier; group 4, RT1-B barrier; and group 5, RT1- D barrier. The mean survival time significantly decreased in group 1 and increased in group 4. The results suggest that MHC matching clearly improves survival of transplanted limbs. Specifically, both RT1-A and D matching is the most effective compatibility in prolonging survival time of allogeneic limb transplants in rats. Copyright (C) 2001 by the American Society for Surgery of the Hand.
• 遺伝子導入による免疫抑制(共著)

  医学のあゆみ  196-  895  -899  2001  [Not refereed][Not invited]
  
• Feasibility of immunosuppression in limb allografts by blocking the CD28/B7 T cell costimularory pathway. (共著)

  47^th Annual Meeting Orthopaedic Research Society  2001  [Not refereed][Not invited]
  
• 血管柄付き関節移植の実験的研究(共著)

  骨・関節 靭帯  13-  1013  -1017  2000  [Not refereed][Not invited]
  
• 部分的手関節固定術のバイオメカニクス(共著)

  13-  (2)  19  -23  2000  [Not refereed][Not invited]
  
• Experimental study of vascularized Joint allograft

  13-  1013  -1017  2000  [Not refereed][Not invited]
  
• Long-term survival of allogeneic limb grufts induced by CTLA4Ig(共著)

  55^th American Society for Surgery of the Hand, Adrian F. Flatt Resident and Fellow Conference  2000  [Not refereed][Not invited]
  
• Biomechanics of Limited Intercarpal Fusions

  Monthly Book Orthopaedics  13-  (2)  19  -23  2000  [Not refereed][Not invited]
  
• 肘屈曲機能再建術(Steinaler法)の筋力数値解析(共著)

  日本臨床バイオメカニクス学会誌  20-  493  -496  1999  [Not refereed][Not invited]
  
• Muscle Force Analysis of Steindler Flexorplasty

  20-  493  -496  1999  [Not refereed][Not invited]
  
• Shapping of Triceps Tendon After Anterior Nerve Transposition for Recurrent Subluxation of the Ulhar Nerve(共著)

  Hand Surgery  4-  (2)  193  -196  1999  [Not refereed][Not invited]
  
• (]G0319[)骨遠位関節面の生理的荷重条件下における応力分布-CT osteoabsorptimetry法を用いて-(共著)

  岩崎倫政  日本臨床バイオメカニクス学会誌  19-  237  -240  1998  [Not refereed][Not invited]
  
• 正常手関節における3次元力学的解析-剛体バネモデルを用いた理論的解析-

  北海道整形災害外科学会雑誌  40-  (2)  34  -41  1998  [Not refereed][Not invited]
  
• In vivo Stress analysis of the joint surface of the distal radius : Using a CT osteoabsorptiometry

  19-  237  -240  1998  [Not refereed][Not invited]
  
• Three-dimensional Biomechanical Analysis of Normal Wrist Joint : Theoretical Analysis Using a Rigid Body Spring Model

  40-  (2)  34  -41  1998  [Not refereed][Not invited]
  
• Force Trunsmission Through the Wrist Joint in Kienb(]E88D8[)ck's Disease : A Two-Dimensional Theoretical Study(共著)

  Journal of Hand Surgery  (234)  415  -424  1998  [Not refereed][Not invited]
  
• Biomechanical analysis of Limited Intercarpal Fusion for the Treatment of Kienb(]E88D8[)ck's Disease : A Three-Dimensional Theoretical Study(共著)

  Journal of Orthopaedic Research  (16)  256  -263  1998  [Not refereed][Not invited]
  
• 剛体バネモデルを用いたkienbock病における理論的応力解析(共著)

  日本手の外科学会雑誌  13-  (6)  1024  -1027  1997  [Not refereed][Not invited]
  
• kienbock病に対する部分的手関節固定術の力学的評価-3次元剛体バネモデルを用いて-(共著)

  日本手の外科学会雑誌  13-  (5)  67  -70  1997  [Not refereed][Not invited]
  
• Theoretical Analysis of Force Transmission Through the Wrist Joint in Keinb(]E88D8[)ck's Disease-Using A Two-Dimensional Rigid Body Spring Model-

  13-  (6)  1024  -1027  1997  [Not refereed][Not invited]
  
• Biomechanical Analysis of Limited Intercarpal Fusion of Treating Kienb(]E88D8[)ck's Disease : Using a Three-Dimensional Rigid Body Spring Model

  13-  (5)  67  -70  1997  [Not refereed][Not invited]
  

Association Memberships

• 北海道整形災害外科学会   日本臨床バイオメカニクス学会   日本手外科学会   日本整形外科学会   整形外科バイオマテリアル研究会   日本運動器移植・再生医学研究会   日本人工関節学会   米国整形外科学会   International Cartilage Regeneration & Joint Preservation Society   米国整形外科基礎学会   米国手外科学会   日本リウマチ学会   日本再生医療学会   日本軟骨代謝学会   日本関節病学会   日本末梢神経学会   東日本整形災害外科学会   日本スポーツ整形外科学会   日本バイオマテリアル学会   日本肘関節学会   

Research Projects

• 培養細胞上の糖鎖抗原変化と自家細胞移植における免疫応答発生機序の解明

  日本学術振興会：科学研究費助成事業 挑戦的研究(萌芽)

  Date (from‐to) : 2019/06 -2023/03 

  Author : 岩崎 倫政, 照川 アラー, 古川 潤一, 宝満 健太郎

   

  間葉系幹細胞や軟骨細胞などの細胞をin vitroで継代すると、細胞の生理的・免疫的な挙動が変化することを明らかにし、継代培養された細胞はマクロファージを含む免疫細胞と交互作用することを突き止めた。これらの作用が生じるための最小限の細胞継代数を決定することは、この免疫的な挙動を担う細胞表面の糖鎖構造解析のターゲットを絞る上で不可欠である。8週齢のC57／B6マウスの腹腔内マクロファージを単離し、軟骨細胞または間葉系幹細胞を含む継代細胞とマクロファージとを共培養することで直接相互作用実験を行った。間接的相互作用実験では、軟骨細胞および間葉系幹細胞をトランスウェルインサートに播種してマクロファージと共培養した。これらの上清を酵素免疫吸着法（ELISA法）を用いて炎症性サイトカインの濃度を測定した。マクロファージと継代細胞の直接共培養では、継代3（P3）の軟骨細胞との培養では、P0の軟骨細胞に比べてIL-6のレベルが増加した。一方、P6軟骨細胞を用いた培養では、P2軟骨細胞を用いた培養と比較して、IL-6のレベルが増加した。間接培養では、IL-6の増加は培養群間で有意差はなかった。これらの結果は、マクロファージの活性化には、継代細胞との直接的な相互作用が必要であることを示唆している。次に、直接共培養モデルにおいて、一酸化窒素（NO）およびTNF-αなどの炎症マーカーのレベルを測定した。P3軟骨細胞やP6間葉系幹細胞と共培養したマクロファージでは、NOやTNF-αのレベルが顕著に上昇した。これらの結果から、軟骨細胞は継代2まで、間葉系幹細胞は継代5まで使用可能であることが明らかになった。
• Search for lipid differentiation markers for safe cartilage regenerative medicine using stem cells and elucidate their functions

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

  Date (from‐to) : 2018/04 -2022/03 

  Author : BABA RIKIYA

   

  In this study, we focused on the fact that the surface of undifferentiated iPS cells were coated with specific glycoconjugates and GSL glycans, we established a method to detect and quantify undifferentiated iPS cells in chondrocytes using cell-specific GSL-glycan analysis by applying the Aminolysis-SALSA method. Using quantification method by glycan analysis, we could determine the optimal conditions for use of R-17F antibody, which recognizes specific glycans of iPS cells and has cytotoxic activity. Furthermore, we transplanted the antibody-treated co-cultured cells into SCID mice and showed that no teratoma was formed.
• An acellular bioresorbable ultra-purified alginate gel promotes intervertebral disc repair

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

  Date (from‐to) : 2016/04 -2019/03 

  Author : Sudo Hideki

   

  The current surgical procedure of choice for lumbar intervertebral disc (IVD) herniation is discectomy. However, defects within IVD produced upon discectomy may impair tissue healing and predispose patients to subsequent IVD degeneration. This study aimed to investigate whether the use of an acellular bioresorbable ultra-purified alginate (UPAL) gel implantation system is safe and effective as a reparative therapeutic strategy after lumbar discectomy. The UPAL gel was biocompatible with human IVD cells and promoted extracellular matrix production after discectomy, demonstrating sufficient biomechanical characteristics without material protrusion. The present results indicate the safety and efficacy of UPAL gels in a large animal model and suggest that these gels represent a novel therapeutic strategy after discectomy in cases of lumbar IVD herniation.
• Elucidation of pathophysiology of joint disease based on analysis of glycosphingolipid function and development of novel treatment

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

  Date (from‐to) : 2016/04 -2019/03 

  Author : Iwasaki Norimasa

   

  We aimed to elucidate the molecular mechanisms of glycosphingolipids (GSLs) on chondrocytes involved in the development of osteoarthritis (OA) and to apply them to clinical treatment. In this project, various GSLs-related synthetase gene knockout mice (KO mice) are used to analyze the signal control function of each GSLs molecule against to IL-1 stimulation, and each of the GSLs existing upstream to downstream of GSLs biosynthetic pathway has been shown to be involved in the onset of OA. Moreover, we have clarified that severe OA develops when KO of GSLs molecule located more upstream. In addition, we have demonstrated that GSLs molecules have the function of controlling the transduction of stimulation into cells via Ca channels in response to mechanical stimulation on chondrocytes.
• Identification and Molecular Analysis of a Potential Disease-causing Mutation in gene A in Congenital Radioulnar Synostosis

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

  Date (from‐to) : 2016/04 -2019/03 

  Author : Kato Hiroyuki, Suzuki Takako

   

  Congenital radioulnar synostosis is a skeletal disorder resulting in fusion of the radius and ulna. Since the etiology is largely unknown, elucidation of pathophysiology of RUS is needed for development of better treatment. We collected DNA samples of 10 trios (an affected patient and his or her biological parents) and performed whole exome-sequencing (WES). We identified mutations in several candidate genes including the gene A. The WES identified the following potential disease-causing de novo heterozygous missense mutation in a patient. We performed whole-mount in situ hybridization (ISH) in zebrafish. ISH showed specific expression of gene A in pectoral fins, which correspond to human upper limbs, and in craniofacial regions. Gene A knockdown in zebrafish caused defects in pectoral fins and dorso-ventral patterning, which are likely caused by inhibitory effects of bone morphogenetic protein (BMP) action. These abnormalities were partially rescued by bmp2b RNA overexpression.
• Functional analysis of cartilage glycans for the elucidation of osteoarthritis pathomechanisms

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

  Date (from‐to) : 2016/04 -2018/03 

  Author : Iwasaki Norimasa, HOMAN Kentaro

   

  Our hypothesis was that early osteoarthritic cahnges induced by alterations in cartilage glycans would be reversible. To test this hypothesis, we created in vivo and in vitro early osteoarthritic models based on alpha-mannosidase administration. The administration of alpha-mannosidase induced early osteoarthritis in in vivo and in vitro models. Additionally, this histological changes were recovered by the discontinuation of alpha-mannosidase adminiatrations. Future studies will be performed to clarify this recovery mechanism in early osteoarthritis pathogenesis.
• Investigation of the mechanism of osteolytic bone destruction in bone metastasis via tumor-associated carbohydrate antigen

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

  Date (from‐to) : 2015/04 -2018/03 

  Author : Arai Ryuta

   

  In bone metastasis of cancer, bone resorption by osteoclast plays an important role. Siglec 15 and sialyl Tn are involved in the differentiation of osteoclasts. We assumed that osteoclast differentiation by these molecules has been implicated in the formation of osteolytic bone metastases. A sialyl Tn-expressing breast cancer cell line was established and administered locally to the femur of nude mice. The differentiation of osteoclasts was not promoted and the formation of bone metastases was small in sialyl Tn-expressing breast cancer group, compared with control group. In vitro, sialyl Tn-expressing breast cancer cell was attenuated in cell adhesion ability. It was suggested that the development of bone metastasis was attenuated in sialyl Tn expressing breast cancer cell group, because of decreased cell adhesion ability.
• Chondroprotective effects of high-molecular-weight cross-linked hyaluronic acid in a rabbit knee osteoarthritis model.

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

  Date (from‐to) : 2014/04 -2017/03 

  Author : Funakoshi Tadanao

   

  Effect of hyaluronic acid (HA) for osteoarthritis is still controversial. We examined the histopathological changes and the friction coefficient in osteoarthritic knee joint after different molecular weight HA injection (low molecular weight HA, 0.8x106 Da or Ultra-high molecular weight, 6x106 Da) using a rabbit osteoarthritis model. Macroscopic findings showed that severe damaged cartilage was observed in 10% of Ultra-high molecular weight HA and 30% of low molecular weight HA and NS. The histological score and the friction coefficient value of Ultra-high molecular weight HA group were significantly lower than those of the control group (P < 0.05). Ultra-high molecular weight HA has potential chondroprotective effects and superior fiction coefficient. These factors would contribute to prevent progression of osteoarthritis. Intrajoint alteration of molecular weight HA should be clarified in future study.
• Functional role of Syndecan-4 in the process of osteochondral repair

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

  Date (from‐to) : 2014/04 -2017/03 

  Author : ONODERA TOMOHORO

   

  We successfully developed novel osteochondral repair model by using young C57Bl/6 mice（Matsuoka M, Onodera T et al., Tissue Eng. 2015）。This novel animal model made us to clarify the cartilage repair mechanisms in glycosphingolipid depletion mice（Matsuoka M, Onodera T et al., Sci Rep. 2017）。In addition, we applied this animal model to Syndecan-4 knockout mice. Surprisingly, osteochondral repair in Syndecan-4 knockout mice is enhanced compare with wildtype mice.
• Identification of functional glyco-biomarkers during chondrogenesis of mouse iPS cells

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

  Date (from‐to) : 2014/04 -2016/03 

  Author : Iwasaki Norimasa, ONODERA Tomohiro

   

  Alterations in the structure of stem cell surface glycoforms were found during chondrogenesis. Based on the obtained results, several glycans are considered to play important roles in stem cell-derived chondrogenesis. The identified glycans have functional potential of chondrogenic biomarkers for the safety of cartilage regenerative medicine.
• Functional analysis of glycosphingolipids in osteochondral homeostasis using knockout mice

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

  Date (from‐to) : 2012/04 -2014/03 

  Author : IWASAKI Norimasa, TAKAHATA Masahiko, ONODERA Tomohiro

   

  Glycosphingolipids (GSLs) are ubiquitous membrane components that modulate transmembrane signaling and mediate cell-to-cell and cell-to-matrix interactions. The purpose of this study was to clarify the functional roles of GSLs in maintaining osteochondral homeostasis using different strains of GSLs synthase knockout (KO) mice. Although all strains of KO mice developed and grew normally, osteoarthritic changes were dramatically enhanced with aging. IL-1 stimulation of chondrocytes from KO mice significantly increased MMP-13 mRNA expression and apoptosis. In addition, KO mice delayed enchondral ossification during fracture repair process. These findings indicate that GSLs have a chondro-/osteo- protective role and prevent disease progression, although GSLs are not essential for osteochondral tissue development in young mice.
• 硬化性ゲルを用いた関節軟骨損傷の治療

  科学技術振興機構：産学が連携した研究開発成果の展開 研究成果展開事業 産学共同実用化事業(NexTEP)

  Date (from‐to) : 2014 

  Author : 岩崎 倫政
• 同種肢・関節移植における遺伝子導入療法の応用

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  Date (from‐to) : 2011 -2012 

  Author : 本宮 真, 岩崎 倫政, 松井 雄一郎, 西田 欽也

   

  臓器移植時に生じる抗原提示細胞とT細胞間のcostimulatory signalのブロックにより、複合組織移植である同種肢移植における拒絶反応の抑制が可能であることを証明する研究を進めた。H23年度までの研究により、costimulatory signalの代表的系であるCD28/B7系をブロックするCTLA41g蛋白単独投与による同種肢移植の生着延長効果を証明したが、単独での効果は不十分であった。H24年度の目標は、第3のCD28ファミリー分子であるICOS/B7RP-1系のブロック効果を持つICOSIgを単独投与またはCTLA41gと併用投与し、同種移植モデルにおける拒絶反応抑制効果を判定することである。まず、遺伝子工学的手法によりICOSIg蛋白を精製し、ラット同種肢移植モデルに単回投与した。vehicle投与群では移植後平均約6日目に拒絶反応(外観上の移植片のescharformationの形成)を生じるのに対し、ICOSIg蛋白単独投与群では約13日と有意な生着期間の延長効果を認めた。また、ICOSIg蛋白とCTLA41g蛋白の併用群では約27日とさらなる延長効果を確認した。術後の血中サイトカイン濃度において、ICOSIg単独群ではIL-4, 10、TNF-αの抑制効果を、一方併用群ではIL-2, 4, 10、IFN-γ、TNF-αの抑制効果を認め、併用群で有意に拒絶反応抑制効果が高いことが明らかとなった。しかしながら、肝臓や心臓といった他臓器移植モデルにおけるcostimulatory signalのブロックの有効性に比べ、複合組織移植では生着延長効果は少なかった。複合組織移植では皮膚や筋などの高い抗原性の臓器を含んでいるため、より高い拒絶反応抑制効果が必要であり、今後持続的に蛋白を作用させるため、ウイルスベクターを用いた群での検討を検討している。
• The role of Syndecan4 in the development of rheumatoid arthritis

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

  Date (from‐to) : 2011 -2012 

  Author : TAKAHASHI Daisuke, IWASAKI Norimasa

   

  In this study, to try to understand the role of Syndecan4 in the development of Rheumatoid Arthritis (RA), we have compared Syn4-deficient (Syn4 KO) mice and wild-type (WT) mice in collagen-induced arthritis (CIA) model. Syn4 KO mice revealed attenuated clinical severity and pathological features in CIA model. Syn4 was mainly expressed on B cells in the draining LN (dLN), and interestingly, Syn4 KO mice showed the drastic hypoplasia of germinal center formation in the dLN. And the numbers of B cell subsets that involve in germinal center formation in the dLN, were also decreased in Syn4 KO mice. In addition, Syn4 KO mice showed reduced production of type-II collagen-specific IgG antibodies (total IgG, IgG2a and IgG2b) compared with WT mice.Our results indicated that Syn4 on B cells possibly regulates the development of RA by modulating germinal center formation and antibody production.
• Development of an acellular cartilage tissue engineering technique using an ultra-purified in-situ forming gel

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

  Date (from‐to) : 2010 -2012 

  Author : IWASAKI Norimasa, KASAHARA Yasuhiko, HUNAKOSHI Tadanao

   

  We succeeded in achieving hyaline-like cartilage repair by local administration of SDF-1 using an ultra-purified in-situ forming (UPIF) gel without cells. The obtained results indicate that UPIF gel enhances chondrogenesis of bone marrow stromal cells recruited by the chemotactic effect of SDF-1, leading to a novel cell-free approach for cartilage tissue engineering.
• グライコミクスによる変形性関節症の早期診断に有効な血清糖鎖マーカー探索

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  Date (from‐to) : 2011 -2011 

  Author : 西田 欽也, 岩崎 倫政, 西村 伸一郎, 天野 麻穂

   

  変形性関節症の早期診断のための血清マーカーの探索を目的に研究を進めた。変形性膝関節症(OA)患者および健常者の血清5-20μ1を用いた。血清中からグライコブロッティング法を用いて高速(5時間程度)かつ高効率に、糖蛋白質からN-結合型糖鎖の遊離精製を行った。得られたN-結合型糖鎖をMALDI-TOF/MSに供することで、各糖鎖構造を推定し、内部標準物質のピーク面積からの比例計算により定量化を行った。解析は現在進行中である。患者検体はX線所見にて膝OAと診断されたKellgren-Lawrence分類grade 2-4の患者より採取している。糖鎖解析は、本申請者が中心となり西村、天野らの協力のもと行っている。独自に開発したグライコブロッティング法は従来の解析法に比べ飛躍的に解析時間の高速化と高効率性を実現し、これまで困難とされていた大規模糖鎖解析を可能とし、本研究で予定している検体数の解析を早急に進めているところである。統計学的解析によりAUC(Area Under the Curve)が0.85以上の糖鎖およびその組み合わせを抽出する。先行研究の結果より、5から10程度の候補糖鎖および組み合わせが予想される。さらに、糖鎖関連分子のOAの病因における機能的役割を解明するためにスフィンゴ糖脂質を軟骨組織特異的にノックアウトしたマウス(UgcgKOマウス)を用いてOAモデルを作成し、その機能解析を行った。その結果、GSLsは軟骨の発生や分化には必須ではないが、正常な軟骨代謝を維持し、OA進行を抑制する機能を持つことが示唆された。
• Elucidating the bone resorption mechanism using a glycobiological approach

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

  Date (from‐to) : 2009 -2011 

  Author : IWASAKI Norimasa, ABE Yuichirou

   

  We established expression profiles of N-linked glycans and glycosphingolipids during osteoclastogenesis. Among glycosphingolipids expressed on osteoclasts and these precursor cells, we identified GD1/ganglioside as a negative regulator of proliferation of osteoclast precursor cells.
• 関節疾患治療のための新規注射剤の実用化研究

  産学が連携した研究開発成果の展開 研究成果展開事業 地域事業 地域イノベーション創出総合支援事業 育成研究

  Date (from‐to) : 2008 -2011 

  Author : 岩崎 倫政

   

  現在、外傷性関節軟骨欠損や変形性関節症などの関節疾患において治療に用いられるヒアルロン酸製剤は動物由来製剤が主流であり、安全のための精製にコストがかかる等の欠点がある。また、最も有効な治療法は人工関節置換術であるが、それは安定したものである反面、高コスト、置換物のゆるみ、感染症など問題が存在している。代表研究者等は、幹細胞を活性化する基材として植物由来の新規マテリアルを用いて、軟骨損傷部に集まる骨髄間葉系幹細胞の活性化による軟骨再生を実現している。既に大型動物での研究で軟骨再生治療の確証を得ており、軟骨修復・再生の作用機序を検証し、実用化を目指す。本成果により介護、QOLへの貢献も大きく期待される。
• 神経特異的遺伝子BRINPファミリーによる脊髄損傷治療のアプローチ

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  Date (from‐to) : 2008 -2009 

  Author : 三浪 明男, 岩崎 倫政

   

  1)引き続きC57BL/6マウスの脊髄損傷モデルを作成中である。モデル作成後は、脊髄損傷後の急性期・亜急性期・慢性期ごとに脊髄組織を摘出し、定量RT-PCRを用いたBRINPファミリーmRNAの発現推移およびWestern blotを用いたBRINPファミリータンパク質の発現推移を評価する予定。 2)マウス海馬初代培養神経細胞に対して、BRINPファミリーの強制発現およびSiRNAによる発現調節により神経細胞の細胞死感受性がどのように変化するかをTime-lapse imagingの手法を用いて評価している。Time-lapse imaging観察中に神経細胞がダメージを受け細胞死を起こし、評価できないという問題は解決しつつあり、引き続き評価を行っている。また、BRINPファミリーの発現調節により細胞死が誘導された場合アポトーシス関連タンパクの発現評価などにより、細胞死誘導のメカニズムも明らかにする。 3)マウスES細胞由来神経幹細胞から神経細胞への分化過程におけるBRINPの発現制御の結果を元に強制発現による発現調節手法を用いて、BRINPファミリーを介して神経幹細胞から神経細胞またはグリア細胞に分化調節が可能かどうか直接的な評価を行った。ES細胞由来神経幹細胞にBRINPを強制発現させた場合、細胞周期を抑制させることが明らかとなった。この結果からBRINPは神経幹細胞から神経細胞への分化調節に関与していると考えられた。このことについてはJournal of Neuroscience Researchに掲載予定である。
• 神経組織再生のための新規多機能生体内吸収性基材の開発

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2006 -2007 

  Author : 三浪 明男, 西村 紳一郎, 眞島 任史, 岩崎 倫政

   

  本年度の研究によって、我々は以下のような成果結果を得ることができた。 1.基盤となる神経組織再建用材料の追加:平成18年度の報告書において我々はヒアルロン酸を導入したキトサン繊維を用いて神経再生の実験を行い、その結果を報告した。平成19年度ではこの素材の他に、新たな細胞外マトリックスが神経再生に有効であることを発見した。具体的にはこの細胞外マトリックスを使用することにより他の細胞外マトリックスを使用した場合と比較し、細胞(神経細胞のモデルとしてPC12細胞を使用)突起の伸長が有意に増加することを証明した。 2.神経組織再生用材料のための細胞接着分子・細胞増殖因子の導入:同様に平成18年度の報告書においてキトサンに細胞接着分子であるRGDモチーフを化学的に安定化した状態で導入したことを報告した。平成19年度ではRGDモチーフのほか、細胞外マトリックスの構成成分であるラミニンの細胞接着モチーフの2種類を化学的に合成(solid phase peptide synthesisにて)し、これらの生理活性の評価を行い、神経再生に対し望ましい効果を有することを証明した。 今後の予定: 前述した神経再生に有用な新しい素材に同じく前述の3つの細胞接着モチーフを化学的に導入することにより新たな神経再生用素材を作成する。これに前述のPC12細胞を播種し、神経突起伸長、神経細胞数の増加などをin vitroで評価をした後、臨床応用を見据え3次元のチューブを作成する予定である。、
• 腱靭帯損傷後のSDF-1の発現の変化とその骨髄間葉系幹細胞による修復への影響

  日本学術振興会：科学研究費助成事業 萌芽研究

  Date (from‐to) : 2006 -2007 

  Author : 末永 直樹, 岩崎 倫政

   

  本年度研究によりSDF-1の靭帯損傷後の治癒過程に対する作用に関して、以下の結果が得られ、その成果は現在国際ジャーナルに投稿中である。 1. ラット膝内側側副靭帯損傷モデルにおいて、損傷靭帯局所でのSDF-1mRNAの発現が有意に上昇していることを証明した。この結果は、SDF-1が損傷靭帯の自然治癒過程においてなんらかの機能を持つことを示唆するものである。 2. SDF-1mRNA発現上昇の時期と、骨髄間葉系幹細胞の局所集積時期に相関性が認められた。これらの結果より、腱・靭帯の損傷後には局所でのSDF-1の発現が上昇し、それにより骨髄間葉系幹細胞のhoming現象が促進され、治癒過程が促進されるという仮説をたてることが出来た。 3. SDF-1のfibroblastに対する細胞増殖作用や器質産生促進等の直接的細胞活性作用は有意なものではなかった。 4. SDF-1の局所投与(外因性)により骨髄間葉系幹細胞の局所集積が生じ、損傷靭帯の治癒促進作用が示された。 以上の結果より、SDF-1は靭帯損傷後の治癒過程において直接的に局所の線維芽細胞に作用するのではなく、骨髄間葉系幹細胞の損傷部への集積を促進し、集積した骨髄間葉系幹細胞により間接的に治癒作用を促進させると推測された。将来的には、靭帯損傷部にSDF-1を投与することにより靭帯損傷部の治癒過程を促進させる新規の治療法の開発が可能になると思われる。
• 腱・靭帯のリモデリングにおけるオステオポンチンの効果の解明と治療への応用

  日本学術振興会：科学研究費助成事業 萌芽研究

  Date (from‐to) : 2005 -2006 

  Author : 真島 任史, 岩崎 倫政, 今 重之, 三浪 明男

   

  除負荷によって起こる腱リモデリング過程におけるメカニズム解明をオステオポンチン(OPN)に基づいて実験を行った。 1.除負荷における腱細胞のコラーゲン産生変化の解析 除負荷によっておこる腱コラーゲン線維径減少について、まずコラーゲン産生の変化が関係するかどうか検討した。Real-time PCR解析結果より、除負荷の腱組織はそれぞれ反対側のコントロール腱組織と比較しコラーゲンmRNAの発現に有意な差は無かった。さらに、除負荷された腱組織中における線維芽細胞のアポトーシスの程度を経時的に調べたが、野生型マウスの除負荷による腱組織リモデリング過程においてアポトーシス陽性細胞の存在は認められなかった。以上より除負荷による腱リモデリング過程でコラーゲン産生変化はないことが証明された。 2.除負荷後の腱リモデリング過程におけるMMP-13の発現変化 次にコラーゲン分解の亢進に関係すると考えられるMMP-13に着目した。除負荷によって起こる腱リモデリング過程のMMP-13発現増強をOPNの有無によって比較した。野生型マウスでは、MMP-13の発現は除負荷後2週目で平均20倍まで増加したが、OPN欠損マウスでは平均4倍のみの増加であり、OPNがMMP-13の調節に関与していることを示唆した。 OPNがMMP-13をどのように調節しているかを解析するためマウス腱線維芽細胞を培養したin vitroの実験を行った。MMP-13の発現はOPNの受容体にその結合を阻害するGRGDSの合成ペプチドの添加により有意に増加した。さらに、OPNの受容体であるαvβ3インテグリン受容体にOPNの結合を阻害する抗αvインテグリン抗体を投与することによりMMP-13の発現は増大した。これらの結果よりOPNはそのインテグリン受容体を通しMMP-13の発現を調節することが示された。
• Detailed molecular design of artificial extra cellular matrix and application for ligament and cartilage tissue engineering

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

  Date (from‐to) : 2003 -2005 

  Author : MAJIMA Tokifumi, IWASAKI Norimasa, MONDE Kenji, NISHIMURA Shin-ichiro, MINAMI Akio

   

  In order to make a model of glycosaminoglycan (proteoglycan), simple method to hybridize hyaluronan, alginate, and chitosan was developed. Cell attachment molecule, RGD (Arg-Gly-Asp) moiety was successfully induced to chitosan. It was suggested that this polysaccharide-peptide conjugate exhibited excellent capacities for both cell adhesion and cell proliferation of chondrocytes and fibroblasts. Considering the growing importance of the biocompatible scaffolds in the recent tailored tissue engineering technique, these results indicate that the present strategy of 2-iminothiolane-based conjugation of polysaccharides with biologically active peptides will become a key and potential technology to develop desirable scaffold materials for the tissue regenerations. To establish medical use of tissue engineering technology for tendon, ligament and cartilage injury, we developed a scaffold which has enough ability for cell growth, cell differentiation, and mechanical properties. The scaffold made from chitosan and 0.1% hyaluronic acid has enough biodegradability and biocompatibility. An animal experiment showed that the scaffold induced less inflammation. Further more, the results that implanted tissue that was regenerated outside the body showed that the tissue engineered tendon/ligament had enough mechanical properties to stabilize the joint. As for cartilage tissue engineering, cartilage tissue was successfully engineered using the newly developed scaffold. It was showed that newly developed hybrid polymer fiber scaffold has feasibility for joint tissue engineering.
• 神経組織再生のための新規多機能生体内吸収性基材の開発

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2003 -2004 

  Author : 三浪 明男, 西村 紳一郎, 眞島 任史, 岩崎 倫政

   

  昨年度は、神経組織再生用チューブの作成のため、基盤材料にRGDモチーフおよび細胞増殖因子(タンパク)を化学的に安定化した状態で導入する技術を確立した。本年度は、基盤材料に導入したタンパクが基盤材料の分解と共に放出され細胞に対し、有効な生理活性を持つことを証明する実験を行った。RGDモチーフおよび細胞増殖因子を導入した基盤材料は、コントロールに比べ明らかに高い細胞接着性および増殖性を示した。さらに、基盤材料の分解と共に導入されたタンパクは基盤から放出され、長期にわたりタンパク活性を維持することも明らかとなった。 しかし、導入基盤の持つこれらの細胞に対する作用は神経細胞に特異的ではないため、本年度はさらに、神経細胞に対しより特異的作用を持つと考えられる糖鎖を基盤に導入し、神経細胞に対する特異的生理活性の有無を確認した。基盤材料に、糖鎖をより安定化した状態で化学的に導入する方法については確立した。糖鎖を導入した基盤の神経細胞へ対する接着性および増殖性評価においては、コントロールに比べ両評価共に有意な向上を認めた。 これら新規に開発した基盤材料へのタンパクおよび糖鎖の化学的導入技術の確立およびin vitro評価におけるその有用性については証明された。今後は、基盤材料の生体内親和性および生分解性のコントロール技術をより確実なものにし、生体内における神経組織再生用チューブの完成と神経組織再生手法の確立を目指す。
• 遺伝子導入療法を用いた同種神経移植における拒絶反応抑制

  日本学術振興会：科学研究費助成事業 萌芽研究

  Date (from‐to) : 2001 -2003 

  Author : 岩崎 倫政, 加藤 博之, 三浪 明男, 岩崎 倫政

   

  我々はT細胞活性化をブロックし、急逝拒絶反応を抑制するとされる可溶性融合蛋白CTLA4Ig遺伝子をadenovirus vectorに組み込んだAdCTLA4Igを用い、同種神経移植において移植神経へのAdCTLA4Ig局所投与によるCTLA4Ig遺伝子導入が可能か、またAdCTLA4Ig全身投与または局所投与により移植神経の急性拒絶反応が抑制可能かについて検討した。 主要組織適合抗原(RT1)亜領域の全て異なるACIとLewisラットを用いて、同種神経移植モデルを作成した。これをsyngeneic graft (Lewis-Lewis)群、allogeneic graft非治療群、allogeneic graftのAdCTLA4Ig全身投与群、allogeneic graftのAdCTLA4Ig局所投与群の4群に分けた。先に作製したAdCTLA4Igウィルス液を、全身投与群は1x10^9pfu/ml、局所投与群は3x10^8pfu/ml投与した。 これまでの実験でAdCTLA4Ig全身投与群では、投与後3週でも高いCTLA4Ig濃度が維持されていたが、移植神経へのAdCTLA4Ig局所投与では投与後2週ではほとんど発現が確認されず、局所投与によるCTLA4Ig遺伝子導入は可能であるがCTLA4Ig蛋白は長期に発現しないことがわかった。また拒絶に対する組織学的評価では、移植後8週では全身投与群では非治療群に対して有意に拒絶が抑制されていたが、局所投与群では拒絶が進行し非治療群と有意差がなかった。電気生理学的評価においても局所投与群が8、16週で神経伝導速度の測定不能であったのに対して、全身投与群では16週では健側の70%以上の伝導側であった。 今年度は更にnを増やしてこれまでと同様の結果を得ており、同種神経移植におけるAdCTLA4Ig局所投与と全身投与では、組織学的評価でも電気生理学的評価でも拒絶反応抑制効果の有効性に差があることが確認された。
• Experimental Study of Allogeneic Joint/Limb Transplantation

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B).

  Date (from‐to) : 1998 -2000 

  Author : MINAMI Akio, IWASAKI Norimasa, ITO Manabu, SUENAGA Noaki

   

  (1) This study suggests that major histocompatibility complex (MHC) matching clearly improves the survival time of allotransplanted limb in rats. Specifically, both RT1-A and D matching is the most effective compatibility in prolonging survival time of allogeneic limb transplantations. (2) In this study, we clarified the optimal timing of FK 506 administration for preventing allograft rejection of the limb. The mean graft survival time was 9 days in no treatment group, 19 days in day 0 group (FK506 5 mg/kg single i.m. at postop. 0 day), 52 days in day 1 group (FK 506 5 mg/kg single i.m. at postop. 1 day), 42 days in day 2 group (FK 506 5 mg/kg single i.m. at postop. 2 day). Histologically, all tissues showed significantly better preservation in day 1 and day 2 groups. On the basis of the current results, the administration of FK 506 for limb allograft is more effective at 1 or 2 days after tranplantation.
• 組織工学的手法を用いた軟骨再生
• 同種肢移植に関する実験的研究
• 上肢におけるバイオメカニクス
• Cartilage Regeneration Using Tissue Engineering Technique
• Experimental Study on Allogeneic Limb Transplantation
• Biomechanics of Upper Extremity

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  須藤 英毅, 山本 強, 安倍 雄一郎, 岩崎 倫政  国立大学法人北海道大学, 株式会社ロバート・リード商会  202003018491341980
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• 特許第6116009号:軟骨再生用組成物  

  岩崎 倫政, 祐川 敦, 三浪 明男, 大澤 伸雄  持田製薬株式会社, 国立大学法人北海道大学  201703002049962534
• 特開2016-093497:脊柱変形矯正固定術支援装置、脊柱変形矯正固定術支援方法、プログラム、及び脊柱変形矯正固定術に使用するロッド製造方法  2016/05/26

  須藤 英毅, 山本 強, 安倍 雄一郎, 岩崎 倫政  国立大学法人北海道大学, 株式会社ロバート・リード商会  201603017508584998
• 特許第5491866号:関節疾患治療用組成物  

  岩崎 倫政, 三浪 明男, 笠原 靖彦, 五十嵐 達弥, 河村 太介, 大澤 伸雄, 今井 真理子  持田製薬株式会社, 国立大学法人北海道大学  201403053616544510
• 特許第5425134号:軟骨疾患治療用組成物  

  岩崎 倫政, 三浪 明男, 笠原 靖彦, 五十嵐 達弥, 河村 太介, 笠原 文善, 宮島 千尋, 大澤 伸雄, 今井 真理子  持田製薬株式会社, 国立大学法人北海道大学  201403027818946350
• WO2013-027854:軟骨再生用組成物  2013/02/28

  岩崎 倫政, 祐川 敦, 三浪 明男, 大澤 伸雄  持田製薬株式会社, 国立大学法人北海道大学  201503070636855015
• 特開2011-224378:軟骨疾患治療用組成物  2011/11/10

  岩崎 倫政, 三浪 明男, 笠原 靖彦, 五十嵐 達弥, 河村 太介, 笠原 文善, 宮島 千尋, 大澤 伸雄, 今井 真理子  持田製薬株式会社, 国立大学法人北海道大学  201103062096402375
• 特許第4740369号:軟骨疾患治療用組成物  

  岩崎 倫政, 三浪 明男, 笠原 靖彦, 五十嵐 達弥, 河村 太介, 笠原 文善, 宮島 千尋, 大澤 伸雄, 今井 真理子  持田製薬株式会社, 国立大学法人北海道大学  201303019032540458
• WO2009-054181:関節疾患治療用組成物  2009/04/30

  岩崎 倫政, 三浪 明男, 笠原 靖彦, 五十嵐 達弥, 河村 太介, 大澤 伸雄, 今井 真理子  持田製薬株式会社, 国立大学法人北海道大学  201103094193230057
• WO2008-102855:軟骨疾患治療用組成物  2008/08/28

  岩崎 倫政, 三浪 明男, 笠原 靖彦, 五十嵐 達弥, 河村 太介, 笠原 文善, 宮島 千尋, 大澤 伸雄, 今井 真理子  持田製薬株式会社, 国立大学法人北海道大学  201003084898393084
• 特開2007-205777:変形性関節症の診断支援方法  2007/08/16

  中川 裕章, 松橋 智弥, 岩崎 倫政, 三浪 明男, 西村 紳一郎, 近藤 裕郷  塩野義製薬株式会社, 国立大学法人 北海道大学  200903037148136641
• 特開2006-104287:共有結合によるグリコサミノグリカンと細胞増殖因子との結合化合物およびその製造方法。  2006/04/20

  三浪 明男, 西村 紳一郎, 眞島 任史, 岩崎 倫政, 益子 竜弥  国立大学法人 北海道大学  200903052684017735
• 特許第3774466号:キトサンと酸性生体高分子とのハイブリッド繊維および動物細胞培養基材  

  眞島 任史, 岩崎 倫政, 船越 忠直, 三浪 明男, 西村 紳一郎, 戸倉 清一, 原田 和夫, 野中 佐智子, 前川 宣彦  株式会社生物有機化学研究所  201103049910191953
• WO2005-049083:腱・靱帯の劣化予防・治療剤  2005/06/02

  森 律明, 岩崎 倫政, 眞島 任史, 三浪 明男, 今 重之, 上出 利光, 前田 雅弘  株式会社 免疫生物研究所, 株式会社ジーンテクノサイエンス  200903089023618407
• 特許第3616344号:軟骨細胞培養方法および軟骨組織再生基材  

  戸倉 清一, 西村 紳一郎, 岩崎 倫政, 田村 裕  西村 紳一郎, 北海道電力株式会社, 株式会社生物有機化学研究所  201103058225768716
• WO2004-003130:キトサンと酸性生体高分子とのハイブリッド繊維および動物細胞培養基材  2004/01/08

  眞島 任史, 岩崎 倫政, 船越 忠直, 三浪 明男, 西村 紳一郎, 戸倉 清一, 原田 和夫, 野中 佐智子, 前川 宣彦  株式会社生物有機化学研究所  200903094404063235
• 特開2002-291461:軟骨細胞培養方法および軟骨組織再生基材  2002/10/08

  戸倉 清一, 西村 紳一郎, 岩崎 倫政, 田村 裕  西村 紳一郎, 北海道電力株式会社, 株式会社生物有機化学研究所  200903097474873578