Faculty Profiles - NISHIDA, Yoshihiro

Papers - NISHIDA, Yoshihiro

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西田佳弘, 酒井智久, 生田国大, 小池宏

日本整形外科学会雑誌 Vol. 96 page： 488 - 493 2022

後腹膜発生軟部肉腫に対する治療戦略 Reviewed

生田国大, 西田佳弘

整形・災害外科 Vol. 65 page： 289 - 294 2022

Successful treatment with denosumab for pelvic fibrous dysplasia: A case report and review of the literature. Reviewed Open Access

Ikuta K, Sakai T, Koike H, Ito K, Imagama S, Nishida Y.

Medicine (Baltimore). Vol. 100 ( 49 ) page： e28138 - e28138. 2021.12

Reconstruction of the extensor mechanism augmented with reverse transferred iliotibial band after proximal tibia tumor resection and mega-prosthetic replacement Reviewed Open Access

Ikuta, K; Nishida, Y; Tsukushi, S; Sakai, T; Koike, H; Imagama, S

KNEE Vol. 33 page： 102 - 109 2021.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Knee

Background: The optimal procedure for functional reconstruction of the extensor mechanism after proximal tibia mega-prosthetic replacement remains unclear. Methods: Since 2006, 14 consecutive patients with aggressive bone tumors in the proximal tibia who underwent mega-prosthetic replacement were prospectively treated with reconstruction of the extensor mechanism using an ipsilateral iliotibial band. The surgical procedure consisted of wrapping the reversed iliotibial band around the tibia component, firmly suturing it to the remaining patellar tendon and tibialis anterior fascia, and covering it with a muscle flap. At the last follow up, the function was assessed based on extensor lag, active flexion of the knee, and Musculoskeletal Tumor Society score. Patellar height was measured with the Insall–Salvati ratio (ISR) preoperatively, postoperatively, and at the last follow up. Results: At the last follow up, the extensor lag and active flexion in 14 patients averaged 2.5° and 86°, respectively. Musculoskeletal Tumor Society score could be obtained in nine surviving patients at the last follow up and was a mean of 20.7 points. The mean ISR preoperatively, postoperatively, and at the last follow up was 1.04, 0.75, and 0.89, respectively. The extensor lag was not associated with the ISR value at any points, while reduced active flexion significantly correlated with a low ISR at the last follow up (P = 0.015). Four patients underwent additional surgeries due to postoperative infection, but none required eventual revision or amputation. Conclusion: The extensor mechanism reconstruction with the reverse transferred iliotibial band for mega-prosthetic replacement after proximal tibia resection yielded reliable outcomes with functional benefit to stabilize active knee extension.

DOI： 10.1016/j.knee.2021.09.006

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Scopus

PubMed

Efficacy and safety of cyclooxygenase 2 inhibitors for desmoid tumor management: a systematic review Reviewed Open Access

Emori, M; Matsumoto, Y; Murahashi, Y; Yoshida, M; Nishida, Y

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 83 ( 4 ) page： 673 - 681 2021.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Nagoya Journal of Medical Science

The efficacy and safety of cyclooxygenase 2 (COX2) inhibitors for the treatment of desmoid-type fibromatosis (DF) are unclear. Therefore, we systematically reviewed related literature to assess the ef-ficacy and safety of COX2 inhibitors for DF treatment. We searched pertinent literature between January 1999 and August 2017 to identify relevant studies using the keywords “Fibromatosis, aggressive” and “Cyclooxygenase inhibitors.” Thereafter, we screened and determined the quality of the studies using the Grading of Recommendations Assessment, Development, and Evaluation system and extracted the article data. The critical outcomes selected were the efficacy and adverse effects of COX2 inhibitors. Efficacy was evaluated in terms of clinical benefit when patients showed complete response, partial response, and stable disease. Thirty-one articles were identified from the database search, and one was identified through the reviewers’ manual search. Finally, we retrieved six studies, including three case reports, comprising 89 patients after the first and second screenings. Fifty-three patients were excluded because three studies were reported from the same institution; hence, in total, 36 patients were included. Clinical benefit was noted in 64% of the patients. Three adverse effects were identified from the records of the six extracted studies. The strategy of watchful waiting using COX2 inhibitors with few side effects is weakly recommended for DF, especially DF patients with pain.

DOI： 10.18999/nagjms.83.4.673

Trends in diagnostic and therapeutic strategies for extra-abdominal desmoid-type fibromatosis: Japanese musculoskeletal oncology group questionnaire survey Reviewed Open Access

Murase, F; Nishida, Y; Hamada, S; Sakai, T; Shimizu, K; Ueda, T

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 51 ( 11 ) page： 1615 - 1621 2021.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Clinical Oncology

Objective: The mainstay of treatment modality for extra-abdominal desmoid-type fibromatosis (DF) has shifted from surgery, which often impairs ADL/QOL, to conservative treatment including active surveillance. In the present study, we conducted a longitudinal survey on the diagnosis and treatment of DF at facilities belonging to the Japanese Musculoskeletal Oncology Group, which is a research group of facilities specializing in the treatment of bone and soft tissue tumors in Japan to clarify the transition of medical care for extra-abdominal DF. Methods: The same questionnaire was administered in 2015 and 2018, and responses were obtained from 46 (69%) of 67 facilities and 42 (53%) of 80 facilities in 2015 and 2018, respectively. Results: Although immunostaining for β-catenin was often used for the pathological diagnosis in both 2015 and 2018, CTNNB1 mutation analysis was not performed either in 2015 or in 2018. As for the treatment strategy for resectable cases, surgical treatment including wide resection was selected at 11 facilities (24% of respondents) in 2015, and further decreased to 5 facilities (12%) in 2018. Conservative treatment with active surveillance or medical treatment was the most common treatment for both resectable and difficult-to-resect cases. COX-2 inhibitors and tranilast were often used in the drug treatment of both resectable and difficult-to-resect cases. Few facilities provided radiotherapy, methotrexate and vinblastine, or DOX-based chemotherapy for refractory cases in both 2015 and 2018. Conclusions: A good trend was found in the questionnaire survey. It will be further necessary to disseminate clinical practice guidelines to physicians more widely, and to have them understand and implement the most up-to-date medical practice strategies for this rare disease.

DOI： 10.1093/jjco.hyab146

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Scopus

PubMed

Untitled Reply Reviewed Open Access

Nishida, Y; Kano, K; Nobuoka, Y; Seo, T

ARTHRITIS & RHEUMATOLOGY Vol. 73 ( 11 ) page： 2148 - 2149 2021.11

Less-invasive fascia-preserving surgery for abdominal wall desmoid Reviewed Open Access

Nishida, Y; Hamada, S; Sakai, T; Ito, K; Ikuta, K; Urakawa, H; Koike, H; Imagama, S

SCIENTIFIC REPORTS Vol. 11 ( 1 ) page： 19379 2021.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports

The mainstay of treatment for desmoid has been shifted to active surveillance (AS). However, surgery is still being performed on abdominal wall desmoid with a wide surgical margin. The purposes of this study are to clarify the treatment results of less-invasive, fascia preserving surgery for patients with abdominal wall desmoid, and to propose a new treatment modality. Since 2009, 34 patients with abdominal desmoid have been treated in our institution. Among them, as a final treatment modality, 15 (44%) were successful with AS, 15 were subjected to less-invasive surgery, and 4 methotrexate and vinblastine treatment. The clinical results of less-invasive surgery were clarified. In the surgical group, although the surgical margin was all microscopic positive (R1), only one patient (6.7%), who has the S45F mutation type of CTNNB1, showed recurrence, at a mean follow-up of 45 months. There were no patients with familial adenomatous polyposis (FAP)-related desmoid in this cohort. Only two patients (13%) required fascia lata patch reconstruction after removal of the tumor. In patients with non FAP-related abdominal wall desmoid, less-invasive, fascia preserving surgery is recommended as a favorable option as active treatment. Based on the results of this study, multi-institutional further research is warranted with an increased number of patients.

DOI： 10.1038/s41598-021-98775-2

Efficacy and Safety of Diclofenac-Hyaluronate Conjugate (Diclofenac Etalhyaluronate) for Knee Osteoarthritis: A Randomized Phase III Trial in Japan Reviewed Open Access

Nishida, Y; Kano, K; Nobuoka, Y; Seo, T

ARTHRITIS & RHEUMATOLOGY Vol. 73 ( 9 ) page： 1646 - 1655 2021.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Arthritis and Rheumatology

Objective: To confirm the efficacy and safety of intraarticular (IA) injection of diclofenac covalently linked to hyaluronic acid (diclofenac etalhyaluronate [DF-HA]; ONO-5704/SI-613) in patients with knee osteoarthritis (OA). Methods: In a phase III multicenter, randomized, double-blind, placebo-controlled trial, eligible subjects ages 40–75 years with symptomatic knee OA (Kellgren/Lawrence score of 2 or 3) were randomly assigned to receive IA injections of DF-HA 30 mg or placebo (citric acid–sodium citrate buffered solution; 1:1) once every 4 weeks for 20 weeks (a total of 6 injections). Subjects were followed up for 24 weeks. The primary end point was the mean change from baseline to 12 weeks in Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC) pain subscale scores, measured on a 100-mm visual analog scale. Safety was evaluated by adverse event monitoring. Results: All 440 subjects received investigational products (220 received placebo and 220 received DF-HA). The full analysis set and safety population comprised 438 subjects (220 in the placebo group and 218 in the DF-HA group) and 440 subjects, respectively. At 12 weeks, subjects receiving DF-HA showed significant improvement from baseline in the WOMAC pain subscale score (–23.2 mm) compared to subjects receiving placebo (−17.1 mm), with a difference of −6.1 mm (95% confidence interval −9.4, −2.8; P < 0.001). The difference between groups was significant as early as week 1, and a difference was maintained for 24 weeks, although the difference at week 24 was not significant. Anaphylactic reactions were observed in 2 subjects receiving DF-HA. Conclusion: Our findings indicate that treatment with DF-HA results in significant improvement in the WOMAC pain subscale score compared to placebo over 12 weeks. Anaphylactic reactions were observed, and further safety evaluation is needed.

DOI： 10.1002/art.41725

Tumor location and type affect local recurrence and joint damage in tenosynovial giant cell tumor: a multi-center study Reviewed Open Access

Ota, T; Nishida, Y; Ikuta, K; Tsukushi, S; Yamada, K; Kozawa, E; Urakawa, H; Imagama, S

SCIENTIFIC REPORTS Vol. 11 ( 1 ) page： 17384 2021.8

Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports

Osteochondral destruction and a high recurrence rate after surgery are major concerns that make difficult the treatment course of tenosynovial giant cell tumor. The aims of this study were to elucidate rates of postoperative local recurrence and osteochondral destruction, as correlated with various demographic factors. Eighty surgically treated patients with intra-articular tumors (knee: 49, ankle and foot: 12, hip: 10, others: 9) were included in this study. Factors including age, disease type (diffuse/localized), location, existence of osteochondral destruction were correlated with local recurrence or development/progression of osteochondral destruction. The 5-year local recurrence free survival rate was 71.4%. Diffuse type (n = 59, localized: n = 21) (P = 0.023) and knee location (P = 0.002) were independent risk factors for local recurrence. Diffuse type (P = 0.009) was a significant risk factor, and knee location (P = 0.001) was a negative factor for osteochondral destruction at the initial examination. Progression of osteochondral destruction was observed more often in cases with local recurrence (P = 0.040) and findings of osteochondral destruction at the initial examination (P = 0.029). Diffuse type is a factor that should be noted for both local recurrence and osteochondral destruction, while local recurrence occurs but osteochondral destruction is less observed in the knee.

DOI： 10.1038/s41598-021-96795-6

Spontaneous Regression of Brown Tumor in a Patient Treated With Peritoneal Dialysis Reviewed Open Access

Ito, K; Ikuta, K; Nishida, Y; Sakai, T; Imagama, S

CUREUS JOURNAL OF MEDICAL SCIENCE Vol. 13 ( 8 ) page： e17078 2021.8

Effect of Neoadjuvant Therapies on Soft Tissue Sarcomas with Tail-like Lesions: A Multicenter Retrospective Study Reviewed Open Access

Aiba, H; Ikuta, K; Asanuma, K; Kawanami, K; Tsukushi, S; Matsumine, A; Ishimura, D; Nagano, A; Shido, Y; Kozawa, E; Yamada, K; Wasa, J; Kimura, H; Sakai, T; Murakami, H; Sakai, T; Nakamura, T; Nishida, Y

CANCERS Vol. 13 ( 15 ) 2021.8

Language：English Publishing type：Research paper (scientific journal) Publisher：Cancers

Several types of soft tissue sarcomas have peripheral infiltrative growth characteristics called tail‐like lesions. The efficacy of neoadjuvant therapy for tumors with tail‐like lesions has not been elucidated. From 2012 to 2019, we analyzed 36 patients with soft tissue sarcoma with tail‐like lesions treated with neoadjuvant therapy, including chemotherapy, radiotherapy, or both. The effect of neoadjuvant therapy on the tail sign was investigated by analyzing the change in tail‐like lesions during neoadjuvant therapy and histological responses. The median length of the tail‐like lesion reduced from 29.5 mm at initiation to 19.5 mm after neoadjuvant therapy. The extent of shrinkage in tail‐like lesions was related to the histopathological responses in the main part of the tumor. Complete disappearance of the tail‐like lesion was observed in 12 patients; however, it was not related to achieving a microscopically negative margin. The oncologic outcomes did not significantly differ between cases with and without the complete disappearance of tail‐like lesions. This study indicated that the shrinkage of tail‐like lesions did not have a significant effect on complete resection or improvements of clinical outcomes. A more comprehensive evaluation is needed to elaborate on the surgical strategy.

DOI： 10.3390/cancers13153901

A Novel Technique to Lengthen the Reverse Latissimus Dorsi Muscle Flap Arc Reviewed

Takanari, K; Nakamura, Y; Uchibori, T; Nakamura, R; Ebisawa, K; Kambe, M; Urakawa, H; Nishida, Y; Kamei, Y

PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN Vol. 9 ( 7 ) page： e3525 2021.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Plastic and Reconstructive Surgery Global Open

Reconstruction of the lower lumbar region is challenging for surgeons due to limited locoregional flap choices. The latissimus dorsi muscle flap is a mainstay for this area; however, there are several limitations, including that the dominant thoracodorsal artery and vein pedicle-based flaps are not reachable for reconstruction of the lumbar region, while perforator of intercostal artery and veins pedicle-based reverse latissimus dorsi (RLD) flap mobility is limited by including multiple perforators. Here, we describe a novel operative technique that lengthens the rotation arc of RLD muscle flaps. The surgical technique is as follows: RLD is elevated based on lower perforator of intercostal artery and veins (usually including two of the eighth-11th perforators); thoracodorsal artery and vein are ligated; and the flap is mobilized toward the defect. When RLD was not reachable to the defect, the far aspect of the intercostal artery and vein from the defect was ligated and the perforator was elevated with the near aspect of the intercostal artery and vein from intercostal space. Because the intercostal space measured between approximately 3 cm and 4 cm, this dissection gained 3-4 cm of rotational arc per intercostal space. Moreover, because the lower ribs follow a medio-cranial to latero-caudal direction, this dissection enabled the flap to extend latero-caudally or medio-cranially while maintaining its blood supply. Other applications using this technique may involve expanding the RLD flap arc caudally, ventrally, and ipsilaterally. We believe this new technique provides a reliable alternative for lower back reconstruction.

DOI： 10.1097/GOX.0000000000003525

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Scopus

PubMed

Establishment of in-hospital clinical network for patients with neurofibromatosis type 1 in Nagoya University Hospital Reviewed Open Access

Nishida, Y; Ikuta, K; Natsume, A; Ishihara, N; Morikawa, M; Kidokoro, H; Muramatsu, Y; Nonobe, N; Ishizuka, K; Takeichi, T; Kanbe, M; Mizuno, S; Imagama, S; Ozaki, N

SCIENTIFIC REPORTS Vol. 11 ( 1 ) page： 11933 2021.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports

Neurofibromatosis type 1 (NF1) is a genetic multisystem disorder. Clinicians must be aware of the diverse clinical features of this disorder in order to provide optimal care for it. We have set up an NF1 in-hospital medical care network of specialists regardless of patient age, launching a multidisciplinary approach to the disease for the first time in Japan. From January 2014 to December 2020, 246 patients were enrolled in the NF1 patient list and medical records. Mean age was 26.0 years ranging from 3 months to 80 years. The number of patients was higher as age at first visit was lower. There were 107 males (41%) and 139 females. After 2011, the number of patients has increased since the year when the medical care network was started. Regarding orthopedic signs, scoliosis was present in 60 cases (26%), and bone abnormalities in the upper arm, forearm, and tibia in 8 cases (3.5%). Neurofibromas other than cutaneous neurofibromas were present in 90 cases (39%), and MPNST in 17 cases (7.4%). We launched a multidisciplinary NF1 clinic system for the first time in Japan. For patients with NF1, which is a hereditary and systemic disease associated with a high incidence of malignant tumors, it will be of great benefit when the number of such clinics in Japan and the rest of Asia is increased.

DOI： 10.1038/s41598-021-91345-6

A comparison of the usefulness of nuclear beta-catenin in the diagnosis of demoid-type fibromatosis among commonly used anti-beta-catenin antibodies. Reviewed

Yamada Y, Hirata M, Sakamoto A, Noguchi T, Ito K, Nishida Y, Matsuda S, Haga H

Pathol Int. Vol. 71 ( 6 ) page： 392 - 399 2021.6

Preoperative paraspinous muscle sarcopenia and physical performance as prognostic indicators in non-small-cell lung cancer Reviewed Open Access

Tanaka, S; Ozeki, N; Mizuno, Y; Nakajima, H; Hattori, K; Inoue, T; Nagaya, M; Fukui, T; Nakamura, S; Goto, M; Sugiyama, T; Nishida, Y; Chen-Yoshikawa, TF

JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE Vol. 12 ( 3 ) page： 646 - 656 2021.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Cachexia Sarcopenia and Muscle

Background: Despite the associations of both preoperative sarcopenia and physical performance with post-operative mortality in non-small-cell lung cancer (NSCLC), there have been no comprehensive studies of the impact of physical status on prognosis. This study was performed to investigate the prognostic significance of preoperative sarcopenia and physical performance in NSCLC. Methods: This retrospective cohort study was performed in NSCLS patients undergoing curative lung resection at a university hospital between January 2014 and December 2017. The patients were divided into four groups according to the skeletal muscle index [sarcopenia (lowest sex-specific tertile) and non-sarcopenia] and 6 min walking distance (6MWD) [short distance (<400 m) and long distance (≥400 m)]. Sarcopenia was assessed by preoperative cross-sectional areas of right and left paraspinous muscles at the level of the 12th thoracic vertebra from computed tomography images, and physical performance was determined by preoperative 6MWD. The primary and secondary endpoints were post-operative overall survival (OS) and disease-free survival (DFS). Results: The 587 patients [mean age: 68.5 ± 8.8 years, 399 men (68%)] included in the study were divided into the non-sarcopenia/long-distance group (58%), sarcopenia/long-distance group (26%), non-sarcopenia/short-distance group (9%), and sarcopenia/short-distance group (7%). A total of 109 (18.6%) deaths and 209 (35.6%) combined endpoints were observed over a mean follow-up of 3.1 ± 1.3 years. After adjusting for other covariates, the sarcopenia/short-distance group showed significant associations with shorter OS (hazard ratio, 3.38; 95% confidence interval, 1.79–6.37; P < 0.001) and DFS (hazard ratio, 2.11; 95% confidence, 1.27–3.51; P = 0.004) compared with the non-sarcopenia/long-distance group on multivariate analyses. Although not significant, adding skeletal muscle index and 6MWD to the pre-existing risk model increased the area under the curve on time-dependent receiver operating characteristic curve analysis for OS and DFS, except within 2 years of surgery. Conclusions: The presence of both preoperative paraspinous muscle sarcopenia and short distance in 6MWD had an adverse effect on post-operative prognosis in patients with NSCLC, suggesting that preoperative assessment of thoracic sarcopenia and physical performance may be useful for risk stratification of surgical candidates with potential for targeted interventions.

DOI： 10.1002/jcsm.12691

The Prognostic Role of β-Catenin Mutations in Desmoid-type Fibromatosis Undergoing Resection Only A Meta-analysis of Individual Patient Data Reviewed Open Access

Timbergen, MJM; Colombo, C; Renckens, M; Kim, HS; van Rosmalen, J; Salas, S; Mullen, JT; Colombo, P; Nishida, Y; Wiemer, EAC; Verhoef, C; Sleijfer, S; Gronchi, A; Grünhagen, DJ

ANNALS OF SURGERY Vol. 273 ( 6 ) page： 1094 - 1101 2021.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Annals of Surgery

Objective:This meta-analysis (PROSPERO CRD42018100653) uses individual patient data (IPD) to assess the association between recurrence and CTNNB1 mutation status in surgically treated adult desmoid-type fibromatosis (DTF) patients.Summary of Background Data:The majority of sporadic DTF tumors harbor a CTNNB1 (ß-catenin) mutation: T41A, S45F, and S45P or are wild-type (WT). Results are conflicting regarding the recurrence risk after surgery for these mutation types.Methods:A systematic literature search was performed on June 6th, 2018. IPD from eligible studies was used to analyze differences in recurrence according to CTNNB1 mutation status using Cox proportional hazards analysis. Predictive factors included: sex, age, mutation type, tumor site, tumor size, resection margin status, and cohort. The PRISMA-IPD guideline was used.Results:Seven studies, describing retrospective cohorts were included and the IPD of 329 patients were used of whom 154 (46.8%) had a T41A mutation, 66 (20.1%) a S45F mutation, and 24 (7.3%) a S45P mutation, whereas 85 (25.8%) patients had a WT CTNNB1. Eighty-three patients (25.2%) experienced recurrence. Multivariable analysis, adjusting for sex, age, and tumor site yielded a P-value of 0.011 for CTNNB1 mutation. Additional adjustment for tumor size yielded a P-value of 0.082 with hazard ratio's of 0.83 [95% confidence interval (CI) 0.48-1.42), 0.37 (95% CI 0.12-1.14), and 0.44 (95% CI 0.21-0.92) for T41A, S45P and WT DTF tumors compared to S45F DTF tumors. The effect modification between tumor size and mutation type suggests that tumor size is an important mediator for recurrence.Conclusions:Primary sporadic DTFs harboring a CTNNB1 S45F mutation have a higher risk of recurrence after surgery compared to T41A, S45P, and WT DTF, but this association seems to be mediated by tumor size.

DOI： 10.1097/SLA.0000000000003698

Short-range UV-LED irradiation in postmenopausal osteoporosis using ovariectomized mice Reviewed Open Access

Ochiai, S; Nishida, Y; Higuchi, Y; Morita, D; Makida, K; Seki, T; Ikuta, K; Imagama, S

SCIENTIFIC REPORTS Vol. 11 ( 1 ) page： 7875 2021.4

Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports

Postmenopausal osteoporosis is crucial condition that reduces the QOL of affected patients just like aged type osteoporosis. The aim of this study was to evaluate the effectiveness of short-range UV-LED irradiation in postmenopausal osteoporosis using ovariectomized mice. Preliminary experiments identified the time of onset of osteoporosis after ovariectomy (8 weeks) in our model. We have set up a total of 4 groups (n = 8/group); vitamin D-repletion with UV irradiation (Vit.D+UV+), vitamin D-repletion without UV irradiation (Vit.D+UV−), vitamin D-deficiency with UV irradiation (Vit.D-UV+), vitamin D-deficiency without UV irradiation (Vit.D-UV−), and. From 8 weeks after ovariectomy, UV was irradiated for 24 weeks. At the time of 16 and 24 weeks’ irradiation, serum Vit.D levels, various markers of bone metabolism, bone mineral density, and bone strength were evaluated, and histological analyses were performed. In addition, muscle strength was analyzed. Serum 25-hydroxyvitamin D [25 (OH) D] levels at 40 and 48 weeks of age were increased in the Vit.D-UV+ group compared to the Vit.D-UV−group. Cortical thickness evaluated with micro-CT and strength of bone were significantly higher in Vit.D-UV+ group than those in Vit.D-UV− group. There was no difference in muscle strength between Vit.D-UV+ group and Vit.D-UV− group. No obvious adverse effects were observed in UV-irradiated mice including skin findings. Short-range UV irradiation may ameliorate postmenopausal osteoporosis associated with a state of vitamin D deficiency.

DOI： 10.1038/s41598-021-86730-0

特集骨粗鬆症-指導に役立つエビデンス紫外線によるビタミンD産生-必要な日照時間と影響因子 Reviewed

西田佳弘, 落合聡史, 牧田和也

総合リハビリテーション Vol. 49 ( 4 ) page： 351 - 355 2021.4

Open-label phase 3 study of diclofenac conjugated to hyaluronate (diclofenac etalhyaluronate: ONO-5704/SI-613) for treatment of osteoarthritis: 1-year follow-up Reviewed Open Access

Nishida, Y; Kano, K; Osato, T; Seo, T

BMC MUSCULOSKELETAL DISORDERS Vol. 22 ( 1 ) page： 233 2021.3

Language：English Publishing type：Research paper (scientific journal) Publisher：BMC Musculoskeletal Disorders

Background: We evaluated the 1-year safety and efficacy of diclofenac etalhyaluronate (DF-HA), a diclofenac-conjugated hyaluronate, in patients with osteoarthritis (OA). Methods: In this multi-centre, open-label, noncomparative phase 3 study in Japan, patients with a diagnosis of knee, shoulder, elbow, hip, or ankle OA received an intra-articular (IA) injection of DF-HA 30 mg every 4 weeks for 1 year (13 times in total). The safety outcomes included treatment-emergent adverse events (TEAEs) and target joint structural changes by X-ray imaging tests. Efficacy outcomes included joint pain scores on an 11-point numerical rating scale. Concomitant use of analgesics was not restricted. Results: Overall, 166 eligible patients were enrolled, comprising knee OA (n = 126) and other OA (n = 40). All TEAEs were experienced by 126/166 patients (75.9%). The incidence of treatment-related TEAEs was not associated with the treatment period. No significant worsening of joint status was observed in X-ray imaging tests at week 52 or at last assessment. The mean joint pain scores (± standard deviation) were 5.9 ± 1.2, 4.9 ± 1.9, and 3.1 ± 2.3 at baseline, and weeks 2 and 52, respectively. Improvement of pain score was observed after the first injection and was maintained until week 52 regardless of knee OA or other joint OA. Conclusions: Repeated IA injections of DF-HA every 4 weeks for 1 year were well tolerated with no clinically significant adverse events indicating they might lead to the long-term improvement of OA symptoms. DF-HA might be a useful treatment for patients with OA. Trial registration number: JapicCTI-183855 (First registered date: 6th February 2018).

DOI： 10.1186/s12891-021-04108-9

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Papers - NISHIDA, Yoshihiro