{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T15:29:04Z","timestamp":1758122944739,"version":"3.41.2"},"reference-count":58,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Although homocysteine accumulation is a reported risk factor for several age-related disorders, little is known about its relationship with osteoarthritis (OA).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We investigated for associations of homocysteine and C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR), which is involved in homocysteine clearance, with the development and progression of spinal OA through a combined cross-sectional and longitudinal cohort study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A total of 1306 Japanese postmenopausal outpatients participating in the Nagano Cohort Study were followed for a mean 9.7-year period. Cross-sectional multiple logistic regression for spinal OA prevalence at registration by serum homocysteine level was performed with adjustment for confounders. In addition to Kaplan\u2013Meier analysis, multivariate Cox regression was employed to examine the independent risk of MTHFR C677T variant for spinal OA progression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Multivariate regression analysis revealed a significant association between homocysteine and spinal OA prevalence (odds ratio 1.38; 95% CI 1.14-1.68). Kaplan\u2013Meier curves showed a gene dosage effect of the T allele in MTHFR C677T polymorphism on the accelerated progression of spinal OA severity (P\u2005=\u20050.003). A statistically significant independent risk of the T allele for spinal OA advancement was validated by Cox regression analysis. Respective adjusted hazard ratios for the CT\/TT and TT genotypes were 1.68 (95% CI, 1.16\u20132.42) and 1.67 (95% CI, 1.23\u20132.28).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Circulating homocysteine and C677T variant in MTHFR are associated with the prevalence rate and ensuing progression, respectively, of spinal OA. These factors may represent potential interventional targets to prevent OA development and improve clinical outcomes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgab591","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T17:30:19Z","timestamp":1628616619000},"source":"Crossref","is-referenced-by-count":4,"title":["Associations of Homocysteine Metabolism With the Risk of Spinal Osteoarthritis Progression in Postmenopausal Women"],"prefix":"10.1210","author":[{"given":"Masaki","family":"Nakano","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5612-4382","authenticated-orcid":false,"given":"Yukio","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiko","family":"Urano","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, International University of Health and Welfare School of Medicine, 4-3 Kozunomori, Narita, Chiba 286-8686, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takako","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan"},{"name":"Department of Human Nutrition, Faculty of Human Nutrition, Tokyo Kasei Gakuin University, 22 Sanban-cho, Chiyoda-ku, Tokyo 102-8341, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuki","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Liberal Arts and Sciences, Tokyo Medical and Dental University, 2-8-30 Kohnodai, Ichikawa, Chiba 272-0827, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masataka","family":"Shiraki","sequence":"additional","affiliation":[{"name":"Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano 399-8101, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"issue":"9","key":"2021082713005379400_CIT0001","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.joca.2010.06.001","article-title":"Association of radiographic and symptomatic knee osteoarthritis with health-related quality of life in a population-based cohort study in Japan: the ROAD study","volume":"18","author":"Muraki","year":"2010","journal-title":"Osteoarthritis Cartilage."},{"issue":"1","key":"2021082713005379400_CIT0002","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/NOR.0000000000000112","article-title":"Symptom clusters, functional status, and quality of life in older adults with osteoarthritis","volume":"34","author":"Jenkins","year":"2015","journal-title":"Orthop Nurs."},{"author":"WHO Department of Chronic Diseases and Health Promotion","key":"2021082713005379400_CIT0003"},{"issue":"11","key":"2021082713005379400_CIT0004","first-page":"1572","article-title":"[Progress of research in osteoarthritis. 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