{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:12:22Z","timestamp":1787314342893,"version":"build-2736575974"},"reference-count":28,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"unspecified","delay-in-days":36,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Ministry of Health, Labor and Welfare, Japan","award":["23AA2003"],"award-info":[{"award-number":["23AA2003"]}]},{"name":"Amgen, Inc"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2026,4,13]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Owing to the underrepresentation of early-stage disease in randomised trials and inconsistent clinical evidence, using oral bisphosphonates to prevent incident osteoarthritis in adults with osteoporosis lacks consensus. We aimed to analyse the causal relationship between oral bisphosphonates and osteoarthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a sequential nested target trial emulation with propensity score matching using longitudinal health insurance claims data from Japan collected between 2015 and 2024. Eligible individuals were aged \u226550\u2009years with osteoporosis who had been receiving vitamin D therapy. We compared those who initiated oral bisphosphonates with those who did not initiate and continued vitamin D therapy. The primary outcome was incident osteoarthritis. Secondary outcomes included joint-specific osteoarthritis (knee, hip and hand) over a 3-year follow-up period. The absolute risk reduction (ARR) and relative risk (RR) at 3 years were estimated using a Kaplan-Meier estimator.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 10\u2009844 bisphosphonate initiators and 21\u2009283 non-initiators. The ARR for incident osteoarthritis was 0.4% (95% CI \u20131.3% to 1.0%), with an RR of 0.97 (95% CI 0.92 to 1.12). In joint-specific analyses, the ARR (95%\u2009CI) and RR (95%\u2009CI) were 0.5% (\u20131.1% to 1.0%) and 0.95 (0.90 to 1.12) for knee osteoarthritis; 0.2% (\u20130.4% to 0.7%) and 0.89 (0.64 to 1.27) for hip osteoarthritis; and \u20130.3% (\u20130.7% to 0.3%) and 1.20 (0.81 to 1.50) for hand osteoarthritis, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Oral bisphosphonate use was not associated with a lower risk of incident osteoarthritis among adults with osteoporosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2026-006832","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T15:15:31Z","timestamp":1778166931000},"page":"e006832","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Oral bisphosphonates and risk of incident osteoarthritis in individuals with osteoporosis: a target trial emulation"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7096-5604","authenticated-orcid":false,"given":"Masaki","family":"Hatano","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisatoshi","family":"Ishikura","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeyuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9210-9414","authenticated-orcid":false,"given":"Sakae","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Yasunaga","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"2026050708151585000_12.2.e006832.1","unstructured":"World Health Organization . Osteoarthritis. Available: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/osteoarthritis [Accessed 6 Feb 2026]."},{"key":"2026050708151585000_12.2.e006832.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.113"},{"key":"2026050708151585000_12.2.e006832.3","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1136\/annrheumdis-2017-212364","article-title":"Bisphosphonates: a therapeutic option for knee osteoarthritis?","volume":"77","author":"Lems","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"2026050708151585000_12.2.e006832.4","doi-asserted-by":"crossref","DOI":"10.1007\/s11657-022-01061-5","article-title":"UK clinical guideline for the prevention and treatment of osteoporosis","volume":"17","author":"Gregson","year":"2022","journal-title":"Arch Osteoporos"},{"key":"2026050708151585000_12.2.e006832.5","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-018-4704-5"},{"key":"2026050708151585000_12.2.e006832.6","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-021-02446-6","article-title":"Bisphosphonates as disease-modifying drugs in osteoarthritis preclinical studies: a systematic review from 2000 to 2020","volume":"23","author":"Fern\u00e1ndez-Mart\u00edn","year":"2021","journal-title":"Arthritis Res Ther"},{"key":"2026050708151585000_12.2.e006832.7","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.joca.2017.11.013","article-title":"Are bisphosphonates efficacious in knee osteoarthritis? 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