{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:45:29Z","timestamp":1792788329658,"version":"4.5.0"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2017,11,4]],"date-time":"2017-11-04T00:00:00Z","timestamp":1509753600000},"content-version":"vor","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":[],"published-print":{"date-parts":[[2018,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>Denosumab reduces bone resorption and vertebral and nonvertebral fracture risk. Denosumab discontinuation increases bone turnover markers 3 months after a scheduled dose is omitted, reaching above-baseline levels by 6 months, and decreases bone mineral density (BMD) to baseline levels by 12 months. We analyzed the risk of new or worsening vertebral fractures, especially multiple vertebral fractures, in participants who discontinued denosumab during the FREEDOM study or its Extension. Participants received \u22652 doses of denosumab or placebo Q6M, discontinued treatment, and stayed in the study \u22657 months after the last dose. Of 1001 participants who discontinued denosumab during FREEDOM or Extension, the vertebral fracture rate increased from 1.2 per 100 participant-years during the on-treatment period to 7.1, similar to participants who received and then discontinued placebo (n\u2009=\u2009470; 8.5 per 100 participant-years). Among participants with \u22651 off-treatment vertebral fracture, the proportion with multiple (&amp;gt;1) was larger among those who discontinued denosumab (60.7%) than placebo (38.7%; p\u2009=\u20090.049), corresponding to a 3.4% and 2.2% risk of multiple vertebral fractures, respectively. The odds (95% confidence interval) of developing multiple vertebral fractures after stopping denosumab were 3.9 (2.1\u20137. 2) times higher in those with prior vertebral fractures, sustained before or during treatment, than those without, and 1.6 (1.3\u20131.9) times higher with each additional year of off-treatment follow-up; among participants with available off-treatment total hip (TH) BMD measurements, the odds were 1.2 (1.1\u20131.3) times higher per 1% annualized TH BMD loss. The rates (per 100 participant-years) of nonvertebral fractures during the off-treatment period were similar (2.8, denosumab; 3.8, placebo). The vertebral fracture rate increased upon denosumab discontinuation to the level observed in untreated participants. A majority of participants who sustained a vertebral fracture after discontinuing denosumab had multiple vertebral fractures, with greatest risk in participants with a prior vertebral fracture. Therefore, patients who discontinue denosumab should rapidly transition to an alternative antiresorptive treatment. Clinicaltrails.gov: NCT00089791 (FREEDOM) and NCT00523341 (Extension). \u00a9 2017 American Society for Bone and Mineral Research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.3337","type":"journal-article","created":{"date-parts":[[2017,11,4]],"date-time":"2017-11-04T09:56:37Z","timestamp":1509789397000},"page":"190-198","source":"Crossref","is-referenced-by-count":668,"title":["Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension"],"prefix":"10.1093","volume":"33","author":[{"given":"Steven R","family":"Cummings","sequence":"first","affiliation":[{"name":"San Francisco Coordinating CenterCPMC Research InstituteSan FranciscoCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Geneva University HospitalGenevaSwitzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Eastell","sequence":"additional","affiliation":[{"name":"The University of SheffieldSheffieldUK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Gilchrist","sequence":"additional","affiliation":[{"name":"The Princess Margaret HospitalChristchurchNew Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens-Erik Beck","family":"Jensen","sequence":"additional","affiliation":[{"name":"Hvidovre University HospitalHvidovreDenmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"McClung","sequence":"additional","affiliation":[{"name":"Oregon Osteoporosis CenterPortlandORUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Roux","sequence":"additional","affiliation":[{"name":"Paris Descartes UniversityParisFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ove","family":"T\u00f6rring","sequence":"additional","affiliation":[{"name":"Karolinska InstitutetS\u00f6dersjukhusetStockholmSweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Valter","sequence":"additional","affiliation":[{"name":"Center for Clinical and Basic ResearchTallinnEstonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea T","family":"Wang","sequence":"additional","affiliation":[{"name":"Amgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques P","family":"Brown","sequence":"additional","affiliation":[{"name":"Laval University and CHU de Qu\u00e9bec-Universit\u00e9 Laval (CHUL)Quebec CityCanada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,11,4]]},"reference":[{"issue":"8","key":"2024021014393972500_jbmr3337-bib-0001","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1056\/NEJMoa0809493","article-title":"Denosumab for prevention of fractures in postmenopausal women with osteoporosis","volume":"361","author":"Cummings","year":"2009","journal-title":"N Engl J Med"},{"issue":"8","key":"2024021014393972500_jbmr3337-bib-0002","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1056\/NEJMoa044459","article-title":"Denosumab in postmenopausal women with low bone mineral density","volume":"354","author":"McClung","year":"2006","journal-title":"N Engl J Med"},{"issue":"11","key":"2024021014393972500_jbmr3337-bib-0003","doi-asserted-by":"crossref","first-page":"4483","DOI":"10.1210\/jc.2013-1597","article-title":"The effect of three or six years of denosumab exposure in women with postmenopausal 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