{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:13:48Z","timestamp":1791843228090,"version":"4.3.4"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T00:00:00Z","timestamp":1706313600000},"content-version":"vor","delay-in-days":1152,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"vor","delay-in-days":680,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002429","name":"Amgen Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>It is uncertain whether the risk of vertebral fracture (VF) and multiple vertebral fractures (MVFs; \u22652 VFs) after denosumab (DMAb) discontinuation is related to treatment duration. A prior analysis of Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) and FREEDOM Extension trials did not find a relationship with DMAb duration and may have underreported MVF incidence because it included women who did not have radiographs. In this post hoc exploratory analysis, the crude incidence and annualized rates of VF and MVF were determined in patients with \u22657\u2009months' follow-up and \u22651 spine radiograph after discontinuing placebo or DMAb. A multivariate analysis was performed to identify predictors of MVF. Clinical characteristics of patients with \u22654 VFs were explored. This analysis included women who discontinued after placebo (n\u00a0=\u2009327) or DMAb either from FREEDOM or FREEDOM Extension (n\u00a0=\u2009425). The DMAb discontinuation group was subsequently dichotomized by treatment duration: short-term (\u22643\u2009years; n\u00a0=\u2009262) and long-term (&amp;gt;3\u2009years; n\u00a0=\u2009213) treatment. For any VF, exposure-adjusted annualized rates per 100 patient-years (95% confidence interval [CI]) were 9.4 (95% CI, 6.4\u201313.4) for placebo, 6.7 (95% CI, 4.2\u201310.1) for short-term DMAb, and 10.7 (95% CI, 7.4\u201315) for long-term DMAb. Annualized rates for MVF were 3.6 (95% CI, 1.9\u20136.3), 2.9 (95% CI, 1.4\u20135.4), and 7.5 (95% CI, 4.8\u201311.1), respectively. Annualized rates for \u22654 VFs were 0.59 (95% CI, 0.1\u20132.1), 0.57 (95% CI, 0.1\u20132.1), and 3.34 (95% CI, 1.7\u20136.0), respectively. In a multivariate regression model, DMAb duration was significantly associated with MVF risk (odds ratio 3.0; 95% CI, 1.4\u20136.5). Of 15 patients with \u22654 VFs, 13 had DMAb exposure (mean\u2009\u00b1\u2009standard deviation [SD], 4.9\u2009\u00b1\u20092.2\u2009years). The risk of MVF after DMAb discontinuation increases with increased duration of DMAb treatment. Patients transitioning off DMAb after 3\u2009years may warrant more frequent administration of zoledronic acid or another bisphosphonate to maintain bone turnover and bone mineral density (BMD) and prevent MVF. \u00a9 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4705","type":"journal-article","created":{"date-parts":[[2022,9,11]],"date-time":"2022-09-11T11:14:01Z","timestamp":1662894841000},"page":"2112-2120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["Multiple Vertebral Fractures After Denosumab Discontinuation: FREEDOM and FREEDOM Extension Trials Additional Post Hoc Analyses"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4554-6616","authenticated-orcid":false,"given":"Felicia","family":"Cosman","sequence":"first","affiliation":[{"name":"Division of Endocrinology\/Department of Medicine Columbia University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Huang","sequence":"additional","affiliation":[{"name":"Amgen Inc. Thousand Oaks CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"McDermott","sequence":"additional","affiliation":[{"name":"Amgen Inc. Thousand Oaks CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"Cummings","sequence":"additional","affiliation":[{"name":"San Francisco Coordinating Center California Pacific Medical Center Research Institute and University of California San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,11]]},"reference":[{"issue":"2","key":"2024012714065339700_jbmr4705-bib-0001","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.bone.2008.04.007","article-title":"Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial","volume":"43","author":"Miller","year":"2008","journal-title":"Bone"},{"issue":"4","key":"2024012714065339700_jbmr4705-bib-0002","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1210\/jc.2010-1502","article-title":"Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass","volume":"96","author":"Bone","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2024012714065339700_jbmr4705-bib-0003","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00198-017-4242-6","article-title":"Significant bone loss after stopping long-term denosumab treatment: a post FREEDOM study","volume":"29","author":"Zanchetta","year":"2018","journal-title":"Osteoporos Int"},{"issue":"1","key":"2024012714065339700_jbmr4705-bib-0004","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/s00223-018-0394-4","article-title":"Bone mineral density changes after 1 year of denosumab discontinuation in postmenopausal women with long-term denosumab treatment for osteoporosis","volume":"103","author":"Popp","year":"2018","journal-title":"Calcif Tissue Int"},{"issue":"2","key":"2024012714065339700_jbmr4705-bib-0005","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/jbmr.3337","article-title":"Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension","volume":"33","author":"Cummings","year":"2018","journal-title":"J Bone Miner Res"},{"issue":"5","key":"2024012714065339700_jbmr4705-bib-0006","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1007\/s00198-017-3919-1","article-title":"Observations following discontinuation of long-term denosumab therapy","volume":"28","author":"McClung","year":"2017","journal-title":"Osteoporos Int"},{"issue":"1","key":"2024012714065339700_jbmr4705-bib-0007","doi-asserted-by":"crossref","first-page":"152","DOI":"10.3390\/jcm10010152","article-title":"Denosumab discontinuation and the rebound phenomenon: a narrative review","volume":"10","author":"Anastasilakis","year":"2021","journal-title":"J Clin Med"},{"key":"2024012714065339700_jbmr4705-bib-0008","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1002\/jbmr.4335","article-title":"Fractures after denosumab discontinuation: a retrospective study of 797 cases","volume":"36","author":"Burckhardt","year":"2021","journal-title":"J Bone Miner Res"},{"issue":"10","key":"2024012714065339700_jbmr4705-bib-0009","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1002\/jbmr.4098","article-title":"Treatment with zoledronate subsequent to denosumab in osteoporosis: a randomized trial","volume":"35","author":"S\u00f8lling","year":"2020","journal-title":"J Bone Miner Res"},{"issue":"6","key":"2024012714065339700_jbmr4705-bib-0010","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1007\/s00774-020-01126-w","article-title":"Zoledronic acid sequential therapy could avoid disadvantages due to the discontinuation of less than 3-year denosumab treatment","volume":"38","author":"Kondo","year":"2020","journal-title":"J Bone Miner Metab"},{"issue":"1","key":"2024012714065339700_jbmr4705-bib-0011","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1210\/clinem\/dgaa756","article-title":"Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS","volume":"106","author":"Tsourdi","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"2024012714065339700_jbmr4705-bib-0012","doi-asserted-by":"crossref","first-page":"115830","DOI":"10.1016\/j.bone.2020.115830","article-title":"Risk factors for vertebral fractures and bone loss after denosumab discontinuation: a real-world observational study","volume":"144","author":"Everts-Graber","year":"2021","journal-title":"Bone"},{"issue":"10","key":"2024012714065339700_jbmr4705-bib-0013","doi-asserted-by":"crossref","first-page":"e4155","DOI":"10.1210\/clinem\/dgab321","article-title":"The duration of denosumab treatment and the efficacy of zoledronate to preserve bone mineral density after its discontinuation","volume":"106","author":"Makras","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2024012714065339700_jbmr4705-bib-0014","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1007\/s00198-015-3458-6","article-title":"Rebound-associated vertebral fractures after discontinuation of denosumab-from clinic and biomechanics","volume":"27","author":"Popp","year":"2016","journal-title":"Osteoporos Int"},{"issue":"6","key":"2024012714065339700_jbmr4705-bib-0015","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1002\/jbmr.3110","article-title":"Clinical features of 24 patients with rebound-associated vertebral fractures after denosumab discontinuation: systematic review and additional cases","volume":"32","author":"Anastasilakis","year":"2017","journal-title":"J Bone Miner Res"},{"issue":"1","key":"2024012714065339700_jbmr4705-bib-0016","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s10549-019-05458-8","article-title":"Sixty spontaneous vertebral fractures after denosumab discontinuation in 15 women with early-stage breast cancer under aromatase inhibitors","volume":"179","author":"Gonzalez-Rodriguez","year":"2020","journal-title":"Breast Cancer Res Treat"},{"key":"2024012714065339700_jbmr4705-bib-0017","doi-asserted-by":"crossref","first-page":"115358","DOI":"10.1016\/j.bone.2020.115358","article-title":"Identification of prevalent vertebral fractures using vertebral fracture assessment (VFA) in asymptomatic postmenopausal women: a systematic review and meta-analysis","volume":"136","author":"Yang","year":"2020","journal-title":"Bone"},{"issue":"8","key":"2024012714065339700_jbmr4705-bib-0018","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":"7","key":"2024012714065339700_jbmr4705-bib-0019","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S2213-8587(17)30138-9","article-title":"10\u2009years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension","volume":"5","author":"Bone","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2024012714065339700_jbmr4705-bib-0020","article-title":"Treatment with zoledronate subsequent to denosumab in osteoporosis: a randomized trial.","volume":"35","author":"S\u00f8lling","journal-title":"J Bone Miner Res"},{"issue":"7","key":"2024012714065339700_jbmr4705-bib-0021","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1002\/jbmr.4305","article-title":"Treatment with zoledronate subsequent to denosumab in osteoporosis: a 2-year randomized study","volume":"36","author":"S\u00f8lling","year":"2021","journal-title":"J Bone Miner Res"},{"key":"2024012714065339700_jbmr4705-bib-0022","doi-asserted-by":"crossref","first-page":"100457","DOI":"10.1016\/j.bonr.2020.100457","article-title":"The effect of denosumab treatment on osteoclast precursor cells in postmenopausal osteoporosis","volume":"13","author":"Fontalis","year":"2020","journal-title":"Bone Rep"},{"issue":"5","key":"2024012714065339700_jbmr4705-bib-0023","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1016\/j.cell.2021.02.002","article-title":"Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption","volume":"184","author":"McDonald","year":"2021","journal-title":"Cell"},{"issue":"10","key":"2024012714065339700_jbmr4705-bib-0024","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s11886-014-0531-2","article-title":"Challenges and solutions to pre- and post-randomization subgroup analyses","volume":"16","author":"Desai","year":"2014","journal-title":"Curr Cardiol Rep"},{"issue":"1","key":"2024012714065339700_jbmr4705-bib-0025","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1001\/jama.1991.03470010097038","article-title":"Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials","volume":"266","author":"Yusuf","year":"1991","journal-title":"JAMA"},{"issue":"3","key":"2024012714065339700_jbmr4705-bib-0026","doi-asserted-by":"crossref","first-page":"e255","DOI":"10.1210\/clinem\/dgz095","article-title":"Bone mineral density after transitioning from denosumab to alendronate","volume":"105","author":"Kendler","year":"2020","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbmr.4705","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbmr.4705","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/37\/11\/2112\/55454759\/jbmr4705.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/37\/11\/2112\/55454759\/jbmr4705.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T10:46:14Z","timestamp":1710326774000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/37\/11\/2112-2120\/7512382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,1]]},"references-count":26,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,9,11]]},"published-print":{"date-parts":[[2020,12,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.4705","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742319729.793596703","asserted-by":"object"}]},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,12,1]]},"published":{"date-parts":[[2020,12,1]]},"assertion":[{"value":"2021-10-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}