{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T16:02:14Z","timestamp":1785513734679,"version":"3.56.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Unopposed denosumab (Dmab) discontinuation is followed by overshoot in bone turnover markers (BTM), rapid BMD loss, and elevated risk of multiple vertebral fractures. To preserve BMD gains and mitigate fracture risk, it is currently recommended to administer bisphosphonates following Dmab discontinuation. We prospectively evaluate the efficacy of alendronate (ALN) in preventing BTM overshoot and BMD loss in women with postmenopausal osteoporosis discontinuing Dmab. This is a 12-mo prospective, observational study among patients treated with Dmab 60\u00a0mg every 6\u00a0mo and achieved osteopenia at the LS and FN. Six months after the last Dmab injection participants received oral ALN 70\u00a0mg weekly for 6\u00a0mo followed by 6\u00a0mo without therapy (Group 1) or for 12\u00a0mo (Group 2). The primary endpoint was the percent change in LS-BMD from baseline to month 12. Eighty women (39 Group 1, 41 Group 2) who had received 2 to 22 Dmab injections (mean 9.8) completed the study. Median age was 67\u00a0yr; 27.5% had prevalent fractures and 59% had prior anti-osteoporotic therapy. At month 12, LS-BMD declined significantly in the overall cohort [\u22125.9% (8.2%), p\u2009&amp;lt;\u2009.001], with no difference between groups (Group 1: \u22126.8% vs Group 2: \u22125.0%, p\u2009=\u2009.50). FN-BMD decreased (\u22123.5%, p\u2009&amp;lt;\u2009.001), and similarly in both groups. Serum P1NP, C-terminal telopeptide of type 1 collagen (CTX), and tartrate-resistant acid phosphatase isoform 5b increased significantly; P1NP and CTX were significantly higher in Group 1 at month 12. One patient sustained multiple vertebral fractures (1.25%). In conclusion, ALN did not consistently attenuate BMD loss and BTM rebound after Dmab discontinuation in women with postmenopausal osteoporosis, with 6\u00a0mo being as effective as 12\u00a0mo of treatment. Importantly, both regimens were associated with low incidence of multiple vertebral fractures.<\/jats:p>\n                  <jats:p>ClinicalTrials.gov identifier: NCT04338529<\/jats:p>","DOI":"10.1093\/jbmr\/zjag103","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T11:53:20Z","timestamp":1781870000000},"source":"Crossref","is-referenced-by-count":1,"title":["Alendronate for 6 or 12\u00a0mo following denosumab discontinuation in women with postmenopausal osteoporosis: a prospective observational study"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3231-3357","authenticated-orcid":false,"given":"Polyzois","family":"Makras","sequence":"first","affiliation":[{"name":"Department of Medical Research, 251 Hellenic Air Force & VA General Hospital , Athens, 11525 ,","place":["Greece"]},{"name":"Department of Endocrinology and Diabetes, 251 Hellenic Air Force & VA General Hospital , Athens, 11525 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9624-6296","authenticated-orcid":false,"given":"Athanasios D","family":"Anastasilakis","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, 424 General Military Hospital , Thessaloniki, 56429 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1143-4926","authenticated-orcid":false,"given":"Andrea","family":"Palermo","sequence":"additional","affiliation":[{"name":"Unit of Metabolic Bone and Thyroid Disorders, Fondazione Policlinico Universitario Campus Bio-Medico , Rome, 00128 ,","place":["Italy"]},{"name":"Unit of Endocrinology and Diabetes, Campus Bio-Medico University , Rome, 00128 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4576-3381","authenticated-orcid":false,"given":"Anda Mihaela","family":"Naciu","sequence":"additional","affiliation":[{"name":"Unit of Metabolic Bone and Thyroid Disorders, Fondazione Policlinico Universitario Campus Bio-Medico , Rome, 00128 ,","place":["Italy"]},{"name":"Unit of Endocrinology and Diabetes, Campus Bio-Medico University , Rome, 00128 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9232-4042","authenticated-orcid":false,"given":"Stergios A","family":"Polyzos","sequence":"additional","affiliation":[{"name":"First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki , Thessaloniki, 54124 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danai","family":"Georgakopoulou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, 251 Hellenic Air Force & VA General Hospital , Athens, 11525 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Papatheodorou","sequence":"additional","affiliation":[{"name":"Department of Medical Research, 251 Hellenic Air Force & VA General Hospital , Athens, 11525 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthaios","family":"Savvidis","sequence":"additional","affiliation":[{"name":"2nd Department of Orthopedics, 424 Military General Hospital , Thessaloniki, 56429 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Socrates","family":"Papapoulos","sequence":"additional","affiliation":[{"name":"Department of Medical Research, 251 Hellenic Air Force & VA General Hospital , Athens, 11525 ,","place":["Greece"]},{"name":"Center for Bone Quality, Leiden University Medical Center , Leiden, 2333 ZA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6501-3692","authenticated-orcid":false,"given":"Maria P","family":"Yavropoulou","sequence":"additional","affiliation":[{"name":"Department of Medical Research, 251 Hellenic Air Force & VA General Hospital , Athens, 11525 ,","place":["Greece"]},{"name":"Endocrinology Unit, First Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens, Medical School , Athens, 11527 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"issue":"8","key":"2026073111215213800_ref1","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":"2026073111215213800_ref2","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S2213-8587(17)30138-9","article-title":"10 years 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"},{"issue":"5","key":"2026073111215213800_ref3","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/s41584-023-00935-3","article-title":"Mechanisms underlying the long-term and withdrawal effects of denosumab therapy on bone","volume":"19","author":"Ferrari","year":"2023","journal-title":"Nat Rev Rheumatol"},{"issue":"11","key":"2026073111215213800_ref4","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1002\/jbmr.4705","article-title":"Multiple vertebral fractures after denosumab discontinuation: FREEDOM and FREEDOM extension trials additional post hoc analyses","volume":"37","author":"Cosman","year":"2022","journal-title":"J Bone Miner Res"},{"issue":"6","key":"2026073111215213800_ref5","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":"10","key":"2026073111215213800_ref6","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"},{"key":"2026073111215213800_ref7","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa756","article-title":"Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS","author":"Tsourdi","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"9","key":"2026073111215213800_ref8","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1002\/jbmr.4335","article-title":"The Swiss denosumab study G. fractures after denosumab discontinuation: a retrospective study of 797 cases","volume":"36","author":"Burckhardt","year":"2021","journal-title":"J Bone Miner Res"},{"issue":"12","key":"2026073111215213800_ref9","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1002\/jbmr.3853","article-title":"Zoledronate for the prevention of bone loss in women discontinuing denosumab treatment. A prospective 2-year clinical trial","volume":"34","author":"Anastasilakis","year":"2019","journal-title":"J Bone Miner Res"},{"issue":"7","key":"2026073111215213800_ref10","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":"Solling","year":"2021","journal-title":"J Bone Miner Res"},{"issue":"1","key":"2026073111215213800_ref11","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s11914-022-00771-6","article-title":"Denosumab discontinuation","volume":"21","author":"Solling","year":"2023","journal-title":"Curr Osteoporos Rep"},{"issue":"10","key":"2026073111215213800_ref12","doi-asserted-by":"crossref","first-page":"e1817","DOI":"10.1210\/clinem\/dgae224","article-title":"Zoledronate after denosumab discontinuation: is repeated administrations more effective than single infusion?","volume":"109","author":"Grassi","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"issue":"9","key":"2026073111215213800_ref13","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/jbmr\/zjaf037","article-title":"Denosumab discontinuation in the clinic: implications of rebound bone turnover and emerging strategies to prevent bone loss and fractures","volume":"40","author":"Kumar","year":"2025","journal-title":"J Bone Miner Res"},{"issue":"5","key":"2026073111215213800_ref14","doi-asserted-by":"crossref","first-page":"748","DOI":"10.3803\/EnM.2024.2227","article-title":"Effects of sequential anti-resorptive agents on bone mineral density following denosumab withdrawal: a Multicenter Real-World Study in Korea (MAXCARE study)","volume":"40","author":"Ha","year":"2025","journal-title":"Endocrinol Metab (Seoul)"},{"issue":"3","key":"2026073111215213800_ref15","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s00198-022-06648-9","article-title":"Bone loss after denosumab discontinuation is prevented by alendronate and zoledronic acid but not risedronate: a retrospective study","volume":"34","author":"Tutaworn","year":"2023","journal-title":"Osteoporos Int"},{"issue":"2","key":"2026073111215213800_ref16","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s00198-023-06932-2","article-title":"The comparison of alendronate and raloxifene after denosumab (CARD) study: a comparative efficacy trial","volume":"35","author":"Ramchand","year":"2024","journal-title":"Osteoporos Int"},{"issue":"1","key":"2026073111215213800_ref17","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s00198-011-1780-1","article-title":"Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women","volume":"23","author":"Freemantle","year":"2012","journal-title":"Osteoporos Int"},{"issue":"12","key":"2026073111215213800_ref18","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1007\/s00198-024-07213-2","article-title":"One versus 2 years of alendronate following denosumab: the CARD extension","volume":"35","author":"Tsai","year":"2024","journal-title":"Osteoporos Int"},{"issue":"3","key":"2026073111215213800_ref19","doi-asserted-by":"crossref","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"},{"issue":"1","key":"2026073111215213800_ref20","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s11657-022-01126-5","article-title":"Prevalence and patterns of anti-osteoporotic drug use based on 2019 real-world nationwide data in 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