{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T10:08:56Z","timestamp":1792318136138,"version":"4.4.0"},"reference-count":83,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Denosumab is a potent antiresorptive agent that substantially increases bone mineral density and reduces fracture rates at all skeletal sites for as long as it is administered. However, its favorable skeletal effects reverse quickly upon its discontinuation, because of a vast increase of osteoclast number and activity, which leads to a subsequent profound increase of bone turnover above pre-treatment values, a phenomenon commonly described as \u201crebound phenomenon\u201d. More importantly, most patients experience rapid, profound bone loss due to this burst of bone resorption that may lead in a minority of these patients to occurrence of fractures, especially multiple vertebral fractures. Therefore, subsequent antiresorptive treatment is mandatory, although the optimal regimen is yet to be clarified. In the present review, we outline what is currently known regarding the negative effects of denosumab discontinuation on different aspects of bone status, the factors that may affect them, and strategies to prevent them.<\/jats:p>","DOI":"10.3390\/jcm10010152","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T21:58:36Z","timestamp":1609797516000},"page":"152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":193,"title":["Denosumab Discontinuation and the Rebound Phenomenon: A Narrative Review"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9624-6296","authenticated-orcid":false,"given":"Athanasios D.","family":"Anastasilakis","sequence":"first","affiliation":[{"name":"Department of Endocrinology, 424 General Military Hospital, 564 29 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3231-3357","authenticated-orcid":false,"given":"Polyzois","family":"Makras","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes and Department of Medical Research, 251 Hellenic Air Force &amp; VA General Hospital, 115 25 Athens, Greece"}],"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":"Endocrinology Unit, 1st Department of Propaedeutic and Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6808-0700","authenticated-orcid":false,"given":"Gaia","family":"Tabacco","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology and Diabetes, Campus Bio-Medico University, 00128 Rome, 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 Endocrinology and Diabetes, Campus Bio-Medico University, 00128 Rome, Italy"}],"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 Endocrinology and Diabetes, Campus Bio-Medico University, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R31","DOI":"10.1530\/EJE-18-0056","article-title":"Therapy of Endocrine Disease: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis","volume":"179","author":"Anastasilakis","year":"2018","journal-title":"Eur. 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