{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:54:15Z","timestamp":1784876055395,"version":"3.55.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"9","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":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":191,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005040","name":"Bontius Stichting","doi-asserted-by":"publisher","award":["Beter Bot"],"award-info":[{"award-number":["Beter Bot"]}],"id":[{"id":"10.13039\/501100005040","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005040","name":"Bontius Stichting","doi-asserted-by":"publisher","award":["Beter Bot"],"award-info":[{"award-number":["Beter Bot"]}],"id":[{"id":"10.13039\/501100005040","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>Denosumab (Dmab) treatment can benefit patients with fibrous dysplasia\/McCune-Albright syndrome (FD\/MAS) by suppressing the receptor activator of nuclear factor \u03baB ligand (RANKL)-mediated increased bone resorption. However, limited data of two pediatric cases indicate that a rebound phenomenon may occur after withdrawal. Therefore we studied the safety of Dmab discontinuation in FD\/MAS. Thirty-seven patients using Dmab, mostly after unsuccessful bisphosphonate (BP) treatment, were included. Health records were screened for pain scores, side effects, and bone turnover markers (BTMs) (calcium, alkaline phosphatase [ALP], procollagen 1 N-terminal propeptide [P1NP], and \u03b2-crosslaps [B-CTX, also termed \u03b2\u2013C-terminal telopeptide]) during treatment, and for BTMs and clinical rebound effects after withdrawal. BTM levels after withdrawal were compared to pretreatment values. Data were calculated as median (interquartile range [IQR]). BTMs normalized in two-thirds of patients and pain scores decreased significantly during treatment (p\u00a0=\u00a00.002). One patient (2.7%) developed osteonecrosis of the jaw. Sixteen patients discontinued Dmab treatment after a median of 1.6\u2009years (IQR 1.0\u2009years) because of insufficient effect on pain (n\u00a0=\u00a010, 63%), side effects (n\u00a0=\u00a04, 25%), or other reasons (n\u00a0=\u00a04, 25%). Follow-up posttreatment was 3.2 (2.8) years, wherein no fractures, pain flares, or lesion progression occurred. Calcium remained normal in all but one patient, who had a mild asymptomatic hypercalcemia (2.73\u2009mmol\/L) 5\u2009months after discontinuation. ALP passed pretreatment levels in five of 11 patients (46%), increased most after 6\u2009months by 18 (43) U\/L, and returned to baseline levels thereafter. P1NP exceeded pretreatment levels in four of nine patients (44%), CTX in eight of nine patients (89%). P1NP rose most after 3\u2009months and stabilized thereafter. CTX showed the highest relative elevation. Patients with high pretreatment levels responding well to Dmab seemed to have the highest rebound. These results suggest beneficial effects of Dmab on pain and BTMs, and show a biochemical but asymptomatic rebound phenomenon after withdrawal in adults with FD\/MAS, mainly in case of high pretreatment levels, good response, and multiple injections. Further studies on the safety of Dmab and withdrawal are needed and ongoing. \u00a9 2021 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.4380","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T05:56:38Z","timestamp":1622613398000},"page":"1729-1738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Safety of therapy with and withdrawal from denosumab in fibrous dysplasia and McCune-Albright syndrome: an observational study"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6258-2531","authenticated-orcid":false,"given":"Maartje E.","family":"Meier","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Center for Bone Quality Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stance N.","family":"Clerkx","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Center for Bone Quality Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0119-1588","authenticated-orcid":false,"given":"Elizabeth M.","family":"Winter","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Center for Bone Quality Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto M.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Center for Bone Quality Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annenienke C.","family":"van de Ven","sequence":"additional","affiliation":[{"name":"Department of 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