{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:26:33Z","timestamp":1792499193463,"version":"4.5.0"},"reference-count":34,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,1]]},"abstract":"Abstract<\/jats:title>\n \n Context<\/jats:title>\n Denosumab, an inhibitor of receptor activator of nuclear factor \u03ba-B ligand, is an approved treatment of giant cell tumor of bone (GCTB) in adults and \u201cskeletally mature\u201d adolescents. Safety concerns include oversuppression of bone remodelling, with risk of osteonecrosis of the jaw (ONJ) and atypical femur fractures during treatment in adults and rebound hypercalcemia after treatment cessation in children. To date, ONJ has never been reported in children or adolescents.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To describe serious adverse effects during and following high-dose denosumab therapy in GCTB patients.<\/jats:p>\n <\/jats:sec>\n \n Patients<\/jats:title>\n Two adolescents (14 and 15 years) and a young adult (40 years) received fixed-dose denosumab for GCTB for 1.3 to 4 years (cumulative dose, 47 to 98 mg\/kg), which was stopped because of development of ONJ in one adolescent and bilateral femoral cortical stress reactions in the young adult. All three patients developed rebound hypercalcemia with acute kidney injury 5.5 to 7 months after denosumab cessation.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The ONJ necessitated surgical debridement. Rebound hypercalcemia (serum calcium, 3.1 to 4.3 mmol\/L) was unresponsive to hyperhydration alone, requiring repeated doses of calcitonin or intravenous bisphosphonate treatment. Hypercalcemia recurred in two patients within 4 weeks, with normal serum calcium profiles thereafter. All patients were naive to chemotherapy, radiotherapy, bisphosphonates, and corticosteroids and were metastases free, confirming the causative role of denosumab in these complications.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n These suppression-release effects of high-dose denosumab on bone remodeling raise questions about safety of fixed dosing and treatment duration. In young people, weight-adjusted dosing and safety monitoring during and after antiresorptive therapy is required.<\/jats:p>\n <\/jats:sec>","DOI":"10.1210\/jc.2017-02025","type":"journal-article","created":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T19:40:20Z","timestamp":1512157220000},"page":"596-603","source":"Crossref","is-referenced-by-count":70,"title":["Osteonecrosis of the Jaw and Rebound Hypercalcemia in Young People Treated With Denosumab for Giant Cell Tumor of Bone"],"prefix":"10.1210","volume":"103","author":[{"given":"Suma","family":"Uday","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Diabetes, Birmingham Women\u2019s and Children\u2019s Hospital NHS Foundation Trust, Birmingham, West Midlands B4 6NH, United Kingdom"},{"name":"Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Czar 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