{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:28:57Z","timestamp":1790882937619,"version":"4.1.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T00:00:00Z","timestamp":1566432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Denosumab has been used successfully to treat disease\u2010associated osteoclast overactivity, including giant cell tumor of bone. Given its mechanism of action, denosumab is a potent potential treatment of other osteoclast bone dysplasias including central giant cell granuloma (CGCG), aneurysmal bone cyst (ABC), and cherubism. Relatively little is known about the safety and efficacy of denosumab in patients with these conditions, especially in children. We report on 3 pediatric patients treated with denosumab over a 3\u2010year period at UCLA Medical Center (Los Angeles and Santa Monica, CA, USA): a 12\u2010year\u2010old with recurrent ABC of the pelvis, a 14\u2010year\u2010old with CGCG of the mandible, and a 12\u2010year\u2010old with cherubism. All were started on a 1\u2010year course of 15 doses 120\u2009mg\u2009s.c., given monthly with two loading doses on day 8 and 15. All patients demonstrated rapid and pronounced clinical improvement while on denosumab, including a significant reduction in pain and sclerosis of lytic lesions on radiographs. Within 1 month of initiating therapy, 2 patients experienced hypocalcemia (Common Terminology Criteria for Adverse Events [CTCAE] grade 2) and hypophosphatemia, with 1 patient experiencing symptoms. One patient went on to experience symptomatic rebound hypercalcemia (CTCAE grade 4) 5 months after completing therapy, requiring bisphosphonates and calcitonin. For the second patient, we developed a schedule to wean denosumab involving the progressive lengthening of time between doses from 1 to 4 months in 1\u2010month increments before cessation. We found that denosumab therapy results in significant clinical and radiographic improvement for pediatric patients with nonresectable ABC, CGCG, and cherubism. Problems with serum calcium may be more common in younger patients, with symptomatic and protracted rebound hypercalcemia after cessation of therapy the most significant. We present a potential solution to this problem with progressive spacing of doses. Potential serious adverse events from alterations in calcium homeostasis should be explored in prospective clinical trials. \u00a9 2019 The Authors. <jats:italic>JBMR Plus<\/jats:italic> published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbm4.10210","type":"journal-article","created":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T20:33:46Z","timestamp":1560458026000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Use of Denosumab in Children With Osteoclast Bone Dysplasias: Report of Three Cases"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3176-1382","authenticated-orcid":false,"given":"Alexander","family":"Upfill\u2010Brown","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery University of California Los Angeles Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Bukata","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of California Los Angeles Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M","family":"Bernthal","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of California Los Angeles Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan L","family":"Felsenfeld","sequence":"additional","affiliation":[{"name":"Department of Oral &amp; Maxillofacial Surgery University of California Los Angeles Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of California Los Angeles Los Angeles CA USA"},{"name":"Department of Pathology University of California Los Angeles Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Hematology &amp; Oncology, Department of Medicine University of California Los Angeles Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9122-7459","authenticated-orcid":false,"given":"Katherine","family":"Wesseling\u2010Perry","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Pediatrics University of California Los Angeles Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritz C","family":"Eilber","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery University of California Los Angeles Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah C","family":"Federman","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of California Los Angeles Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,22]]},"reference":[{"key":"e_1_2_8_1_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40272-013-0051-3"},{"key":"e_1_2_8_1_3_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-015-4634-9"},{"key":"e_1_2_8_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70010-3"},{"key":"e_1_2_8_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2295"},{"key":"e_1_2_8_1_6_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0714.2003.00126.x"},{"key":"e_1_2_8_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63432-3"},{"key":"e_1_2_8_1_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-013-2715-7"},{"key":"e_1_2_8_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(03)00064-4"},{"key":"e_1_2_8_1_10_1","first-page":"3692","article-title":"Denosumab: non\u2010surgical treatment option for selective arterial embolization resistant aneurysmal bone cyst of the spine and sacrum","volume":"20","author":"Ghermandi R","year":"2016","journal-title":"Case report. 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