{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:23:28Z","timestamp":1793255008275,"version":"4.5.0"},"reference-count":20,"publisher":"The Endocrine Society","issue":"9","funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002429","name":"Amgen, Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Fibrous dysplasia (FD) is a rare skeletal mosaic disease associated with fractures and disability. A phase 2 trial of the RANKL inhibitor denosumab (NCT03571191) reported profound reductions in lesion activity and increased lesional mineralization after 6 months of high-dose treatment. Denosumab was well tolerated; however, discontinuation was associated with severe hypercalcemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Investigate the safety and efficacy of moderate-dose denosumab (120\u2005mg\/3 months) compared to the standard high-dose regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Clinical research center.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients<\/jats:title>\n                    <jats:p>Adults with FD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Eight adults received high-dose denosumab for 6 months (120\u2005mg\/month with loading doses on weeks 2 and 3) followed by an 8-month posttreatment observation. The protocol was amended to restart moderate-dose denosumab (120\u2005mg\/3 months) if clinically indicated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcome Measures<\/jats:title>\n                    <jats:p>Bone turnover markers, 18F-sodium fluoride positron emission tomography\/computed tomography (18F-NaF PET\/CT), lesion biopsies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In 6 subjects who restarted moderate-dose treatment, changes in serum markers at the initial and final dose were comparable (procollagen type 1 N-terminal propeptide \u221282% and \u221291%, C-terminal telopeptide \u221286% and \u221286% for moderate- and high-dose, respectively). There was no difference in 18F-NaF PET\/CT lesional activity or absolute change in avid lesion volume between moderate- and high-dose regimens. Sequential tissue histological analyses in 1 subject demonstrated progressive lesional mineralization and reduced cellularity with moderate-dose treatment. Bone turnover markers on moderate-dose treatment showed a sustained decline in 4 subjects; however, 2 severely affected subjects developed rebound between doses, with recurrent hypercalcemia in 1 subject.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Moderate-dose denosumab may provide clinical benefits comparable to the high-dose regimen in adults with FD while potentially lowering associated risks. However, discrepancies in the duration of efficacy are an important potential safety concern.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgae867","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T23:40:10Z","timestamp":1733960410000},"page":"2666-2673","source":"Crossref","is-referenced-by-count":11,"title":["Safety and Efficacy of Moderate-dose Denosumab in Fibrous Dysplasia: Observational Results From a Phase 2 Clinical Trial"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3513-1671","authenticated-orcid":false,"given":"Vivian","family":"Szymczuk","sequence":"first","affiliation":[{"name":"Metabolic Bone Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim I","family":"Elbashir","sequence":"additional","affiliation":[{"name":"Metabolic Bone Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramzy","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Metabolic Bone Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]},{"name":"School of Medicine, Eastern Virginia Medical School , Norfolk, VA 23507 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis F","family":"de Castro","sequence":"additional","affiliation":[{"name":"Metabolic Bone Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Milligan","sequence":"additional","affiliation":[{"name":"Metabolic Bone Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobai","family":"Li","sequence":"additional","affiliation":[{"name":"Biostatistics and Clinical Epidemiology, Mark O. 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