{"doi":"10.1210/clinem/dgae867","title":"Safety and Efficacy of Moderate-dose Denosumab in Fibrous Dysplasia: Observational Results From a Phase 2 Clinical Trial","abstract":"CONTEXT: 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. OBJECTIVE: Investigate the safety and efficacy of moderate-dose denosumab (120 mg/3 months) compared to the standard high-dose regimen. SETTING: Clinical research center. PATIENTS: Adults with FD. INTERVENTIONS: Eight adults received high-dose denosumab for 6 months (120 mg/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 mg/3 months) if clinically indicated. MAIN OUTCOME MEASURES: Bone turnover markers, 18F-sodium fluoride positron emission tomography/computed tomography (18F-NaF PET/CT), lesion biopsies. RESULTS: 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 -82% and -91%, C-terminal telopeptide -86% and -86% 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. CONCLUSION: 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.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2024,"id":448067,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1267118,"name":"Ibrahim I Elbashir","orcid":null,"position":1,"is_corresponding":false},{"id":1267119,"name":"Ramzy Ahmed","orcid":null,"position":2,"is_corresponding":false},{"id":335186,"name":"Luis F de Castro","orcid":"0000-0003-3194-9780","position":3,"is_corresponding":false},{"id":989923,"name":"Kelly Milligan","orcid":null,"position":4,"is_corresponding":false},{"id":413699,"name":"Xiaobai Li","orcid":"0000-0001-9615-3543","position":5,"is_corresponding":false},{"id":292051,"name":"Babak Saboury","orcid":"0000-0002-8632-6292","position":6,"is_corresponding":false},{"id":686413,"name":"Alison M Boyce","orcid":"0000-0003-2987-3887","position":7,"is_corresponding":false},{"id":684433,"name":"Vivian Szymczuk","orcid":"0000-0002-3513-1671","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-19T02:02:08.018689Z","pmid":"39673171","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}