Denosumab For Fracture Prevention In Osteoporosis Induced By Glucocorticoids, Androgen Deprivation, Or Aromatase Inhibitors: A Systematic Review And Meta-Analysis

Abstract

Background: Secondary osteoporosis attributable to long-term glucocorticoid therapy (GIOP), androgen-deprivation therapy (ADT) in prostate cancer, or aromatase-inhibitor (AI) therapy in breast cancer markedly elevates fracture risk. Denosumab, a monoclonal antibody to RANK-ligand, is licensed for fracture prevention in these settings, yet its comparative efficacy across secondary causes remains incompletely quantified.

Objectives: To systematically evaluate randomized and observational evidence on denosumab for preventing vertebral and non-vertebral fractures in adults with GIOP, ADT-induced, or AI-induced bone loss, and to pool risk estimates where appropriate.

Methods: MEDLINE, Embase, Cochrane CENTRAL and trial registries were searched through 1 May 2025. Eligible studies enrolled adults (≥18 y) exposed to systemic glucocorticoids, ADT, or AIs and compared denosumab (60 mg SC 6-monthly) with placebo or active bone-specific comparators for fracture or bone-mineral-density (BMD) outcomes ≥12 months. Dual extraction and GRADE appraisal were performed. Random-effects meta-analyses generated pooled risk ratios (RRs) for incident fractures.

Results: Twenty-six studies (11 254 participants) met inclusion: 8 GIOP, 9 ADT, 9 AI. Denosumab reduced vertebral fractures by 62 % versus control overall (pooled RR 0.38, 95 % CI 0.28–0.52; I² = 5 %). Effects were similar across subgroups (P-interaction = 0.73). Non-vertebral fracture reduction was 18 % and did not reach conventional significance (RR 0.82, 0.66–1.02; I² = 21 %). Lumbar-spine BMD gains averaged +3.7 % at 12 months over comparators. Serious adverse events and hypocalcaemia were uncommon, without excess atypical femoral fracture or osteonecrosis of the jaw.

Conclusions: Denosumab confers substantial vertebral-fracture protection and consistent BMD benefits across the three principal secondary-osteoporosis phenotypes examined. Evidence supports its preferential use when bisphosphonates are contraindicated or poorly tolerated. Long-term surveillance for rare harms remains warranted.