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This review compares the efficacy and safety of denosumab and bisphosphonates for managing bone metastases from breast cancer.

June 4, 2026

Denosumab versus bisphosphonates for the management of bone metastases originating from breast cancer: a systematic review and meta-analysis

Key Points

This review compares the efficacy and safety of denosumab and bisphosphonates for managing bone metastases from breast cancer.
Systematic review of five publications, including three randomized trials and one retrospective cohort study.
Data were sourced from PubMed, Scopus, Cochrane Library, and Google Scholar up to October 2025.
Outcomes assessed included skeletal-related events and various adverse events.
Denosumab showed a significant reduction in skeletal-related events with a p-value of 0.04.
Other outcomes such as osteonecrosis of the jaw and serious adverse events were comparable between treatments.
Findings were consistent when limited to randomized trial analyses.

Abstract

BACKGROUND: Bone metastases from breast cancer cause skeletal-related events (SREs), including pain, fractures, and the need for radiation or surgery. Denosumab and bisphosphonates (BP) reduce these complications, but their relative efficacy and safety remain unclear. METHODS: PubMed, Scopus, Cochrane Library, and Google Scholar were searched through October 2025. Five publications (four unique studies: three randomized trials and one retrospective cohort) were included. Sensitivity analyses were limited to randomized trials when feasible. Outcomes included SRE incidence and skeletal endpoints, plus renal, metabolic, hematologic, musculoskeletal, gastrointestinal, infectious adverse events, osteonecrosis of the jaw (ONJ), and serious, grade ≥ 3, and treatment-related events. RESULTS: = 0.04) were reduced. Other outcomes, including uNTx, ONJ, serious and grade ≥ 3 events, thrombocytopenia, infectious, gastrointestinal, and respiratory events, were comparable. Results were consistent in randomized-only analyses. CONCLUSION: In breast cancer patients with bone metastases, denosumab may benefit those at higher risk of renal toxicity or skeletal complications, while treatment decisions should remain individualized. PROTOCOL REGISTRATION: www.crd.york.ac.uk/PROSPERO identifier is CRD420251231881.

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