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

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

Denosumab reduced SREs compared to BP (RR 0.77, p < 0.001). It lowered arthralgia (RR 0.62; p = 0.01), myalgia (RR 0.31; p = 0.005), and bone pain (RR 0.77; p = 0.001), with similar back and extremity pain. Renal adverse events (RR 0.55; p = 0.0002), non-serious events (RR 0.98; p = 0.008), and pyrexia (RR 0.33; p = 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.