Efficacy and safety of denosumab compared with conventional medications in the treatment of osteoporosis: A meta-analysis with trial sequential analysis.

BACKGROUND

This meta-analysis aimed to systematically evaluate the efficacy and safety of denosumab versus conventional medications in treating osteoporosis.

METHODS

Randomized controlled trials from PubMed, ScienceDirect, Web of Science, CNKI, WanFang Data, and VIP were searched via the web from the onset to April 2025. RevMan 5.4 software was used for performing a systematic review. Trial sequential analysis (TSA) of serious adverse events (SAEs) was performed using TSA 0.9.5.10 Beta.

RESULTS

A total of 15 studies with 16,437 patients were included. Compared to the control group (conventional medications), the experimental group with denosumab showed no significant difference in increasing total hip bone mineral density (BMD) (mean difference [MD] = 0.03, 95% confidence interval [CI] = [0.00-0.06], P = .06) and femoral neck BMD (MD = 0.02, 95% CI = [-0.04 to 0.08], P = .43), but it significantly improved lumbar spine BMD (MD = 0.07, 95% CI = [0.03-0.11], P = .003). In addition, there were no differences between the 2 groups in terms of reducing osteonecrosis of the jaw (odds ratio [OR] = 1.49, 95% CI = [0.65-3.46], P = .35), atypical fractures (OR = 1.77, 95% CI = [0.38-8.31], P = .47), AEs (OR = 0.98, 95% CI = [0.91-1.07], P = .71), and SAEs (OR = 0.94, 95% CI = [0.53-1.69], P = .85), and TSA showed an insufficient information size with SAEs of denosumab compared with conventional medications in the treatment of osteoporosis.

CONCLUSION

It can be concluded that denosumab can improve lumbar spine BMD compared with conventional medications for osteoporosis; furthermore, no evidence was found that the denosumab had a significantly higher incidence of SAEs than the control group and it is safe to apply. However, given the potential bias of the included studies, more high-quality, large-sample randomized controlled trials are needed to validate this conclusion further and to provide a more reliable basis for the use of medication in the clinical treatment of osteoporosis. The registration number in PROSPERO is CRD420251051061 (http://www.crd.york.ac.uk/PROSPERO/).