Objective To systematically evaluate the efficacy and safety of bisphosphonate therapy for fracture prevention in patients with postmenopausal osteoporosis.

Methods PubMed, Embase, the Cochrane Library, Web of Science, CNKI, VIP, and WanFang Data were searched from inception to June 1, 2026. Randomized controlled trials (RCTs) comparing bisphosphonates with placebo or non-active control strategies were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Meta-analyses were performed using RevMan 5.4 and R 4.4.2.

Results Fifteen RCTs were included. Bisphosphonates significantly reduced the risks of any osteoporotic fracture [OR=0.62, 95%CI(0.54, 0.72)], vertebral fracture [OR=0.48, 95%CI(0.33, 0.68)], non-vertebral fracture [OR=0.73, 95%CI(0.63, 0.85)], and hip fracture [OR=0.56, 95%CI(0.41, 0.77)]. The risk of any adverse event (AE) did not differ significantly between the bisphosphonate and control groups [OR=1.28, 95%CI(0.98, 1.67)]. Neither Egger's nor Begg's test indicated significant publication bias for vertebral fracture. GRADE assessment showed moderate certainty for any osteoporotic fracture, non-vertebral fracture, and hip fracture, and low certainty for vertebral fracture and any AE.

Conclusion Bisphosphonates reduce fracture risk at different skeletal sites in patients with postmenopausal osteoporosis. The pooled effect was larger for vertebral fracture, although substantial heterogeneity was present. No significant difference in the risk of any AE was observed. Given the limited number, methodological quality, and follow-up duration of the included studies, long-term efficacy and rare safety outcomes require further high-quality evidence.

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