Background: Aging and menopause accelerate bone loss, increasing susceptibility to osteoporotic vertebral compression fractures (OVCFs), which cause severe pain, compromise respiratory function, and elevate mortality risk. Therefore, to mitigate this risk, various 10 medications have been used to prevent secondary fractures. However, a comprehensive summary of the efficacy of these medications remains limited, prompting our systematic review and meta-analysis of randomized controlled trials (RCTs) to elucidate the effects of these medications on the prevention of subsequent OVCFs. Materials and Methods: A comprehensive systematic search was conducted across five electronic databases—PubMed, EMBASE, Scopus, Web of Science (WOS), and the Cochrane Library—to identify peer-reviewed studies published in English. Eligible studies were included in a quantitative synthesis. Pooled effect estimates were calculated as odds ratios (ORs) or risk ratios (RRs), along with the associated 95% confidence intervals (CIs). Additionally, heterogeneity was assessed using the Cochrane Q statistic and quantified with the I2 metric, and meta-analytic procedures were performed using Review Manager (RevMan) software, version 5.4 (The Cochrane Collaboration, Copenhagen, Denmark). The systematic review protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD420251176522), and the full protocol is available at: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251176522. Results: High- to moderate-quality evidence from pooled randomized controlled trials indicates that most bisphosphonates (zoledronate, alendronate, risedronate, etidronate, and ibandronate) and non-bisphosphonate therapies (denosumab, teriparatide, bazedoxifene, estrogen, calcitonin, and parathyroid hormone) are associated with a significant reduction in fracture risk. Overall, most bisphosphonates demonstrated an approximate 40–60% reduction in fracture risk (risk ratio RR range: 0.40–0.60; 95% confidence intervals CIs spanning 0.23–0.77), while non-bisphosphonates were associated with a 30–50% reduction (RR range: 0.30–0.50; 95% CIs: 0.19–0.71), acknowledging that individual agents exhibited varying magnitudes of effect. Pooled analyses also showed that both drug classes increased bone mineral density, with bisphosphonates producing an approximate 3–7% increase (odds ratio OR range: 0.33–0.54; 95% CI: 0.19–0.74) and non-bisphosphonates a 3–5% increase (OR range: 0.36–0.57; 95% CI: 0.23–0.83). Furthermore, safety data synthesized from the included trials indicated a low incidence of adverse events for both treatment classes, with bisphosphonates showing RRs ranging from 0.19 to 0.44 (95% CI: 0.09–0.81) and non-bisphosphonates from 0.23 to 0.49 (95% CI: 0.12–0.89). Conclusion: High- to moderate-quality evidence supports the efficacy of zoledronate, alendronate, risedronate, etidronate, ibandronate, parathyroid hormone (PTH), denosumab, and selective estrogen receptor modulators (SERMs) in preventing secondary OVCFs. Zoledronate, risedronate, and PTH reduced both vertebral and non-vertebral fractures. Denosumab outperformed alendronate, and PTH surpassed risedronate, although with increased risk of adverse events.
Zhang et al. (Sat,) studied this question.