Meta-analysis of clinical fracture risk reduction of anti-osteoporosis drugs: direct and indirect comparisons and meta-regressions.

Abstract

OBJECTIVE\nAnti-osteoporotic drug (AOD) trials have variabilities in duration and fracture risks. This study evaluated AOD s versus controls regarding reduction in relative rates (rr) and rate differences (rd) of vertebral and hip fractures and comparative costs.\n\n\nMETHODS\nPrimary randomized-controlled trials (RCT s) of AOD s in post-menopausal women with documentation of vertebral fracture rates (VFR) or hip fracture rates (HFR) were extracted from meta-analyses and PubMed through February 2021. Direct and indirect meta-analysis and meta-regression analyzed fracture reductions.\n\n\nRESULTS\nThere were 24 RCT s of drug-versus-placebo (73,862 women) and 10 drug-versus-drug trials. Reduction in rr of VFR were significant for anti-resorptive (alendronate, risedronate, zoledronate, denosumab, raloxifene) and anabolic (teriparatide, abaloparatide, romosozumab) drugs. Denosumab, teriparatide and abaloparatide were more effective in reducing VFR compared to oral bisphosphates (all p <0.05) but not to zoledronate. Reduction in HFR were significant for alendronate, denosumab and zoledronate (all p <0.05), without significant differences among drugs. Anabolic drugs did not show significant HFR reduction. Meta-regression of rd s allowed for calculation of costs per vertebral fracture prevented, which were estimated at >$100,000 for anabolic drugs and between $2,289-$28,947 for anti-resorptive drugs. Drug-versus-drug trials were underpowered to demonstrate changes.\n\n\nCONCLUSIONS\nThis study suggests goal-directed, cost-effective therapy relative to a patient s risk for vertebral and hip fractures. Anabolic drugs are better at preventing vertebral fractures compared to oral bisphosphonates. Anabolic drugs are not superior to zoledronate or denosumab, and at substantially higher cost. In comparing drugs which prevented hip fractures, there was no statistical benefit of any drug.