Drug efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of postmenopausal osteoporosis: a network meta-analysis of randomized controlled trials

OBJECTIVE: This study aims to compare the efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic ac-id for the treatment of women with postmeno-pausal osteoporosis. MATERIALS AND METHODS: Randomized controlled trials (RCTs) were searched in Med-line, Embase, and Cochrane up to April 2022. Statistical analysis was performed using R 4.1.3 software, and quality evaluation was conducted using Review Manager 5.3. RESULTS: 51 RCTs containing 39,095 patients met our selection criteria. The efficacy results indicated that teriparatide was more effective than ibandronic acid in reducing vertebral fractures [relative risk (RR) = 0.536; 95% confidence inter-val (CI) (0.266, 0.998)]. Denosumab [mean difference (MD) =-4.19; 95% CI (-8.03,-0.355)] and teriparatide [MD = 4.64; 95% CI (1.60, 7.72)] showed better efficacy than ibandronic acid in improv-ing spine bone mineral density (BMD). Denosum-ab showed better efficacy than teriparatide in improving radius BMD [MD =-4.14; 95% CI (-6.72,-1.54)], hip bone mineral density (BMD) [MD =-2.01; 95% CI (-3.80,-0.162)], and one-third radius BMD [MD =-3.63; 95% CI (-7.04,-0.151)]. Deno-sumab was associated with the greatest benefit in increasing radius BMD [the surface under the cumulative ranking curve area (SUCRA) = 0.999], hip BMD [surface under the cumulative ranking curve area (SUCRA) = 0.979], femoral neck BMD (SUCRA = 0.971), one-third radius BMD (SUCRA = 0.994) and preventing vertebral fractures (SU-CRA = 0.806). Teriparatide was associated with the greatest benefit in preventing non-vertebral fractures (SUCRA = 0.927) and improving spine BMD (SUCRA = 0.899). The safety results indicated that teriparatide was safer than zoledronic acid regarding the risk of adverse events [RR = 0.958; 95% CI (0.919, 0.988)]. Teriparatide was associated with the greatest benefit in preventing adverse events (SUCRA = 0.908) and serious ad-verse events (SUCRA = 0.813). CONCLUSIONS: Our current results suggested that when considering both safety and efficacy, denosumab or teriparatide might be a better choice for women with postmenopausal osteoporosis.