It is estimated that osteoporosis affects over 200 million people globally. Postmenopausal women (PMW) have an increased risk of developing osteoporosis due to low estrogen levels. This study assessed the safety and effectiveness of denosumab (Prolia®) relative to placebo, selective estrogen receptor modulators (SERMs) (bazedoxifene and raloxifene), and bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) for the treatment of osteoporosis in PMW.

Systematic searches were conducted in three biomedical databases (PubMed, the Cochrane Library, and Embase) to identify randomized controlled trials (RCTs) of PMW with osteoporosis allocated to denosumab, placebo, bisphosphonates, or SERMs. The Cochrane Risk of Bias 2.0 tool was used to critically appraise included RCTs. Pairwise and Bayesian network meta-analyses were performed on the following predetermined outcomes: fractures (vertebral and nonvertebral); adverse events (AEs); mortality; serious AEs (SAEs); withdrawals due to AEs; bone mineral density (BMD); and AEs caused by denosumab discontinuation.

The analyses included 12 RCTs (22 publications, 25,879 participants). Denosumab, ibandronate, alendronate, zoledronate, and risedronate produced a statistically significant improvement in total hip (TH) and lumbar-spine (LS) BMD, compared with placebo. Similarly, ibandronate, risedronate, and alendronate showed a statistically significant improvement in femoral neck (FN) BMD. Risedronate produced a statistically significant decrease in nonvertebral fractures (risk ratio 0.20, 95% confidence interval: 0.00, 0.97) relative to placebo. However, there were no significant differences between any of the interventions for rates of vertebral fractures, AEs, SAEs, withdrawals due to AEs, or mortality, compared with placebo.

None of the included trials reported evidence on AEs caused by denosumab discontinuation.

Denosumab was associated with significant improvements in both LS and TH BMD relative to placebo. Similarly, compared with placebo, denosumab was not associated with significant changes in nonvertebral or vertebral fractures. Denosumab was not associated with significant changes in safety outcomes relative to placebo. Given that some of the analyses suffered from statistical imprecision, these findings should be interpreted with caution. Regarding policy, continued funding of denosumab needs to be reviewed.