Effect Of Denosumab, A Fully Human Monoclonal Antibody To Rankl, On Bone Mineral Density And Fractures: A Meta-Analysis

Receptor activator of nuclear factor kB ligand (RANKL) is the principal regulator of osteoclast differentiation, activity, and survival; denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and is approved for the treatment of women with postmenopausal osteoporosis at high risk of fractures. By searching the PubMed and Embase databases, we conducted a meta-analysis to examine the bone mineral density (BMD) and the fracture rate in osteoporosis patients being treated with denosumab. Studies were pooled, and mean difference (MD), the relative risk (RR) and its corresponding 95% confidence interval (CI) were calculated. Twelve relevant articles were included for this meta-analysis study. Compared to placebo, denosumab treatment significantly decreased the risk of fracture (RR = 0.42, 95% CI = 0.27-0.68, P-heterogeneity = 0.005, l(2) = 73.1%) and increased the percent change in bone mineral density at the total hip (MD = 5.06%, 95% CI = 4.76-5.36, P-heterogeneity < 0.001, l(2) = 99.7%) and lumbar spine (MD = 7.6%, 95% CI = 6.91-8.30, P-heterogeneity < 0.001, l(2) = 99.9%). Compared to alendronate, denosumab treatment significantly increased the percent change in bone mineral density at the total hip (MD = 1.18%, 95% CI = 1.00-1.35, P-heterogeneity < 0.001, l(2) = 98.1%) and lumbar spine (MD = 1.36%, 95% CI = 0.96-1.76, P-heterogeneity < 0.001, l(2) = 99.3%), however, there was no significant difference in the incidence of fractures. In conclusion, these results indicate that denosumab can effectively prevent the resorption of bone and increase BMD compared with the placebo or alendronate group and there is a significant reduction in fractures risk in the denosumab compared with the placebo group.