Safety of denosumab versus zoledronic acid in the older adults with osteoporosis: a meta-analysis of cohort studies.

Abstract

A head-to-head comparison of the safety profiles between denosumab (60mg subcutaneously every 6months) and zoledronic acid (5mg, intravenously yearly) was performed in cancer-free adults aged 50years or older with osteoporosis. MEDLINE, EMBASE, and Cochrane Library databases were searched for cohort studies comparing the safety of denosumab and zoledronic acid in cancer-free adults aged 50years or older with osteoporosis till December 2021. The outcomes included the risk of fracture and other severe adverse events. Based on the Cochrane Handbook for Systematic Reviews of Interventions 5.0.2, we identified the eligible studies. Three cohort studies having 38,845 cancer-free adults aged 50years or older were included in the study. The results showed that denosumab was not superior to zoledronic acid in reducing fracture risk [RR (95% CI): 1.05 (0.90, 1.23), P = 0.52]. However, denosumab had a low risk of composite cardiovascular disease [RR (95% CI): 0.82 (0.70, 0.96), P = 0.01]. There were no significant differences between the hazards of serious infection, and total adverse events (P > 0.05). The present meta-analysis demonstrated that for cancer-free adults aged 50years or older with osteoporosis, denosumab was as safe as zoledronic acid for the risk of drug-induced fractures. However, denosumab had a lower incidence of composite cardiovascular disease, and may be a better option for the population with cardiovascular disease. Nonetheless, due to limitations like a short-term follow-up, gender, and incomplete types of adverse effects, more randomized controlled trials (RCTs) are required to further verify this conclusion.