Introduction:
The aim of the study was to compare the safety of denosumab (Dmab) versus zoledronic acid (ZA) in patients with bone-related diseases. Both Dmab and ZA have been widely used in the treatment of bone-related diseases, but which drug is an optimal treatment in terms of safety remains controversial.

Material and methods:
PubMed, Embase, Web of Science, the Cochrane Central Library, and ClinicalTrials.gov were systematically searched up to 1st January 2021, and were evaluated by Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Randomized controlled trials comparing relevant outcomes of Dmab versus ZA in patients with bone-related diseases were included.

Results:
A total of 13 studies involving 21,042 participants were included. The incidence of total adverse events was significantly lower in patients receiving Dmab treatment than in those undergoing ZA treatment (OR = 0.84, 95% CI: 0.75–0.94, p = 0.003). Nine trials comparing Dmab with ZA further indicated that Dmab was significantly better than ZA in controlling the incidence of serious adverse events (OR = 0.91, 95% CI: 0.85–0.99, p = 0.02). Compared to ZA, Dmab administration was correlated with a lower risk of skeletal-related events (OR = 0.77, 95% CI: 0.70–0.85, p = 0.00001). However, no significant difference was found in the rate of infection events between Dmab and ZA (OR = 1.06, 95% CI: 0.93–1.20, p = 0.39).

Conclusions:
This study demonstrated superiority of Dmab over ZA in treating bone-related diseases in terms of safety and efficacy.