Introduction Both Dmab and ZA have been widely used in the prevention and treatment of bone-related diseases, while which drug is an optimal treatment in terms of safety and efficacy 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 Dmab versus ZA in patients with bone-related diseases were included. Results A total of 13 studies involving 21042 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). 9 trials comparing Dmab with ZA further showed that Dmab was significantly better than ZA in controlling serious adverse events (OR = 0.91, 95% CI = 0.85–0.99, P = 0.02). Compared to ZA, Dmab was correlated with a lower incidence 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.