Objective: To explore the efficacy of denosumab (DEN) and zoledronic acid (ZOL) in the treatment of senile osteoporosis (SOP) and the influence on bone mineral density (BMD) and risk of falls. Methods: A total of 168 patients with SOP were selected as research subjects, and were assigned into ZOL group (n=85, routine treatment and ZOL treatment) and DEN group (n=83, routine treatment and DEN treatment) according to different treatment regimens. The clinical efficacy, BMD (lumbar spine and femoral neck), bone metabolism indicators [N-MID osteocalcin (N-MID), calcitonin (CT), carboxy-terminal propeptide of type I procollagen (PICP), β-crosslaps (β-CTX)], bone pain degree [visual analogue scale (VAS)], risk of falls [short physical performance battery (SPPB)] and adverse reactions were compared between the two groups. Results: There were no statistical differences in clinical efficacy and adverse reactions between DEN group and ZOL group (P > 0.05). BMD values of lumbar spine and femoral neck and SPPB score at 12 months after treatment in DEN group were higher than those in ZOL group (P < 0.05), while the bone metabolism indicators and VAS score were lower compared to ZOL group (P < 0.05). Conclusion: Both DEN and ZOL exhibit good efficacy and safety in the treatment of SOP, but DEN has more advantages than ZOL in improving BMD, inhibiting bone turnover, alleviating bone pain and reducing the risk of falls.