Efficacy and safety of zoledronic acid versus denosumab in the treatment of primary osteoporosis: a single-center retrospective cohort study

Objective To compare the long-term efficacy and safety of zoledronic acid versus denosumab in the treatment of primary osteoporosis. Methods This retrospective cohort study analyzed 328 patients diagnosed with primary osteoporosis at the Department of Rheumatology and Immunology, Changhai Hospital, between January 2017 and December 2020. After applying inclusion and exclusion criteria, 164 patients were enrolled and divided into the zoledronic acid group (n = 88) and the denosumab group (n = 76). Bone mineral density (BMD) at the lumbar spine (L1–L4) and hip, bone turnover markers (including bone alkaline phosphatase, serum C-terminal telopeptide of type I collagen, and serum N-terminal propeptide of type I procollagen), and adverse events were evaluated at baseline and at 1, 2, and 3 years post-treatment. Results At baseline, the two groups exhibited no statistically significant differences in most parameters except for parathyroid hormone (PTH), lumbar spine BMD, and lumbar T-score. After three years of treatment, denosumab demonstrated superior efficacy compared to zoledronic acid in key outcome measures, including lumbar spine BMD (0.85 ± 0.17 vs. 0.81 ± 0.14), hip BMD (0.85 ± 0.13 vs. 0.79 ± 0.12), and β-CTX (0.27 ± 0.19 vs. 0.38 ± 0.23), with statistically significant differences (P < 0.05). Both treatments demonstrated favorable safety profiles, with no serious adverse events reported. Conclusion Denosumab exhibits superior long-term efficacy over zoledronic acid in improving bone mineral density and suppressing bone turnover. Both agents demonstrate excellent safety profiles and represent effective therapeutic options for the management of osteoporosis.