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

Date Published: 2026-08-18

Abstract:
To compare the long-term efficacy and safety of zoledronic acid versus denosumab in the treatment of primary osteoporosis. 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. 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 ?-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. 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.

Introduction:
Osteoporosis (OP) is a systemic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, leading to increased bone fragility and elevated fracture risk ( 1 , 2 ). As a major global public health concern, osteoporosis significantly impairs quality of life in the elderly population and imposes substantial socioeconomic burdens. Statistics indicate that an osteoporotic fracture occurs every three seconds worldwide, with vertebral and hip fractures being the most common types.…

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