Denosumab versus zoledronic acid for primary osteoporosis: a 36-month retrospective cohort study on bone mineral...

To explore and compare the clinical efficacy and safety of denosumab versus zoledronic acid for the treatment of primary osteoporosis.

This retrospective cohort study included 413 primary osteoporosis patients (denosumab, n = 198; zoledronic acid, n = 215). All received daily calcium (600 mg) and vitamin D (400 IU), representing the total combined daily intake from diet and supplements. The denosumab group received subcutaneous denosumab 60 mg every 6 months and the zoledronic acid group annual intravenous zoledronic acid 5 mg over 36 months. Outcomes assessed at baseline and after 36 months included bone mineral density (BMD) at the lumbar spine, femoral neck, and total hip; bone turnover markers β-CTX (β-isomerized C-terminal telopeptide of type I collagen) and P1NP (procollagen type I N-terminal propeptide); pain severity using the Visual Analog Scale (VAS); functional impairment using the Oswestry Disability Index (ODI); and incidence of adverse reactions.

After 36 months, BMD at all sites significantly increased from baseline in both groups (P < 0.001). The denosumab group demonstrated greater mean absolute increases in BMD at the lumbar spine (0.13 ± 0.10 vs. 0.10 ± 0.10 g/cm², P < 0.001), femoral neck (0.14 ± 0.06 vs. 0.12 ± 0.05 g/cm², P < 0.001), and total hip (0.09 ± 0.12 vs. 0.05 ± 0.09 g/cm², P < 0.001) compared to the zoledronic acid group. Both groups showed significant decreases in β-CTX and P1NP levels (P < 0.001), with the denosumab group exhibiting a greater reduction in β-CTX (-0.54 ± 0.47 vs. -0.34 ± 0.44 ng/mL, P < 0.001) and P1NP (-23.68 ± 5.44 vs. -19.98 ± 5.28 ng/mL, P < 0.001). VAS and ODI scores improved significantly in both groups (P < 0.001), with a greater reduction in the VAS score in the denosumab group (-5.17 ± 1.58 vs. -4.61 ± 1.48, P < 0.001). The overall incidence of adverse reactions was lower in the denosumab group compared to the zoledronic acid group (5.56% vs. 20.00%, P = 0.008). Adverse events were collected via passive EMR retrieval (see Methods).

Over 36 months, both agents were effective. Denosumab was associated with greater BMD gains, stronger bone resorption suppression, and fewer recorded adverse reactions. These findings are hypothesis-generating and await prospective validation.