SUN-812 - Phenotype-Based Predictors of Delayed Antiresorptive Redosing in Postmenopausal Osteoporosis: A Prospective Study of Zoledronic Acid and Denosumab

Background: Fixed-interval redosing of potent antiresorptive therapies may cause unnecessary prolonged suppression of bone remodelling in some patients. Individuals with lower baseline bone turnover and lower body mass may sustain antiresorptive effects, allowing safe deferral of redosing. However, integrated biochemical and anthropometric predictors across antiresorptive agents remain limited.

Objective: To identify baseline predictors of delayed antiresorptive redosing and evaluate combined biochemical and anthropometric models in postmenopausal osteoporosis.

Methods: In this prospective observational study, 106 postmenopausal women with densitometrically confirmed osteoporosis received zoledronic acid (n=56) or denosumab (n=50) as first-line therapy and were followed for up to 24 months. Redosing was guided by biochemical recovery of bone turnover using plasma β-CTX, with ≥300 pg/mL indicating reactivation of bone resorption. Patients were classified into standard or delayed dosing groups based on observed redosing intervals. Baseline clinical, biochemical, and bone mineral BMD parameters were analysed. Multivariable logistic regression identified predictors of delayed redosing, and ROC analysis assessed model performance.

Results: 53 patients received standard dosing and 53 underwent delayed redosing. Baseline age and BMD were comparable. The delayed group had lower BMI (23.8 vs 25.45 kg/m²; p=0.0003) and lower baseline β-CTX (500.5 vs 823.0 pg/mL; p< 0.001). Lower β-CTX (OR 0.995 per pg/mL; 95% CI 0.993–0.997; p< 0.001) and lower BMI (OR 0.69 per kg/m²; 95% CI 0.57–0.85; p< 0.001) independently predicted delayed redosing, while alkaline phosphatase showed a borderline association. Median delayed redosing was 9.5 months with denosumab and 18.5 months with zoledronic acid. A combined β-CTX–BMI–ALP model showed excellent discrimination (AUC 0.85), while a simplified BMI–ALP model performed well (AUC 0.74). No new vertebral fractures were detected, and follow-up BMD outcomes were comparable.

Conclusion: Lower baseline bone turnover and lower BMI identify postmenopausal women who may safely tolerate delayed antiresorptive redosing with denosumab and zoledronic acid. A phenotype-based, biomarker-guided strategy using either a combined β-CTX–BMI–ALP model or a simplified BMI–ALP phenotype offers a clinically actionable approach for individualized redosing. These findings are particularly relevant to postmenopausal Indian women, who commonly exhibit lower BMI and baseline bone turnover. In such populations, routine fixed-interval redosing may increase the risk of prolonged oversuppression of bone remodelling. A precision-based approach may minimize unnecessary antiresorptive exposure while maintaining antifracture efficacy and potentially reducing long-term skeletal complications, including atypical femoral fractures.

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