Understanding the impact of multimorbidity, medications and frailty on zoledronic acid efficacy in treating osteoporosis among older adults.

Aims: This study investigates the interplay between drug effects, multimorbidity, frailty and comprehensive geriatric evaluation on zoledronic acid (ZA) treatment success in osteoporosis (OP), particularly among frail, older adults, a group often excluded from research.

Methods: In this retrospective cohort study, a retrospective analysis of 156 OP-treatment-naïve geriatric outpatients who received their first ZA treatment was conducted. Bone mineral density (BMD) and T-scores in the lumbar, femoral neck and total femur regions were assessed using dual-energy X-ray absorptiometry and patients' fall history was assessed. BMD decrease exceeding the LSC was considered sufficient to define treatment failure, alongside the occurrence of two or more new fragility fractures.

Results: In a predominantly female cohort (76%) with a median age of 75 years, 23.1% experienced frailty and 17.3% had malnutrition, yet most remained independent and cognitively intact. Over a median follow-up of 14.4 months, significant improvements in BMD and reduced fragility fractures were observed, with 70.5% responding successfully to treatment. Univariate analysis identified advanced age, prolonged dosing intervals, illiteracy, multimorbidity, polypharmacy and diabetes mellitus as factors that reduced treatment efficacy. Regression analysis supported these findings, highlighting the complexities of managing OP in older adults.

Conclusions: The study emphasizes that identifying barriers to treatment success is crucial for optimizing OP management. ZA improves BMD and reduces fractures, even in frail older adults with multimorbidity, supporting its use across diverse patient profiles and stressing the need for personalized treatment strategies.