Clinical Efficacy of Zoledronic Acid on Fracture Reduction in Youth With Primary and Secondary Skeletal Fragility.

Context: Prior studies have demonstrated the safety and efficacy of zoledronic acid (ZA) to increase bone mineral density (BMD) in children. By contrast, the efficacy of ZA on fractures in the pediatric population remains uncertain.

Objective: To investigate the effect of ZA on fracture rate in a clinical cohort of children and young adults with skeletal fragility.

Methods: This retrospective cohort study, conducted at an academic medical center, included 102 individuals (65 male; 39 with primary and 63 with secondary skeletal fragility), aged 0 to 21 years, treated with ZA for skeletal fragility between 2010 and 2017. ZA was prescribed at discretion of the treating clinician using a standardized protocol. The primary outcome was change in annualized fracture rate. Secondary outcomes included long bone and spine fracture rates. Areal BMD was analyzed in a subset of individuals with dual energy x-ray absorptiometry (DXA) scans.

Results: The overall median fracture rate decreased from 0.6 (IQR 0.3-1.1) to 0 (IQR 0-0.4) fractures per year, P < .001, over a median treatment duration of 1.8 (IQR 0.6-3.0) years. Significant reductions in fracture rate were observed in both primary (1.0 [IQR 0.6-1.5] to 0.3 [IQR 0-0.6]) and secondary (0.5 [IQR 0.1-0.8] to 0 [IQR 0-0.3]) forms of skeletal fragility, P < .001 for both. Significant reductions in fracture rate persisted when limited to long bone or long bone plus spine fractures.

Conclusion: ZA treatment as a component of clinical care was associated with significant declines in fracture rate in this cohort of children and young adults with skeletal fragility.