A recent study published in the Journal of Clinical Endocrinology & Metabolism indicates that zoledronic acid treatment is associated with a significant reduction in fracture rates among pediatric patients with skeletal fragility. The retrospective cohort study, conducted at the Children’s Hospital of Philadelphia, provides valuable insights into managing this challenging condition in young patients.
Study Design and Patient Population
Researchers analyzed data from 102 patients aged 21 years and younger who received at least one dose of zoledronic acid for skeletal fragility between 2010 and 2017. The cohort included patients with both primary (38%) and secondary (62%) skeletal fragility. Osteogenesis imperfecta was the most common primary disorder (90%), while neuromuscular weakness resulting from genetic or acquired conditions was the leading cause of secondary fragility (30%).
The individualized zoledronic acid dose ranged from 0.0125 to 0.1 mg/kg/dose, up to a maximum of 5 mg, administered every 3 to 12 months. Data on fracture occurrence and site were collected from the hospital database, along with information on calcium, vitamin D, and steroid use.
Significant Reduction in Fracture Rates
After a median follow-up of 3.1 years (IQR 2.0-4.4), the median fracture rate significantly declined from 0.6 (IQR 0.3-1.1) to 0.0 (IQR 0.0-0.4) fractures per year following zoledronic acid treatment (P < .001). This reduction remained significant when considering only long bone fractures (0.4 to 0.0; P < .001) or long bone plus spine fractures (0.5 to 0.0; P < .001).
Specifically, in patients with primary skeletal fragility, the median fracture rate decreased from 1.0 (IQR 0.6-1.5) to 0.3 (IQR 0.0-0.6) fractures per year. For those with secondary skeletal fragility, the rate dropped from 0.5 (IQR 0.1-0.8) to 0.0 (IQR 0.0-0.3) fractures per year.
Consistent Fracture Rate Trends
The fracture rates post-infusion showed no increasing or decreasing trends over time. A decline in fracture rate was observed in 66% of patients, no change in 24%, and an increase in 10%. Notably, among patients with no change or increased fractures, a significant proportion (52% and 30%, respectively) had a baseline of 0 fractures per year before treatment.
Limitations and Implications
The study authors acknowledge limitations, including variability in zoledronic acid exposure and outcome assessment, potential information bias, and incomplete fracture documentation. The exclusion of patients starting therapy before age 1 also limits generalizability.
Despite these limitations, the authors stated, "We expect the results of this study to be helpful to clinicians caring for pediatric patients and to provide important preliminary data for investigators planning future clinical trials."
The findings suggest that zoledronic acid is an effective treatment for reducing fracture rates in pediatric patients with skeletal fragility, supporting its use in clinical practice and providing a foundation for further research.
