Background: Bisphosphonates are anti-osteoclastic agents used to treat osteoporosis. Zoledronic acid (ZA) is a third-generation IV bisphosphonate commonly used in pediatrics. Several studies have demonstrated ZA safety for children, but efficacy to prevent fractures is uncertain.
Objective: Investigate the effectiveness of ZA to reduce fractures in children with osteogenesis imperfecta (OI) and other forms of osteoporosis.
Methods: Retrospective chart review of patients treated with ZA for low bone density and fracture at The Children's Hospital of Philadelphia between 07/2010-10/2017. The primary outcome was the fracture (fx) rate, expressed as fx/yr. Treatment duration was calculated as time from first infusion to end of study or loss to follow-up. A pre-treatment baseline for each subject was determined using time period pre-ZA equal to treatment duration. We extracted demographics, diagnostic data, and details of ZA treatment. The Wilcoxon signed-rank test was used to compare pre- and post-ZA and present the results as median [interquartile range (IQR)].
Results: 125 patients (80 male), median age at first infusion 11 yrs (range of 0.5- 19), met inclusion criteria, including 39 OI and 86 non-OI patients. Median post-ZA follow-up time was 2.8 yrs (IQR: 1.5-4.5). Patients received a median of 3 ZA doses (IQR: 2-5) with median cumulative dose of 0.08 mg/kg (IQR: 0.04-0.16). ZA treatment led to statistically significant decreases in overall, long bone, and long bone and spine fx rate in the overall cohort and the subset with OI (Table 1). For non-OI patients, statistically significant decreases occurred for overall and long bone and spine fx rates. Decreases in fx rate were more likely in subjects with OI vs non-OI (67% vs 48%, p=0.05). Decreased fx rate was associated with greater number of infusions [4(IQR:2-6) vs 2(IQR:1-4), p<0.01] and greater cumulative ZA dose [0.11 mg/kg(IQR:0.04-0.20) vs 0.06 mg/kg(IQR:0.03-0.11), p<0.01] but did not differ by age or gender at first infusion.
Conclusions:
We showed that ZA is effective at reducing fractures in pediatric patients with OI and other forms of osteoporosis. Non-OI patients showed a trend towards reduction in long bone fractures that did not reach statistical significance, likely due to the small number of pre-ZA fractures. This data supports the use of ZA to reduce fx rates in youth with OI and other forms of osteoporosis.
