Zoledronic acid versus placebo in pediatric glucocorticoid-induced osteoporosis: A randomized double-blind phase 3 trial.

Abstract

CONTEXT\nGlucocorticoids (GC) prescribed for chronic pediatric illnesses are associated with osteoporotic fractures.\n\n\nOBJECTIVE\nTo determine the efficacy and safety of intravenous (IV) zoledronic acid (ZA) compared with placebo to treat pediatric GC-induced osteoporosis (GIO).\n\n\nPATIENTS, DESIGN AND SETTING\nChildren 5-17 years of age with GIO were enrolled in this multi-national randomized, double-blind, placebo-controlled phase 3 trial (ClinicaTrials.gov NCT00799266).\n\n\nINTERVENTIONS AND MAIN OUTCOME MEASURES\nEligible children were randomized 1:1 to six monthly IV ZA 0.05\xa0mg/kg or IV placebo. The primary endpoint was the change in lumbar spine bone mineral density Z-score (LSBMDZ) from baseline to month 12. Incident fractures and safety were assessed.\n\n\nRESULTS\nThirty-four children were enrolled (mean age 12.6 ± 3.4 years [18 on ZA, 16 on placebo]), all with low-trauma vertebral fractures. LSBMDZ increased from -2.13 ± 0.79 to -1.49 ± 1.05 on ZA, compared with -2.38 ± 0.90 to -2.27 ± 1.03 on placebo (least squares means difference 0.41 [95% confidence interval 0.02, 0.81; p=0.04]); when corrected for height Z-score, the least squares means difference in LBMDZ was 0.75 [0.27, 1.22; p=0.004]. Two children on placebo had new low-trauma VF versus none on ZA. Adverse events (AEs) were reported in 15/18 children (83%) on ZA, and in 12/16 (75%) on placebo, most frequently within 10 days after the first infusion. There were no deaths, nor treatment discontinuations due to treatment-emergent AEs.\n\n\nCONCLUSIONS\nLSBMDZ increased significantly on ZA compared with placebo over one year in children with GIO. Most AEs occurred after the first infusion.