Objectives: We evaluated the efficacy and safety of intravenous zoledronic acid (IV ZA) in children with glucocorticoid-induced osteoporosis (GIOP) through a randomized, placebo (PBO)-controlled trial.
Methods: In this multi-national Phase 3 trial (NCT00799266), children 517 years of age with GIOP and low-trauma vertebral fractures (VF) were randomized 1:1 to IV ZA 0.05 mg/kg or IV PBO every six months for one year. Changes in lumbar spine areal bone mineral density Z-scores (BMDZ, primary outcome) and the frequency of new low-trauma VF were assessed centrally with treatment blinding. Adverse events (AEs) and serious AEs (SAEs) were recorded.
Results: Thirty-four children (38% with Duchenne, 35% rheumatic conditions, 27% Crohns disease, mean age 12.6±3.4 years, 68% boys) were enrolled in the study (ZA, n=18; PBO, n=16). Thirty-three and 30 children completed 6 and 12 months of the trial, respectively; two children (ZA) withdrew for logistical reasons (school commitments, participation in another trial), and two withdrew after incident fractures (clavicle, ZA; new VF, PBO). Data are presented on 33 children with at least one follow-up visit. The mean ± standard deviation change in spine BMDZ over 1 year was −2.1±0.8 to −1.5±1.0 on ZA compared with −2.4±0.9 to −2.3±1.0 on PBO, least squares (LS) mean between-group BMDZ difference 0.414, 95% confidence interval 0.022, 0.806; P=0.039. Two children on PBO had new low-trauma VF in previously normal vertebrae. Eight-three percent of children had AEs on ZA vs 75% on PBO. Sixty-seven percent (ZA) vs 25% (PBO) of AEs occurred within 10 days following the first infusion, largely due to transient post-dose gastrointestinal complaints. Five children on ZA and one child on PBO had SAEs; 4/5 children on ZA had gastrointestinal SAEs, and two of these children had SAEs within 10 days following ZA (transient, one with hypocalcemia, one with acute phase reaction symptoms). There were no deaths, nor treatment discontinuations due to ZA.
Conclusions: Over one year, spine BMDZ in children with GIOP significantly increased on ZA compared with PBO. AEs and SAEs were consistent with the known, transient side effects of ZA.
Disclosure: Dr. Ward has been a consultant to Novartis Pharmaceuticals. The other co-authors have nothing to declare.