Randomized Controlled Trial Evaluating the Use of Zoledronic Acid in Duchenne Muscular Dystrophy

Abstract

Context: Patients with glucocorticoid-dependent Duchenne muscular dystrophy (DMD) have increased fracture risk and reduced bone mineral density (BMD), often precipitating mobility loss. Objective: To investigate use of zoledronic acid (ZA) in DMD in improving BMD. Methods: Two arm, parallel, randomized controlled trial, set in pediatric hospitals across Australia and New Zealand. Sixty-Two (31 per arm) boys with glucocorticoid-dependent DMD between 6 and 16 years were included. Five ZA infusions (0.025 mg/kg at months 0, and 3, and 0.05 mg/kg at months 6, 12, and 18), plus calcium and vitamin D, were compared with calcium and vitamin D alone. The main outcome measures were change in lumbar spine (LS) BMD raw and Z-score by dual energy absorptiometry x-ray (DXA) at 12 and 24 months, secondary outcomes assessing mobility, fracture incidence, bone turnover, peripheral quantitative computerized (pQCT) and pain scores. Results: At 12 and 24 months, mean difference in changes of LS BMD Z-score from baseline was 1.2 SD (95% CI 0.9-1.5), higher by 19.3% (14.6-24.0) and 1.4 SD (0.9-1.9), higher by 26.0% (17.4-34.5) in ZA than control arms respectively (both P