Randomised controlled trial evaluating the use of Zoledronic acid in Duchenne Muscular Dystrophy.

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. DESIGN Two arm, parallel, randomised controlled trial. SETTING Paediatric hospitals across Australia and New Zealand. PATIENTS Sixty-two (31 per arm) boys with glucocorticoid dependent DMD between 6-16 years. INTERVENTION(S) Five ZA infusions (0.025mg/kg at months 0,3, 0.05mg/kg at months 6, 12 and 18), plus calcium and vitamin D, compared with calcium and vitamin D alone. MAIN OUTCOME MEASURES 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, pQCT and pain scores. RESULTS At 12 and 24 months, mean difference in changes of LSBMD 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 compared to control arms respectively (both p < 0.001). Five controls developed Genant 3 vertebral fractures, 0 in the ZA arm. Mobility, pain and bone turnover markers were similar between arms at 12 and 24 months Trabecular BMC and vBMD pQCT at radius and tibia were greater at 12 months in the ZA cohort compared to control; difference remaining at 24 months for radius. CONCLUSION ZA improved BMD in glucocorticoid dependent DMD boys. Whilst the small cohort precluded demonstrable fracture benefit, improved BMD might reduce incident vertebral fracture.