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. 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.

Effectiveness of Neridronate in the Management of Bone Loss in Patients with Duchenne Muscular Dystrophy: Results from a Pilot Study

“…It is key to note that our study provides data about BMD changes in a specific site (lumbar vertebrae) that is affected during GIO and DMD. Consistent with our findings, a recent randomized controlled trial assessing effects of five zoledronic acid infusions on BMD in patients with DMD showed higher BMD value in the treated arm versus control arm both at 12 and 24 months (both p < 0.001) [ 23 ].…”

Efficacy and safety of bisphosphonates on childhood osteoporosis secondary to chronic illness or its treatment: a meta-analysis

“…Finally, nine RCTs ( n = 429 in total) were included in our meta-analysis. 7 – 15 Of note, we excluded three articles because of no available outcome data 16 – 18 and another one article because of data not consistent with other studies 19 when assessing the full articles. The details of included studies are shown in Table 1 .…”

Bone Mineral Density and Current Bone Health Screening Practices in Friedreich’s Ataxia

“…For adults with low bone density, there are approved medications that in other populations have been shown to meaningfully reduce the risk of future fracture. These medications are also used in children with low bone density, in particular those who fracture related to fragile bones ( Zacharin et al, 2021 ). One study in different condition characterized by early onset of mobility impairment, Duchenne Muscular Dystrophy, found that boys (ages 6–16 years) treated with bisphosphonates had increased aBMD and potentially decreased risk of incident fracture ( Zacharin et al, 2021 ).…”

“…These medications are also used in children with low bone density, in particular those who fracture related to fragile bones ( Zacharin et al, 2021 ). One study in different condition characterized by early onset of mobility impairment, Duchenne Muscular Dystrophy, found that boys (ages 6–16 years) treated with bisphosphonates had increased aBMD and potentially decreased risk of incident fracture ( Zacharin et al, 2021 ). In FRDA, despite the apparent prevalence of low bone density and the capacity for screening to lead to actionable information, our survey indicated that very few individuals have undergone a screening DXA scan, even those who use wheelchairs who are likely at greatest risk for low bone density.…”