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Lead investigator

Collaborators & Co-Investigators

• Jerome Frenette, MScPT, PhD
• Laura McAdam MSc, MD
• Marie-Eve Robinson MD, C.M. MSc

Research Sites & Affiliations

• Universite Laval, Quebec City, Quebec
• University of Toronto, Toronto, Ontario
• Children's Hospital of Eastern Ontario, Ottawa, Ontario

Budget: $49,596.00

Disorders: Duchenne/Becker Muscular Dystrophy

Research Areas: Enhance Care

Abstract: 

Boys with glucocorticoid (GC)-treated Duchenne muscular dystrophy (DMD) are at risk for vertebral and long bone fractures due to osteoporosis. Vertebral fractures in DMD cause chronic back pain and spine deformity, while leg fractures can lead to premature, permanent loss of ambulation. Prevalence studies have shown that 20-60% of boys will sustain long bone fractures and up to 30% will have painful vertebral fractures. Fractures have also been linked in DMD to fat embolus syndrome causing acute respiratory distress and sudden death. The goal of this study, a pilot trial, is to evaluate the safety and feasibility of a novel therapy in the treatment of osteoporosis (denosumab) compared to our standard of care approach (intravenous bisphosphonate therapy, zoledronic acid) in boys with DMD. Denosumab is a human monoclonal antibody that inactivates RANKL, thereby inhibiting bone resorption and increasing bone strength at both trabecular (spine) and cortical (long bone) sites. A large study on close to 8,000 women with post-menopausal osteoporosis (the FREEDOM trial) showed that denosumab reduced vertebral and hip fracture risks without an increased frequency of side effects compared to placebo. The use of this agent is particularly compelling in the DMD setting, since studies in a murine model of DMD by co-investigator J. Frenette have shown that RANKL inhibition protects against DMD muscle dysfunction, degeneration and inflammation.

 

Impact: