Secondary Osteoporosis & Its Therapy in Duchenne Muscular Dystrophy
Secondary Osteoporosis & Its Therapy in Duchenne Muscular Dystrophy – ScOT-DMD
Duration of Study in the UK
2 years, 11 months, 28 days
Summary of Research
There is increasing evidence that boys with Duchenne Muscular Dystrophy (DMD) have a greater fracture risk. Up to 40% may sustain a fracture. Fractures not only cause pain but may lead to premature loss of walking ability in this group.
Until now, the natural history of osteoporosis and development of bone fragility in DMD boys have not been studied throughly. The risk of fractures may be influenced by multiple factors including inflammation, physical inactivity, delay in puberty, deficiency of growth factors, vitamin D insufficiency and steroid therapy. The relative importance of these factors on development of osteoporosis remains unclear in this group. The evidence base for managing secondary osteoporosis therefore, remains scant and more evidence is required to improve bone health.
To understand the current practice and quantify the extent of bone morbidity, I have been funded by the CSO to perform the following set of studies.
1. A survey of the Scottish Muscle Network and the North Star Database to understand current practice.
2. Over a period of 9 months, affected boys with DMD between the ages of 5 and 16 years will be recruited into a 2-year prospective study. The changes in bone health will be studied using combination of imaging techniques including dual energy x-ray absorptiometry (DXA), lateral vertebral morphometry, plain X-rays and bone biomarkers. In a subset of patients, high resolution magnetic resonance imaging (MRI) will be employed to look at bone microarchitecture and bone marrow adiposity.
3. The opinion of affected families and boys as well as the clinicians will be collected to assess the feasibility of a future interventional trial of bone protective therapy.
This application for ethics approval applies specifically to the prospective study outlined under '2' above.
Summary of Results
A successful completion of the research projects Secondary Osteoporosis & Its Therapy in Duchenne Muscular Dystrophy (ScOT-DMD) was achieved over the 3-year academic clinical training fellowship. Overall aim was to evaluate the extent of osteoporosis (fragility of bone) in boys with DMD and assess the feasibility of an interventional trial aimed at improving bone health. To achieve this overall aim, the following studies were conducted over the 3-year fellowship: -
• A retrospective study of bone health (fractures, bone density, vitamin D levels) and its management in boys with DMD in Scotland managed within the Scottish Muscle Network (SMN)
• Retrospective study of bone health and its management in the UK via the NorthStar Database
• A prospective two-year longitudinal study of bone health (lateral spine x-ray/ bone density/ bone markers) in DMD
• Cross-sectional MRI study of bone microarchitecture (structure of bone) and bone marrow adiposity (how fatty the bone marrow is)
• Feasibility study of a bone-protective therapy trial
The results revealed the extent of fracture burden in boys with DMD and generated novel insights into incidence vertebral fracture rate, progression, and clinical predictors. Better characterisation of the natural history of secondary osteoporosis will inform future clinical trials of bone-protective therapy aimed to reduce the fracture burden in this at-risk population. Feasibility of much needed clinical trials was studied in order to guide future development. Publications from the research study are as follows;
• Choong Wong S, Joseph S, Capaldi N, Marco MD, Dunne J, Guglieri M, et al. A survey of the feasibility of developing osteoporosis clinical trials in Duchenne muscular dystrophy: Survey of the opinion of young people with Duchenne muscular dystrophy, families, and clinicians. Clin Trials. 2021; 18(1): 39-50.
• Joseph S, Wang C, Bushby K, et al. Fractures and Linear Growth in a Nationwide Cohort of Boys With Duchenne Muscular Dystrophy With and Without Glucocorticoid Treatment: Results From the UK NorthStar Database. JAMA Neurol. Published online March 11, 2019. doi: 10.1001/jamaneurol.2019.0242
• Joseph S, Wang C, Di Marco M, Horrocks I, Abu-Arafeh I, Baxter A, et al. Fractures and bone health monitoring in boys with Duchenne muscular dystrophy managed within the Scottish Muscle Network. Neuromuscul Disord. 2019; 29(1): 59-66.
West of Scotland REC 5
Date of REC Opinion
5 Oct 2015
Further Information Favourable Opinion