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.

BACKGROUND/AIMS: Given the extent of osteoporosis in people with Duchenne muscular dystrophy treated with glucocorticoids and the limited evidence of bone-protective therapies, clinical trials are needed. We conducted surveys to obtain the opinion of young people with Duchenne muscular dystrophy, parents/guardians and neuromuscular clinicians on the feasibility of osteoporosis clinical trials in this population. METHODS: Online surveys were sent to three groups: (a) people with a confirmed diagnosis of Duchenne muscular dystrophy (≥14 years), (b) parents and guardians and (c) neuromuscular clinicians in the UK NorthStar Clinical Network. Surveys (a) and (b) were distributed via the UK Duchenne muscular dystrophy Registry. RESULTS: Survey respondents included 52 people with Duchenne muscular dystrophy with a median age of 17 years (range: 14, 40) and 183 parents/guardians. Fourteen out of 23 (61%) NorthStar centres responded. Of the 52 people with Duchenne muscular dystrophy, 13 (25%) were very concerned about their bone health and 21 (40%) were slightly concerned. Of the 183 parents/guardians, 75 (41%) were very concerned about their son's bone health and 90 (49%) were slightly concerned. Fractures and quality of life were the top two main outcome measures identified by people with Duchenne muscular dystrophy. Fractures and bone density were the top two main outcome measures identified by parents/guardians and neuromuscular clinicians. Thirty percent of people with Duchenne muscular dystrophy and 40% of parents/guardians would not take part if an osteoporosis trial involved a placebo that was administered parenterally. Only 2 of the 14 NorthStar centres (14%) would enrol people with Duchenne muscular dystrophy if a parenteral placebo was used in an osteoporosis trial in Duchenne muscular dystrophy. CONCLUSION: There is great awareness of bone health and the need for bone-protective trials among people with Duchenne muscular dystrophy and their carers. However, a proportion of people with Duchenne muscular dystrophy and parents are reluctant to participate in a placebo-controlled osteoporosis trial that included a parenteral therapy. A larger proportion of health care experts are unwilling to enrol their patients in such a trial. Our finding is relevant for the design of bone-protective studies in Duchenne muscular dystrophy.

Skeletal disproportion in glucocorticoid-treated boys with Duchenne muscular dystrophy.

We aimed to compare body segment and bone lengths in glucocorticoid-treated boys with Duchenne muscular dystrophy (DMD) with healthy controls using dual-energy absorptiometry (DXA) images. Total height (Ht), sitting height (SH), leg length (LL) and bone lengths (femur, tibia) in boys with DMD and age-matched control boys were measured using DXA. Thirty boys with DMD (median age 10.0 years (6.1, 16.8)) were compared with 30 controls. SH in DMD was 3.3 cm lower (95% CI - 6.1, - 0.66; p = 0.016). LL in DMD was 7.3 cm lower (95% CI - 11.2, - 3.4; p < 0.0001). SH:LL of boys with DMD was higher by 0.08 (95% CI 0.04, 0.12; p < 0.0001). Femur length in DMD was 2.4 cm lower (95% CI - 4.6, - 0.12; p = 0.04), whereas tibial length in DMD was 4.8 cm lower (95% CI - 6.7, - 2.9; p < 0.0001). SH:LL was not associated with duration of glucocorticoid use (SH:LL ß = 0.003, 95% CI - 0.01 to 0.002, p = 0.72).Conclusion: Glucocorticoid-treated boys with DMD exhibit skeletal disproportion with relatively shorter leg length and more marked reduction of distal long bones. As glucocorticoid excess is not associated with such disproportion, our findings raise the possibility of an intrinsic disorder of growth in DMD. What is Known • Severe growth impairment and short stature are commonly observed in boys with Duchenne muscular dystrophy (DMD), especially those treated with long-term glucocorticoids (GC). • In other groups of children with chronic conditions and/or disorders of puberty, skeletal disproportion with lower spinal length has been reported. What is New • Growth impairment in GC-treated boys with DMD was associated with skeletal disproportion in relation to age, with lower limbs and distal long bones affected to a greater degree.