ESPE Abstracts (2018) 89 P-P2-280

Skeletal Disproportion and Growth Impairment in Glucocorticoid Treated Boys with Duchenne Muscular Dystrophy

Kung-Ting Kaoa, Shuko Josephb,a, Sarah Brownb, Nadia Capaldia, Jennifer Dunneb, Iain Horrocksb, Marina DiMarcob,c, Martin McMillana, Sheila Shepherda, Syed Faisal Ahmeda & Sze Choong Wonga


aDevelopmental Endocrinology Research Group, University of Glasgow, Glasgow, UK; bPaediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow, UK; cScottish Muscle Network, Queen Elizabeth University Hospital, Glasgow, UK


Introduction: Although short stature is common in boys with Duchenne Muscular Dystrophy (DMD), little information on body proportions and the GH/IGF-1 axis exists.

Methods: Total height (Ht), sitting height (SH), leg length (LL) and bone lengths (femur, tibia, humerus) in boys with DMD (n=30) and healthy boys (n=79) were measured using DXA digital images by 1 observer. Insulin growth factor-1 (IGF1), IGF binding protein-3 (IGFBP-3) and acid labile subunit (ALS) were converted to sex and bone age adjusted SDS. Ht, SH, LL, SH:LL ratio and bone lengths in DMD were compared to healthy controls adjusted for age and puberty. Results expressed as median (range).

Results: Median age of boys with DMD and controls was 10.0 years (6.1, 16.8) and 12.4 years (5.8, 17.0), respectively (P=0.03). All DMD boys were treated with glucocorticoids with a median duration of 7.1 years (1.3,15.2). 26 (87%) and 31 (39%) were pre-pubertal, respectively. 3 (10%) boys with DMD were on testosterone, 8 had vertebral fractures. None had significant scoliosis. Ht (β=−14.3 cm, 95% CI=−18.3,−10.4), SH (β=−5.0 cm, 95% CI −6.9, −3.1) and LL (β=−9.3 cm, 95% CI −11.7, −6.8) were significantly lower in DMD compared to controls. Femur (β=−3.6 cm, 95% CI −5.5, −2.2), tibia (β=−5.7 cm, 95% CI −6.9, −4.4) and humerus lengths (β=−1.4 cm, 95% CI −2.5, −0.5) were also significantly lower in DMD compared with controls. In a sub-analysis of 20 boys with no knee and hip contractures from joint angle measurements, SH:LL ratio (β=+0.10, 95% CI +0.04, +0.13) remained significantly higher in DMD compared with healthy controls. Median IGF1, IGFBP3 and ALS Z-scores were +1.2 (−2.1,+3.7),+1.5 (+0.2,+3.7) and −0.5 (−1.5,+0.9) respectively. IGF1 (β=−0.001, 95% CI −0.02,+0.014), IGFBP-3 (β=−1.8, 95% CI −4.5,+1.0) and ALS (β=+0.001, 95% CI −0.004,+0.005) showed no association with Ht after adjusting for bone age.

Conclusion: As glucocorticoid excess is not usually associated with disproportionate growth, the finding of disproportionate growth in boys with DMD raises the question whether there is an intrinsic and localized disorder of growth in this condition. Despite the growth impairment in these boys, abnormalities in GH/IGF1 axis were not seen and were not associated with stature.