IMPE Abstracts

Duchenne and Becker’s Muscular Dystrophy are X-linked progressive muscular disorders caused by mutations in dystrophin, leading to progressive muscle weakness. Glucocorticoids prolong ambulation and lifespan but cause significant endocrine complications. We assessed the prevalence of growth impairment, pubertal delay, and osteoporosis, along with the impact of growth hormone (GH), testosterone, and/or bisphosphonate in a longitudinal study of 27 males with dystrophinopathies on chronic glucocorticoids. At their initial endocrine consultation, participants’ median age was 13.5 years. They had been on chronic glucocorticoids for 8.5 years. After a median follow-up of 2.3 years, the prevalence of growth impairment was 96% (52% utilized GH), pubertal delay was 86% (72% utilized testosterone), and osteoporosis was 87% (72% utilized bisphosphonates). The median growth velocity of participants not on GH was 2.5 cm/year. When treated with GH, growth velocity increased to 7.8 cm/year the first year, and 5.9 cm/year beyond one year of treatment. Seventy percent of participants treated with testosterone progressed through puberty spontaneously, while 30% required continuation of testosterone to complete pubertal development. While the standard of care for osteoporosis in children with dystrophinopathies is bisphosphonates, we evaluated if GH and/or testosterone altered risk of vertebral compression fractures (VF) using multivariable Accelerated Failure Time (AFT) models. AFT model beta >1 indicates longer time to next VF, while beta <1 indicates shorter time to next VF. Participants on GH/testosterone treatment only compared to bisphosphonate only experienced prolonged time to next VF (beta 1.228; P=0.001), with GH being the significant contributor when analyzed independently from testosterone (beta 1.121; P=0.008). The coupling of bisphosphonates with GH/testosterone treatment also prolonged time to next VF (beta 1.201; P< 0.001), with testosterone being the significant contributor (beta 1.108; P=0.011). An increase in total body less head height adjusted Z-score reduced time to next VF (beta 0.984; P< 0.001), likely confounded by prior bisphosphonate utilization. Overall, our results suggest a protective role of GH and testosterone against VF independent of bisphosphonates, with GH having a stronger effect prior to first VF and testosterone having a stronger effect on subsequent VFs in children with dystrophinopathies on chronic glucocorticoids.