Bone Abstracts

Osteoporosis in Duchenne Muscular Dystrophy (DMD) is arguably one of the most severe bone fragility conditions among children with chronic illnesses. This is hardly surprising, given the deleterious effects of the myopathy and glucocorticoid (GC) therapy on bone strength. The severity of the osteoporotic phenotype is highlighted by observations that 60% of boys will sustain long bone fractures during childhood and a third will present with back pain due to vertebral fractures (VF). Since VF prevalence studies in other GC-treated pediatric cohorts underscore that VF are frequently asymptomatic, studies to date have likely grossly under-estimated the total VF burden in DMD. Long bone fractures can lead to premature permanent loss of ambulation, and death due to fat embolism syndrome following long bone injury has also been described. Long bone fractures can occur prior to the onset of GC therapy, while VF manifest on average 1-2 years (and as early as 6 months) following GC start. VF are detected in their earliest stages when spine health is routinely monitored through periodic lateral spine imaging starting no later than the time of GC initiation. Left untreated, boys with DMD are at risk for “the vertebral fracture cascade” (more painful, numerous and severe collapse following an initial VF event); prevention of the cascade is one of the main goals of intervention, particularly important in DMD since vertebral body reshaping following VF has never been reported in this setting. Treatment to date has largely been restricted to bisphosphonates given their long-standing track record in pediatric osteoporotic conditions. With such an approach, back pain and further vertebral collapse are mitigated and overall the benefits of late-stage osteoporosis intervention are out-weighed by early fracture detection and timely initiation of osteoporosis therapy. Trans-iliac bone histormophometric and density distribution studies show classic signs of a low-turnover osteoporosis prior to bisphosphonate therapy (reduced trabecular bone volume, thin cortices, low bone formation rates and an increased number of highly mineralized areas), followed by further reductions in bone turnover and a drop in mineralization heterogeneity after anti-resorptive intervention. Reductions in bone turnover both pre- and post-bisphosphonate therapy point to the pressing need for anabolic and growth-promoting therapies; intervention trials which aim to prevent first fractures are also needed.

Disclosure: Consulting honoraria and active participation in a clinical trial for Novartis. Consulting honoraria and active participation in a clinical trial for Amgen.