Evaluation of bone turnover, bone metabolism, bone density, and fractures in children with Duchenne Muscular Dystrophy and possible side effects of long-term corticosteroid therapy (BON-DMD)

The project (BON-DMD), for which this funding application is presented, is ancillary to another international multicenter project (FOR-DMD), already independently financed, starting in March 2012. The study object is one of the most frequent X-linked genetic diseases (transmitted from carrier mother to male children through the X chromosome, with a risk of 50%), Duchenne's Muscular Dystrophy (DMD). The main aim of FOR-DMD is the evaluation of three different therapeutic regimens based on corticosteroids (CS), the only treatment that, even if not resolutive, has demonstrated positive effects in DMD, regarding both the preservation of muscular function and the prolongation of life. Unfortunately, long-term, high-dose use of CS has several negative side effects, often severe, including the early development of secondary osteoporosis (reduction of bone mineral mass and micro-architectural deterioration, with increased bone fragility and risk of fractures). FOR-DMD will consider the bone aspects only marginally, following the evolution of bone mass and recording the occurrence of vertebral fractures. On the contrary BON-DMD, if funded, will offer a significant expansion of the bone study within the FOR-DMD. Within the BON-DMD ancillary study, the 300 patients enrolled will undergo a thorough evaluation of bone metabolism and turnover, through the analysis of specific biochemical "bone markers", as well as a more accurate study of the evolution of bone mass, thanks to a strict quality control procedure involving all the participating Centers. The unique opportunity of studying a large population of DMD patients is expected first to answer the unresolved question about whether DMD per se, even before CS use and independently of it, causes loss of bone mass and weakening of bone structure, and second to provide clues to the identification of the patients with the greater risk of developing severe osteoporosis and sustaining fractures.