PROJECT 1: LONGITUDINAL STUDIES

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PROJECT SUMMARY (Longitudinal Study of OI) The Brittle Bone Disorders Rare Disease Clinical Research Consortium (BBD RDCRC) longitudinal study of Osteogenesis Imperfecta (OI) seeks to 1) characterize the phenotypes of OI that occur across the lifespan, 2) understand how various issues effect individuals with OI and 3) assess the response to routine clinical care. There are over 18 genes that cause BBDs and they have pleiotropic effects resulting in a broad spectrum of physical and health challenges and life experiences. Biochemical and molecular mechanisms of OI include haploinsufficient type I collagen OI, dominant negative type I collagen OI, disorders of type I collagen post-translational modification, disorders of type I collagen transport, and an emerging number of disorders due to abnormal signaling. There is great need to understand the natural histories of these conditions as well as correlating genotypes with phenotypes to define a standard of care and improve therapeutic options. Based on our experience to date in the BBDC years 1-5, we have identified the following important issues in need of longitudinal assessment: 1) Evaluate the difference in phenotype, disease progression and response to therapies in individuals with dominant and recessive forms of OI to assess the natural history of these disorders. 2) Describe the incidence of vertebral fractures in type I collagen haploinsufficient OI (OI-HI or OI type I) through a prospective, multi-center observational study, and evaluate the impact of clinical susceptibility factors on the development of incident vertebral fractures 3) Describe the natural history of scoliosis in various forms of OI and assess the characteristics predisposing to progression of the deformity, effects of scoliosis on pulmonary function, mobility & quality of life and impact of scoliosis interventions (bracing, surgery, etc.) on scoliosis and pulmonary function. 4) Utilize patient reported outcomes tools to assess factors that contribute to increased anxiety and pain interference in adults and children with OI, in order to develop interventions to improve quality of life. 5) Characterize the effect of pregnancy and lactation on bone health in women with OI by analyzing pre- and post-pregnancy bone mineral density and content and fracture incidence. 6) Evaluate dental malocclusion & craniofacial abnormalities and determine the dynamic changes over time and impact upon oral-health related quality of life. The BBD RDCRC longitudinal study will be performed by all 11 clinical sites of the consortium. V. Reid Sutton at Baylor College of Medicine and Frank Rauch at the Montreal Shriners Hospital for Children will be the co-PIs of the overall longitudinal study.