Project 1: Longitudinal Study of OI

Baylor College Of Medicine, Houston TX

Investigators

Linked publications, trials & patents

Abstract

PROJECT SUMMARY (PROJECT 1 - LONGITUDINAL STUDY OF OI) Osteogenesis imperfecta (OI) is a group of genetic disorders that results in brittle bone. In the first two cycles the Longitudinal Study generated novel insights on topics that are priorities for individuals with OI, including pain, quality of life, mobility, bone growth, dental and orthodontic issues and pregnancy. After reaching the target goal of 1000 participants, we closed enrollment to the more frequent COL1A1/COL1A2- related forms of OI while continuing enrollment of ultra-rare OI. Our overall goal for the final LS cycle is to collect at least 6 years of data for each participant, and to create radiographic and genomic data sets to empower future studies by the rare bone community. We will continue to collect the same elements as in previous cycles, while expanding our focus on spine pathology, women's health, and oral health, and completing radiographic central reading and generating whole genome sequencing data using an innovative low-cost platform. The upcoming study cycle will be structured around the following topics: (a) General phenotype characteristics: Baseline LS data has shown the dramatic effect of OI severity on basic characteristics such as pain, quality of life, mobility, bone density and height. We will continue to collect longitudinal data in each participant until we have 6 years of follow-up. Whole genome sequencing will be performed on all subjects employing the Ultima Genomics platform for unified diagnosis, genotype- phenotype correlations, CLINVAR deposition to accelerate diagnoses by the community. (b) Spine pathology: We will assess the natural history of vertebral fractures and spine deformities in children and adults. Data will be related to clinical variables including disease-causing variants, to identify predisposing factors for spine pathology as well as consequences of spine pathology in OI. This data will provide potential benchmarks for therapeutic interventional studies in the future. (c) Women's health: Little is known about the effects of pregnancy, lactation, and menopause on bone mineral density and vertebral fractures in women with OI. We will collect bone density and spine radiograph data on women, along with medication use, surveys, and other clinical variables to understand bone health and changes across the lifespan with new focus on menopause. (d) Oral health: Our previous studies indicate that dysplastic shape of the temporomandibular joint is common in all types of OI, except OI type I; however, the consequences are not known. We will assess malocclusion and the temporomandibular joint to evaluate dental and orthodontic sequelae of OI. We will also develop an artificial intelligence driven model to identify abnormal temporomandibular joint structure in individuals with OI. These data will be correlated with longitudinal cone beam computed tomographic imaging from Project 3. IMPACT: Longitudinal data on a broad range of phenotypes in OI will inform clinical management to improve care, identify topics for future research and improve clinical trial readiness. The data will establish an enduring clinical, radiographic, and genomic dataset that will be publicly available for future research.