Project 3: 3D Imaging

Baylor College Of Medicine, Houston TX

Investigators

Linked publications, trials & patents

Abstract

PROJECT SUMMARY (Project 3 – CT Imaging in OI) Osteogenesis imperfecta (OI), the most common osteodysplasia in humans, presents with increased bone fragility, recurrent fractures, and bone deformities. Despite significant advances in understanding the genetic bases of OI and mechanisms underlying bone fragility, there are currently no FDA-approved therapies for OI. A major hurdle in developing new therapies for OI is the challenge to conduct trials that are adequately powered to detect a decrease in fracture rate. The majority of randomized trials in OI have thus used surrogate markers of bone fragility and fracture risk, i.e, 2-dimensional areal bone mineral density (aBMD). However, correlations between aBMD and fracture in OI have been weak, thus aBMD is not an accepted efficacy endpoint by regulatory bodies. Furthermore, abnormalities of craniofacial bones in OI confer significant morbidity, but there are no validated endpoints to assess such abnormalities. Cutting-edge, innovative 3- dimensional imaging modalities, such as high-resolution peripheral quantitative computed tomography (HR- pQCT) (for the appendicular skeleton) and cone beam computed tomography (CBCT) (for the cranial skeleton) provide us with exciting opportunities to develop and validate reliable imaging outcome measures in OI. Therefore, we propose to improve our clinical trial readiness and developing novel imaging biomarkers with minimum radiation risk. We hypothesize: 1) HR-pQCT indices at the radius and tibia predict incident fracture risk independently of lumbar aBMD, 2a) (Re)modeling results in larger changes in bone structure in children than adults, 2b)(re)modeling is greater in OI type I than in types III/IV, and 2c) for a given mechanical strain level, there is decreased mechano-adaptation in OI types III/IV compared to OI type I, and 3) Temporomandibular joint (TMJ) dysplasia is associated with TMJ dysfunction and predicts degenerative changes in the TMJ. We will identify imaging biomarker(s) (HR-pQCT indices) as surrogate marker for fracture risk in OI (Aim 1). We will use state-of-the-art time-lapse imaging to elucidate bone (re)modeling activity during growth in children and during adulthood to understand mechano-adaptation (Aim 2). Finally, we will identify how bone formation and resorption contribute to abnormal TMJ structure (Aim 3). This project will improve clinical trial-readiness in OI by assessing novel outcome measures from HR-pQCT and CBCT imaging modalities.