Bone strength, or bone's resistance to fracture is an important outcome in studies of bone health. The independent roles of trabecular microarchitecture and trabecular and cortical volumetric bone mineral density (vBMD) as determinants of bone's mechanical competence and fracture risk have been established. Thus, there is great interest in high-resolution imaging methods capable of measuring these parameters in vivo in order to derive new quantitative densitometric, microstructural and mechanical measures of fracture risk. This application requests funds to purchase a high resolution peripheral quantitative computed tomography (HR- pQCT) scanner. The instrument will be installed in the Clinical and Translational Research Center (CTRC) Nutrition Assessment Core, supported by the joint Children's Hospital of Philadelphia (CHOP) - University of Pennsylvania (Penn) Clinical and Translational Science Award. The Core is centrally located and currently supports 14 NIH-funded protocols (including multiple clinical trials) that include dual energy x-ray absorptiometry (DXA) and conventional pQCT bone scans. Both pQCT and HR-pQCT are in vivo imaging modalities for the peripheral skeleton with low radiation dose and fast scan time. However, HR-pQCT has markedly higher image resolution compared to pQCT, and provides detailed 3D measures of the microarchitecture of trabecular bone and porosity of cortical bone, as well as geometry and vBMD of cortical and trabecular bone. Importantly, HR-pQCT images can be used as input for ?-Finite Element Analysis (FEA) for estimation of whole bone strength or elastic moduli of trabecular bone. The proposal is a unique multidisciplinary collaboration among (1) investigators dedicated to the development of new image-processing algorithms and ?-FEA models for the quantitative assessment of the structural and mechanical implications of bone disease, and (2) clinical investigators that will use HR-pQCT and these advanced imaging methods as additional significant and innovative outcomes for current NIH funded studies. These studies span the spectrum from a clinical trial of mesenchymal stem cell therapy to treat severe osteogenesis imperfecta in children, to a randomized weight loss and exercise intervention trial in a multi-ethnic cohort of overweight and obese breast cancer survivors. This will be the first HR-pQCT scanner in the greater Philadelphia area. The addition of this instrument to the Nutrition Assessment Core will result in rapid and wide-spread adoption of this technique at minimal cost to investigators. We have a detailed and ready-to-execute plan for operation that includes technical expertise and support, and full institutional commitment.
Investigators at CHOP and Penn have developed a multidisciplinary program to improve the diagnosis and treatment of bone fragility disorders across the lifespan. The addition of HRpQCT to the Clinical and Translational Science Award Nutrition Assessment Core will be a cost effective and efficient strategy to accelerate progress in existing research projects and generate new insights into the microstructural and biomechanical consequences of bone diseases and therapies.