Project Abstract In this Shared Instrument Grant application, we are requesting funds to acquire an XtremeCT II High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) scanner. HR-pQCT is a non-invasive, low radiation approach for assessing compartment-specific volumetric bone mineral density (vBMD) and bone microarchitecture in the peripheral skeleton to estimate bone strength and fracture risk. Integration of this state- of-the-art skeletal imaging modality into the repertoire of biomedical imaging tools available at Wake Forest School of Medicine (WFSM) advances the initiatives of 18 NIH-funded centers, institutes, and departments; and bolsters collaborative efforts with several of our regional partners. Specifically, acquisition of HR-pQCT technology will allow the proposed major and minor user groups to: 1) better understand the effects of lifestyle- based strategies — such as weight-bearing exercise and a high protein diet — on skeletal health among older adults losing weight; 2) expand the investigation of the role of age-related biological changes in skeletal muscle on the decline in mobility to include interactions with bone; 3) demonstrate the potential of advanced image analyses techniques to augment histostructural outcomes; 4) provide insight into the genomic architecture of bone health to aid in the development of novel treatment strategies to mitigate bone loss in aging; 5) better capture musculoskeletal comorbidities among motor vehicle crash occupants, and understand their influence on injury incidence and rehabilitation success; 6) address important gaps on the effects of weight management interventions on the growing skeleton; 7) evaluate whether bone microarchitecture varies across ethnically diverse populations; 8) augment computational modeling strategies assessing change in bone health across the lifespan to include bone microarchitecture and strength; and 9) determine the timing of and extent to which intracortical bone loss occurs among adults with diabetes mellitus and chronic kidney disease. To promote cost effectiveness, encourage optimal sharing, and foster multidisciplinary collaborations, the HR-pQCT will be housed in the Translational Imaging Program Core at WFSM, where it will be overseen by qualified leadership, operational, and advisory committees in accordance with well-organized and self-sustaining administrative and financial plans. Ultimately, the addition of a HR-pQCT system will enable WFSM to engage in more multidisciplinary collaborations, compete more successfully for external research funding, and remain at the forefront of musculoskeletal research endeavors.