DESCRIPTION (provided by applicant): Osteoporotic fracture has a complex etiology involving skeletal fragility, risk of falling, and impaired reaction to a fall once it is initiated. Currently, quantitative bone assessments such as dual x-ray absorptiometry (DXA) and quantitative computed tomography (QCT) act as surrogates for skeletal strength but are of limited value as surrogates of fracture risk because they do not provide information on non-skeletal risk factors such as falls. Studies have shown that fall risk is associated with reduced muscle strength, particularly of the proximal femoral musculature. The QCT image of the hip provides information on the size and composition of the proximal femoral muscles, and studies at various skeletal sites have shown correlations between muscle strength and muscle size and attenuation measured by x-ray CT. In our laboratory, we have recently shown that combination of muscle size and attenuation data with the CT skeletal measures markedly improves the discriminatory power of the CT measurement. Here, we propose to develop computer algorithms to assess muscle size and attenuation from QCT hip images, prospectively validate that these measures improve fracture prediction when used in combination with hip QCT bone variables, and determine the mechanism by which they predict fracture. The study cohort will be selected from 5000 elderly individuals who have had baseline QCT examinations in the prospective Age Gene/Environment -Reykjavik (AGES-R) study and who are now being followed for incident fractures of the hip and other skeletal sites. The ultimate goal of this research program is to develop a quantitative assessment of an important non-skeletal risk factor that can be combined with QCT bone measurements, thus significantly improving diagnostic efficacy without the cost of an additional procedure. PUBLIC HEALTH RELEVENCE: Development of a muscle quantification procedure based on clinically available hip QCT skeletal imaging is an important pathway to improving estimation of hip fracture risk. It would potentially modify management of patients at risk for hip fractures by providing an additional non-skeletal measure reflective of fall risk. This quantitative measurement is modifiable and could become a treatment endpoint for specific exercise or drug therapies.