The lack of validated guidelines for predicting the risk of pathologic fracture increases morbidity for many of the one million new patients who develop cancer each year. Our previous studies have led to an understanding of the geometric and densitometric factors that determine strength reductions due to metastatic defects in bone, and have resulted in non-invasive methods that can predict fractures ex-vivo. Before initiating a prospective study to determine it these non-invasive tools can also be used clinically, we must first extend our methods to include patients with vertebral metastases who am examined using magnetic resonance imaging (MRI) instead of quantitative computed tomography (QCT), determine whether simple densitometric measures can be used to predict pathologic fractures in the proximal femur for loads that represent several different activities of daily living, and determine worst-case loading conditions for the proximal femur. In addition, we will obtain pilot clinical data that are required to design a follow-on prospective study. Aim 1: During the previous funding period, we have determined that failure of vertebrae with metastatic defects can be predicted by measuring the axial rigidity from QCT data. However, vertebral metastases in many patients are examined using MRI. Our first specific alm is therefore to develop and test methods whereby we can also predict pathologic fractures from MRI. Vertebrae with simulated metastatic defects will be examined using both MRI and QCT, tested to failure using combined compressive and forward flexion loads and the data used to determine whether MRI can also be used to predict failure. Aim 2: The femur must resist a range of complex loads during the activities of daily living. We have developed methods that can be used to non-invasively predict failure of proximal femora with simulated metastatic defects using loads representing single-legged stance. We have pilot data that suggest the same measure can be used to predict failure for loads that represent stair climbing. Our second aim is to determine whether a simple bone density measurements can be used to predict proximal femur fractures for loads that represent other common activities of daily living. Aim 3: A proximal femur with a metastatic defect may be particularly likely to fracture when a patient engages in certain activities of daily living. Our third Specific Aim is therefore to determine the activities of daily living that are most likely to cause pathologic fracture in a femur with a metastatic defect. Aim 4: Finally, our fourth Specific Aim is to analyze clinical data for cancer patients and determine the number of patients required to test the sensitivity and specificity of potential fracture risk guidelines. The data will be used to justify a prospective clinical study of these fracture risk predictors in patients with osseous metastatic lesions in the hip and spine.