Pathologic fracture is a significant risk for patients afflicted with metastatic or benign skeletal tumors. The quandary for physicians who treat these patients is that after making the diagnosis they must try to predict the load bearing capacity of the involved bone and the fracture risk from images seen in radiological examinations. Since bone fails at a relatively constant strain independent of density we demonstrate that using a mechanics of materials approach that the cross-sectional structural properties of the bone most affected by the lytic defect governs the load bearing capacity of the entire bone.Homogeneous cylindrical cores of trabecular bone were harvested from the vertebral bodies of whale spines, and prepared with circular or slotted through-hole defects of varying sizes to simulate lytic skeletal tumors. Each specimen was imaged using quantitative computed tomography (CT), dual energy X-ray absorptiometry (DXA), and magnetic resonance imaging (MRI) to obtain data for calculating cross-sectional structural properties: axial, flexural, and torsional rigidity. The specimens were then divided into groups uniformly distributed with respect to defect sizes and shapes, and subjected to uniaxial tension, four-point bending or torsion until failure.A strong positive relationship was found between measured tensile yield loads, bending, and torsional yield moments vs. axial, flexural and torsional structural rigidities respectively, calculated from QCT, DXA, and MRI data [QCT: tension r' = 0.951, bending r' = 0.909, torsion 9 = 0.914 ( p < 0.001); DXA: tension t2 = 0.926, bending r2 = 0.841, torsion rZ = 0.916 (p < 0.001); MRI: tension Y' = 0.916; bending r' = 0.856, torsion r2 = 0.852 ( p < 0.00l)l.For cylindrical cores of trabecular bone with simulated lytic defects, the load bearing capacity of the entire core was directly proportional to the axial, bending, or torsional rigidity at the weakest cross-section through the core containing the defect. Therefore structural rigidity analysis of cross-sectional geometric data measured non-invasively by QCT, DXA, and MRI of bones containing lytic defects may be used to predict the load bearing capacity of the involved bone and the relative fracture risk in vivo.