Fractures of the proximal femur and distal radius, both regions where trabecular bone has a major load bearing function, are common. Such fractures are most often associated with abnormal stresses, such as shear with respect to the principal axes of the trabecular bone, as occurs during a fall. As such, understanding and ultimately predicting fracture risk in whole bones requires knowledge of the mechanical behavior of trabecular bone subjected to off-axis and multiaxial loading conditions at the material level. Bone mineral density and trabecular architecture have been the primary indices of trabecular bone quality, but the accumulation and propagation of microdamage may also be important. The level of microdamage in trabecular bone increases with age in vivo, and is further increased by anti-resorptive therapies currently used to treat osteoporosis. Microdamage accumulated during activities of daily living may serve as initiation sites for further damage propagation, particularly during off-axis loads, thereby increasing fracture risk. The effects of damage initiation and propagation on bone strength during off-axis loading has not been addressed, nor have the relative affects of microdamage burden and bone mineral density on trabecular bone strength. The overall goal of this proposal is to determine the effect of microdamage and damage propagation on the fracture toughness of trabecular bone subjected to on-axis and off-axis loads, thereby providing data necessary to predict the fracture susceptibility of whole bones. The hypotheses are 1) microcracks caused by normal loading have a self limiting length, but can be induced to grow further when the bone is subsequently subjected to off-axis loads; 2) crack propagation results in lower energy to failure for trabecular bone with pre-existing damage which would increase the fracture risk in the whole bone; and 3) the microdamage accumulation in on-axis loading and microcrack propagation during subsequent off-axis loading are greater in osteoporotic bone than in normal bone due to changes in the trabecular architecture. [unreadable] [unreadable]