Bone has a complex hierarchical microstructure that spans from the nanoscale of the collagen molecules to the macroscopic physiological scale. In order to assess bone's risk of fracture with issues such as aging, disease, or irradiation it is critical to have a clear mechanistic framework which analyzes bone's mation and fracture behavior at each structurally significant length scale. In this context, this present study seeks to characterize the fracture properties of bone by applying a hierarchical approach. Accordingly, this study utilizes x-ray microtomography from synchrotron radiation in order to identify the crack resistant extrinsic mechanisms in different types of cortical bone. It was found that bone, which is a highly anisotropic material, displays toughening through crack deflection, out of plane twist and crack bridging. Next this study utilizes in situ tensile tests with X-ray scattering to investigate the submicron deformation in bone;​ at this length scale bone toughens intrinsically through plasticity mechanisms such as fibrillar sliding. Lastly, this study uses this mechanistic framework to evaluate the effects of irradiation on the fracture properties of bone. Here it was found that bone exposed to high doses of irradiation, greater than 70 KGy (Gy=J/Kg), leads to a severe progressive dose dependent degradation in strength, ductility, and toughness which is attributed to a change in the crack path (extrinsic effect) and a degradation of the collagen integrity from altered collagen cross-link (intrinsic effect). Overall, the goal of this work is to outline a framework that can be applied to future studies investigating the effects of disease and aging on bone.