Bone has a complex hierarchical structure, resulting in elevated strength and toughness compared to a homogeneous material of the same composition. In this project, we investigated the association of material parameters across the bone hierarchical structure with the initiation, propagation and fracture toughness for mouse models of bone pathology. Initiation toughness is affected by material parameters such as the amount and the quality of collagen molecules and size of mineral particles at the nanoscale. Propagation and fracture toughness are also influenced by the amount of collagen in bone, mineral size and the degree of alignment and the AGE cross-links. We investigated the hierarchical association of material parameters in bone and showed that the energy dissipation capacity at the nanoscale, which arises from the amount and the quality of collagen molecules, size of mineral particles and collagen cross-links have the most dominant effect on mouse bone toughness.