The influence of wet and dry apparent density, apparent and real percentage of mineral, organic and water contents on the tension and shear fracture toughness, i.e., the mode I and mode II strain energy release rate (G_Ic and G_IIc), respectively, was investigated for the human femur and the tibia. The results suggest that the water content, apparent density, and age were the best explanatory parameters for G_Ic and G_IIc. Both G_Ic and G_IIc significantly increase with increasing wet or dry apparent density. They also decrease with increasing water content;​ the decrease is nonsignificant for G_IIc in the femur only. Mineral and organic percentage did not change in the bone with age, while the apparent percentages did change. Compositional parameters altogether can explain 35%–59% of the variation in fracture toughness. We conclude that bone composition and density have an important influence on fracture resistance of the cortical bone.