The risk of undergoing a fracture due to trauma may be increased by previous damage, i.e. nano- and micro-cracks initiated and accumulated under repeated physiological loading conditions. Accordingly, this research aimed at exploring the loading mode dependent damage accumulation in bone tissue and its role in femoral fracture risk. An experimental program was designed and launched to visualize and quantify the damage interaction mechanisms along different loading modes. Fluorescence microscopy and high-resolution synchrotron computer tomography protocols were tested to examine the morphology of nano- and micro-cracks in tension, compression and shear of bone tissue. A constitutive model including plasticity and damage that accounts for distinct damage in tension and compression as well as kinematic hardening was formulated and successfully implemented in a mathematical programming environment.