The mechanical properties of demineralized bovine cortical femur bone were investigated by cyclic loading-unloading compression in three anatomical directions (longitudinal, radial, transverse) within the physiological strain range. The loading responses in the radial and transverse directions were nearly linear up to 2% strain, while the response in longitudinal direction was strongly non-linear in that range. The unloading responses were non-linear for each anatomical direction, giving rise to overall loading-unloading hysteresis and cyclic dissipation of energy. The mechanical properties were observed to be anisotropic: the radial direction was found to be the most energy dissipative, while the longitudinal direction appeared to be the stiffest bone direction. The cyclic loading mostly affects the bone stiffness in the radial and transverse directions, while the longitudinal direction was found to be the least affected. These anisotropic properties can be attributed to the differences in collagen fibers alignment and different microstructural architecture in three different anatomical bone directions.