The present study intends to develop a fatigue damage model to assess the fatigue response of human cortical bone by incorporating stiffness degradation of bone materials as the number of loading cycles progresses. The proposed fatigue damage model is defined based on mechanical properties and biological parameters of human cortical bone subjected to repeated loads. Stiffness loss in bone and bone constituents was used as a damage index to model the response of fatigue damage. The proposed damage model in this thesis considered bone as a natural composite material consisting of Haversian osteons (fibres) embedded in interstitial bone (matrix) and separated by weak cement-line intrfaces.Predicted fatigue damage results were found in good agreement with many experimentally obtained damage results of human cortical bone. The proposed damage equation also showed a higher degree of success in damage assessment of cortical bone samples tested by different laboratories as compared to other earlier developed damage models.The proposed damage model, for the first time, successfully correlated the mechanical and histological properties of human cortical bone with damage accumulation of bone constituents. These parameters represent mechanical and histological properties of cortical bone specimens such as osteon volume fraction, donor age, cyclic stress magnitude, secant modulus of osteons, cement line interfacial strength and other bone constituent mechanical properties.A computer program was also developed to assess fatigue damage of cortical bone by the proposed damage model and evaluate the proposed model with experimental data extracted from the literature.