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Scanning electron microscope (SEM) was used to observe and analyze the microstructure of the cross section of cortical bone. The observation results illustrated that the cortical bone is composed of cylindrical osteons and interstitial bone between osteons, and the osteon are unevenly distributed. Based on the microstructure characteristics of cortical bone, three types of cortical bone mesoscopic analysis models were established. Then, the extended finite element method (X-FEM) was used to simulate the microcrack propagation process in bone. The simulate results show that the crack initiation strain of the two-phase model is 19.1% larger than that of the single-phase model, and the three-phase model is 57.8% larger than that of the two-phase model, which demonstrated that the osteons and cement line can significantly enhance the crack initiation strain of bone. In addition, under the same boundary conditions, the model with cement line can effectively change the propagation path of microcrack and prevent the propagation of crack. Therefore, the cement lines in cortical bone can effectively increase the fracture resistance of bone and enhance the fracture toughness of cortical bone.