Effects of Estrogen on Fracture Healing in Mice

Background: Fracture healing is a complex and sequential process. One important step in fracture healing is callus remodeling. Estrogen deficiency is known to increase osteoclast bone resorption, whereas estrogen replacement can reverse this effect. Therefore, the aim of our study was to analyze whether estrogen deficiency and estrogen treatment, respectively, would affect callus remodeling in the fracture healing process. Methods: Standardized femoral fractures were produced in 10 weeks old C57BL/6 mice using a guillotine-like fracture device. Mice were separated into three groups. The first group obtained a continuous administration of estrogen. Ovariectomy (OVX) was performed in the second group to generate an estrogen-deficiency model. The control group obtained no special treatment. At different stages of fracture healing, contact X-ray, micro-computed tomography, histologic, and biomechanical analyses were performed. Results: We observed that, in early stages of fracture healing, OVX leads to an impaired periosteal callus formation. When compared with the control group, chondrocytes area was decreased, and the subsequent mineralization was less distinctive. In the late stage of fracture healing, the OVX mice showed a thin and porous cortex. In sharp contrast, estrogen treatment led to an enhanced fracture healing. Chondrocyte areas were larger, callus mineralization was increased, and the neocortex was thicker. Biomechanical testing confirmed the beneficial effects of estrogen on restoration of biomechanical competence. Conclusion: These results indicate that estrogen seems to be an important factor in all stages of fracture healing. The application of estrogens enhances fracture healing of long bones at least in mice.