Changes of substance P during fracture healing in ovariectomized mice

Neuropeptides may play an important role in the healing process of osteoporotic fractures. The objective of this study was to determine the role of substance P during osteoporotic fracture healing. One hundred ninety-two mice were randomized into ovariectomy (OVX) and control (CON) group (n=96, respectively). Femoral shaft fracture was created 3 weeks after OVX. Bone mineral density (BMD), micro-CT (microCT) analysis of fracture callus formation and mineralization, microCT analysis of fracture site neovascularization and biomechanical property as well as substance P levels were evaluated 1, 2, 4, and 8 weeks after fracture and compared with CON group. Following OVX-induced bone loss, fracture healing in OVX mice was significantly poorer than that in CON mice, with a significant decrease of substance P at the fracture site at all time points and with the level at early stage (1 and 2 weeks) higher than later stage (4 and 8 weeks). Impaired angiogenesis was also noted in OVX mice. No significant change of substance P level in serum was found between different groups or time points. In conclusion, fracture healing is inferior in OVX-induced bone loss and associated with a significant decrease of substance P. Substance P may play an important role during osteoporotic fracture healing.