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.
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