The impact and mechanism of nerve injury on bone metabolism

With an increasing understanding of the mechanisms of fracture healing, it has been found that nerve injury plays a crucial role in the process, but the specific mechanism is yet to be completely revealed. To address this issue and provide novel insights for fracture treatment, we compiled this review. This review aims to study the impact of nerve injury on fracture healing, exploring the role of neurotrophic factors in the healing process. We first revisited the effects of the central nervous system (CNS) and the peripheral nervous system (PNS) on the skeletal system, and further explained the phenomenon of significantly accelerated fracture healing under nerve injury conditions. Then, from the perspective of neurotrophic factors, we delved into the physiological functions and mechanisms of neurotrophic factors, such as nerve growth factor (NGF), Neuropeptides (NPs), and Brain-derived neurotrophic factor (BDNF), in bone metabolism. These effects include direct actions on bone cells, improvement of local blood supply, regulation of bone growth factors, control of cellular signaling pathways, promotion of callus formation and bone regeneration, and synergistic or antagonistic effects with other endocrine factors, such as Sema3A and Transforming Growth Factor β (TGF-β). Finally, we discussed the treatments of fractures with nerve injuries and the future research directions in this review, suggesting that the relationship between nerve injury and fracture healing, as well as the role of nerve injury in other skeletal diseases.