Involvement of Nerve Growth Factor in the Reparative Reaction to Osteonecrotic Lesions

The reparative zone in femoral head osteonecrosis is pivotal for repair; however, the repair response mechanism remains poorly understood. Although neurotrophic nerve growth factor significantly contributes to bone formation in fatigue fractures and ectopic ossification, the relationship between nerve growth factor and the repair response to osteonecrosis remains unexplored. We aimed to elucidate the role of nerve growth factor in osteonecrosis repair. Twenty-seven wholly resected femoral heads diagnosed with Japanese Investigation Committee Stage 3 femoral head osteonecrosis, excluding those with severe collapse, were analyzed. Histopathological diagnosis confirmed the presence of necrotic, reparative, and viable zones in all examined femoral heads. Quantitative evaluation of immunohistological staining, including nerve growth factor, vascular endothelial growth factor, osteocalcin, CD31, and TUBB3, was conducted in each zone. Additionally, micro-computed tomography was used to measure the trabecular bone microstructure in the reparative zone. Nerve growth factor expression was detected in all 27 femoral heads with osteonecrosis, exhibiting a significantly higher prevalence in the reparative zone than in other regions (p < 0.0001). Nerve growth factor was predominantly distributed on the necrotic side within the reparative zone, rather than the viable side. In the reparative zone, nerve growth factor expression was positively correlated with bone formation parameters derived from micro-computed tomography images. Vascular endothelial growth factor, osteocalcin, CD31(+) vascular endothelial cells, and TUBB3(+) nerve cells also significantly increased in the reparative zone. In conclusion, nerve growth factor expression was consistent across all femoral heads with osteonecrosis and may play a role in reparative reaction to osteonecrotic lesions.