A novel mouse trauma model for osteonecrosis of the femoral head

Osteonecrosis of the femoral head (ONFH) is a devastating condition characterized by the disruption of vascular supply, progressive bone degeneration, and eventual collapse of the femoral head. While corticosteroid- and alcohol-induced ONFH models are well established, a reliable trauma-induced ONFH model in mice has not been previously described. However, traumatic ONFH is commonly seen in clinical settings-such as following FN fracture, dislocation, or hip trauma-but remains poorly understood at the mechanistic level due to a lack of appropriate small-animal models. To address this gap, we established and validated a novel, reproducible trauma-induced ONFH model in C57BL/6 mice. Eight-week-old male C57BL/6 mice (n = 45) underwent surgical disruption in the left hip, while the right hip served as an internal control. Mice were sacrificed 1-12 wk post-surgery at 2-wk intervals. Gross morphological changes, trabecular bone loss, and histological features, such as marrow adiposity, empty osteocyte lacunae, and myeloid cell infiltration, were observed over time, indicating ONFH development. Histological analyses demonstrated decreased glycosaminoglycan content, suggesting cartilage degeneration, and increased empty osteocyte lacunae in the operated femoral heads. Immunofluorescence analyses demonstrated fragmentation of CD31- and endomucsin (EMCN)-positive vessels, vascular invasion into cartilage and growth plate, and dynamic changes in vascular architecture accompanying trabecular bone degeneration. The knowledge gained from this reproducible trauma-induced ONFH model, which mimics key features of human disease, provides a valuable platform for mechanistic studies of vascular dysfunction, cartilage degeneration, and bone remodeling, and may facilitate the development of early diagnostic markers and novel therapeutic strategies for osteonecrosis.