Avascular necrosis of the femoral head (ANFH) is a type of osteonecrosis due to the cessation of blood supply, characterized by persistent local pain and collapse of the joint. The etiology of ANFH is multifaceted, and while its precise pathogenesis remains elusive, it is currently widely believed that the femoral head is highly dependent on the vascular system. A large number of studies have shown that vascular injury is the initial factor in the onset of ANFH. In this review, we briefly introduced the process of angiogenesis and the blood supply to the femoral head, with a focus on summarizing the existing research on promoting angiogenesis for the treatment of ANFH. We conclude that providing alternative pathways through angiogenesis to resolve the problem of the obstructed free flow of the blood is an important means of treating ANFH. Moreover, we also looked forward to the mechanism of endothelial metabolism, which has not yet been studied in femoral head necrosis models, providing potential strategies for more effective use of angiogenesis for the treatment of femoral head necrosis.

Steroid-induced osteonecrosis of the femoral head (SONFH) develops with early microvascular injury, but the systemic signals connecting glucocorticoid exposure to the femoral head remain incompletely defined. We examined whether intestinal epithelial Piezo1–TPH1–serotonin signaling contributes to this process. A glucocorticoid-induced SONFH model was studied in male C57BL/6 mice (8–10 weeks old), using pharmacological inhibition of peripheral serotonin synthesis, intestinal epithelial-specific Piezo1 deletion, micro-computed tomography, histological and vascular analyses, bone microvascular endothelial cell (BMEC) assays, and independent public transcriptomic datasets. Glucocorticoid exposure increased intestinal Piezo1 and TPH1 expression and circulating serotonin, together with loss of CD31^hiEMCN^hi type H vessels and trabecular deterioration. Inhibiting peripheral serotonin synthesis reduced vascular and structural injury. Intestinal epithelial Piezo1 deletion blunted TPH1 upregulation, preserved femoral-head microvasculature, and improved trabecular architecture. In BMECs, serotonin impaired tube formation and increased Bax-, Caspase-3-, and NLRP3-associated signaling; intestinal Piezo1 deletion reduced the corresponding injury signals in vivo. Intestinal epithelial Piezo1–TPH1–serotonin signaling therefore contributes to SONFH-associated microvascular injury in this model.