Programmed Cell Death in Steroid-Induced Osteonecrosis of the Femoral Head: Molecular Mechanisms and Potential Traditional Chinese Medicine Interventions

Steroid-induced osteonecrosis of the femoral head (SONFH) remains a challenging orthopedic condition with an incompletely understood pathogenesis and limited therapeutic options. This review synthesizes current knowledge regarding the involvement of programmed cell death (PCD) pathways—including autophagy, pyroptosis, apoptosis, ferroptosis, and cuproptosis—in SONFH, and summarizes the regulatory effects of traditional Chinese medicine (TCM) interventions. A comprehensive literature search was conducted in the PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) databases up to July 2026. The search terms included “steroid-induced osteonecrosis of the femoral head,” “programmed cell death,” “autophagy,” “pyroptosis,” “apoptosis,” “ferroptosis,” “cuproptosis,” “traditional Chinese medicine,” “TCM monomers,” and “TCM compound formulas.” No language restrictions were applied. Studies were eligible if they investigated PCD mechanisms in SONFH or the effects of TCM interventions on PCD in SONFH. This is a narrative review and does not follow the PRISMA guidelines. Glucocorticoid-induced apoptosis of osteoblasts, osteocytes, and vascular endothelial cells is a well-established mechanism of bone injury. Autophagy exerts context-dependent dual effects, with both excessive activation and insufficient activity contributing to cell death. Pyroptosis, ferroptosis, and cuproptosis have emerged as additional PCD pathways closely linked to disease progression. TCM monomers and compound formulas have shown potential in regulating these pathways through multi-target mechanisms. PCD plays a central role in SONFH pathogenesis, and TCM offers promising intervention strategies by modulating these pathways. However, current evidence is predominantly preclinical, and standardized TCM-based protocols are needed to facilitate clinical translation.