Steroid-induced osteonecrosis of the femoral head (SONFH) is a terrible side effect of glucocorticoid therapy that causes problems with microvascular integrity, lipid metabolism, and a range of programmed cell death pathways. Recent studies have shown that autophagy can have different effects on osteoblasts and endothelial cells depending on the situation. These effects are mediated by the AMPK/mTOR, PINK1/Parkin, SIRT1/FoxO1, and PI3K/Akt/mTOR pathways. At the same time, apoptosis is caused by lowering Wnt/β-catenin, raising STAT1/caspase-3, and throwing off the balance of the OPG/RANKL/RANK axis. This makes it harder for bones to develop and makes osteoclasts work too hard. The growing contributions of ferroptosis (SLC7A11/GPX4 axis), necroptosis (RIPK1/RIPK3/MLKL), oxidative stress (NOX-JNK-c-Jun and Keap1-Nrf2), and pyroptosis (NLRP3/Caspase-1 and Caspase-4/5/11 inflammasomes) show that there is a complex network of cell death that makes SONFH worse. Preclinical treatments such as rapamycin, puerarin, lithium, NAC, necrostatin-1, luteolin, MCC950, antler peptides, and FGF23 inhibitors show promise in working together to change these pathways. A better knowledge of pathway crosstalk and dosage-dependent effects is the first step toward tailored, multi-modal therapeutics that can stop and treat SONFH. This review article looks at the signalling pathways that are currently thought to be involved in the pathogenesis of SONFH. Its goal is to help people better understand the disease and how to avoid and treat it more effectively.
NIU et al. (Thu,) studied this question.