• Dexamethasone induces mitochondrial dysfunction in osteoblasts, characterized by structural damage, decreased membrane potential, and reduced ATP production.
• Dexamethasone triggers oxidative stress, increasing mitochondrial superoxide and total reactive oxygen species while depleting glutathione.
• Dexamethasone promotes apoptosis by upregulating Bax and downregulating Bcl-2, and enhances autophagy as indicated by increased LC3B-II/I ratio and decreased p62.
• Mitochondrial dysfunction and oxidative stress synergistically regulate apoptosis and autophagy, impairing osteoblast function and contributing to steroid-induced osteonecrosis of the femoral head.