Table 1_Ferroptosis in osteoporosis: core mechanisms, cell-specific effects in bone remodelling, and therapeutic perspectives.docx

Ferroptosis, characterised by iron-dependent membrane phospholipid peroxidation and failure of anti-lipid-peroxidation defences, is emerging as a mechanistic link between oestrogen deficiency, glucolipotoxicity, glucocorticoid exposure, ageing, iron overload, and dysfunction of bone-remodelling cells.

This structured narrative review summarises iron homeostasis, lipid peroxidation, the System Xc⁻–GSH–GPX4 axis, ferritinophagy, mitochondrial metabolism, and non-GPX4-dependent defence systems, and compares the direction and strength of ferroptotic effects in osteoblasts, osteocytes, osteoclasts, and bone marrow mesenchymal stem cells. Current evidence indicates that ferroptosis in osteoblasts and bone marrow mesenchymal stem cells impairs osteogenic differentiation, matrix formation, and mineralisation; ferroptosis in osteocytes may further disrupt RANKL-related remodelling communication; whereas ferroptosis in osteoclasts may limit bone degradation under high-resorption conditions.