• Ferroptosis, a novel iron-dependent cell death, is regulated by multiple signaling pathways and plays a crucial role in the pathogenesis of various orthopedic diseases.
• Dysregulation of iron metabolism, lipid peroxidation, and glutathione peroxidase 4 (GPX4) antioxidant defense are key molecular mechanisms underlying ferroptosis.
• Targeting signaling pathways that modulate ferroptosis offers a promising therapeutic strategy for orthopedic diseases such as osteoarthritis, spinal cord injury, and osteosarcoma.
• Current evidence is preliminary; further research is needed to fully elucidate the complex interplay between signaling pathways, ferroptosis, and orthopedic diseases.