• Cuproptosis is a newly identified copper-dependent cell death mechanism that disrupts the tricarboxylic acid cycle and induces oxidative stress, contributing to orthopedic disease pathogenesis.
• In osteoarthritis, excess copper promotes cartilage degradation via metal-regulatory transcription factor 1 and matrix metalloproteinases, while cuproptosis accelerates chondrocyte death.
• Cuproptosis disrupts bone homeostasis in osteoporosis by inhibiting osteoblast mineralization and promoting osteoclast differentiation, and in rheumatoid arthritis it exacerbates synovial inflammation.
• In osteosarcoma, high copper levels selectively kill tumor cells via ferredoxin 1, suggesting potential therapeutic applications for copper chelators or ion carriers.