Abstract: BACKGROUND:  Iron is an essential metal for the human body. Its storage and transportation mechanism is complex, and various factors are involved in the balance of iron metabolism. When the metabolic balance is destroyed, iron overload in the body will produce a large number of reactive oxygen species and cytotoxicity and even lead to ferroptosis, resulting in functional dysfunction of tissues and organs. However, the current research on iron overload mainly focuses on cardiovascular, nervous system and tumor diseases, while the research on the imbalance of bone homeostasis caused by iron overload and its mechanism in bone diseases is still limited.
OBJECTIVE: To review the recent studies on iron overload in bone diseases and provides new ideas for the treatment of bone diseases by reviewing the latest findings of iron overload in bone diseases.
METHODS: The search terms “iron, iron overload, ferroptosis, osteoporosis, osteoarthritis, osteosarcoma, bone related diseases” in Chinese and English were used for the retrieval of literature published from January 1978 to January 2022 in CNKI, WanFang Database, PubMed, and Web of Science, respectively. A total of 1 085 articles were initially retrieved. According to the inclusion criteria, 79 articles were included for review.
RESULTS AND CONCLUSION: Ferroptosis caused by iron overload has great potential in the treatment of bone diseases, but there are some limitations such as lack of clinical application data and lack of clinical trials. Research on ferroptosis caused by iron overload focuses on the enzyme binding to iron to produce reactive oxygen species and irons that directly participate in Fenton reaction to mediate reactive oxygen species accumulation. Ferroptosis, as an independent form of cell death, offers a new approach to treating these diseases, as well as the possibility of combining existing treatment options and helping to address drug resistance in some diseases. Iron overload is involved in the development of osteoporosis by inhibiting the activity and function of osteoblasts and promoting the differentiation and activation of osteoclasts. Iron overload accelerates the progression of osteoarthritis and promotes chondrocyte apoptosis and matrix degradation. Iron overload can induce ferroptosis, apoptosis and autophagy of osteosarcoma cells and inhibit their invasion ability. Studies on the mechanism of ferroptosis caused by iron overload provide a new target and direction for the treatment of bone diseases such as osteoporosis, osteoarthritis, and osteosarcoma.

Key words: iron overload, ferroptosis, osteoporosis, osteoarthritis, osteosarcoma, bone diseases