Mitochondria-Associated Ferroptosis and Diabetic Osteoporosis: Exploration of Traditional Chinese Medicine Treatment and Mechanisms of Action.

Diabetic osteoporosis (DOP) is a serious skeletal complication of diabetes mellitus. Its pathogenesis is complex, and its clinical prevention and treatment face significant challenges. In recent years, ferroptosis - particularly mitochondria-associated ferroptosis, which is closely linked to mitochondrial dysfunction - has been identified as a key mechanism underlying osteoblast injury in DOP. A chronic high-glucose environment can induce mitochondrial oxidative stress, iron metabolic dysregulation, and a lipid peroxidation cascade, leading to failure of the antioxidant systems (e.g., the GPX4 and Nrf2 pathways) and ultimately resulting in ferroptosis of osteoblasts and disruption of bone homeostasis. Traditional Chinese medicine (TCM) offers the advantages of multi-target and holistic regulation in the prevention of DOP. Its therapeutic principle of "tonifying the kidney and replenishing essence, activating blood circulation and removing blood stasis" is highly consistent with modern strategies aimed at intervening in mitochondrial ferroptosis. This review examines the central role of mitochondrial ferroptosis in DOP and elucidates the pathogenesis of DOP from a modern biological perspective. Furthermore, it summarizes experimental evidence demonstrating that astragaloside IV, ginsenoside Rg1, puerarin, icariin, curcumin, and Zuogui Pills can effectively inhibit mitochondrial ferroptosis by activating the Nrf2/GPX4 antioxidant axis, improving mitochondrial function, and regulating iron homeostasis, thereby conferring bone-protective effects. In conclusion, targeting mitochondria-associated ferroptosis represents a promising therapeutic strategy for DOP, and TCM interventions that modulate this pathway offer a novel direction for drug development and clinical management.