Knee osteoarthritis(KOA)is a common musculoskeletal disease,and ferroptosis is a new type of programmed cell death involving iron ions.This paper summarized the relationship between the pathological changes of ferroptosis and the onset of KOA,and reviewed the progress of traditional Chinese medicine(TCM)intervention in KOA based on the pathological changes of ferroptosis.The pathological changes of ferroptosis are mainly related to the imbalance of amino acid antioxidant system,iron metabolism disorder and lipid peroxide accumulation.The cystine/glutamate antiporter(System XC-),glutathione(GSH)and glutathione peroxidase 4(GPX4)are the core targets for regulating ferroptosis,involving the main signaling pathways for studying the TCM intervention of KOA via ferroptosis.Single herbs such as Drynariae Rhizoma,Scutellariae Barbatae Herba,Epimedii Folium,Astragali Radix,Ligustri Lucidi Fructus,and Achyranthis Bidentatae Radix,and multi-herb formulae such as Duhuo Jisheng Decoction and Yougui Pills,can inhibit the ferroptosis of chondrocytes through multiple targets and multiple pathways,thus treating KOA.The research of the TCM intervention on the ferroptosis of chondrocytes and its associated signaling pathways can provides a novel approach for expanding the TCM therapy of KOA.

ObjectiveTo explore the therapeutic mechanism of Bushen Huoxue prescription from the perspective of bone metabolism by observing the clinical efficacy of this prescription in treating femoral head necrosis （ONFH， syndrome of liver and kidney deficiency） and its influences on bone metabolism indexes： N-terminal propeptide （PINP） and β-collagen degradation product （β-CTX）. MethodSixty-six ONFH patients with the syndrome of liver and kidney deficiency in Zhengzhou Traditional Chinese Medicine Hospital of Orthopedics from December 2021 to September 2022 were selected. The patients were randomized into an experimental group and a control group by the parallel control method， with 33 patients in each group. The experimental group received Bushen Huoxue prescription orally， while the control group received Xianlinggubao Capsules orally， with a treatment cycle of 6 months. The visual analogue scale （VAS） score， Harris score， Association Research Circulation Osseous （ARCO） staging， imaging changes， quantitative scores of TCM symptoms， and serum levels of PINP and β-CTX were determined before and after treatment. The occurrence of adverse events and reactions was recorded. ResultThe total response rate in the experimental group was 83.87% （26/31）， which was higher than that （68.75%， 22/32） in the control group （Z=-2.096， P<0.05）. After treatment， the single and total scores of TCM symptoms， VAS score， and β-CTX level decreased in the two groups （P<0.05）. Moreover， the decreases in the scores of hip pain， lower limb mobility， soreness of waist and knees， and lower limb flaccidity， total score of TCM symptoms， VAS score， and β-CTX level in the experimental were larger than those in the control group （P<0.05）. After treatment， the imaging results showed no significant improvement in the two groups. The Harris score and PINP level in both groups increased after treatment （P<0.05）， and the increases were more obvious in the experimental group than in the control group （P<0.05）. No serious adverse event or adverse reaction appeared during the observation period. ConclusionBushen Huoxue prescription can relieve pain and TCM symptoms and improve the hip joint function in treating ONFH patients with the syndrome of liver and kidney deficiency. It can inhibit the development of ONFH， increase PINP， and decrease β-CTX. No obvious side effect appears during the clinical observation period， which shows that Bushen Huoxue prescription has good safety.