| Objective To verify the role of cuproptosis in the pathogenesis of diabetic osteoporosis (DOP) and to explore the mechanism by which Liuwei Dihuang pill regulates the SLC31A1/FDX1 axis and its protective effects on DOP. Methods Clinical research: Blood samples from DOP, osteoporosis (OP), and control patients were collected to detect serum copper levels, copper ceruloplasmin (Cp) levels, and bone tissue copper content. The relationship between copper homeostasis and DOP was analyzed Animal experiments: In this study, eighty mice were randomly divided into four groups: control group, model group, low-dose herbal formulation group, and high-dose herbal formulation group. After an 8-week intervention, the effects of the herbal formulation on blood glucose, body weight, food intake, and urine output in the mice were observed. Copper levels in mouse serum and bone tissue were detected using Elabscience legal method. Bone microstructure (BV/TV,Tb.Th,Tb.N) was examined using micro-CT. Bone structural changes were assessed using hematoxylin and Eosin staining and immunohistochemistry. Western blotting was used for the expression levels of cuproptosis-related proteins (PDHA1, DLD, DLAT) and the SLC31A1/FDX1 axis. Results Clinical research: Serum and bone tissue copper levels, as well as copper ceruloplasmin levels, were significantly higher in diabetic bone quality deficiency patients than in osteoporosis patients and healthy controls, suggesting a close relationship between copper metabolism and DOP. Animal experiments: Liuwei Dihuang pill effectively inhibited copper-induced apoptosis, improved bone microstructure and bone tissue organization, thereby exerting protective effects against diabetic bone quality deficiency. Conclusion Liuwei Dihuang pill regulates the SLC31A1/FDX1 axis by inhibiting cuproptosis, thereby improving bone microstructure and bone tissue organization, ultimately achieving its therapeutic effect on diabetic bone quality deficiency. |