| Objective To explore the effects of metformin combined with icaritin on the regulation of the Wnt/β-catenin signaling pathway in ovariectomized osteoporotic rats. Methods Rats were randomly divided into a control group, a model group, a raloxifene group, a metformin group, an icariin group, and a metformin+icariin group. Except for the control group, osteoporosis models were established in the other groups via ovariectomy. Serum bone metabolism markers were detected with ELISA. Microarchitecture of the tibia and bone mineral density (BMD) of the femur were analyzed with micro-CT. The biomechanical properties of the femur were assessed. Histomorphology of the femur was observed with HE staining. Expression of bone-associated proteins was detected with immunohistochemistry. Expression of Wnt/β-catenin pathway-related proteins in femoral tissue was detected with Western blotting. Results Compared with the control group, the model group showed significant deterioration of bone microarchitecture, characterized by sparse, fractured, and widened trabeculae, and enlarged lacunae. Expressions of TRACP5b, RANKL, and GSK-3β increased. BALP, OC, ALP, BMD, BV/TV, Tb.Th, Tb.N, OPG, Wnt3a, β-catenin, and LRP5/6 decreased (all P<0.05). Compared with the model group, all treatment groups (raloxifene, metformin, icariin, and the combination) reversed the aforementioned changes to varying degrees. Among them, the metformin and icariin combination treatment group showed the most significant effects. Conclusion Both metformin and icariin effectively ameliorate osteoporosis in ovariectomized rats. The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway. Their combination exhibits a synergistic effect and a better therapeutic outcome. |