| Objective To observe the protective effect of simvastatin (ST) on osteoporosis caused by ketogenic diet by analyzing the alleviation of microstructure of the femur, mechanical properties, and bone morphology in mice treated with simvastatin. Methods A total of 40 C57 mice were randomly divided into Sham group, ovariectomized group (OVX), ovariectomized with simvastatin treatment group (OVX + ST), ketogenic diet group (KD), and the ketogenic diet with simvastatin treatment group (KD + ST) group, with 8 mice in each group. The mice in OVX and OVX+ST groups were undergone ovariectomy and fed with standard diet. The mice in KD and KD+ST groups were fed with ketogenic diet in which the ratio of carbohydrate and fat was 1:3. The mice in the OVX + ST and KD + ST groups were administered with a dosage of 20mg/(kg?d) ST by gavage. Mice were sacrificed in 12 weeks. Serum ketone, glucose, calcium, and phosphorus were measured. The bone trabecular microstructure, biomechanical properties, and bone morphological changes were observed with micro CT scan, three-point bending tests, finite element analysis, and HE staining. Results The serum ketone level was significantly higher in the KD group (1.28 mmol/L) and the KD+ST group (1.48 mmol/L) than that in the Sham group (0.60 mmol/L). There were no significant differences in blood glucose, serum calcium, or phosphorus among these groups. Simvastatin treatment improved the cancellous bone number and the femoral compression stiffness in finite element analysis and the stiffness of three-point bending test in the KD+ST group. Compared with the KD group, the bone volume/tissue volume (BT/TV) in KD + ST group increased from 4.1% to 6.6%, the compression stiffness of finite element analysis increased from 35 N/mm to 161 N/mm, and the stiffness of three-point bending test increased from 44 N/mm to 60 N/mm. Histology analysis also showed that the distal femoral trabeculae in KD+ST group increased significantly than that in KD group. Conclusion Simvastatin alleviates bone loss in terms of the volume fraction of femoral cancellous bone, stiffness in three-point bending test, compression stiffness in finite element analysis, and trabeculae number in mice treated with ketogenic diet. |