【Animal modeling】-Effect of simvastatin combined with risedronate on dexamethasone-induced bone loss in rats

  Objective To analyze the effects of simvastatin and risedronate sodium alone and in combination on dexamethasone-induced osteoporosis in rats.

  Methods Female 3-month-old SD rats were used in this study, and they were divided into five groups (8 rats in each group): control group, osteoporosis model group, simvastatin group, risedronate sodium group and combination drug group. Except for the control group, the other groups were given subcutaneous injection of dexamethasone (2.5 mg, twice a week), and the drug intervention group was given simvastatin 5 mg/kg, risedronate sodium 0.1 mg/kg and both The combined intervention was performed once a day, and all rats were sacrificed after 8 weeks to obtain materials. The left femur was taken to detect its bone mineral density, and the maximum load was analyzed by three-point bending test. The right femur was decalcified and embedded in paraffin, and the expression of OPG and RANKL was detected by immunohistochemical staining. The RNA of the right tibia was extracted to detect the expression of osteoprotegerin (OPG) and osteoclast differentiation factor (RANKL).

  Results (1) BMD: the model group (0.207±0.02) g/cm² was significantly lower than the other groups, the simvastatin group (0.226±0.023) g/cm², the risedronate sodium group (0.237±0.021) g/cm² cm² was significantly lower than the control group (0.282±0.013) g/cm² combined treatment group (0.257±0.012) g/cm² (P<0.05). (2) Biomechanics: Maximum load: The model group (90.2±7.1) was significantly lower than the control group and the combination group (P<0.05). (3) micro-CT: trabecular bone number (Tb.N) and trabecular bone volume fraction (BV/TV) in the model group were significantly lower than those in the other four groups, and the trabecular bone separation degree (Tb.Sp) in the model group were significantly higher than those in the other four groups. In 4 groups (P<0.05), the BV/TV of simvastatin group (21.6±2.8) and risedronate sodium group (21.9±2.6) were significantly lower than those of control group (29.5±2.7) and combination group (25.3±2.9) ), TbSp was significantly higher than that in the control group (P<0.05). (4) Immunohistochemical staining: OPG: model group, risedronate sodium group, combined drug group were significantly lower than those in the control group (P<0.05), and the C group and E group were significantly higher than the model group (P<0.05) . The expression of RANKL in the model group, simvastatin group, risedronate sodium group, and combination group was significantly higher than that in the control group (P<0.05), and the expression in group E was significantly lower than that in the model group (P<0.05). (5) PCR: The expression of OPG in the model group (0.74±0.17) was significantly lower than that in the control group (1.00±0.16) and the simvastatin group (1.27±0.19) (P<0.05); the expression of RNAKL in the model group was significantly higher than that in the other groups group (P<0.05), the simva│statin group (1.31±0.16) was significantly higher than the control group (1.00±0.18).

  Conclusion Dexamethasone can induce the establishment of a rat model of bone loss, and the combined treatment of simvastatin and risedronate sodium can partially prevent the bone loss and bone quality decline in this model, and the effect is better than that of single medication.