【Animal Modeling】-Effect of Simvastatin Combined with Risedronate on Bone Loss Induced by Tail Suspension in Mice

  Objective: To investigate and compare the effects of simvastatin and risedronate sodium alone or in combination on dexamethasone-induced osteoporosis in mice.

  Methods: Thirty 12-week-old female C57BL6 mice were randomly divided into 5 groups (6 mice in each group): control group (group A), model group (group B), simvastatin group (group C), risedronic acid The sodium group (group D) and the combined intervention group (group E). Except for group A, the mouse osteoporosis model was established by tail suspension, and groups C, D, and E were given simvastatin (5 mg/(kg·d), respectively. )), risedronate sodium (1 mg/(kg·d)) and the combined intervention of the two, and sacrificed after 3 weeks to collect the materials. Micro-computed tomography (micro-CT) was used to detect the cancellous bone and cortex of the left proximal tibia. Bone mass and microstructural parameters, and three-point bending test were used to analyze the biomechanical properties of the left femur. RNA was extracted from the right tibia, and the expressions of OPG and RNAKL were detected by real-time fluorescent quantitative polymerase chain reaction (PCR), and the protein of the right femur was extracted. Western blot was used to detect the expression of OPG and RNAKL proteins.

  Results: Micro-CT:Bone trabecular volume ratio (BV/TV), trabecular bone number (Tb.N) in group B were significantly lower than those in other groups, and trabecular bone separation degree (Tb.Sp) was significantly higher than that in other groups. group (P<0.05), BV/TV in groups C and D were significantly lower than those in groups A and E, and Tb.Sp was significantly higher than that in group A (P<0.05); ② Biomechanics: the maximum load and elastic modulus in group B were significantly lower In groups A and E (P<0.05), there="" was="" no="" statistical="" difference="" between="" the="" other="" groups="" p="">0.05); ③ PCR detection results: the mRNA expression of OPG in groups C and E was significantly higher than that in group B (P<0.05); The expression of RNAKL in group B was significantly higher than that in group A (P<0.05); ④Western blot: the expression of OPG in group A was significantly higher than that in other groups (P<0.05), and group E was significantly higher than that in group B (P<0.05); The expression of RANKL in group A was significantly lower than that in other groups (P<0.05).

  Conclusion: Tail suspension can cause bone loss and bone quality decline in mice. Simvastatin and risedronate sodium combined can prevent bone loss and bone quality decline in this model, and the effect is better than single drug use.