The Effect Of Simvastatin On Bone Biomechanical Characteristics And BMP-2 And Smad1/5 Expression In Ovariectomized Rats

Objective To investigate the effect of Simvastain on the expression of BMP-2 and Smadl/5 and biomechanical characteristics of bone in rats with ovariectomy-induced osteoporosis, and thus elucidate the mechanism ofBMP-2,Smad1/5 in nosogenesis of osteoporosis and the regulating effect of simvastain.Methods 54 female SD rats were divided into three groups by randomized block design: Sham-operated group(SHAM), ovariectomized group(OVX)and Simvastatin ovariectomized rats group(OVX+SIM).8 weeks after ovariectomy and sham-operation, Simvastatin of 5mg'kg~-1·d~-1 were administered orally to OVX+SIM group and normal saline to the other two groups. Half of the rats were killed separately 4 weeks and 12 weeks after administration. The femur were extracted for three-point bending test to measure their maximal loading, flexibility loading, flexibility strain, maximal strain, coefficient of bending stiffness, coefficient of bending ductility. Expression of BMP-2 and Smad1/5 in metaphysis of tibia was detected by SABC method.Results 1,①4 weeks after administration, number of BMP-2 positive cells and BMP-2 gradation was higher in OVX+SIM group and SHAM group (P＜0.05 or P＜0.01).②12 weeks after administration, number of BMP-2/Smad1/5 positive cells and BMP-2/Smad1/5 gradation was higher in OVX+SIM group and SHAM group (P＜0.05 or P＜0.01).③Number of Smad1/5 positive cells and Smad1/5 gradation in OVX+SIM group was higher at 12 weeks after administration than 4 weeks(P＜0.01). 2,①4 weeks after administration, flexibility loading of femur in OVX+SIM group was lower than OVX group (P＜0.05), coefficient of bending ductility group was higher than OVX group (P＜0.01); maximal loading, maximal strain of femur in SHAM group was higher than OVX group(P＜0.05).②12 weeks after administration, The maxima loading,fracture energe,flexibility loading in OVX+SIM group was higher than OVX group(P＜0.05 or P＜0.01), The coefficient of bending ductility was lower than OVX group (P＜0.01); The maximal loading,fracture energy in SHAM group was higher than OVX group, in OVX+SIM group was higher than OVX group(P＜0.05 or P＜0.01).③The maximal loading,flexibility loading of OVX+SIM group, coefficient of bending ductility of OVX group was higher at 12 weeks after administration than 4 weeks (P＜0.01).Conclusion 1. Simvastain can improve ductility of femur in rats with ovariectomy-induced osteoporosis in the initial stage. Long time administration of Simvastain can promote osteogenesis and improve strength of femur in rats. 2. Hypo-expression of BMP-2 and Smad1/5 may be an important mechnism in nosogenesis of primary osteoporosis. Simvastain can up-regulate BMP-2 expression in bone, Long time administration can up-regulate Smad1/5 expression that may be an important mechanism of prevention and cure osteoporosis.