| [Objective] To study the influence of simvastatin on osseointegration around Titanium Implants and investigate the mechanism of the effect of simvastatin on osseointegration of the Titanium Implants by established animal model of osteoporosis rats.[Material and Methods] Thirty-six female SD rats(3-month-old) were divided into twelve block according homogeneity principle and then the three rats of each block were divided into three groups randomly , 12 rats in each group. They included a sham-operated group(Sham group), an ovariectomized group(OVX group) and an ovariectomized add simvastatin therapy group(OVX+Simv group). After the animal models of osteoporosis were established, pour titanium screw implants were placed in the proximal metaphyses of both tibiae of the rats. simvastatin was given orally in the OVX+Simv group and normal saline was given to the rats of the other two groups. Four rats from each group were killed at 4,8 and 12 weeks after implantation surgery respectively。The alveolar bone,fumer and the implanted tibiae were got。alveolar bone and fumer were collected to examine change of bone mineral density (BMD), The implant tibiae were taken out to prepare undecalcified grinding slice. The grinding slice were examined histologically and bone histomorphometric parameters were measured to quantify the changes of new bone around titanium implants. The results were statistically analyzed by General Linear Modle GLM univariate. Date were reported as mean±standard deviation at a significance level of P<0．05．[Results] establishment of Osteoporotic modle : At the 12th week after ovariotomy surgery, the weight of rats increased significantly in OVX group and OVX+Simv group compared with Sham group(P<0．01) , while there were no significant difference of weight between the OVX group and the OVX+Simv (P > 0．05) . Meanwhile, The BMD of the rats in Sham group increased significantly compared with OVX group and OVX+Simv group,but there were no significant difference of the BMD between OVX group and OVX+Simv group (P > 0．05) . Bone Mineral Density:At the 4th week after implant surgery, in the Sham groups, the BMD of both alveolar bone and fumer were higher than others group, while the OVX group and OVX+Simv group have no significant difference. At the 8th week after implant surgery, the BMD in the Sham groups were higher than the OVX group and OVX+Simv group, the OVX+Simv group were higher than the OVX group. At the 12th week after implant surgery, the BMD in the OVX group were much lower than others group, while the Sham group and OVX+Simv group have no significant difference. the BMD of alveolar bone and fumer have high positive correlationship. Fluorescence observation: At the 4th week after implant surgery, i n the Sham groups, the fluorescence intensity was high, and both the single and double fluorochrome labelled lines could easily be observed;The OVX+Simv group showed similar to the Sham group,but the fluorescent was more widespread;While in OVX group, the fluorescence intensity was low. The fluorochrome labelled surfaces and the width of fluorochrome labelled lines were less compared with above two groups.At the 8th week after implant surgery, the Fluorescence observation of each group were similar to they showed at the 4th week after implant surgery. At the 12th week after implant surgery, The fluorescence intensity in Sham group decreased significantly, the width of fluorescent lines also decreased obviously;While in the OVX group,the fluorescence intensity only slightly decreased,but greater than those in Sham group. The OVX+Simv group have similar change to the OVX group,but the fluorescence intensity was higher and the fluorescent was more widespread. Histological findings after implantation: At the 4th week after implant surgery, in the Sham group,the new bone was mainly formed by woven bone which was in direct contact with implants, the combinded bone lamella was thicker, Haversian system can be seen, the density of trabecular bone was greater;In the OVX group, the combinded bone lamella was thin and was not contacted with implants somewhere. The trabecular bone volume was lower; In the OVX+Simv group, the interface bone lamella were thicker and the contact of new bone around implant were greater than OVX group, the trabeculars pattern were rarefaction.At the 8th week after implant surgery, the Sham group combinded bone lamella was thicker and the surface of it was smooth, The woven bone was substituted by lamella-like new bone; In the OVX group,the combinded bone lamella was thin;In the OVX+Simv group,the combinded bone lamella was thicker and the woven bone was substituted by lamella-like new bone also, the density of trabecular bone were greater than that of 4th week after implant surgery. At the 12th week after implant surgery,The bone around implant have no significant change in Sham group; In the OVX group , the combinded bone lamella were constructed by lamella-like bone,but thinner than others group yet;the density of trabecular bone and contact of new bone around implants in OVX+Simv group were similar to Sham group. Bone histomorphometrie analysis :At the 4th week after implant surgery, Trabercular Area (Tb·Ar%),Trabercular Width (Tb·Wi),Combinded Bone Lamella Width (CBLW),osteointegration index (OI %) in Sham group were significantly increased compared with OVX group (P<0．01) ; Tb·Ar%,Tb·Wi,CBLWinSham group were significantly increased compared with OVX+Simv group(P<0．01) , But OI% was no significant compared with OVX+Simv group(P>0．05) ; Tb·Ar% in OVX+Simv group was no significant compared with OVX group (P>0．05) , Tb·Ar%, Tb·Wi, CBLW in OVX+Simv group were significantly increased compared with OVX group(P<0．01) . At the 8th week after implant surgery, Tb·Ar%,Tb·Wi,CBLW,OI% in Sham group were significantly increased compared with OVX group (P<0．01) ; Tb·Wi,OI% in Sham group were no significant compared with OVX+Simv group (P >0．05) , Tb·Ar%,CBLW in Sham group was significantly increased compared with OVX+Simv group (P<0．05) ; All the histomorphometric parameters in OVX+Simv group were significantly increased compared with OVX group (P<0．05)。At the 12th week after implant surgery, Tb·Ar%,Tb·Wi,CBLW,in Sham group were significantly increased compared with OVX group (P<0．01) , OI% in Sham group was no significant compared with OVX group; Tb·Ar%,Tb·Wi,CBLW,OI% in Sham group were no significant compared with OVX+Simv group(P>0．05) . All the histomorphometric parameters in OVX+Simv group except OI% were significantly increased compared with OVX group (P<0．01) .[Conclusion] 1．Ovariectomy is a good method to establish osteoporotic model of rats simulate to clinical osteoporosis. 2．Osteoporosis can block osseointegration of titanium implants and decrease the support of bone to titanium implants. 3．The administration of Simvastatin can promote osseointegration of titanium implant in osteoporosis and increase the mass of bone around implant. 4．The BMD of alveolar bone and skeletal bone were high positive correlation.
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