Local single administration of simvastatin exerts positive effect on the early titanium screws fixation in an osteoporosis rat model

Abstract

Objective To evaluate the effect of locally applied single dose of simvastatin in the femurs of osteoporotic rats on the initial stability of titanium screws inserted into distal femurs,and to explore the mechanism related to the effect.Methods Twenty-four female 3-month-old SD rats were ovariectomized (OVX) to induce osteoporosis.12 weeks later,the animals were randomly divided into three groups with 8 in each.After the titanium alloy screw was implanted into the right femoral condyle,simvastatin 5 mg,l0 mg and a blank PBS buffer were injected into the medullary cavity.Four weeks after the implantation combined with simvastatin or vehicle injection,femurs with implants were evaluated with dual-energy X-ray absorptiometry,micro-computed tomography,scanning electron microscopy,quantitative analysis of screw around bone microstructure was operated.Observe the bone tissue structure around the bolt by scanning electron microscopy and toluidine blue staining.Measure the maximum load by the screw press and observe the expression of BMP-2 by immunohistochemical staining.Results Compared with the control group,simvastatin doses of 5 and 10 mg caused a significant increase in BMD (201±23.3,207.9±23.5 vs.170.8±13.8 mg/cm2),and significantly improve osseointegration (51.4％±3.0％,52.6％±4.1％ vs.27.3％±4.9％),peri-implant microarchitecture,and thus leading to enhanced early mechanical fixation of titanium implants (161.5±9.4,161.9±11.4 vs.145.7±9.6 N) in the OVX rats.The osteointegration effect may result from the high expression of BMP-2.Conclusion This study showed that a single local injection of simvastatin in osteoporotic bone of OVX rats could promote osseointegration implant surrounding and enhance the stability of internal fixation.The mechanism of action is correlated to the high expression of BMP-2 promoted by local injection of simvastatin. Key words: Osteoporosis; Fracture fixation, internal; Simvastatin; Osseointegration