The Enhancement of Peri-implant Osteogenesis by Local Application of Statin

Objectives: Statins are widely-used medicine for hyperlipidemia patients. In addition to the cholesterol-lowering effect of statins, the stimulation of osteoblast activity and successive bone formation have recently been reported. In the present study we examined whether the local application of fluvastatin led to increase peri-implant bone volume, bone-implant contact, implant fixation strength and the pattern of gene expression in a rat tibial implant model. Methods: Ten-week-old Wistar rats received pure titanium implants in both tibiae with or without fluvastatin, administered with propylene glycol alginate (PGA) as a carrier. Rats were divided into control and 4 fluvastatin treatment groups. The animals were sacrificed at 1, 2 and 4 weeks after implantation, then peri-implant bone formation was assessed using histomorphometric procedures which included bone-implant contact (BIC), peri-implant osteoid volume (OV), mineralized bone volume (MBV), as well as the biomechanical analysis of the measurement of implant detachment force. Bone related gene expression in the new bone around the implant was also evaluated by quantitative RT-PCR. Statistical differences were determined by ANOVA and p<0.05 was considered significant. Results: At week 1, OV was significantly higher in highest-dose fluvastatin treatment group than the other groups. However, 2 weeks after the implantation in fluvastatin treatment groups, BIC, MBV and mechanical value were significantly higher than non-fluvastatin groups. There were same tendencies at week 4. The histomorphometric data showed good correlation between MBV and mechanical test value. Furthermore, in fluvastatin treatment groups, the expressions of BMP-2 and vascular endothelial growth factor (VEGF) mRNA, both of which may play crucial roles in peri-implant osteogenesis, were up-regulated. Conclusion: Locally-applied fluvastatin up-regulated both BMP-2 and VEGF around the implant. Both may play a role in the increase of implant fixation strength through the enhancement of early stage osteogenesis and mineralization.