Simvastatin enhances bone formation around titanium implants in rat tibiae

Abstract

Statins are cholesterol-lowering drugs that have been reported to promote bone formation. The purpose of this study was to investigate the effect of simvastatin on the enhancement of bone formation around titanium implants. Thirty-week-old female rats received pure titanium implants in both tibiae. The animals were intra-peritoneally administered 0, 0.125, 1, 5 or 10 mg kg(-1) of simvastatin daily. After 30 days, the animals were sacrificed, and specimens were prepared. The bone contact ratio of the implant, bone density in the medullary canal and percentage of cortical bone were obtained. Markers for bone turnover were also measured using sera collected at the time of euthanasia. In the medullary canal, a scanty amount of bone was observed in the 0, 0.125 and 1 mg kg(-1) groups. In contrast, in both the 5 and 10 mg kg(-1) groups, thicker bone trabeculae were abundant. Histometric observations showed that the bone contact ratio and the bone density of both groups were significantly greater than those of the other groups (anova, P < 0.01). However, no significant difference in the percentage of cortical bone was found between groups. Serum chemistry showed that statin increased bone formation markers and decreased bone resorption markers. In conclusion, although the dose equivalent to that used in human patients with hypercholesterolemia was not effective, a simvastatin dose of 5 mg kg(-1) or higher increased medullary bone formation around the titanium. In contrast, no effect of simvastatin on pre-existing cortical bone was indicated.

The effect of a single remote injection of statin-impregnated poly (lactic-co-glycolic acid) microspheres on osteogenesis around titanium implants in rat tibia

“…Several studies have shown positive effects of statins on the bone around implants after systemic administration [13] or local administration around the implants [14,25]. However, the former requires daily administration of a considerable amount of the statin, while the latter requires the establishment of a drug delivery system (DDS) with an adequate release profile of the statin that is free from contamination for the microtextured implant surface [15].…”

“…Taking their clinical use in relation to dental implant therapy into consideration, systemic administration of statins is less preferable. However, local administration of statins has some drawbacks, including the possibility of implant surface contamination by the statin-loaded carrier and the difficulty associated with local retention of the statin-loaded carrier because of the blood flow [15].…”

Local controlled release of simvastatin and PDGF from core/shell microspheres promotes bone regeneration in vivo

“…[20][21][22] Indeed, the effects of simvastatin on bone formation mainly relied on the way and dose of it administrated. The enhanced bone formation was only observed when oral administration of high-dose simvastatin at 20 mg per kg per day in rats.…”

Osteogenic effect of fluvastatin combined with biodegradable gelatin-hydrogel

“…Statins are widely used to lower cholesterol levels, which is an important factor in the treatment of hyperlipidemia and arteriosclerosis. Recently, another in vivo effect of statins has also attracted attention, with a number of studies finding that statins promote differentiation of osteoblasts produced by stimulation with bone morphogenetic protein-2 (BMP-2) [2][3][4][5][6][7] , indicating their potential in the development of new osteogenic drugs. Statins are expected as a new treatment modality for bone diseases instead of BMP-2, because they can be easily synthesized and be made 16,000-times cheaper to produce than BMP-2 2) .…”