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Statins, inhibitors of 3-hydroxy-2-methyl-glutaryl coenzyme A reductase, were recently reported to promote the differentiation of osteoblasts produced by the stimulation of bone morphogenetic protein-2 (BMP2). The aim of this study was to investigate the osteogenic effect of a local administration of fluvastatin in senile osteoporosis model rats using a fluvastatin-gelatin complex. The gelatin-hydrogel was put into cylindrical titanium tubes 1.5 mm in diameter and 2.2 mm high. It was then crosslinked by ultraviolet irradiation, after which it was lyophilized. Subsequently, the carriers were placed in the fluvastatin solution (300 μM) for one day to bind the alkaline gelatin and acidic statin electrostatically (fluvastatin-gelatin complex; statin group). A control group consisted of the carriers immersed in sterilized water. Specimens of both the statin group and the control group were implanted into the femur of 15-week-old male senile osteoporosis model rats (SHRSP). Radiographic analysis, histologic examination, and immunohistochemical staining (BMP-2 and Runx2) were then performed. At 14 and 21 days, the bone volumes of the newly formed bone in the statin group was significantly higher compared to those of the control group (P<0.05). Histological observation showed that a high level of new bone formation was present in the statin group compared to that of the control group during all time periods. At 7 days, positive immune reactions with BMP-2 and Runx2 were seen in the statin group. The local administration of the fluvastatin-gelatin complex facilitated bone formation in senile osteoporosis model rats.

Osteogenic Effect of Local Administration of Fluvastatin using a Fluvastatin-gelatin Complex in Senile Osteoporosis Model Rat