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Correspondence to: Dr. Masao Yoshinari, Division of Oral Implants Research, Oral Health Science Center, Tokyo Dental College, 1-2-2 Masago, Mihama, Chiba, 261-8502 Japan. Phone: +81-43-270-3536; Fax: +81-43-270-3780; E-mail:yosinari@tdc.ac.jp Abstract: The aim of this study was to examine the effects of orally administered simvastatin on the bone healing process in stroke-prone spontaneously hypertensive rat. Twenty-week-old female stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY) as a control were used. Bone defects were created in the femur of each rat. From the first day following surgery, half of each of the WKY and SHRSP rats were orally administered simvastatin (10 mg/kg/day). The WKY and SHRSP rats were each divided into experimental groups: 1) WKY simvastatin administration group (WKY-S), 2) WKY control group (WKY-C), 3) SHRSP simvastatin administration group (SHR-S), and 4) SHRSP control group (SHR-C). Experimental periods were set at 1, 2 and 4 weeks after surgery. After each experimental period, the animals were sacrificed. Radiographic analysis and histologic and histomorphometric examinations and immunohistochemical staining for BMP-2 were performed on the harvested samples. The data were statistically analyzed. The radiological analysis and histomorphometry parameters showed that the amount of newly formed bone in the trabecular bone area and cortical bone area increased significantly in the WKY-S group compared to that in the WKY-C group at 2 weeks. In addition, a positive immune reaction with BMP-2 was seen in osteoblasts located on the surface of newly formed bone and the outer periosteum around the marginal area of existing bone in WKY-S. In contrast, in both SHR-S and SHR-C 4 weeks after surgery, no differences in bone formation in the trabecular bone area and cortical bone area were recognized as being based on simvastatin administration. In addition, in the expression of BMP-2, there was no significant difference between the presence and absence of simvastatin administration. The oral administration of simvastatin under our experimental conditions had a facilitating effect on bone formation in WKY rats, whereas no effect was recognized in SHRSP rats.

Effects of Oral Administration of Simvastatin on Bone Formation in Senile Osteoporosis Rat