The Effect of Simvastatin and 17 beta-Estradiol on Bone Mineral Density in Ooforectomized Rats

Objective: This study evaluated the effect of simvastatin at different doses on proximal femur and lumbal vertebra bone mineral density (BMD) in rats receiving estrogen replacement therapy. Materials and Methods: Fourty-eight Wistar Albino rats were divided into six groups, containing 8 rats each. Ooforectomy was performed to the rats of the first 5 groups, whereas the last group was sham operated. Four groups of ooforectomized rats were treated with 150 mu g/kg body weight/day 17 beta-estradiol and/or high (6 mg/kg body weight/day) or low (3 mg/kg body weight/day) dose simvastatin for 120 days by gavage. BMD of the proximal femur and lumbal vertebra were compared between groups at the end of the study. Results: Proximal femur BMD of ooforectomized rats decreased significantly (0.145 +/- 0.01 g/cm2 and 159 +/- 0.01 g/cm(2); p=0.001), whereas the lumbal vertebral bone loss did not reach statistical significance (0.161 +/- 0.01 g/cm(2) and 0.168 +/- 0.01 g/cm(2); p=0.471). 150 mu g/kg body weight/day 17 beta-estradiol treatment preserved proximal femur and lumbal vertebra BMD. The effect of 150 mu g/kg body weight/day 17 beta-estradiol and 3 mg/kg body weight/day on proximal femur and lumbal vertebra BMD were comparable. The estrogen and low dose simvastatin combination provided greatest protection of proximal femur (0.176 +/- 0.01 g/cm(2) ve 0.145 +/- 0.01 g/cm(2); p< 0.001) and lumbal vertebra (0.179 +/- 0.01 g/cm(2) and 0.161 +/- 0.01 g/cm(2); p=0.002) BMD, when compared with ooforectomized rats. Although, adding low or high dose simvastatin to estrogen thearpy did increase or decrease proximal femur and lumbal vertebra BMD, this effect did not reach statistical significance. Discussion: In rats, prophylactic administration of high dose oral simvastatin treatment alone prevents ooforectomyinduced bone loss to comparable degree as oral estrogen replacement therapy. Estrogen and low simvastatin combination increased the BMD most effectively. Adding higher dose of simvastatin to estrogen has no additional beneficial effect on BMD.