OBJECTIVE: This study evaluated the effect of simvastatin at different doses on rat proximal femur and lumbal vertebra bone mineral density (BMD) in rats receiving estrogen replacement therapy. MATERIAL-METHOD: Fouty-eigth 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 μg/kg body weight/day 17 β-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 ve 159 ± 0.01 g/cm²; p=0.001), whereas the lumbal vertebral bone loss did not reach statistical significance (0.161 ± 0.01 g/cm² ve 0.168 ± 0.01 g/cm²; p=0.471). 150 μg/kg body weight/day 17 β-estradiol treatment preserved proximal femur and lumbal vertebra BMD. The effect of 150 μg/kg body weight/day 17 β-estradiol and 3 mg/kg body weight/day on proximal femur and lumbal vertebra BMD were comparable. The estrogen and low dose simvastatin combination povided greatest protection of proximal femur (0.176 ± 0.01 g/cm² ve 0.145 ± 0.01 g/cm²; p CONCLUSIONS: In rats, prophylactic administration of high dose oral simvastatin treatment alone prevents ooforectomy-induced 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. Turkish Simvastatin ve 17 β-estradiolün ooforektomi yapilmis siçanlarda kemik mineral dansitesi üzerine etkisi AMAÇ: Ooforektomize siçanlarda östrojen yerine koyma tedavisine eklenen farkli simvastatin miktarlarinin proksimal femur ve lomber vertebra kemik mineral dansitesi (KMD) üzerine etkisini arastirmak. MATERYAL ve METOT: Kirksekiz tane Wistar Albino cinsi disi siçan her biri 8 hayvandan olusan 6 gruba ayrildi. Ilk 5 gruba ooforektomi, son gruba sham operasyonu yapildi. Ooforektomi yapilmis 5 grubun 4’üne 120 gün boyunca gavaj yoluyla 150 μg/kg/gün dozunda 17 β-estradiol ve/veya yüksek (6 mg/kg/gün) veya düsük (3 mg/kg/gün) doz simvastatin verildi. Çalismanin sonunda herbir grubun proksimal femur ve lomber vertebra KMD’si birbiriyle karsilastirildi. BULGULAR: Ooforektomi sonrasi proksimal femur KMD’si anlamli oranda azalirken (0.145 ± 0.01 g/cm² ve 159 ± 0.01 g/cm²; p=0.001), lomber vertebradaki kemik kaybinin anlamli olmadigi saptandi (0.161 ± 0.01 g/cm² ve 0.168 ± 0.01 g/cm²; p=0.471). 150 μg/kg/gün 17-β-estradiol tedavisinin proksimal femur ve lomber vertebra KMD’sini korudugu saptandi. Tek basina 6mg/kg/gün simvastatin ile 150 μg/kg/gün 17-β-estradiol tedavisinin proksimal femur ve lomber vertebra KMD’si üzerine etkisi benzer bulundu. Ooforektomi yapilan siçanlara kiyasla proksimal femur (0.176 ± 0.01 g/cm² ve 0.145 ± 0.01 g/cm²; p SONUÇ: Siçanlarda, ooforektomi sonrasi KMD’sini korumaya yönelik profilaktik olarak tek basina yüksek doz oral simvastatin, oral östrojen replasman tedavisi kadar etkili bulundu. Östrojen ile birlikte düsük doz simvastatin kombinasyonu KMD’sini en fazla arttirdi. Östrojen tedavisine yüksek doz simvastatin eklenmesi KMD üzerine olumlu etki göstermedi.

Keywords: bone mineral density, estrogen, osteoporosis, rat, statin