Chang Baocheng, Yang Juhong, Li Hechao, Lu Shan, Chen Liming, Fang Peihua
Nephropathy Department, Tianjin Metabolic Diseases Hospital, Tianjin Medical University, Tianjin, China.
Pharmazie. 2011 Jul;66(7):535-7.
To investigate the effects of atorvastatin on bone formation, bone resorption and bone mineral density in Wistar rats.
Sixty healthy male Wistar rats were randomly divided into one control group treated with vehicle alone and three drug treatment groups, which were treated with atorvastatin at 5 mg/kg x d, 25 mg/kg x d and 50 mg/kg x d respectively. Left femur BMD and bone metabolic parameters were measured after 8 weeks of treatment. In high dose of atorvastatin group, 20 rats were randomly allocated into persistent treatment group or atorvastatin washout group for another 4 weeks; bone metabolic parameters were retested.
Compared with vehicle alone, atorvastatin treatment significantly increased serum levels of ALP and BGP, but had no effects on serum Ca or P levels. Moreover, atorvastatin significantly decreased bone resorption markers including 24 h urinary Ca/Cr ratio, P/Cr ratio and serum IL-6 level. There was no significant difference among atorvastatin treatment groups. After 4 weeks of washout period, the effects of atorvastatin on bone formation and resorption markers decreased. Atorvastatin treatment did not alter BMD compared with the control group, even in the highest dose of atorvastatin group.
Atorvastatin treatment in a certain extent inhibits bone resorption and promotes bone formation, but has no significant effects on bone mineral density in healthy rats.
研究阿托伐他汀对Wistar大鼠骨形成、骨吸收及骨密度的影响。
将60只健康雄性Wistar大鼠随机分为1个单独给予赋形剂的对照组和3个药物治疗组,分别给予5mg/kg×d、25mg/kg×d和50mg/kg×d的阿托伐他汀治疗。治疗8周后测量左侧股骨骨密度和骨代谢参数。在高剂量阿托伐他汀组中,将20只大鼠随机分为持续治疗组或阿托伐他汀洗脱组,再治疗4周;重新检测骨代谢参数。
与单独给予赋形剂相比,阿托伐他汀治疗显著提高了血清碱性磷酸酶(ALP)和骨钙素(BGP)水平,但对血清钙或磷水平无影响。此外,阿托伐他汀显著降低了骨吸收标志物,包括24小时尿钙/肌酐比值、磷/肌酐比值和血清白细胞介素-6水平。阿托伐他汀治疗组之间无显著差异。洗脱期4周后,阿托伐他汀对骨形成和吸收标志物的作用减弱。与对照组相比,阿托伐他汀治疗即使在最高剂量组也未改变骨密度。
阿托伐他汀治疗在一定程度上抑制骨吸收并促进骨形成,但对健康大鼠的骨密度无显著影响。