Policosanol prevents bone loss in ovariectomized rats.

M Noa, R Más, S Mendoza, R Gámez, N Mendoza, J González
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Abstract

Osteoporosis is characterized by reduced bone mass, abnormal bone architecture and increased fracture risk. Ovariectomy impairs bone mass and metabolism in rats and ovariectomized rats are considered as a suitable model of postmenopausal osteoporosis. Mevalonate is required for producing lipoids that are important in osteoclast activity and thus drugs affecting mevalonate production can prevent bone loss in rodents. Policosanol is a cholesterol-lowering drug isolated from sugar cane wax that inhibits cholesterol biosynthesis through an indirect regulation of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity. The purpose of this study was to determine whether policosanol could prevent bone loss in the bones of ovariectomized rats by comparing its effects with those induced by estradiol. Sprague Dawley female rats were randomly distributed in four groups: a sham-operated group treated with Tween/H2O vehicle and three groups of ovariectomized rats treated with 17beta-estradiol (30 microg/kg/day) or policosanol (50 and 200 mg/kg/day), respectively, for 3 months. At treatment completion the rats were sacrificed, their bones removed and variables of bone resorption and formation were investigated by histomorphometry. Ovariectomy increased trabecular separation but diminished the number and thickness of trabecules. Estradiol and policosanol prevented these effects compared with ovariectomized controls. Both treatments also prevented an increase in the number of osteoclasts and their surface area induced by ovariectomy. Estradiol, but not policosanol, significantly prevented an increase of osteoblast surface area compared with ovariectomized controls. In conclusion, policosanol prevented bone loss and decreased bone resorption in ovariectomized rats, suggesting that it should be potentially useful in preventing bone loss in postmenopausal women.

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胆甾醇防止去卵巢大鼠骨质流失。
骨质疏松症的特点是骨量减少,骨结构异常和骨折风险增加。卵巢切除对大鼠骨量和代谢有损害,卵巢切除大鼠被认为是绝经后骨质疏松症的合适模型。甲羟戊酸是产生对破骨细胞活性很重要的类脂所必需的,因此影响甲羟戊酸产生的药物可以防止啮齿动物的骨质流失。乙醇醇是一种从甘蔗蜡中分离出来的降胆固醇药物,通过间接调节羟甲基戊二酰辅酶a (HMG-CoA)还原酶活性来抑制胆固醇的生物合成。本研究的目的是通过比较胆甾醇与雌二醇的作用,确定胆甾醇是否可以预防去卵巢大鼠的骨质流失。将Sprague Dawley雌性大鼠随机分为4组,假手术组分别给予吐温/水灌胃,去卵巢大鼠分别给予17 -雌二醇(30 mg/kg/d)或胆甾醇(50和200 mg/kg/d)灌胃,疗程3个月。治疗结束后处死大鼠,取骨,用组织形态学法观察骨吸收和骨形成的变化。卵巢切除术增加了小梁分离,但减少了小梁的数量和厚度。与去卵巢对照相比,雌二醇和胆甾醇可以防止这些影响。这两种治疗方法还可以防止卵巢切除术引起的破骨细胞数量和表面积的增加。与去卵巢对照相比,雌二醇,而非胆甾醇,显著阻止了成骨细胞表面积的增加。总之,在去卵巢的大鼠中,胆甾醇可以防止骨质流失并减少骨吸收,这表明它可能对预防绝经后妇女骨质流失有潜在的作用。
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