Effect of statins on bone mineral density and bone histomorphometry in rodents
Effect of statins on bone mineral density and bone histomorphometry in rodents
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DOI：
10.1161/hq1001.097781
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发表时间：
2001-10-01
影响因子：
8.7
通讯作者：
Hough, S
中科院分区：
文献类型：
--
作者：
Maritz, FJ;Conradie, MM;Hough, S
他汀类药物已被假定影响骨代谢。我们研究了不同剂量的辛伐他汀（1、5、10和20 www.example.com（-1）. d（-1））、阿托伐他汀mg.kg和普伐他汀（10 mg. kg（-1）. d（-1））连续12周口服给药于完整雌性Sprague-Dawley大鼠，以及20 mg. kg（-1）. d（-1）辛伐他汀对假手术和卵巢切除大鼠股骨骨密度（BMD）和定量骨组织形态计量学（QBH）的影响并与对照组进行比较。辛伐他汀（P = 0.042）、阿托伐他汀（P = 0.0002）和普伐他汀（P = 0.002）使BMD降低。不同剂量辛伐他汀对QBH参数的影响不同（ANOVA，P = 0.00012）。在两个独立的完整大鼠组中，20 d辛伐他汀可使骨形成和骨吸收的QBH参数显著增加，并反映为BMD相对不变。在较低剂量下，1 www.example.com（-1）. d（-1）辛伐他汀减少骨形成，同时增加骨吸收，这反映在BMD显著降低。接受20天辛伐他汀的卵巢切除动物与未治疗的卵巢切除对照组相比，BMD没有变化;它们骨形成的增加小于接受辛伐他汀的假手术大鼠，骨吸收没有变化。辛伐他汀对骨形成和骨吸收的剂量反应曲线不同。这些研究表明：（1）他汀类药物降低啮齿类动物的BMD，（2）高剂量辛伐他汀增加骨形成和骨吸收，（3）低剂量辛伐他汀降低骨形成并增加骨吸收，（4）辛伐他汀对QBH的影响在不同剂量下不同，（5）在完整大鼠中观察到的辛伐他汀的影响在卵巢切除大鼠中未观察到，和（6）辛伐他汀不能预防卵巢切除术引起的骨丢失。
Statins have been postulated to affect bone metabolism. We investigated the effects of different doses of simvastatin (1, 5, 10, and 20 mg.kg(-1).d(-1)), atorvastatin (2.5 mg.kg(-1).d(-1)), and pravastatin (10 mg.kg(-1).d(-1)) administered orally for 12 weeks to intact female Sprague-Dawley rats and the effect of 20 mg.kg(-1).d(-1) simvastatin in sham-operated and ovariectomized rats on femoral bone mineral density (BMD) and quantitative bone histomorphometry (QBH) and compared them with controls. BMD was decreased by 1 mg.kg(-1).d(-1) simvastatin (P=0.042), atorvastatin (P=0.0002), and pravastatin (P=0.002). The effect on QBH parameters differed with different doses of simvastatin (ANOVA, P=0.00012). QBH parameters of both bone formation and resorption were equivalently and markedly increased by 20 mg.kg(-1).d(-1) simvastatin in 2 separate groups of intact rats and were reflected by a relatively unchanged BMD. At lower doses, 1 mg.kg(-1).d(-1) simvastatin decreased bone formation while increasing bone resorption, as reflected by a marked decrease in BMD. Ovariectomized animals receiving 20 mg.kg(-1).d(-1) sinivastatin showed no change in BMD relative to the untreated, ovariectomized controls; their increase in bone formation was smaller than in sham-operated rats receiving simvastatin, and there was no change in bone resorption. Dose-response curves of simvastatin for bone formation and resorption differed. These studies indicate that (1) statins decrease BMD in rodents, (2) high-dose simvastatin increases bone formation and resorption, (3) low-dose simvastatin decreases bone formation and increases bone resorption, (4) the effects of simvastatin on QBH differ at different dosages, (5) the effects of simvastatin seen in intact rats are not observed in ovariectomized rats, and (6) sinivastatin is unable to prevent bone loss caused by ovariectomy.