THIAZIDE EFFECTS ON BONE AND ARTERIES

雌激素缺乏的绝经后妇女会发生骨质疏松症， 冠状动脉粥样硬化（CAA）。 因此， 还必须评估用于治疗骨质疏松症的潜力， 对CAA的影响 像女性一样，手术绝经后的猕猴会出现骨质减少， CAA。 本研究的主要目的是评估，在手术 绝经后的猴子，无论是常用的抗高血压药物 药物（氢氯噻嗪）可以防止绝经后骨质流失。 一 补充目的是评估噻嗪类药物对 CAA。 目的是：1）确定每日噻嗪治疗是否能保护 与手术绝经后猴子的骨质流失相比， 确定噻嗪类药物治疗是否与激素（雌激素和 孕酮）替代疗法（HRT） 绝经后骨质流失; 2）确定是否同时使用噻嗪类药物治疗 激素替代疗法可增加骨体积、密度和强度 在手术绝经后的猕猴; 3）研究机制， 这些化合物可以防止骨质流失;和4）评估是否长- 长期噻嗪类药物治疗对手术绝经后饮食诱导CAA的影响 猴子 这种性质的前瞻性试验不能在人类中进行， 由于入侵的性质，费用，复杂化， 不可控变量 实验：将100只年轻成年雌性食蟹猴分为 分成4组，每组25只动物：组1）卵巢切除（OVX）， 未治疗组（2组）OVX，氢氯噻嗪治疗24个月; 组3）OVX，用HRT治疗24个月;组4）OVX，用HRT治疗24个月。 氢氯噻嗪和HRT每日24个月。 在24个月内， 试验、血压、血清和尿液化学、血清和尿液 骨转换标志物，血脂，非侵入性密度测定， 放射摄影术，骨活检组织形态计量学分析，性激素 水平和身体测量将被评估。 结束时 试验中，将对所有猴进行尸检，并比较各组的骨 参数和CAA程度通过组织形态计量学。

Estrogen-deficient postmenopausal women develop both osteoporosis and coronary artery atherosclerosis (CAA). Consequently, drugs with potential for use in treating osteoporosis must also be evaluated for their effect on CAA. Like women, surgically postmenopausal macaques develop osteopenia and CAA. The primary objective of this study is to evaluate, in surgically postmenopausal monkeys, whether a commonly prescribed antihypertensive drug (hydrochlorothiazide) can prevent postmenopausal bone loss. A complementary objective is to evaluate the effects of the thiazide on CAA. The goals are: 1) to determine if daily thiazide therapy protects against the bone loss seen in surgically postmenopausal monkeys, and to determine if thiazide therapy is as effective as hormonal (estrogen and progesterone) replacement therapy (HRT) in protecting against postmenopausal bone loss; 2) to determine if concurrent thiazide therapy and HRT provides additive increases in bone volume, density, and strength in surgically postmenopausal macaques; 3) to study mechanisms by which these compounds may prevent bone loss; and 4) to evaluate whether long- term thiazide treatment affects diet-induced CAA in surgically menopausal monkeys. A prospective trial of this nature cannot be done in human beings because of the invasive nature, expense, and complicating and uncontrolled variables. Experiment: 100 young adult female cynomolgus macaques will be divided into 4 groups of 25 animals each: Group 1) ovariectomized (OVX), untreated; Group 2) OVX, treated with hydrochlorothiazide for 24 months; Group 3) OVX, treated for 24 months with HRT; Group 4) OVX, treated with hydrochlorothiazide and HRT daily for 24 months. Throughout the 24-month trial, blood pressure, serum and urinary chemistry, serum and urinary markers of bone turnover, plasma lipids, noninvasive densitometry, radiography, histomorphometric analysis of bone biopsies, sex hormone levels, and body measurements will be evaluated. At the end of the trial, all monkeys will be necropsied and the groups compared for bone parameters and CAA extent by histomorphometry.