THIAZIDE EFFECTS ON BONE AND ARTERIES

雌激素缺乏的绝经后妇女会患上骨质疏松症和 冠状动脉粥样硬化(CAA)。因此，毒品与 还必须评估用于治疗骨质疏松症的潜力 它们对CAA的影响。 和女性一样，外科手术后的绝经后猕猴也会出现骨量减少和 CAA。这项研究的主要目标是在外科手术中评估 绝经后的猴子，是否常用降压药 药物(氢氯噻嗪)可以预防绝经后骨丢失。一个 辅助性目标是评价噻嗪的疗效 CAA。研究的目标是：1)确定每日服用噻嗪类药物是否有保护作用 防止绝经后手术猴子的骨质流失，并 确定噻嗪治疗是否与激素治疗一样有效(雌激素和 黄体酮)替代疗法(HRT)预防 绝经后骨丢失；2)确定是否同时接受噻嗪治疗 HRT增加了骨的体积、密度和强度。 对绝经后猕猴进行手术治疗；3)研究 这些化合物可以防止骨质流失；以及4)评估长期- TERM TIMAZIZED治疗对手术绝经期饮食诱发CAA的影响 猴子。这种性质的前瞻性试验不能在人类身上进行。 因为入侵的性质，费用，和复杂的 不受控制的变量。 实验：将100只年轻成年雌性食蟹猴 分为4组，每组25只：1)去卵巢(OVX)组， 2)OVX组，用氢氯噻嗪治疗24个月； 3)OVX组，用HRT治疗24个月；4)OVX组，用 氢氯噻嗪和激素替代疗法每日一次，疗程24个月。在整个24个月中 试验，血压，血和尿化学，血和尿 骨转换标记物，血脂，无创密度测定， 骨活检的放射摄影术、组织形态计量学分析、性激素 水平，和身体尺寸将被评估。在结束时， 试验中，所有猴子都将被解剖，并对这两组猴子的骨骼进行比较 通过组织形态计量学测量参数和CAA范围。

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.