Effects of ACE Inhibitor (ACEI) use on bone turnover in humans: a clinical trial

描述（由申请人提供）：骨质疏松症和高血压（HTN）是老年人的两个主要慢性公共卫生问题。增加的骨转换与形成和再吸收之间的不平衡导致年龄相关的骨丢失和骨质疏松症。钙稳态的改变和肾素-血管紧张素系统（RAS）的激活被认为是导致HTN患者骨量减少的原因，这可能在老年时增强。影响RAS的抗高血压药物，特别是血管紧张素转换酶抑制剂（ACEI），在动物中降低骨转换，并在初步的人体研究中改善BMD。ACEI阻止血管紧张素II的产生，血管紧张素II通过受体AT 1和AT 2影响骨骼。AT 1和AT 2均在骨细胞中表达，并与RANKL功能上调相关，导致高破骨细胞生成活性。ACEI的抗破骨细胞生成作用来自于血管紧张素II诱导的骨吸收增加的逆转。接受ACEI的动物显示骨吸收减少和骨转换改善。我们假设ACEI治疗老年人（~ 55岁）HTN 3个月将降低研究参与者的骨转换和血清RANKL水平。我们建议进行一项随机试验，收集30名男性和30名女性（年龄约55岁;对于每种性别，15名接受ACEI治疗，15名未接受任何RAS相关药物治疗，以控制HTN 3个月）的初步数据，以确定ACEI是否以与动物相同的方式降低人类骨转换。为了进一步证实这一概念，我们建议在用ACEI治疗HTN控制三个月后检查人的血清RANKL。

DESCRIPTION (provided by applicant): Osteoporosis and hypertension (HTN) are two major chronic public health problems of old age. Increased bone turnover with imbalance between formation and resorption leads to age related bone loss and osteoporosis. Altered calcium homeostasis and activation of the renin-angiotensin system (RAS) are thought to be responsible for decreased bone mass in patients with HTN which may be enhanced in older age. Antihypertensive medications affecting RAS, specifically angiotensin converting enzyme inhibitors (ACEI), decreased bone turnover in animals, and improved BMD in preliminary human studies. ACEI prevents generation of angiotensin II, which impacts bone via receptors AT1 and AT2. Both AT1 and AT2 are expressed in bone cells and are linked with up-regulation of RANKL function resulting in high osteoclastogenic activity. Anti-osteoclastogenic effects of ACEI result from a reversal of the increased bone resorption induced by angiotensin II. Animals receiving ACEI show decreased bone resorption and improved bone turnover. We hypothesize that ACEI use for 3 months to treat HTN in older adults (¿55 years) will decrease bone turnover and decrease serum RANKL in study participants. We propose a randomized trial to collect pilot data in 30 men and 30 women (¿55 years old; for each gender, 15 treated with ACEI and 15 not treated with any RAS- related medications for HTN control for 3 months) to determine if ACEI decreases bone turnover in humans the same way described in animals. To further confirm this concept, we propose to check serum RANKL in humans after treatment with ACEI for HTN control for three months.