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）是老年两大慢性公共卫生问题。骨转换增加，形成和吸收之间的不平衡导致与年龄相关的骨质流失和骨质疏松症。钙稳态的改变和肾素-血管紧张素系统（RAS）的激活被认为是HTN患者骨量减少的原因，这种情况在老年时可能会加剧。抗高血压药物影响RAS，特别是血管紧张素转换酶抑制剂（ACEI），在动物中减少骨转换，并在初步的人类研究中改善骨密度。ACEI阻止血管紧张素II的产生，血管紧张素II通过受体AT1和AT2影响骨骼。AT1和AT2均在骨细胞中表达，并与RANKL功能上调相关，从而导致高破骨细胞活性。ACEI的抗破骨细胞作用源于逆转血管紧张素II诱导的骨吸收增加。接受ACEI治疗的动物表现出骨吸收减少和骨转换改善。我们假设使用ACEI治疗老年人（55岁）HTN 3个月将减少研究参与者的骨转换和降低血清RANKL。我们建议进行一项随机试验，收集30名男性和30名女性（55岁，男女各15名，接受ACEI治疗和15名未接受任何RAS相关药物治疗的HTN控制3个月）的试点数据，以确定ACEI是否以与动物相同的方式减少人类的骨转换。为了进一步证实这一概念，我们建议在ACEI治疗HTN控制3个月后检测人类血清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.