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

描述(申请人提供)：骨质疏松症和高血压(HTN)是老年两大慢性公共健康问题。骨转换增加，骨形成和吸收失衡，导致年龄相关性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HTN患者骨量减少的原因，老年人的骨量可能会增加。在初步的人类研究中，影响RAS的降压药物，特别是血管紧张素转换酶抑制剂(ACEI)，可以降低动物的骨转换，并改善骨密度。血管紧张素转换酶抑制血管紧张素II的产生，血管紧张素II通过AT1和AT2受体影响骨骼。AT1和AT2都在骨细胞中表达，并与RANKL功能上调有关，从而导致高破骨活性。ACEI的抗破骨作用是通过逆转血管紧张素II诱导的骨吸收增加而产生的。接受ACEI的动物表现出减少骨吸收和改善骨转换。我们假设ACEI用于治疗老年人(55岁)HTN的3个月将降低研究参与者的骨转换和血清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；每一性别，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)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，我们建议在接受ACEI治疗以控制HTN三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.