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

使用 ACE 抑制剂 (ACEI) 对人类骨转换的影响：一项临床试验

基本信息

批准号：
8554986
负责人：
Nahid J. Rianon
金额：
$ 7.6万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8554986
关键词：
AGTR2 gene Affect Aftercare Age Age-Related Bone Loss Angiotensin II Angiotensin Receptor Angiotensin-Converting Enzyme Inhibitors Angiotensins Animals Antihypertensive Agents Bed rest Biological Markers Biology Bone Density Bone Resorption C-terminal Calcium Cardiovascular system Chronic Clinical Trials Comorbidity Cyclophosphamide Data Data Set Diabetes Mellitus Disease Effectiveness Elderly Equilibrium Excretory function Fracture Future Gender Generations Guidelines Health Heart Hip region structure Homeostasis Human Hypertension Intervention Kidney Diseases Knowledge Lead Link Longitudinal Studies Monitor Neck Newly Diagnosed Osteoporosis Outcome Outcome Measure Participant Pathway interactions Patients Peptides Pharmaceutical Preparations Pilot Projects Polypharmacy Population Prevention Procollagen Proteins Public Health Randomized Randomized Controlled Trials Regimen Renin-Angiotensin System Reporting Research Research Design Retrospective Studies Risk Serum Staging TNFSF11 gene Up-Regulation Veterans Woman Work bone bone cell bone loss bone mass bone metabolism bone turnover clinical practice cohort crosslink diabetes risk hypertension control improved men older patient prevent randomized trial receptor skeletal

项目摘要

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.

描述（由申请人提供）：骨质疏松症和高血压（HTN）是老年时期的两个主要慢性公共卫生问题。骨转换增加以及骨形成和吸收之间的不平衡导致与年龄相关的骨丢失和骨质疏松症和肾素激活。 -血管紧张素系统（RAS）被认为是导致高血压患者骨量减少的原因，特别是在老年患者中，影响RAS、血管紧张素的抗高血压药物可能会导致骨量减少。转化酶抑制剂 (ACEI)、动物骨转换减少以及人体初步研究中的 BMD 改善可防止血管紧张素 II 的产生，而血管紧张素 II 通过受体 AT1 和 AT2 影响骨骼。 RANKL 功能的上调导致高破骨细胞生成活性，ACEI 的抗破骨细胞生成作用是由接受血管紧张素 II 的动物引起的骨吸收增加的逆转所致。 ACEI 显示骨吸收减少并改善骨转换，我们追求使用 ACEI 3 个月来治疗老年人的高血压（¿ 55 岁）将减少研究参与者的骨转换并降低血清 RANKL 我们提出了一项随机试验，收集 30 名男性和 30 名女性（55 岁；对于每个性别，15 人接受 ACEI 治疗，15 人未接受任何治疗）的试点数据。用于控制 HTN 的 RAS 相关药物持续 3 个月），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，我们建议检查人类血清 RANKL。使用 ACEI 治疗三个月后控制高血压。