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（由适用提供）：骨质疏松和高血压（HTN）是老年的两个主要慢性公共卫生问题。骨骼更新随着形成和分辨率之间的不平衡增加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）的激活被认为是造成HTN患者的骨骼量的原因，这可能会增强。影响RAS的降压药，特别是血管紧张素转化酶抑制剂（ACEI），动物的骨转换减少，并改善了初步人类研究的BMD。 ACEI可防止生成血管紧张素II，这会通过AT1和AT2影响骨骼。 AT1和AT2均在骨细胞中表达，并与RANKL功能的上调有关，导致骨质碎片性高。 ACEI的抗骨构成作用是由血管紧张素II引起的骨骼分辨率增加而导致的。接受ACEI的动物显示骨骼分辨率减少并改善了骨转换。我们假设ACEI使用3个月的老年人治疗HTN（55年）将减少骨转换，并减少研究参与者的血清RANKL。我们提出了一项随机试验，以收集30名男性和30名女性（55岁的女性；对于每种性别，15种接受ACEI治疗的性别，15例未接受与HTN控制的任何RAS-RAS相关药物3个月），以确定ACEI是否会在动物中以相同方式描述的人类中的骨骼更换。为了进一步确认这一概念，我们建议用ACEI治疗HTN控制三个月后检查人类的血清RANKL。