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.

Public Health Relevance

Osteoporosis and hypertension are two major public health problems of older age. Previous research, including our preliminary data, indicated potentials for angiotensin converting enzyme inhibitor (ACEI, a commonly used antihypertensive medication) in preventing osteoporosis due to age-related bone loss. We propose a proof of concept study to determine if ACEI decreases bone turnover in humans the same way described in animals. The proposed study will collect pilot data and set the stage for a clinical trial to confirm effect of ACEI on prevention and treatment of age-related bone loss in older adults. Further, results from this study may have future implications on prevention of bone loss in other populations, e.g., bed-rest patients.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Small Research Grants (R03)
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Special Emphasis Panel (ZAG1)
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Salive, Marcel
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University of Texas Health Science Center Houston
Schools of Medicine
United States
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