Category Archives: Antihypertensives

ACE Inhibitors, But Not ARBs, Marginally Increase Bone Loss in Men


Does the use of ACE inhibitors or angiotensin receptor blockers affect bone loss in older men?

In a prospective cohort study of 5,995 older American men (MrOS), users of angiotensin-converting enzyme (ACE) inhibitors had a small but significant increase in bone loss at the hip over 4 years after adjustment for confounders. Use of angiotensin II AT1 receptor blockers (ARB) was not significantly associated with bone loss.
Experimental evidence suggests that angiotensin II promotes bone loss by its effects on osteoblasts. It is therefore plausible that ACE inhibitor and ARB may reduce rates of bone loss. The objective of this study is to examine the independent effects of ACE inhibitor and ARB on bone loss in older men.
Out of 5,995 American men (87.2%) aged ≥65 years, 5,229 were followed up for an average of 4.6 years in a prospective six-center cohort study-The Osteoporotic Fractures in Men Study (MrOS). Bone mineral densities (BMD) at total hip, femoral neck, and trochanter were measured by Hologic densitometer (QDR 4500) at baseline and year 4.
Out of 3,494 eligible subjects with complete data, 1,166 and 433 subjects reported use of ACE inhibitors and ARBs, respectively. When compared with nonusers, continuous use of ACE inhibitors was associated with a small (0.004 g/cm(2)) but significant increase in the average rate of BMD loss at total hip and trochanter over 4 years after adjustment for confounders. Use of ARB was not significantly associated with bone loss.
Use of ACE inhibitors but not ARB may marginally increase bone loss in older men.

Kwok T, Leung J, Zhang YF, Bauer D…
Osteoporos Int Aug 2012
PMID: 22080379


ACE Inhibitor Moexipril Doesn’t Harm Bones in Ovariectomized Rats


Impact of antihypertensive therapy on postmenopausal osteoporosis: effects of the angiotensin converting enzyme inhibitor moexipril, 17beta-estradiol and their combination on the ovariectomy-induced cancellous bone loss in young rats.

No data are available on whether angiotensin converting enzyme (ACE) inhibition affects the skeleton, though this might be of clinical relevance when antihypertensive therapy is initiated, particularly in hypertensive women after menopause who typically suffer from a concomitant rapid onset of osteoporosis. In the present study we investigated the effects of the new ACE inhibitor moexipril, 17beta-estradiol and their combination on the bone turnover in ovariectomized Sprague-Dawley rats, an established animal model for studying human postmenopausal osteoporosis.
We studied 119 12-week-old virgin female Sprague-Dawley rats. Seven rats were killed on day 0 as basal controls. The remaining rats were divided into sham-ovariectomy or ovariectomy groups. Vehicle, moexipril at 10 mg/kg per day alone (orally), 17beta-estradiol at 10 mu g/kg per day alone (subcutaneously) or both were administered to both groups immediately after the operation for 14 (short-term effects) or 56 (long-term effects) days. A stereology computer program was used for measurements. Static histomorphometric measurements, using a stereology computer program, were taken on double-fluorescent labeled undecalcified proximal tibial metaphyseal (cancellous bone site) and tibial shaft (cortical bone site) sections.
Ovariectomy induced dramatically cancellous bone loss due to increased bone turnover, with resorption exceeding formation. Moexipril had no effect on the cancellous bone site in either ovariectomized or sham-operated rats. 17beta-Estradiol treatment added extra cancellous bone in the sham-operated rats and prevented cancellous bone loss in the ovariectomized rats by inhibiting bone resorption. The combination of moexipril and 17beta-estradiol gave similar results to those of 17beta-estradiol alone. Comparable results were observed in the cortical bone site.
The results of this study show that ACE inhibition by moexipril has no effect on the skeleton when given alone and that it does not hamper the osteoprotective effects of 17beta-estradiol. These findings are relevant for the use of antihypertensive therapy in postmenopausal women treated or not with hormone replacement therapy.

Stimpel M, Jee WS, Ma Y, Yamamoto N…
J. Hypertens. Dec 1995
PMID: 8903666

Resveratrol + Enalapril Improves Microcirculation and Prevents Microfractures in Rats


[Comparative evaluation of the osteoprotective effects of resveratrol and resveratrol/enalapril combination in the treatment of experimental osteoporosis].

The osteoprotective effect of resveratrol and a combination of resveratrol with enalapril has been investigated in white Wistar female rats with experimental osteoporosis. It is established that, in rats after ovariectomy, the endothelial dysfunction of microcirculation vessels of the osteal tissue is developed, resulting in the occurrence of osteoporosis. Resveratrol and the combination of resveratrol with enalapril prevented depression of the microcirculation level in the osteal tissue, thus preventing the thinning of osteal trabecules and preventing their microfractures.

Faĭtel’son AV, Koklina NIu, Gudyrev OS, Dubrovin GM…
Eksp Klin Farmakol 2012
PMID: 22834128