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.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Cardiovascular Clinical Research, Schwarz Pharma AG, Monheim, Germany.
M
M
Stimpel
W S
WS
Jee
Y
Y
Ma
N
N
Yamamoto
Y
Y
Chen
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000627:therapeutic use*; D005260:Female; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D007546:Isoquinolines / Q000627:therapeutic use*; D008593:Menopause / Q000187:drug effects*; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology; D010052:Ovariectomy / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044005:Tetrahydroisoquinolines; D013977:Tibia / Q000187:drug effects / Q000473:pathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D004958:Estradiol; C058302:moexipril