IMPACT OF ANTIHYPERTENSIVE THERAPY ON POSTMENOPAUSAL OSTEOPOROSIS - EFFECTS OF THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR MOEXIPRIL, 17-BETA-ESTRADIOL AND THEIR COMBINATION ON THE OVARIECTOMY-INDUCED CANCELLOUS BONE LOSS IN YOUNG-RATS

Objective: No data are available on whether angiotensin converting enz yme (ACE) inhibition affects the skeleton, though this might be of cli nical relevance when antihypertensive therapy is initiated, particular ly in hypertensive women after menopause who typically suffer from a c oncomitant rapid onset of osteoporosis. In the present study we invest igated the effects of the new ACE inhibitor moexipril, 17 beta-estradi ol and their combination on the bone turnover in ovariectomized Spragu e-Dawley rats, an established animal model for studying human postmeno pausal osteoporosis. Materials and 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), 17 beta-estradiol at 10 mu g/kg per day alone (subcutaneously ) or both were administered to both groups immediately after the opera tion for 14 (short-term effects) or 56 (long-term effects) days. A ste reology computer program was used for measurements. Static histomorpho metric measurements, using a stereology computer program, were taken o n 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 t o increased bone turnover, with resorption exceeding formation. Moexip ril had no effect on the cancellous bone site in either ovariectomized or sham-operated rats. 17 beta-Estradiol treatment added extra cancel lous bone in the sham-operated rats and prevented cancellous bone loss in the ovariectomized rats by inhibiting bone resorption. The combina tion of moexipril and 17 beta-estradiol gave similar results to those of 17 beta-estradiol alone. Comparable results were observed in the co rtical bone site. Conclusions: The results of this study show that ACE inhibition by moexipril has no effect on the skeleton when given alon e and that it does not hamper the osteoprotective effects of 17 beta-e stradiol. These findings are relevant for the use of antihypertensive therapy in postmenopausal women treated or not with hormone replacemen t therapy.