IMPACT OF ANTIHYPERTENSIVE THERAPY ON THE SKELETON - EFFECTS OF MOEXIPRIL AND HYDROCHLOROTHIAZIDE ON OSTEOPENIA IN SPONTANEOUSLY HYPERTENSIVE OVARIECTOMIZED RATS

Skeletal effects of moexipril, an angiotensin-converting enzyme (ACE) inhibitor, and hydrochlorothiazide (HCTZ), a thiazide diuretic, were s tudied in ovariectomized (OVX) spontaneously hypertensive rats (SHR). Moexipril (10 mg/kg per day), HCTZ (10 mg/kg per day), alone or in com bination, as well as 17 alpha-estradiol (30 mu g/kg per day) were give n to OVX SHR immediately after surgery and studied for short-and long- term effects (14 and 56 days respectively). All drugs were given orall y. Histomorphometric data on the secondary spongiosa of proximal tibia l metaphyses (cancellous bone) and tibiofibular junctions of tibial sh afts (cortical bone) were analyzed. Ovariectomy induced cancellous bon e loss in SHR by inducing negative bone balance. Estrogen prevented ov ariectomy-induced cancellous bone loss in the SHR by reducing bone tur nover and partially suppressing the coupling of bone formation to reso rption on the endocortical surface. HCTZ reduced blood pressure after 1 week of treatment, yet this effect was no lower than that seen in co ntrols after 3 weeks of treatment. Two weeks of HCTZ transiently preve nted ovariectomy-induced increases in bone turnover rate and eroded su rface. This delayed ovariectomy induced trabecular bone loss in the pr oximal tibial metaphysis, but had no effect on the tibial shaft. Like HCTZ, moexipril also reduced blood pressure after the first week of tr eatment but it had no apparent effect on either the proximal tibial me taphysis or the tibial shaft. A combination of moexipril and HCTZ exhi bited a much more potent hypotensive effect and had the same effects o n bone mass and dynamic end-points as HCTZ alone. Our data indicate th at (1) HCTZ treatment has some transient beneficial effects on both an tihypertension and osteoprotection in hypertensive osteopenic rats, (2 ) the combination of moexipril with HCTZ improved the antihypertensive effect but did not potentiate or hamper the osteoprotective effect of HCTZ, and (3) the skeletal effect of estrogen is not impacted by the hypertensive state. These findings are relevant for the use of ACE inh ibitor and thiazide diuretics, alone or in combination, in antihyperte nsive therapy in postmenopausal women.