Combination of Thiazide Diuretics and Angiotensin Receptor Blockers Attenuates Osteoporosis in Hypertensive Rats

A series of clinical studies have shown that thiazide diuretics (TD) might reduce the risk of bone fractures. We also recently demonstrated that angiotensin receptor blockers (ARB) ameliorated ovariectomy (OVX)-induced osteoporosis in a hypertensive rat model. In this study, we examined whether a combination of TD and ARB might have additional effects on osteoporosis in a hypertensive rat model. In spontaneous hypertensive rats, estrogen deficiency induced by OVX resulted in a significant increase in osteoclast activation as assessed by tartrate-resistant acid phosphatase (TRAP) activity in the tibia, accompanied by a significant decrease in bone mineral density (BMD) evaluated by dual-energy X-ray absorptiometry and an increase in urinary deoxypyridinoline. Treatment with high-dose ARB, valsartan (3 mg Kg-1day-1), attenuated the OVX-induced decrease in BMD and increased TRAP activity and urinary deoxypyridinoline, whereas low-dose ARB, valsartan (1 mg Kg-1day-1), or low-dose TD, hydrochlorothiazide (0.2 mg Kg-1day-1), did not. Of importance, administration of low-dose valsaltan in combination with hydrochlorothiazide significantly decreased the magnitude of bone mineral loss compared with the effect of administration of high-dose valsartan alone. These results demonstrated that treatment with TD in combination with ARB attenuated osteoporosis additionally in a hypertensive rat model.