Different Doses of Nitric Oxide Donor Prevent Osteoporosis in Ovariectomized Rats

Abstract

Nitric oxide has important effects on bone cell function. To verify that nitric oxide can protect against bone loss associated with estrogen deficiency, which is dependent on different concentrations of nitric oxide, we applied different doses of nitric oxide to ovariectomized rats. Fifty 12-week-old Sprague-Dawley female rats had ovariectomies, and 10 rats had sham operations. The ovariectomized rats were randomized into five groups: ovariectomized only; 17-beta-estradiol; low-dose nitroglycerin; middle-dose nitroglycerin; and high-dose nitroglycerin. After 12 weeks, the bone mineral density, dry weight, ash weight, calcium content, and nitric oxide concentration were determined. Compared with these same measurements in the sham-operated group, the bone mineral density, dry weight, ash weight, calcium content, and nitric oxide concentration decreased in the control group. Treatment with low-dose nitroglycerin, middle-dose nitroglycerin, and 17-beta-estradiol maintained bone mineral density and reversed the effects of ovariectomy on dry weight, ash weight and calcium content when compared with those in the control group. There were no differences in the bone mineral density, dry weight, ash weight, or calcium concentration between the ovariectomized-only rats and the rats treated with high-dose nitroglycerin. Results of this study suggest that nitric oxide treatment can counteract bone loss in ovariectomized rats. Furthermore, supplementation with a similar or slightly greater than physiologic concentration of nitric oxide has a potentially positive impact on osteoporosis.