Olmesartan Reduces Pentosidine Production and Ameliorates Fragility of Bone in Ovariectomized Fructose-Fed Rats

Recent epidemiological studies have demonstrated that diabetes mellitus (DM) is a risk factor for bone fracture. Both hyperglycemia and oxidative stress induce a reduction in enzymatic beneficial cross-links and the accumulation of disadvantageous non-enzymatic cross-linking by advanced glycation end products (AGEs) such as pentosidine in bone. On the other hand, some antihypertensive drugs have been reported to improve peripheral conditions such as retinopathy or kidney dysfunction induced by DM. In this study, ovariectomized rats with a high-fructose diet were treated with or without olmesartan, for investigating aspects of bone and mineral metabolism derangement in DM. High-fructose loading increased insulin resistance and serum pentosidine concentration. Immunohistochemical analysis also demonstrated pentosidine accumulation in bone. These results were in accordance with the results of a three point bending test, which revealed fragility of bone. Of interest, treatment with olmesartan improved insulin resistance and decreased the accumulation of the AGE pentosidine. Three point bending test also revealed improvement in fragility of bone induced by a highfructose diet. Overall, olmesartan treatment might be a useful approach in the treatment of hypertensive patients with DM.