Carvedilol Ameliorates Low-Turnover Bone Disease in Non-Obese Type 2 Diabetes

Abstract

Background: Diabetic bone disease is a major complication in diabetes mellitus and is characterized by low-turnover bone formation. Recent studies have demonstrated that oxidative stress could be associated with diabetic bone disease and that β-adrenergic antagonists could increase bone formation. Our study investigated the effect of carvedilol (β-blocker), possessing an antioxidant effect, on diabetic bone disease. Methods: We used the non-obese, type 2 diabetes model Spontaneously Diabetic Torii (SDT) rats in this study. Sprague-Dawley rats were used as controls (control, n = 6). SDT rats were divided into four groups: diabetic (DM, n = 8), DM+insulin (DM+I, n = 7), DM+carvedilol (DM+C, n = 8), and DM+N-acetylcysteine (DM+N, n = 10) at 20 weeks. The rats were sacrificed at 30 weeks, after which blood and urine samples, bone mineral density, histomorphometry, and oxidative stress were evaluated. Results: The number of 8-hydroxydeoxyguanosine-positive cells in bone tissue was significantly lower in the DM+C and DM+N groups than in the DM group. Mineral apposition rate and bone formation rate per bone surface in the DM+C and DM+N groups were significantly higher than those in the DM group, and these parameters were better in the DM+C group than in the DM+N group. Conclusion: Our data suggest that carvedilol has stronger effects on diabetic low-turnover bone disease beyond that which can be attributed to its antioxidative stress mechanism.