Mechanism for the Development of Bone Disease in Diabetes: Increased Oxidative Stress and Advanced Glycation End Products

  • Sho-ichi YamagishiEmail author


The prevalence and incidence of osteoporosis is high in diabetic patients. There is a growing body of evidence that advanced glycation end products (AGEs), senescent macroprotein derivatives formed at an accelerated rate under hyperglycemic and oxidative stress conditions, play a central role in osteoporosis and bone fractures in diabetes. Indeed, accumulation of AGE-modified cross-links of collagen alters bone strength and impairs its biomechanical properties. Further, AGE-modified proteins in the bone have been shown to disturb physiological function of osteoblasts and osteoclasts via oxidative stress generation through the interaction with the receptor for AGEs (RAGE). Therefore, activation of the AGE-RAGE system in the bone not only decreases bone mineral density but also impairs bone quality in patients with diabetes. In this review, I discuss the molecular mechanism for osteoporosis in diabetes, especially focusing on the AGE-RAGE-induced oxidative stress axis.


AGEs Osteoporosis Oxidative stress RAGE Diabetes 



This work was supported in part by Grants-in-Aid for Scientific Research (B) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. No potential conflicts of interest relevant to this article were reported.


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© Springer Japan 2016

Authors and Affiliations

  1. 1.Department of Pathophysiology and Therapeutics of Diabetic Vascular ComplicationsKurume University School of MedicineKurume-shiJapan

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