Role of Advanced Glycation End Products (AGEs) in Osteoporosis in Diabetes

Author(s): Sho-ichi Yamagishi

Journal Name: Current Drug Targets

Volume 12 , Issue 14 , 2011

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Recent meta-analyses have revealed that the risk of bone fracture is increased in both type 1 and type 2 diabetic patients. Low bone mineral density (BMD) can not necessarily explain the link, because BMD is increased rather than decreased in type 2 diabetes, while it is consistently low in type 1 diabetes subjects. Although multiple factors could influence the quality of bone and increase the bone fragility in diabetes, there is accumulating evidence for the association between osteoporosis and vascular calcification, which is an independent predictor of cardiovascular disease morbidity and mortality. Advanced glycation end products (AGEs) are formed by a non-enzymatic reaction between aldehydes of reducing sugars and the amino groups of proteins, lipids and nucleic acids that could contribute to the aging of macromolecules. The formation and accumulation of AGEs have been known to progress at an accelerated rate under diabetes. There is a growing body of evidence that AGEs and their receptor (RAGE) system elicit oxidative stress generation and subsequently evoke inflammatory responses in vascular wall cells, osteoblasts and osteoclasts, thereby being involved in both vascular calcification and osteoporosis in diabetes. Further, cross-linking in the organic bone matrix by AGEs could adversely affect the fracture resistance of bone. Therefore, in this paper, I review the pathophysiological role of the AGEs-RAGE-oxidative stress system in decreased BMD and increased bone fragility in diabetes. I also discuss here the potential therapeutic interventions of the AGEs-RAGE axis for preventing osteoporosis in diabetes.

Keywords: AGEs, osteoporosis, oxidative stress, RAGE, Diabetes, bone mineral density, vascular calcification, apoptosis, SERM, biomarker

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Article Details

Year: 2011
Page: [2096 - 2102]
Pages: 7
DOI: 10.2174/138945011798829456
Price: $65

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