Diabetes, Collagen, and Bone Quality
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Diabetes increases risk of fracture, although type 2 diabetes is characterized by normal or high bone mineral density (BMD) compared with the patients without diabetes. The fracture risk of type 1 diabetes as well as type 2 diabetes increases beyond an explained by a decrease of BMD. Thus, diabetes may reduce bone strength without change in BMD. Whole bone strength is determined by bone density, structure, and quality, which encompass the micro-structural and tissue material properties. Recent literature showed that diabetes reduces bone material properties rather than BMD. Collagen intermolecular cross-linking plays an important role in the expression of bone strength. Collagen cross-links can be divided into beneficial enzymatic immature divalent and mature trivalent cross-links and disadvantageous nonenzymatic cross-links (Advanced glycation end products: AGEs) induced by glycation and oxidation. The formation pathway and biological function are quite different. Not only hyperglycemia, but also oxidative stress induces the reduction in enzymatic cross-links and the formation of AGEs. In this review, we describe the mechanism of low bone quality in diabetes and the usefulness of the measurement of plasma or urinary level of AGEs for estimation of fracture risk.
KeywordsDiabetes Bone quality Collagen Cross-links Advanced glycation end products Pentosidine Homocysteine Fracture risk
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Conflict of Interest
M. Saito, Y. Kida, S. Kato, and K. Marumo declare that they have no conflicts of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 16.•Kato S, Saito M, Funasaki H, et al. Distinctive collagen maturation process in fibroblasts derived from rabbit anterior cruciate ligament, medial collateral ligament, and patellar tendon in vitro. Knee Surg Sports Traumatol Arthrosc. 2013. In vitro study for exploring the relationship between lysyl oxidase, lysine hydroxylase, and enzymatic cross-link formation. Google Scholar
- 28.Satio M, Marumo K, Soshi S, et al. Raloxifene ameliorates detrimental enzymatic and non-enzymatic collagen cross-links and bone strength in rabbits with hyperhomocysteinemia. Osteoporos Int. 2010;21:655–66.Google Scholar
- 36.•Thaler R, Agsten M, Spitzer S, et al. Homocysteine suppresses the expression of the collagen cross-linker lysyl oxidase involving IL-6, Fli1, and epigenetic DNA methylation. J Biol Chem. 2011;286:5578–88. In vitro study for exploring the roles of homocysteine on lysyl oxidase expression.PubMedCentralPubMedCrossRefGoogle Scholar
- 45.Saito M. Age-related changes in biochemical characteristics of collagen from human weight-bearing and non-weight-bearing bone. Tokyo Jikeikai Med J. 1999;114:327–37. Available at: http://sciencelinks.jp/j-east/article/200010/000020001000A0286989.php.Google Scholar
- 50.•Saito M, Marumo K, Uhsiku C, et al. Changes in the contents of enzymatic immature, mature, and non-enzymatic senescent cross-links of collagen after once-weekly treatment with human parathyroid hormone (1–34) for 18 months contribute to improvement of bone strength in ovariectomized monkeys. Osteoporos Int. 2011;22:2373–83. Use of monkey OVX model to explore the contribution of collagen cross-link formation to bone strength and the effects of teriparatide treatment on bone strength.PubMedCrossRefGoogle Scholar
- 60.Viguet-Carrin S, Gineyts E, Bertholon C, et al. Simple and sensitive method for quantification of fluorescent enzymatic mature and senescent cross-links of collagen in bone hydrolysate using single-column high performance liquid chromatography. J Chromatogr B Anal Technol Biomed Life Sci. 2009;877:1–7.CrossRefGoogle Scholar
- 66.••Tanaka K, Yamaguchi T, Kaji H, et al. Advanced glycation end products suppress osteoblastic differentiation of stromal cells by activating endoplasmic reticulum stress. Biochem Biophys Res Commun. 2013;438:463–7. In vitro study for exploring the roles of AGEs on cellular dysfunction.PubMedCrossRefGoogle Scholar
- 74.••Mitome J, Yamamoto H, Saito M, et al. Non-enzymatic cross-linking pentosidine increase in bone collagen and are associated with disorders of bone mineralization in dialysis patients. Calcif Tissue Int. 2011;88:521–9. Human biopsy data from the patients with chronic renal failure.PubMedCrossRefGoogle Scholar
- 82.••Hammond MA, Gallant MA, Burr DB, et al. Nanoscale changes in collagen are reflected in physical and mechanical properties of bone at the microscale in diabetic rats. Bone. 2013;60C:26–32. Using diabetic rat model to explore the collagen alignment in bone.Google Scholar
- 93.Yamamoto M, Yamaguchi T, Yamauchi M, et al. Low serum level of the endogenous secretory receptor for advanced glycation end products (esRAGE) is a risk factor for prevalent vertebral fractures independent of bone mineral density in patients with type 2 diabetes. Diabetes Care. 2009;32:2263–8.PubMedCentralPubMedCrossRefGoogle Scholar
- 99.••Schwartz AV, Vittinghoff E, Bauer DC, et al. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA. 2011;305:2184–92. Usefulness of the combination of FRAX and the estimation of diabetes on fracture risk assessment.PubMedCentralPubMedCrossRefGoogle Scholar
- 100.Satio M, Fujii K, Soshi S, et al. Effects of vitamin B6 and Vitamin K2 on bone mechanical properties and collagen cross-links in spontaneously diabetic WBN/Kob rats. J Bone Miner Res. 2005;(Suppl):SU420.Google Scholar