Advanced Glycation End Products, Diabetes, and Bone Strength

Abstract

Diabetic patients have a higher fracture risk than expected by their bone mineral density (BMD). Poor bone quality is the most suitable and explainable cause for the elevated fracture risk in this population. Advanced glycation end products (AGEs), which are diverse compounds generated via a non-enzymatic reaction between reducing sugars and amine residues, physically affect the properties of the bone material, one of a component of bone quality, through their accumulation in the bone collagen fibers. On the other hand, these compounds biologically act as agonists for these receptors for AGEs (RAGE) and suppress bone metabolism. The concentrations of AGEs and endogenous secretory RAGE, which acts as a "decoy receptor" that inhibits the AGEs-RAGE signaling axis, are associated with fracture risk in a BMD-independent manner. AGEs are closely associated with the pathogenesis of this unique clinical manifestation through physical and biological mechanisms in patients with diabetes mellitus.

Keywords: Bone quality; Crosslink; Fracture; Material properties; Pentosidine; Receptor for advanced glycation end products (RAGE).

Fig. 1

The association between the serum levels of pentosidine as well as endogenous secretory receptor for advanced glycation end products (esRAGE) and vertebral fractures in patients with type 2 diabetes mellitus. The data are expressed as odds ratios of vertebral fracture after adjusting for age, body mass index, HbA1c levels, creatine levels, duration of diabetes, and spine bone mineral density per standard deviation increase in each factor. OR, odds ratio; CI, confidence interval; esRAGE, endogenous secretory receptor for advanced glycation end products. *P < 0.05; **P < 0.01. Adapted from ref. [49]