Glycation endproducts in osteoporosis--is there a pathophysiologic importance?

Advanced glycation endproducts (AGEs) are chemical modifications of proteins by carbohydrates including those metabolic intermediates formed during the Maillard reaction. The generation of AGEs is an inevitable process in vivo. AGEs constitute a heterogeneous class of compounds characterized by brown color, fluorescence and a tendency to polymerize. These unique compounds are specifically recognized by AGE receptors (RAGE) present on different cell types. A remarkable feature of AGE-mediated cross-linked proteins is decreased solubility and resistance to proteolytic digestion. This effect results in altered biomechanical properties in affected tissues including increased stiffness and rigidity. The AGE-RAGE interaction additionally induces activation of nuclear factor kB (NF-kB) in RAGE bearing cells (e.g., cells participating in bone turnover). This interaction results e.g. in increased expression of cytokines, growth factors and adhesion molecules. Recent findings provide important evidence that bone proteins are also affected by AGE modification. Investigations conducted by other groups, as well as ours, support the hypothesis that bone protein glycation influences osteoclasts (bone resorption) and osteoblasts (bone formation).