While initiation fracture toughness provides a measure of resistance against the initiation of a crack from a point of weakness in bone, the propagation fracture toughness provides a measure of fracture resistance against the propagation of pre-existing cracks, which initiate in bone during daily loading. Therefore, measuring the propagation toughness not only allows more accurate characterization of bone toughness, but also directly relates to fracture. Bone differs from all other tissues in a body by being composed predominantly of a mineral and a small amount of organic material that contains a uniquely large proportion of collagen. Based on this unusual composition, it is generally agreed that collagen plays a critical role in the structure and function of bone. In bone matrix, collagen fibers provide ductility and ability to absorb energy. Alterations of collagen properties can therefore affect the mechanical properties of bone and increase fracture susceptibility. Several studies indicate that the large variation in bone strength may be in part related to differences in the quality of the collagenous matrix, including the nature and extent of its posttranslational modifications. During synthesis and maturation, fibrillar collagens undergo numerous posttranslational modifications, which are performed by different enzymes. Enzymatic trivalent mature crosslinks such as pyridinoline and deoxypyridinoline are the predominant stabilizing inter- and intra-molecular crosslinks in mature tissues. The formation of these crosslinks in the extracellular matrix is initiated by the conversion of telopeptidyl lysine and hydroxylysine residues to aldehyde form through the action of lysysl oxidase. The LOX-mediated crosslinking is crucial to the integrity and function of bone tissue. The content of PYD and DPD reaches a maximum concentration Arecaidine propargyl ester tosylate between 15�C17 years of age in human bone and generally is AZD 3988 maintained at a steady level over a lifetime through the actions of IGF1 via enzymatic pathways. In contrast to enzymatic crosslinks, non-enzymatic crosslinks vary with age. Consequently, our study is focused on non-enzymatic processes that lead to crosslinking of bone matrix proteins in healthy, normally aging donors. In particular, it has been established that due to low turnover in a body, long-lived proteins accumulate advanced-glycation end-products and the accumulation levels of AGEs are high in diabetes and during aging. Formation of AGEs in bone accounts largely for the increase of collagen crosslinking after skeletal maturation. There are several molecularly welldefined AGEs that are specific to non-enzymatic glycation such as pentosidine, glucosepane or vesperlisines. Pentosidine is a naturally fluorescent, mature crosslink of clinical relevance. It is commonly used as a biomarker of non-enzymatic glycation of bone matrix proteins.