In adult bone, the PYD and DPD concentrations are lower in trabecular than cortical bone. We did not observe any abnormal levels of PYD and DPD in the analyzed bone samples that originated from healthy, normally aging human donors. Due to the fundamental importance of maintaining a healthy glucose/energy metabolism, an array of hormones and morphogenetic proteins evolved in vertebrates to control and tune the glucose/energy metabolism. Therefore, it is a major challenge to determine the nature of the interactions within the investigated IGF1/sugar metabolism/ bone quality axis. The complexity of IGF1 BMS 961 functions and the role of the lifestyle and environmental factors in the aforementioned axis are still poorly understood. During evolution, a single insulin/IGF1 pathway diverged into two hormonal pathways in mammals; insulin evolved to perform primarily a metabolic role in energy metabolism, while IGF1/growth hormone axis evolved to serve growth, development, and likely, longevity. Therefore, the contemporary model assigns IGFs a central role in regulating growth, development and reproduction in mammals, while insulin DMPO serves to regulate energy accumulation, storage and expenditure. However, IGF1 and insulin exert overlapping roles in many physiological processes. Animal studies using a variety of species, including nondiabetic and diabetic animals, have demonstrated that IGF1 lowers glucose levels in blood by stimulating glucose uptake from the bloodstream. We propose that the increased/high levels of IGF1 during development as well as growth and puberty exert desired effects on bone quality, and thus, protect bone from fracture. Conversely, decreased/ low levels of IGF1 lead to poor bone quality. Thus, due to its involvement in glucose metabolism and the reciprocal cross-talk between the IGF1- and insulin- receptors, IGF1 may play an important role in the age-related accumulation of AGEs in bone tissue. Interestingly, osteocalcin was recently identified as an osteoblast-secreted hormone regulating insulin secretion and sensitivity. Osteocalcin is a part of a complex signaling network between bone and the organs classically associated with the regulation of energy homeostasis, such as the pancreas and adipose tissue. OC��s function is regulated by insulin and leptin. In mice and humans, osteocalcin can be present in the serum in both carboxylated and undercarboxylated form. It has been shown that in mice the undercarboxylated form of osteocalcin acts as a hormone integrating bone with energy metabolism and alters insulin expression, secretion and sensitivity. Delineation of the role of carboxylated and undercarboxylated osteocalcin in glucose metabolism in humans is difficult, because it is obscured by many factors, in particular, by vitamin-K-dependent gamma-carboxylation of glutamic acid residues. Systematic investigations are required to get insight into these important processes.