Endocrine Abstracts

Both type 1 and 2 diabetes are associated with an increased fracture risk. Whereas in type 1 bone fragility is mostly explained by a lower peak bone mass and low bone turnover state, which is a common feature of several chronic and/or inflammatory diseases starting during growth, in type 2 diabetes there is not necessarily low bone mass, rather a higher aBMD related to overweight/obesity in these subjects. To explain the increased propensity to fractures in this case, a higher risk of falls and decreased bone quality have both been advocated. The latter includes alterations in collagen crosslinks by advanced glycation end-products (AGEs) such as pentosidine; higher sclerostin levels associated with low bone formation; and microstructural alterations, particularly an increased cortical porosity. The molecular mechanisms relating glucose, fat and bone metabolism appear increasingly complex. They involve the transcription factor Ppar gamma, which promotes fat accumulation at the expenses of bone forming cells; Wnt-beta-catenin signaling; inflammatory factors, -i.e. interleukins-, and adipokines, -such as leptin and adiponectin-, that influence both insulin resistance and bone loss; and bone-derived molecules, including (undecarboxylated) osteocalcin and RANK Ligand, both recently found to regulate glucose metabolism. Moreover, genome wide association studies (GWAS) have started to unveil common genes that exert pleiotropic effects on the susceptibility to both diabetes and osteoporosis.