Endocrine Abstracts

Bone remodelling is regulated by many endogenous factors, with recent attention on the pivotal role of gut-derived peptide hormones in this regard. Indeed, a gut-bone axis has now been described, that is coordinated largely by the secretion and action of intestinal-derived peptide hormones. In addition to this, obesity and diabetes are highly prevalent metabolic disorders that negatively affect health, and there is now a clear link between these diseases and impaired bone health. To add to this, both obesity and diabetes are associated with impaired secretion and action intestinal-derived hormones, alongside an elevated risk of bone fracture that is not fully dependent on bone mineral density (BMD) measurements. It follows that gut-derived hormones and their related long-acting analogues, with some already clinically approved for diabetes and/or obesity as well as short bowel syndrome, possess positive effects on bone to reduce fracture risk within these specific diseases. In particular, the incretin peptides, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), as well as glucagon-like peptide-2 (GLP-2), exert key direct and/or indirect benefits on bone metabolism. Furthermore, novel unimolecular gut peptide drugs that can simultaneously target multiple receptors also show particular promise for treating bone disorders. In this presentation we will provide an initial appraisal of the relationship between obesity, diabetes and bone remodelling, with a focus on the positive impact of these gut-derived peptide hormones for bone health in obesity/diabetes. Overall, drugs engineered to promote GIP, GLP-1 and GLP-2 receptor signalling, either alone or in combination, offer therapeutic promise for improving bone health and merit further preclinical and clinical investigation.