GIP and the gut-bone axis – Physiological, pathophysiological and potential therapeutic implications

The influence by gut-derived hormones on bone remodelling appears increasingly important as research on the enteroendocrine-osseous axis accelerates. Glucose-dependent insulinotropic polypeptide (GIP) is secreted from the gut and potentiates insulin secretion in a glucose-dependent manner. GIP has, like the two other gut-derived hormones, glucagon-like peptide 1 and glucagon-like peptide 2, been shown to affect bone remodelling as part of the enteroendocrine-osseous axis. Observational studies have shown that a mutation in the GIP receptor causing reduced receptor signalling leads to lower bone mineral density and increased fracture risk. Rodent as well as human studies have shown that GIP causes serum levels of the bone resorption marker carboxy-terminal type 1 collagen crosslinks to decline. GIP may also increase bone formation indicating a potential uncoupling of bone resorption and formation. Here, we review past and recent discoveries elucidating the enteroendocrine-osseous axis with a special focus on GIP.