Bone: incretin hormones perceiver or receiver?

Abstract

Novel incretin-based drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i), have been last introduced in the pharmacological treatment of type 2 diabetes. In the last few years, the interest on the relationship of gut hormones with bone metabolism in diabetes has been increasing. The aim of present paper is to examine in vitro and in vivo evidence on the connections between incretin hormones and bone metabolism. We also discuss results of clinical trials and metaanalysis, explore the effects of incretin drugs in vitro on osteogenic cells and osteoclasts, and speculate on the possibility of different effects of GLP-1 RA and DPP-4i on the risk of bone fractures risk in humans. Although existing preliminary evidence suggests a protective effect on the bone, at least for DPP-4i, further controlled, long-term studies with measurement of bone markers, bone density, and clinical fractures rates are needed to substantiate and confirm those findings.

Figure 1

Gut mediators of the acute bone turnover in response to feeding. GLP-1: glucagon-like peptide-1; GLP-2: glucagon-like peptide-2; GIP: glucose-dependent insulinotropic peptide; PYY: peptide YY; CNS: central Nervous System. Broken lines represent putative pathways.