Incretins and bone: Evolving concepts in nutrient-dependent regulation of bone turnover

Abstract

Postprandial variation of bone turnover markers and the closed relationship between bone remodeling and nutrient supply has been extensively studied in the past few years, but the underlying pathophysiologic mechanisms remain largely unknown. recent studies have shown that the acute regulation of bone turnover induced by feeding is probably mediated by gastrointestinal (GI) peptides. The greater response of bone remodeling during oral versus intravenous glucose administration and the inhibition of this response after administration of octreotide, that inhibits the release of GI peptides, further support the existence of a gutbone axis. Glucose-dependent insulinotropic peptide and glucagon-like peptides-1 and -2 are released from K and L cells of the gastrointestinal tract, respectively, and are considered the main mediators of the postprandial response of bone turnover. In this review we outline the most recent evidence that demonstrates the role of incretins in nutrient-dependent regulation of bone metabolism. Further elucidation of the underlying mechanisms can be exploited therapeutically in the future.

GLP-1 Receptor Agonist Treatment Increases Bone Formation and Prevents Bone Loss in Weight-Reduced Obese Women

“…While several studies support that the gut hormones glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 2 (GLP-2) are modulators of bone growth (20 -22) and remodeling (23)(24)(25) the possible role of the gut hormone GLP-1 and its analogues on bone turnover is less clear (26). However, cortical osteopenia and bone fragility (27) as well as reduced cortical bone strength and bone quality (28) have been demonstrated in GLP-1 receptor knock-out mice.…”

Long-Acting Glucose-Dependent Insulinotropic Polypeptide Ameliorates Obesity-Induced Adipose Tissue Inflammation

“…Of note, similar effects were obtained in mice on RC with shortterm [d-Ala 2 ]GIP treatment, indicating that GIP may be involved with immune-regulatory pathways responsible for the development and migration of BM-derived neutrophils and monocytes, independently of the metabolic status of the organism. GIPR is present in the bone, both on osteoclasts and osteoblasts, and mediates GIP regulation of bone turnover, suggesting that GIP may act directly in the bone to prevent egress of immune cells (35). A second mechanism by which GIP may induce egress of immune cells from BM is via increased formation of corticosterone (36), a hormone that negatively regulates BM hematopoietic stem cells (37).…”

Bone damage in type 2 diabetes mellitus

“…Available data from animal models (mainly) and small studies in humans indicate that these drugs could positively modify the balance of bone turnover, increasing bone formation and reducing nocturnal bone resorption [61,67]. Moreover, a meta-analysis of relatively short-term studies [68] suggests that therapy with DPP-4 inhibitors might be associated with reduced fracture risk.…”