The Role of Glucose-Dependent Insulinotropic Polypeptide (GIP) in Bone Metabolism

TL;DR

This paper reviews how the hormone GIP affects bone health by reducing bone breakdown and promoting bone formation, suggesting it could be a treatment for bone diseases.

Contribution

The paper integrates recent findings on GIP's role in bone metabolism and highlights its therapeutic potential in various bone-related conditions.

Findings

GIP inhibits osteoclast activity and promotes osteoblastic bone formation in vitro.

Exogenous GIP reduces bone resorption and increases bone formation markers in humans.

GIP protects against bone deterioration in conditions like osteoporosis and diabetes.

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin hormone identified, best known for promoting glucose-stimulated insulin secretion. Increasing evidence has expanded its physiological relevance beyond glucose metabolism, revealing a significant role for GIP in the gut–bone axis. In vitro studies demonstrate that GIP inhibits osteoclast differentiation and activity while promoting osteoblastic bone formation. Findings from genetic animal models and human variant analyses further support the essential role of endogenous GIP signaling in maintaining bone mass and quality. Exogenous administration of GIP suppresses the bone-resorption marker C-terminal telopeptide of type I collagen (CTX) and increases the bone-formation marker procollagen type I N-terminal propeptide (P1NP) in healthy individuals, reflecting an acute shift toward reduced bone resorption and enhanced bone formation. Moreover, GIP confers protection against bone deterioration in multiple pathological conditions, including postmenopausal osteoporosis, inflammatory bone loss, obesity, and diabetes, etc., suggesting therapeutic potential beyond physiological contexts. Recent evidence also shows that GIP attenuates orthodontic tooth movement by limiting mechanically induced osteoclast activity, highlighting its broader skeletal actions. In this review, we summarize recent advances regarding the role of GIP in bone metabolism, integrating evidence from cellular studies, animal models and human investigations, and discuss future directions for GIP-based interventions.

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