Bone Abstracts

Objectives: Glucose-dependent insulinotropic polypeptide (GIP) is secreted by intestinal K-cells into the blood supply in response to nutrient ingestion and absorption. Although osteoblasts and osteoclasts express the GIP receptor (GIPR), the main action of the GIP/GIPR pathway in bone physiology and bone quality is unknown. The aim of the present study was to investigate bone quality in a mouse model of GIPR deficiency.

Materials/methods: Eleven 16 weeks old GIPR knock-out male mice, with a deletion of the first six exons of the GIPRr gene, were age- and sex-matched with 12 wild-type (WT) mice for this study. Resistance to fracture was studied by three-point bending in femur, whilst cortical microarchitecture was determined by high resolution microCT and quantitative X-ray imaging. Intrinsic material properties were investigated by nanoindentation. In addition, bone mineral and collagen properties were assessed by quantitative backscattered electron imaging (qBEI) and Fourier-transformed infrared microscopy (FTIRM). Non-parametric Mann–Whitney U test was used to compare differences between groups.

Results: As compared with control mice, GIPR KO animals presented a reduction in bone strength as evidenced by significant decreases in ultimate load (−11%) and absorbed energy (−28%). Cortical microarchitecture was also affected by the lack of a functional GIPR as demonstrated by significant reductions in cortical thickness (−20%) and cross-sectional moment of inertia (−18%). These microarchitectural modifications were accompanied by alterations of intrinsic material properties. Indeed maximal load and hardness as assessed by nanoindentation on hydrated bone were significantly reduced by 13 and 16% respectively. Furthermore, bone mineral density distribution was also decreased by 12% and the ratio of mature/immature collagen cross-links was reduced by 16%.

Conclusion: The inactivation of the GIP/GIPR pathway resulted in marked alterations of cortical microarchitecture, bone matrix properties and bone strength. Overall, these data support a fundamental role of the GIP/GIPR pathway in bone physiology.