Bone Abstracts

Objectives: A role for the gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in controlling bone mass and strength has previously been reported. However, lack of one gut hormone is compensated by an elevated sensitivity to the other in single receptor knockout mice. As such the exact role of GIP and GLP-1 in bone is unclear. The aims of the present study were to assess bone mass and strength in mice with functional deletion of both the GIP and GLP-1 receptors.

Materials and methods: Eight (26 week-old) mice with deletion of the GIP and GLP-1 receptors (DIRKO mice) were age- and sex-matched with 10 WT mice. Trabecular and cortical bone microarchitecture was studied by high-resolution microCT at the femur. Bone strength and intrinsic material properties were studied respectively by three-point bending and nanoindentation. Bone mineral and collagen properties were assessed by quantitative backscattered electron imaging and Fourier-transformed infrared microscopy. Non-parametric Mann–Whitney U-test was used to compare differences between groups.

Results: As compared with control mice, DIRKO animals exhibited significant increases in BV/TV (210%, P=0.003) and trabecular number (207%, P=0.012). Cortical microarchitecture was affected in DIRKO mice as demonstrated by a significant reduction in bone outer diameter (−9%, P=0.028) with unchanged marrow diameter. Cortical thickness and cortical area were significantly reduced by 17% and 14% respectively. Investigation of bone strength by 3-point bending revealed significant reductions in yield stress (−48%, P=0.032), ultimate stress (−44%, P=0.034) and post-yield work to fracture (−31%, P=0.034) in DIRKO mice. Alterations of intrinsic material properties were evident in DIRKO animals with significant decreases in maximum force (−21%, P=0.027), hardness (−29%, P=0.014) and dissipated energy (−25%, P=0.014). Interestingly, bone mineral density distribution was not affected by in DIRKO mice, but the ratio of mature/immature collagen cross-links was significantly reduced by 9% (P=0.011).

Conclusions: Overall, these data demonstrate the role of gut hormones in bone physiology. This is important regarding the use of GLP-1 mimetics in type 2 diabetes.