ECTS Abstracts (2015) 1 P20

Effects of stable incretin mimetic on cortical bone micromorphology and strength in a murine model of type 1 diabetes mellitus

Sity Mansur1, Aleksandra Mieczkowska2, Peter Flatt1, Daniel Chappard2, Nigel Irwin1 & Guillaume Mabilleau2

1Ulster University, Coleraine, UK; 2LUNAM University, Angers, France.

Background: Type 1 diabetes mellitus is associated with a high risk for bone fractures. Although bone mass is reduced, bone quality is also dramatically altered in this disorder. However, recent evidence suggests a beneficial role of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) pathways on bone quality. The aims of the present study were to conduct a comprehensive investigation of cortical bone strength at the organ and tissue level and to ascertain whether enzyme-resistant GIP or GLP-1 mimetics could be beneficial for treating bone fragility in type 1 diabetes mellitus.

Methods: Streptozotocin-injected mice were used as a model of type 1 diabetes mellitus. Control and streptozotocin-injected animals were treated with an enzymatic-resistant GIP peptide ([D-Ala2]GIP) or with the GLP-1 mimetic, liraglutide. Bone quality was assessed at the organ and tissue level by microCT, qXRI, 3-point bending, qBEI, nanoindentation and Fourier-transform infrared microspectroscopy. Non-parametric Mann-Whitney U-test was used to compare differences between groups.

Results: Cortical bone strength was dramatically altered in STZ-injected mice as compared with control animals. [D-Ala2]GIP and liraglutide treatment did not significantly improve whole bone strength in STZ mice, except for post-yield displacement that was substantially higher in both treatment groups. Cortical microarchitecture was also severely impacted in the STZ-injected mice with an 18% reduction in cortical thickness. [D-Ala2]GIP and liraglutide treatment did not significantly increase cortical thickness. Alterations of tissue material properties were evidenced in STZ-injected mice with significant reductions in maximum force, hardness, indentation modulus and dissipated energy. Treatment with [D-Ala2]GIP or liraglutide significantly improved these parameters. STZ mice also presented with a reduction in collagen integrity that was restored by treatment with [D-Ala2]GIP or liraglutide.

Conclusions: Treatment of STZ-diabetic mice with [D-Ala2]GIP or liraglutide significantly improves the quality of bone matrix. Further studies are required to further elucidate the molecular mechanisms involved and to validate whether these findings can be translated to the human setting.

Disclosure: The authors declared no competing interests.

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