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Bone Abstracts (2016) 5 OC4.5 | DOI: 10.1530/boneabs.5.OC4.5

ECTS2016 Oral Communications Catabolism and metabolism (6 abstracts)

Effects of glucagon-like peptide-1 receptor agonists on bone blow flow and architecture in diabetic mice

Marie Pereira , Stephanie Gohin , Mark Cleasby & Chantal Chenu


Royal Veterinary College, London, UK.


Type 2 diabetes mellitus prevalence increases with age and the disease predisposes to increased risk of fractures and skeletal complications. One possible contributor to skeletal weakening in diabetes is a decline in blood supply. We hypothesised that bone blood flow is impaired in diabetic mice and that chronic administration of glucagon-like peptide-1 receptor agonists (GLP-1RA) can increase blood flow to bone, thereby stimulating bone formation and improving bone architecture.

Nine weeks old male diabetic (db/db) and control mice were daily injected subcutaneously for 28 days with saline or the GLP-1RA Exenatide (Ex-4) (10 μg/kg per day) (n=10/group). The effect of Ex-4 on hind limb perfusion was measured by laser Doppler imaging. Tibial bone architecture was imaged by micro-CT ex-vivo.

Diabetic mice had −40% lower bone blood flow than control mice (P<0.0001) at baseline. Ex-4 acutely increased tibial blood flow in diabetic mice from 15 min of injection to a maximum of 25% increase compared to saline (P<0.0001). Similarly, blood flow was increased with Ex-4 in control mice but at a lower extend than in diabetic mice (+20%, P<0.05). No chronic effect of Ex-4 was shown when blood flow was monitored after the last injection.

Diabetic mice have lower trabecular bone mass compared to controls, due to decreases in trabecular number and thickness. They also exhibit impaired bone connectivity, structure and cortical bone geometry. Ex-4 treatment increased trabecular bone volume (+49%, P<0.01), thickness (+8%, P<0.01) and number (+38%, P<0.01) in diabetic but not in control mice. Connectivity and structure were also improved as shown by decreased trabecular pattern factor (−29%, P<0.0001) and structure model index (−11%, P<0.01).

In conclusion, our results suggest that diabetic mice have lower blood flow and impaired skeletal structure and that Ex-4 exert a bone anabolic action in diabetic mice that could be in part due to its increased skeletal perfusion.

Volume 5

43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

European Calcified Tissue Society 

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