Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2014) 34 P8 | DOI: 10.1530/endoabs.34.P8

SFEBES2014 Poster Presentations Bone (30 abstracts)

Liraglutide, a glucagon-like peptide-1 receptor agonist, improves bone mass and architecture in ovariectomised mice

Marie Pereira , Jeshmi Jeyabalan , Camilla Sofie Jørgensen , Mark Cleasby , Mark Hopkinson & Chantal Chenu


Royal Veterinary College, London, UK.


The increased incidence of type 2 diabetes mellitus (T2DM) among the aged is associated with an impaired skeletal structure and a higher prevalence for bone fractures. Besides, anti-diabetic therapies can also negatively affect bone mass. In this study, we tested the skeletal effects of chronic administration of two glucagon-like peptide receptor (GLP-1R) agonists and examined the expression of GLP-1R in bone tissue and cells. Twelve week-old female C57Bl/6N mice were ovariectomised (OVX) to induce bone loss. Four weeks after OVX, mice were treated with either: Liraglutide (LIR) 0.3 mg/kg per day, Exenatide (Ex-4) 10 μg/kg per day or saline for 4 weeks (n=10/group). Cortical and trabecular bone architecture was analysed in tibias by micro-CT and serum samples collected for evaluation of sclerostin levels, an inhibitor of bone formation. RNA was extracted from control femora and osteoblastic cell lines to analyse the presence of GLP1R using RT-PCR. Our results show that LIR significantly increases bone mass compared to controls manifested by higher trabecular bone volume percent (+61%, P<0.01), trabecular number (+46%, P<0.05), while trabecular pattern factor (−15%, P<0.05) and structure model index (SMI) (−9%, P<0.05) were significantly decreased, reflecting improvement in trabecular bone structure and connectivity. The cortical indexes were not significantly affected by LIR. EX-4 showed a similar tendency for improvement of trabecular mass and architecture, although the effects were non-significant, except for SMI (−9%, P<0.05). We could not detect GLP1R in bone, UMR-106 rat osteoblastic and MLO-A5 mouse osteocytic cell lines, suggesting that GLP1R agonists may affect bone indirectly. Serum sclerostin levels were significantly decreased by Ex-4 (−23%, P<0.05) but not LIR, suggesting that Ex-4 may decrease the inhibition of bone formation induced by sclerostin. Our data suggest that GLP1R agonists may have beneficial effects on bone and further studies will determine their mechanisms of action.

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