Optimal bone mechanical and material properties require a functional GLP-1 receptor

Bone is permanently remodeled by a complex network of local, hormonal and neuronal factors that affect osteoclast and osteoblast biology. Among these factors a role for gastro-intestinal hormones has been proposed based on evidence that bone resorption dramatically falls after a meal. Glucagon like peptide-1 (GLP-1) is one of these gut hormones and despite several reports suggesting an anabolic effect of GLP-1, or its stable analogues, on bone mass, little is known about the effects of the GLP-1/GLP-1 receptor on bone strength. In the present study we investigated by three-point bending, quantitative x-ray microradiography, microCT, qBEI and FTIRI bone strength and bone quality in male GLP-1R knockout (GLP-1R KO) mice as compared with control wild-type (WT) animals. Animals with a deletion of the GLP-1R presented with a significant reduction of ultimate load, yield load, stiffness, total absorbed and post-yield energies as compared with WT animals. Furthermore, cortical thickness and bone outer diameter were significantly decreased in deficient animals. The mineral quantity and quality were not significantly different between GLP-1R KO and WT animals. On the other hand, the maturity of the collagen matrix was significantly reduced in deficient animals and associated with lowered material properties. Taken together, these data support a positive effect of the GLP-1R on bone strength and quality.