Understanding the Gut-Bone Signaling Axis

Walter Ramsey, Carlos M. Isales

Although originally identified as modulators of nutrient absorption, the gut hormones gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon-like peptide-2 (GLP-2) have also been found to play an important role in the regulation of bone turnover. These "incretin" hormones promote bone anabolism by stimulating osteoblast differentiation as well as increasing osteoblast longevity. In addition, GIP and perhaps GLP-2 attenuate the activity of osteoclastic cells, leading to a net increase in bone deposition and ultimately increasing bone mass. Studies have demonstrated that these hormones are important for bone mineralization and overall bone quality and function evolutionarily as important nutritional links signaling nutrient availability for skeletal anabolic functions. Accordingly, these entero-osseous hormones (EOH) have therapeutic potential for the management of osteoporosis. Although this chapter primarily focuses on skeletal effects of these incretin hormones, the GIP, GLP-1, and GLP-2 receptors are actually widely expressed throughout the body. Therefore, we will also briefly discuss these extraosseous receptors/effects and how they may indirectly impact the skeleton.