Potential role of pancreatic and enteric hormones in regulating bone turnover

It is clear that the traditional nutrients and classical regulators of bone metabolism are no longer adequate to explain all the observed interactions between diet and bone health (or disease). The evidence supports a role for the pancreatic or enteric hormones in both the acute and chronic regulation of bone metabolism (Table 1). Despite this, the physiological regulator(s) involved in the acute nutrient-induced suppression of bone turnover remain elusive. There are a substantial number of bone-active peptides that are acutely responsive to nutrients, and current evidence suggests that these may represent a highly complex, integrated network of physiological regulators acting on bone metabolism. The model in Fig. 5 summarizes the information currently available, showing a stimulatory, inhibitory, or potential effect of the pancreatic and enteric hormones on bone metabolism. Preliminary evidence suggests that the effects of pancreatic or enteric hormones may be through direct modulation of osteoblast and osteoclast function. In addition, studies support effects on maturation and differentiation of osteoblasts and osteoclasts. These actions may include regulation of monocyte and lymphocyte function, with indirect effects on osteoblasts and osteoclasts. Several transgenic and knock models for the gut and pancreatic hormones or their receptors showed a bone phenotype in vivo in response to a number of Stressors (e.g., oophorectomy), suggesting a functional role for the hormone (or receptor) in bone metabolism. However, feeding studies have not yet been performed in these transgenic and knock models, and until these data are available, it will not be possible to implicate these hormones in the regulation of nutrient-induced changes in bone turnover. Furthermore, the factors regulating the integration of energy and bone metabolism are clearly multifactorial and are likely to exhibit significant redundancy. It is possible, therefore, that double knockout mouse models as well as complex human studies may be required to elucidate the full impact of the pancreatic or enteric hormones on bone physiology. What is clear is that we have a significant amount to learn about the impact of nutrients on bone health and the factors regulating these responses. © 2005 American Society for Bone and Mineral Research.