A paradigm of integrative physiology, the crosstalk between bone and energy metabolisms.

Thanks to integrative physiology, new relationships between organs and homeostatic functions have emerged. This approach to physiology based on a whole organism approach has allowed the bone field to make fundamental progress. In the last decade, clinical observations and scientific evidences in vivo have uncovered that fat with leptin controls bone mass through brain including a hypothalamic relay and sympathetic nervous system. The finding that energy metabolism affects bone remodelling suggested that in an endocrine perspective, a feedback loop should exist. Beside its classical functions, bone can now be considered as a true endocrine organ secreting osteocalcin, a hormone pharmacologically active on glucose and fat metabolism. Indeed osteocalcin stimulates insulin secretion and beta-cell proliferation. Simultaneously, osteocalcin acts on adipocytes to induce Adiponectin which secondarily reduce insulin resistance. This cross regulation between bone and energy metabolism offers novel therapeutic targets in type 2 diabetes and osteoporosis.