Bone is a peculiar connective tissue which functionally interacts with many other organs and tissues, including bone marrow, lymphoid tissue, kidney, adipose tissue, endocrine pancreas, brain and gonads. Bone functions are accomplished by three principal cell types: the osteoblasts, cells of mesenchymal origin having osteogenic functions, the osteoclasts, giant multinucleated cells arising from the monocyte-macrophage line and devoted to resorb bone, and the osteocytes, the latter arising from mature osteoblasts that, once deposited the bone matrix, remain trapped in it, becoming quiescent cells. Osteocytes are known for their role as mechanosensors, however, old and new evidence showed their active contribution to mineral homeostasis. Moreover, the cross-talk between bone cells is crucial, since a correct bone homeostasis relies on a right coupling between osteoblast and osteoclast functions. Any deregulation of this coupling is responsible for bone disease condition, which reflects on other organs with which bone interacts.