Crosstalk between the brain and bone

Bone alters its metabolic and anabolic activities in response to the variety of systemic and local factors such as hormones and growth factors. The responsiveness of bone is accomplished by the action of osteoblasts, osteoclasts and osteocytes through the process of bone remodeling. The importance of the nervous system on body homeostasis systems has been described (1) and has been suggested that organogenesis and tissue repair are under neuronal control. The first documentation of an anatomic relationship between nerves and bone was made via woodcut, by Charles Estienne in Paris in 1545, which demonstrated nerves entering and leaving the bones of a skeleton (2). Later, several authors showed that cortical bone is densely innervated (3) and differentiated myelinated and non-myelinated fibers are associated with the arterial vessels and venous sinusoids in bone (4). This began a steady flow of studies of various nerve types in bone by a number of different groups (2). The field has recently been reinvigorated by the observation of an important role of neural control of many aspects of bone metabolism (2