Bone and brain: a review of neural, hormonal, and musculoskeletal connections.

Nerves have been identified in bone. Their function has recently become the focus of intense study. Metabolic control of bone is influenced by the nervous system. Potential transmitters of this influence include glutamate, calcitonin gene-related protein (CGRP), substance P, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP), leptin, and catecholamines. Disorders of nerves - central or peripheral--can have substantial influence on bone health and repair. Specifically considered are the potential neural influences at work in such conditions as osteoporosis, fracture healing, Charcot osteoarthropathy, musculoskeletal pain syndromes, heterotopic ossification, skeletal growth and development, and obesity-related increased bone density. In this article, we review the current state of experimental and clinical evidence implicating the role of nervous tissue in regulating bone biology and discuss the current understanding of molecular signaling between nervous and osseus tissue in the homeostatic maintenance of the skeleton.