Osteocytes.

For a long time, osteocytes were regarded as passive bystanders of bone metabolism. Bone remodeling was considered to be an interplay between bone forming osteoblasts and bone degrading osteoclasts. However, the dogma of osteocytes as bystanders within the bone has changed fundamentally since the turn of the millenium. Rather than being silent bystanders, osteocytes are the master cells of bone metabolism. To illustrate the central role of osteocytes, we performed a selective literature research in PubMed and Google Scholar using the search terms "osteocyte", "fracture healing", "bone healing", "bone remodeling", "bone metabolism", "sclerostin", "RANKL/OPG", "Wnt signaling pathway" and "FGF23". We included German and English clinical and preclinical studies as well as literature reviews. Osteocytes develop out of osteoblasts and are the key player in bone metabolism. They build a network within bone and make up 90 - 95% of all bone cells. In contrast to osteoblasts and osteoclasts, osteocytes can reach the age of the organism itself. Their morphology - with its dendritic connection through nexus - forms the perfect basis of osteocyte function. Besides the role as mechanosensor in bone, osteocytes control osteoblasts via sclerostin and osteoclasts via the RANK/RANKL/OPG pathway. Bone mineralisation is controlled by directing local phosphate concentrations. The systemic phosphate levels are regulated in interaction with the kidneys by the hormone FGF23. Understanding the role of osteocytes promises better therapies in clinical practice. Sclerostin antibodies and denusomab, an OPG agonist, are already established for clinical application in osteoporosis therapy. Antibodies against FGF23 or its receptors are used in preclinical and clinical trials. Bortezomib, an antibody which improves vitality of osteocytes, is already used for multiple myeloma therapy. For orthopaedic surgery, understanding the role of osteocytes promises new therapeutic approaches in future. Improvement in osseous integration of metallic implants and medical treatment of disturbed fracture healing are future fields in which therapies may be established by manipulating osteocytes.