Cytokines and local factors which affect osteoclast function.

Bone remodeling is a local phenomenon which occurs in discrete packets throughout the skeleton. The cellular events which comprise the remodeling sequence are controlled by cytokines which are generated in the microenvironment of the bone resorbing pockets. These cytokines are derived from marrow mononuclear cells or from bone cells themselves, or they are incorporated into the bone matrix and released in biologically active form as bone resorbs. Evidence is accumulating that some of these cytokines play an important role not just in physiological bone remodeling, but also in common diseases of bone remodeling such as osteoporosis, osteopetrosis, Paget's disease, and malignant diseases which involve bone and chronic inflammatory diseases such as rheumatoid arthritis and periodontal disease. Normal bone remodeling is clearly under local control. It occurs in discrete packets throughout the skeleton, each of which is geographically distinct. Local packets of bone remodeling are also asynchronous with respect to each other. The cellular events which comprise the remodeling sequence are thus regulated primarily by factors which are enriched in that microenvironment. The remodeling sequence, which is continuous, is the same on cancellous bone surfaces as it is within the Haversian systems of cortical bone. Since it is now known that powerful osteoclastotropic factors are produced in the microenvironment of these bone remodelling packets, these local factors or cytokines are the most likely major regulators of osteoclast function.