Last update:
16-Oct-2008

The complex interactions between immune system and bone cells have created an interdisciplinary research field of osteoimmunology, which is focused on the molecular understanding of the interplay between the immune and skeletal systems to better understand the pathogenesis of several diseases, including autoimmune disorders, cancer, inflammatory diseases and osteoporosis. In this review, all available data for the organogenesis of the bones and immune systems, the role of the bone in the regulation of the immune response, the role of the immune cells on the regulation of bone homeostasis and finally, the clinical applications of the reveal of these complex interactions are summarized. The two major questions concern the following: (a) Can immune cells be involved in the development of bone-related pathology? and (b) can deregulation of the bone be causing immune-related diseases? The identification of a novel set of proteins within the tumor necrosis factor (TNF)/TNF receptor families that are required for the control of bone remodelling, such as the receptor activator of nuclear factor kappa B (RANK), osteoprotegerin (OPG) and their ligand RANK ligand (RANKL) has revealed some very interesting observations. These molecules are not only responsible for normal osteoclast regulation and function but they also play crucial role in the pathogenesis of several bone disorders, including postmenopausal and steroid-induced osteoporosis, beta-thalassemia-induced bone loss, myeloma bone disease, bone metastases in solid tumors, HIV-infection, that also vascular calcification. This molecular triad also appears to be associated with the development of the immune system through dendritic cells, and constitutes a molecular bridge spanning bone metabolism and immunity. The development of novel agents that target this system may lead to a better management of several "immune-related" bone disorders.

Key words: Bone metastases, Cancer, Multiple myeloma, Osteoimmunology, Osteoporosis.