Immunoregulation of osteoclast differentiation in multiple myeloma bone disease

Studies have given new insights into the pathogenesis of myeloma bone disease and demonstrated a strong interdependence between the immune and skeletal system as well as tumor growth and osteoclast activity. Discovery of the receptor activator of the nuclear factor kB (RANK)/RANK ligand (RANKL)system brought a rapid progress in the understanding of the regulatory mechanism of osteoclast differentiation in physiological and pathological conditions. However, numerous connections have been discovered in osteoimmunology beyond merely the actions of RANKL. These include both cells and cytokines participating in osteoclast development and bone destruction. The resulting bone destruction releases several cytokines which in turn promote myeloma cell growth, thus maintaining a vicious circle between the bone destructive process and tumor progression. Therefore, the inhibition of bone resorption could not only decrease myeloma bone disease, but also the tumor progression. Furthermore, research into osteoimmunology promises the discovery of new strategies and the development of innovative therapeutics to cure or alleviate bone loss in multiple myeloma bone disease