The abnomalities in cytokines may be an pathogenetic factor in human diseases as diverse as rheumatoid arthritis (RA), some bone diseases, multiple myeloma, metastatic bone tumors. A cytokine imbalance in favour of pro-inflammatory mediators may be a central pathogenic mechanism in RA. Pro-inflammatory mediators include the cytokines TNF-alpha and IL-1, which activate osteoclasts to resorb subchondral bone. A further important mediator is the recently described osteoclast differentiation factor (ODF) (also reffered to as TNF-related activation-induced cytokine [TRANCE], receptor activator of nuclear factor kappaB ligand [RANKL], or osteoprotegerin ligand).