 Osteoclasts OCs are cells specialized in bone degradation that participate in bone and joint destruction in Rheumatoid Arthritis RA. Experimental models have clearly demonstrated that OCs are essential for local bone resorption in arthritis. In RANKL knockout mice1; 2, in rats receiving OPG3-6 or in c-fos-- hTNF transgenic mice7 induction of arthritis leads to inflammation but not to bone erosion. Systemic osteoporosis is an important comorbidity in RA8; 9. Increased systemic bone resorption due to OC activation occurs even in early 2 years RA and correlates with disease activity10. Bisphosphonates are effective in preventing systemic bone loss in inflammatory diseases, but for unknown reasons do not seem to influence periarticular bone erosion and joint destruction. Finally, a systemic factor affecting osteoclastogenesis seems to be present in RA, as shown by an increased formation of OCs from bone marrow of patients with severe arthritis when compared to controls11. 