 TNF-alpha is a major pathologic mediator in RA. It may induce bone resorption either directly, stimulating osteoclastogenesis12; 13 or indirectly, by influencing RANKL, OPG and prostaglandin production by osteoblasts14; 15. These pathways may be important for the pathophysiology of several diseases such as periodontitis, Rheumatoid arthritis and osteoporosis16; 17. In mice, TNF-alpha increases the number of osteoclast precursors in vivo but its role may, however, be more complex and implicate also osteoclastogenesis-inhibiting mechanisms18; 19; in fact, in certain conditions, TNF-alpha may decrease osteoclastogenesis20, so the in vivo effect of blocking TNF may be difficult to predict from these models. 