In the present study, we investigated the role of RANKL as a disease modifier in TNF-driven inflammatory arthritis employing two proprietary genetic models of RANKL-mediated pathologies; an osteopetrosis model caused by osteoclast absence due to a functional mutation in the RANKL gene (22) (Rankltles/tles mice) and osteoporosis transgenic models that overexpress human RANKL (TgRANKL mice) displaying increased osteoclast activity and bone resorption (23). This evidence concerns the gene TNFSF11 and osteopetrosis.