Several studies in a variety of animal models have proved not only the dominance of RANKL blockade with OPG in inhibiting osteoclastogenesis and bone resorption, but also the role of deregulation of the RANK/RANKL/OPG system in the pathophysiology of multiple bone remodeling disorders such as osteoporosis, glucocorticoid-induced bone loss, erosive arthritis including rheumatoid arthritis, hypercalcemia of malignancy, Paget's disease of the bone and bone metastasis [6]. This evidence concerns the gene TNFRSF11B and bone Paget disease.