Denosumab directly targets osteoclastgenesis by its specific action on the RANKL pathway, while bisphosphonate acts as antiresorptive agents mainly by their suppression on function of osteoclasts. The previous clinical trials showed that denosumab resulted in a quicker decrease in markers of bone resorption than bisphosphonate, that denosumab has beneficial effect against the prevention of fracture in postmenopausal women and bone erosion in patients with rheumatoid arthritis and that recombinant osteoprotegerin provided the therapeutic efficacy in two adult siblings with juvenile Paget's disease. Taken together, it is strongly expected that denosumab would be developed to be one of potent therapeutic agents for Paget's disease of bone which is characterized with the accerelated bone resorpton by osteoclasts as the primitive pathological condition.