Osteoclasts are the only cells that destroy and resorb bone. The differentiation and activation of osteoclasts are tightly regulated by osteoblasts. Osteoblasts express RANKL essential for osteoclast differentiation. Osteoclast precursors express RANK, a receptor of RANKL, recognized RANKL through cell-cell interaction. Serum levels of RANKL were markedly elevated in deficiency of osteoprotegerin (OPG), a soluble decoy receptor for RANKL. Calcitonin and bisphosphonate are used for inhibitory drugs of bone resorption by osteoclasts. In addition, a specific anti-RANKL monoclonal antibody is expected as well-tolerated bone antiresorptive agent.