Osteoclasts, the multinucleated cells that resorb bone, originate from monocyte-macrophage lineage cells. Various hormones, cytokines and growth factors are involved in osteoclastogenesis, via interaction with osteoblasts. Deficiency of osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of NF-kappa B ligand (RANKL), in mice induces osteoporosis caused by enhanced bone resorption but also accelerates bone formation. OPG-deficient mice exhibite high serum alkaline phosphatase activity and osteocalcin concentration, both of which are decreased to the levels of wild-type mice by the bisphosphonate injection. This suggests that bone formation is coupled with bone resorption in vivo. RANKL expressed by osteoblasts is a requirement for osteoclastogenesis, osteoblasts also play important roles in osteoclastogenesis through offering the critical microenvironment for the action of RANKL.