Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand 
(RANKL) are dominant regulators of bone resorption. Many hormones, cytokines and 
growth factors mediate bone resorption by altering the ratio of RANKL to OPG. 
RANKL and OPG expression is also altered in numerous bone diseases, and these 
changes can reflect disease etiology or compensatory responses to disease. RANKL 
stimulates osteoclast formation, function and survival, and each of these 
effects is inhibited by OPG. OPG suppresses bone resorption and increases the 
density, area and strength of both cancellous and cortical bone. Denosumab (AMG 
162), a fully human monoclonal antibody to RANKL, shares the pharmacologic 
attributes of OPG but has a significantly longer half-life that allows less 
frequent administration.