The importance of this system in bone metabolism is demonstrated by the facts that pharmacologic blockade of RANKL is an effective treatment for osteoporosis [37], that an inherited deficiency of RANK or RANKL causes osteopetrosis, and that loss-of-function OPG mutations cause juvenile Paget’s disease [38,39,40]. The gene discussed is TNFRSF11B; the disease is juvenile Paget disease.