Osteolytic bone diseases directly associated with an increased RANK/OPG ratio may result either from RANK over-activation/expression, such as in familial expansile osteolysis (FEO, OMIM #174810) and Paget disease of Bone 2—early onset (PDB2, OMIM #602080), or from decreased OPG expression/function, such as in Paget disease of Bone 5—Juvenile-Onset (PDB5, OMIM #239000). This evidence concerns the gene TNFRSF11A and familial expansile osteolysis.