The ratio of RANKL to OPG is a critical determinant of bone resorption activity.48,50,94 Elevated RANKL levels and reduced OPG expression, commonly observed in periodontal inflammation, create a pro-resorptive environment conducive to alveolar bone loss (Fig. 6).121 Previous studies demonstrate that RANKL-deficient (RANKL−/−)129 and RANK-deficient (RANK−/−)130 mice develop severe osteopetrosis due to impaired osteoclast formation, highlighting the essential role of the RANKL–RANK pathway in bone resorption. This evidence concerns the gene TNFRSF11A and osteopetrosis.