A recent study revealed that tumor necrosis factor (TNF) directly enhances RANKL expression and promotes osteoclast formation (29).In bone metabolism (30), multiple target genes on the TNF pathway regulate osteoclast differentiation, thereby regulating physiological bone remodeling and participating in the pathogenesis of various bone diseases, such as osteoporosis and bone loss under inflammatory conditions. The gene discussed is TNFSF11; the disease is osteoporosis.