It is possible that, although 1,25(OH)2D3 is capable of inducing RANKL expression by interacting with VDREs in the RANKL promoter in the physiological state, upregulation OPG/RANKL ratio and accordingly suppressing inflammation-induced osteoclastogenesis might support the protective role of 1,25(OH)2D3 in arthritis models and RA patients. This evidence concerns the gene TNFRSF11B and rheumatoid arthritis.