In addition, the RANKL/osteoprotegerin (OPG) ratio is considered a serum biomarker for clinical investigation of bone loss in RA.49 Moreover, the suppression or deletion of RANKL or RANK or enhanced expression of osteoprotegerin has been reported to be associated with severe osteoporotic development, which shows the vital role of these factors in bone physiology and maintenance.50 This evidence concerns the gene TNFRSF11B and rheumatoid arthritis.