These cytokines are known to upregulate osteoclast activity via increased expression levels of receptor activator NF kappa B ligand (RANKL) relative to osteoprotegerin (OPG) (as explored below) and increase localized bone loss in diseases such as RA, periodontal disease, and periprosthetic osteolysis [5–10]. The gene discussed is TNFSF11; the disease is periodontal disorder.