Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor (OCIF), is a protein that in humans is encoded by the TNFRSF11B gene. Osteoprotegerin is a cytokine receptor, and a member of the tumor necrosis factor (TNF) receptor superfamily. Elevated OPG levels has been reported in heart diseases, in placebo effect serum responses in IBS patients and in severe mental disorders.

Mutations in TNFRSF11B are associated with osteoarthritis. It has been found that osteoprotegerin is expressed on mesenchymal stem cells, which mediates their suppressive effect on osteoclastogenesis. In recent years, it has been hypothesized that osteoprotegerin may be a link between bone and cardiovascular disease. It has been particularly related to the increase in cardiovascular risk in patients suffering from diabetes.