expression. During osteoclastogenesis the different TRAIL receptors on the cell surface change resulting in an increase of apoptosis inducing TRAIL receptors expressed on mature osteoclasts. As a decoy receptor for both RANKL and TRAIL, OPG simultaneously suppresses osteoclastogenesis while also inhibiting TRAIL induced cell death of mature osteoclast cells. OPG has an equally high affinity for RANKL and TRAIL suggesting that it is equally effective at inducing osteoclastogenesis and inhibiting osteoclast apoptosis. Disease Atrophic nonunion shaft fractures A normal steady state of bone metabolism seems to be present in patients with atrophic nonunion fractures, despite the high serum OPG. Only serum OPG was significantly higher in the patients compared to healed and healing controls. (49) Osteoporosis Osteoporosis is a bone-related disease caused by increased rates of bone resorption compared to bone formation. A higher rate of resorption is often caused by increased osteoclastogenesis and results in symptoms of osteopenia such as excessive bone loss and low bone mineral density. Osteoporosis is often triggered in post-menopausal women due to reduced estrogen levels associated with the depletion of hormone-releasing ovarian follicles. Decreasing estrogen levels result in the downregulation of OPG expression and reduced inhibition of RANKL. Therefore RANKL can more readily bind to RANK and cause the increased osteoclastogenesis and bone resorption seen in osteoporosis. Decreased estrogen is a common cause of osteoporosis that can be seen in other conditions such as ovariectomy, ovarian failure, anorexia, and hyperprolactinaemia. Osteoblastic synthesis of bone does not increase to compensate for the accelerated bone resorption as the lower estrogen levels result in increased rates of osteoblast apoptosis. The higher rate of bone resorption compared to bone formation leads to the increased porosity and low bone mineral density of individuals with osteoporosis. Cancer Tumour endothelial cells have been found to express higher levels of OPG when compared to normal endothelial cells. When in contact with tumour cells, endothelial cells express higher levels of OPG in response to integrin αvβ3 ligation and the stimulation of NF-kB signalling. OPG expression has been found to promote tumour growth and survival through driving tumour vascularisation and inhibiting TRAIL-induced apoptosis. OPG has been identified as one of the many pro-angiogenic factors involved in the vascularisation of tumours. Tumour angiogenesis is required for tumour growth and movement as it supplies the tumour with nutrients and allows metastatic cells to enter the bloodstream. As a decoy receptor for TRAIL, OPG also promotes tumour