Pathophysiology of bone metastases

Normal bone remodeling maintains an appropriate balance between the action of osteoclasts (bone-resorbing cells) and osteoblasts (bone-forming cells). Skeletal malignancies including bone metastases, disrupt the OPG-RANKL-RANK signal transduction pathway and promote enhanced osteoclast formation, thereby accelerating bone resorption and inducing bone loss. This osteolysis in turn leads to the release of bone-derived growth factors, contributing to a "vicious cycle" in which interactions between tumor cells and not only lead to increased osteoclastogenesis and osteolytic activity, but also growth and behavior of the tumor cells. The osteolytic complications associated bone metastases are caused by tumor-induced alterations of the OPG-RANKL-RANK which are accompanied by enhanced bone resorption and disassociated from bone formation by osteoblasts.