oa Osteoclast Apoptosis in Rheumatic Diseases Characterized by a High Level of Bone Resorption (Osteoporosis, Rheumatoid Arthritis, Myeloma and Paget's Disease of Bone)

The resorption and formation of bone are closely linked during bone remodeling. The cessation of bone resorption precedes bone formation, and is characterized by osteoclast apoptosis. The two most common apoptotic pathways consist of the activation of one of the membrane death receptors, including Fas that binds FasL, and the TRAIL receptors that bind TRAIL (TNF-Related Apoptosis-Inducing Ligand), and the mitochondrion-activated pathway involving members of the Bcl-2 family. Apoptosis occurs in osteoclasts, and is an important point of control of bone resorption. M-CSF and RANKL, the two critical factors involved in osteoclast formation and activation, are osteoclast survival factors and down-regulate osteoclast apoptosis. The regulation of this process may be important in controlling bone homeostasis, and could be altered in vivo under conditions characterized by a high level of osteoclast formation. Bone diseases, such as osteoporosis, malignant osteolysis, and Paget's disease of bone, are characteristically associated with bone hyper-resorption, as rheumatoid arthritis where peri-articular or subchondral bone resorption may occur. There is now increasing evidence suggesting that changes in the regulation of osteoclast death may contribute to these clinically important bone diseases, and that the induction of osteoclast apoptosis is a potential therapeutic tool for treating them.