Regulation of bone lysis in inflammatory diseases

Focal bone erosion is a major pathological feature of several common inflammatory diseases. Over the past decade there have been major advances in our understanding of the factors that regulate osteoclast formation and activity. It is now apparent that receptor activator for NFkappaB (RANK), its ligand RANKL (also known as TRANCE, osteoclast differentiation factor and osteoprotegerin (OPG) ligand) and the RANKL inhibitor OPG, are the major factors regulating osteoclast formation. These molecules influence normal bone physiology and now there is growing evidence that RANK-RANKL interactions also regulate osteoclast formation in disease. This paper reviews recent findings showing expression of RANK, RANKL and OPG in inflammatory diseases including rheumatoid arthritis, periodontal disease and peri-implant loosening. It is emerging that OPG and RANKL are key molecules regulating bone loss in disease and therapeutic intervention that targets these molecules may be helpful in treating a wide range of diseases.