Osteoprotegerin, an endogenous antiosteoclast factor for protecting bone in rheumatoid arthritis

Pharmacologic actions of OPG observed in animals and human patients suggest that this therapeutic protein rapidly terminates osteoclastic skeletal destruction in many pathologic conditions, including inflammatory, metabolic, and neoplastic diseases of bone. The impact of OPG on osteoclast numbers is mediated by 3 distinct mechanisms: inhibiting the function of mature activated osteoclasts, preventing the differentiation of precursor cells into new osteoclasts, and curtailing osteoclast survival. The primary consideration for using exogenous OPG to treat RA is that control of osteoclast net activity depends on the ratio of OPG to OPGL. Thus, OPG therapy will shift the balance toward preservation of bone. Prior animal arthritis studies (20,38,85) and a human osteoporosis trial (95) indicate that the bone-protective response will depend on both the OPG dose as well as the injection frequency. Data on the ability of OPG to preserve bone mineral density and skeletal integrity in human patients will be required to definitively establish its potential, including dose and schedule, as a bone-preserving therapy in clinical practice. The most important message is that OPG will almost completely halt bone destruction, even in the presence of severe inflammation, with maximal efficacy if treatment is started before bone damage has begun (38).