Metal ions as inflammatory initiators of osteolysis

Osteolysis and aseptic loosening currently contribute 75 % of implant failures. Furthermore, with over four million joint replacements projected to be performed in the United States annually, osteolysis and aseptic loosening may continue to pose a significant morbidity. This paper reviews the osteolysis cascade leading to osteoclast activation and bone resorption at the biochemical level. Additionally, the metal ion release mechanism from metallic implants is elucidated. Even though metal ions are not the predominating initiator of osteolysis, they do increase the concentration of key inflammatory cytokines that stimulate osteoclasts and prove to be a contributor to osteolysis and aseptic loosening. Osteolysis is a competitive mechanism among a number of biological reactions, which includes debris release, macrophage and osteoclast activation, an inflammatory response as well as metal ion release. Pharmacological therapy for component loosening has also been reviewed. A non-surgical treatment of osteolysis has not been found in the literature and thus may become an area of future research. Even though this research is warranted, comprehensively understanding the immune response to orthopedic implants and their metallic ions, and thus, creating improved prostheses appears to be the most cost-effective approach to decrease the morbidity related to osteolysis and to design implants with greater longevity. The ionic forms, cytokines, toxicity, gene expression, biological effects, and hypersensitivity responses of metallic elements from metal implants are summarized as well.