Periprosthetic osteolysis: an immunologist's update.
OBJECTIVE
Inflammation-induced osteolysis is a problem in both inflammatory arthritis and total joint arthroplasty. New drug therapies have been shown to slow, halt, or even reverse the osteolysis associated with inflammatory arthritis. Unfortunately, similar advances in the medical treatment of periprosthetic osteolysis have not occurred. This review will update the state of periprosthetic osteolysis.


RESULTS
Preliminary results with phase I and II clinical trials with AMG-162, a human IgG2 that binds receptor activator of nuclear factor kappaB (RANK) ligand, have been reported. Based on these results AMG-162 appears to be safe and to have a potent effect on osteoclast function. Based on animal studies, it is expected that regents such as AMG-162 that block RANK-ligand/RANK interaction will have activity in inflammation-induced osteolysis. Volumetric three-dimensional and magnetic resonance imaging scans for detecting and quantifying periprosthetic osteolysis have been validated in cadaver studies. Lymphocytic infiltrates and positive skin tests to cobalt have been found in patients with periprosthetic osteolysis after second generation metal-on-metal prostheses. These findings again raise the question of whether metal allergy may contribute to implant failure in these patients. A new subset of T helper cells that are neither Th1 nor Th2, but secrete a unique pattern of cytokines including IL-17, has recently been discovered. The importance of these cells in modifying particle-induced osteolysis remains to be determined.


CONCLUSIONS
There have been significant advances in our understanding of periprosthetic osteolysis, imaging technology to quantify osteolysis, and drug development. The time now seems ripe to translate these advances in clinical trials.
Looney
R John
RJ
Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, NY 1442, USA. John_Looney@URMCRochester.Edu
Schwarz
Edward M
EM
Boyd
Allen
A
O'Keefe
Regis J
RJ
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D019643:Arthroplasty, Replacement / Q000009:adverse effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D000069448:Denosumab; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000628:therapy; D008670:Metals / Q000009:adverse effects / Q000276:immunology; D010014:Osteolysis / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D011475:Prosthesis Failure; D053245:RANK Ligand
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D008670:Metals; D053245:RANK Ligand; D000069448:Denosumab