Adverse local tissue reaction (ALTR) associated with corrosion products in metal‐on‐metal and dual modular neck total hip replacements is associated with upregulation of interferon gamma‐mediated chemokine signaling

Abstract

Adverse local tissue reactions (ALTR) associated with tribocorrosion following total hip arthroplasty (THA) have become a significant clinical concern in recent years. In particular, implants featuring metal-on-metal bearing surfaces and modular femoral stems have been reported to result in elevated rates of ALTR. These tribocorrosion-related tissue reactions are characterized by marked necrosis and lymphocytic infiltration, which contrasts sharply with the macrophagic and foreign body giant cell inflammation associated with polyethylene wear particle induced peri-implant osteolysis. In this study, we characterize tribocorrosion-associated ALTR at a molecular level. Gene expression profiling of peri-implant tissue around failing implants identifies upregulation of numerous inflammatory mediators in ALTR, including several interferon gamma inducible factors, most notably the chemokines MIG/CXCL9 and IP-10/CXCL10. This expression profile is distinct from that associated with polyethylene wear induced osteolysis, which is characterized by induction of markers of alternative macrophage activation, such as chitotriosidase (CHIT-1). Importantly, MIG/CXCL9 and IP-10/ CXCL10 are also elevated at the protein level in the synovial fluid and, albeit more moderately, the serum, of ALTR patients, raising the possibility that these factors may serve as circulating biomarkers for the early detection of ALTR in at-risk patients.

Adverse reactions to metal on polyethylene implants: Highly destructive lesions related to elevated concentration of cobalt and chromium in synovial fluid

“…OPG has an important role in bone metabolism by inhibiting osteoclastogenesis . A recent study, through analysis of RNA from tissue homogenates, also found high expression of CC and CXC chemokines in ALTR (CCL19, CCL13 and CCL8, and CXCL9, CXCL10 and CXCL13) . The same study also found high expression of MIG and IP‐10; proteins that are up regulated by IFN‐γ, which is responsible of the Th1 switch in the immune response .…”

“…In all the cases an experienced pathologist confirmed the presence of ALTR. Patients with evidence of bone resorption were excluded, since it has been demonstrated that osteolysis is associated with different gene expression than ALTRs . Patients with infection or previous revision operations were also excluded.…”

“…Patients with evidence of bone resorption were excluded, since it has been demonstrated that osteolysis is associated with different gene expression than ALTRs. 20 Patients with infection or previous revision operations were also excluded. A metal allergy was not noted in any of the patients, as is a contraindication for a metal femoral head.…”

The biological response to orthopaedic implants for joint replacement: Part I: Metals

“…ALVaL describes a periprosthetic inflammatory reaction that is similar to a type IV hypersensitivity response in the soft tissue surrounding metal‐on‐metal implants . It is characterized by soft tissue necrosis, lymphocytic infiltration, and abnormal joint fluid.…”

“…ALVaL describes a periprosthetic inflammatory reaction that is similar to a type IV hypersensitivity response in the soft tissue surrounding metal-on-metal implants. 142,143 It is characterized by soft tissue necrosis, lymphocytic infiltration, and abnormal joint fluid. In TJR patients who needed revision surgery due to symptoms of implant failure, tissue samples showed perivascular infiltrates of T-cell and B-cell lymphocytes, as well as an accumulation of plasma cells and macrophages (Figure 7).…”