There are several potential biological mechanisms that may influence aseptic implant failure including excessive innate and adaptive immune responses to implant debris. We investigated the hypothesis that patients with painful total joint replacements will exhibit elevated levels of metal reactivity and inflammatory markers compared to patients with well-performing TJA. We evaluated this hypothesis by testing for metal hypersensitivity using in vitro LTT assay and analyzing serum levels of selected inflammatory markers. Subject Groups: Blinded de-identified data from patients with TJR referred for metal hypersensitivity testing using a lymphocyte transformation test (LTT) and serum markers of inflammation using Luminex Multi-Analyte Assay was approved by Rush University IRB and retrospectively reviewed. None of the patients had radiographically identifiable osteolysis. Two groups of TJA patients were tested: Group 1: Well-functioning implant (<3 yrs. post-op), with no self-reported pain, i.e. <1 on 0–10 VAS scale (n=8) and Group 2: Painful TJR (<3 yrs. post-op), with self-determined pain of >8 on a 0–10 VAS scale at the time of blood draw (n=25). Metal-LTT: Peripheral blood mononuclear cells (PBMCs) were collected from 30mL of peripheral blood by Ficoll gradient separation. PBMCs were cultured with NiCl2. 3H Thymidine was added at day 5 of culture and 3H thymidine incorporation was analyzed using a beta scintillation counter at day 6. A stimulation index (SI) of reactivity was calculated by dividing scintillation counts per minute (cpms) of Ni challenged cells by those of untreated controls. A SI of <2 was considered nonreactive, 2 to <4 was mildly reactive and 4 to <8 was reactive. Luminex Assay: Serum samples were collected from whole blood and were analyzed according to manufacturer's protocols. Statistical analysis: Statistical differences were determined using unpaired t-test with Welch's correction with statistical significance at p≤0.1 (90% confidence interval).Introduction
Methods
Recently, corrosion at the head-neck junction in metal-on-polyethylene bearing total hip arthroplasty (THA) has been recognized as a cause of adverse local tissue reactions (ALTR). Serum metal levels have been advocated as a tool for the diagnosis of ALTR, however no prior studies have specifically examined their utility. The purpose of this study was to determine the optimal cut-off values for serum cobalt and chromium in diagnosing ALTR after metal-on-polyethylene bearing THA. We reviewed 447 consecutive patients with serum metal levels tested at our institution and identified 62 with a metal-on-polyethylene bearing who had axial imaging or underwent reoperation to confirm the presence or absence of ALTR. Receiver operating characteristic curves were produced to identify cut-off thresholds to optimize sensitivity and diagnostic test performance was characterized. 42 Of the 62 patients (66%) were positive for an ALTR. The best test for the diagnosis of ALTR was the serum cobalt level (area under the curve [AUC]=99%). A threshold cut-off of ≥ 1.0 ng/ml had a sensitivity of 100%, specificity of 90%, positive predictive value (PPV) of 96%, and negative predictive value (NPV) of 100%. Serum chromium levels were also diagnostic (AUC=87%). A threshold cut-off of ≥ 0.15 ng/ml had a sensitivity of 100%, specificity of 50%, PPV of 81%, and NPV of 100%. Finally, serum cobalt to chromium ratio was also helpful for diagnosis (AUC=90%). A threshold cut-off of 1.4 for the cobalt to chromium ratio offered a sensitivity of 93%, specificity of 70%, PPV of 87%, and NPV of 82%. Measurement of serum cobalt with a threshold value of 1.0 ng/ml in our experience is the best test for identifying the presence of ALTR in patients with a metal-on-polyethylene THA. Measurement of chromium and the ratio of cobalt to chromium are also of value.
