A meta-analysis of synovial biomarkers in periprosthetic joint infection: Synovasure™ is less effective than the ELISA-based alpha-defensin test

PURPOSE (1) To determine the overall accuracy of synovial alpha-defensin, synovial C-reactive protein (sCRP), interleukin-6 (sIL-6), and leukocyte esterase (sLE) as diagnostic markers for periprosthetic joint infection (PJI) and (2) to independantly evaluate the accuracy of both the laboratory-based ELISA alpha-defensin test and the Synovasure™ alpha-defensin test kit. METHODS An EMBASE and MEDLINE (PubMed) database search was performed using a set of professionally set search terms. Two independent reviewers rated eligible articles. Sensitivity and specificity were meta-analysed using a bivariate random-effects model. RESULTS Accuracy values were extracted from 42 articles. Pooled sensitivity and specificity of the represented biomarkers were: alpha-defensin ELISA 0.97 (95% CI 0.91-0.99) and 0.97 (95% CI 0.94-0.98), respectively; Synovasure™ test kit assay 0.80 (95% CI 0.65-0.89) and 0.89 (95% CI 0.76-0.96), respectively; sLE 0.79 (95% CI 0.67-0.87) and 0.92 (95% CI 0.87-0.92), respectively; sIL-6 0.76 (95% CI 0.65-0.84) and 0.91 (95% CI 0.88-0.94), respectively; sCRP 0.86 (95% CI 0.81-0.91) and 0.90 (95% CI 0.86-0.93), respectively. CONCLUSION The labararory-based alpha-defensin ELISA test showed the highest ever reported accuracy for PJI diagnosis. However, this did not apply for the Synovasure™ alpha-defensin test, which was comparable in its overall diagnostic accuracy to sCRP, sIL-6 and sLE. The later biomarkers also did not yield an overall diagnostic accuracy higher than that previously reported for synovial white cell count (sWBC) or culture bacteriology. Based on current evidence, no synovial biomarker should be applied as a standalone diagnostic tool. Furthermore, the use of the laboratory-based alpha-defensin ELISA test should be encouraged, still, the Synovasure™ alpha-defensin test kit should be critically appreciated. LEVER OF EVIDENCE III.