Synovial Fluid Biomarkers for the Diagnosis of Periprosthetic Joint Infection: A Systematic Review and Meta-Analysis

Abstract

Background: The search for a single standard reference test for determining periprosthetic joint infection (PJI) through analysis of synovial fluid has yielded numerous biomarkers as potential candidates. The purpose of the present systematic review and meta-analysis was to evaluate the diagnostic accuracy of synovial fluid biomarkers and to determine which test has the highest diagnostic odds ratio (DOR) for the diagnosis of PJI.

Methods: An online literature search of the MEDLINE, Embase, and Cochrane databases identified 33 articles reporting a total of 13 major parameters for diagnosing PJI through analysis of synovial fluid. Each of the included articles was independently analyzed for risk of bias and for concerns regarding applicability utilizing the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) tool. The mada (meta-analysis of diagnostic accuracy) tool was used to generate forest plots for sensitivity, specificity, and the log of the DOR, as well as summary statistics.

Results: In this analysis, 13 index tests (leukocyte count; measurement of the percentage of polymorphonucleocytes [PMN%] and the levels of C-reactive protein [CRP], α-defensin, leukocyte esterase [LE], interleukin [IL]-6, IL-8, IL-10, IL-1β, vascular endothelial growth factor [VEGF], and granulocyte-colony stimulating factor [G-CSF]; culture; and polymerase chain reaction [PCR] analysis) were evaluated on the basis of ≥2 articles. Of these tests, 8 (leukocyte count, PMN%, CRP, α-defensin, LE, IL-6, IL-8, and culture) were appropriate for pooled analysis. The overall sensitivity of these 8 markers was 0.85, and all but culture showed a sensitivity of ≥0.8. All markers showed a specificity of ≥0.9. Of the 8 tests, measurement of the α-defensin level showed the highest log DOR.

Conclusions: Synovial fluid leukocyte count, PMN%, CRP, α-defensin, LE, IL-6, and IL-8 all demonstrated high sensitivity for diagnosing PJI, with α-defensin being the best synovial marker based on the highest log DOR. However, other synovial fluid tests that demonstrate good diagnostic performance can also be used in combination for the diagnosis of PJI.

Level of evidence: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.