Synovial Biomarkers C-Reactive Protein and Calprotectin for Diagnosing Chronic Periprosthetic Joint Infection: A Prospective Multicenter Evaluation

Abstract

Background: The diagnosis of periprosthetic joint infection (PJI) remains a challenge in clinical practice, and synovial fluid (SF) analysis is a valuable diagnostic tool. Recently, two synovial biomarkers (leukocyte esterase strip test and alpha-defensin [AD]) have been incorporated within the MSIS (Musculoskeletal Infection Society) algorithm for PJI diagnosis. Although AD is promising, with high sensitivity and specificity, it remains expensive. Calprotectin, another protein released upon activation of articular neutrophils, offers a low-cost alternative. Calprotectin and CRP (serum C-reactive protein) joint determination is now feasible in routine laboratory practice. This study aimed to evaluate the diagnostic performance of two synovial biomarkers, calprotectin and CRP, for PJI diagnosis.

Methods: From April 2022 to June 2024, all adult patients undergoing preoperative or intraoperative aspiration of hip or knee prosthetic joints were included in this prospective, multicenter, noninterventional study. Patients who had prosthetic implantation less than three months prior or those who had systemic inflammatory diseases were excluded. For each SF sample, calprotectin and CRP synovial measurements were performed. Patients were classified as infected (PJI group) or noninfected (non-PJI group) based on decisions made during multidisciplinary meetings. During the study period, 157 patients were enrolled. There were 59 patients excluded due to insufficient synovial fluid volume or failure to meet inclusion criteria. There were 52 patients classified into the PJI group and 46 into the non-PJI group.

Results: The sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of synovial calprotectin were 94.23%, 78.26%, 4.24, and 0.07, respectively, while those of synovial CRP were 80.77%, 86.96%, 6.19, and 0.22, respectively.

Conclusions: The present study demonstrates that synovial calprotectin and synovial CRP assays have excellent accuracy for the diagnosis of PJI. These findings suggest that these two synovial biomarkers should be incorporated into a new decision-making algorithm for PJI diagnosis.

Keywords: C-reactive protein; biomarker; calprotectin; periprosthetic joint infections; synovial fluid.