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Comparative Study
. 2025 Aug 28;145(1):428.
doi: 10.1007/s00402-025-06045-x.

Comparison of synovial calprotectin and alpha-defensin for the diagnosis of persistent periprosthetic joint infections at second stage of a two-stage revision arthroplasty

Jennyfer A Mitterer  1 , Susana Gardete Hartmann  2 , Sebastian Simon  2   3 , Sujeesh Sebastian  2 , Leonie Chlud  2 , Jochen G Hofstaetter  4   5
Affiliations
Comparative Study

Comparison of synovial calprotectin and alpha-defensin for the diagnosis of persistent periprosthetic joint infections at second stage of a two-stage revision arthroplasty

Jennyfer A Mitterer et al. Arch Orthop Trauma Surg. .

Abstract

Background: Two-stage revision arthroplasty is the standard treatment for chronic hip and knee periprosthetic joint infections (PJI). Accurate diagnosis of persistent infections at 2nd stage using established biomarkers and diagnostic criteria is of paramount importance. This study aimed to evaluate the diagnostic value of synovial calprotectin and alpha-defensin, and compare established diagnostic criteria from the International Consensus Meeting (ICM 2018) and the European Bone and Joint Infection Society (EBJIS 2021) to determine persistent PJI at the 2nd stage of a two-stage revision arthroplasty.

Methods: We retrospectively analyzed 97 patients who underwent 100 two-stage revisions (hip: 39, knee: 61). Synovial fluid samples were assessed for calprotectin and alpha-defensin levels. ICM 2018 and EBJIS 2021 were applied to all patients undergoing 2nd stage revision. Receiver operating characteristic (ROC) curves and Youden Index were utilized to determine optimal cut-off values, and correlations between biomarkers were evaluated. The microbiological spectrum was analyzed at 2nd stage and re-revision surgery.

Results: Calprotectin levels showed a sensitivity of 66.7%, specificity of 32.9%, and accuracy of 38.0% in predicting septic failure. Alpha-defensin showed sensitivity of 28.6%, specificity of 87.8%, and accuracy of 79.2%. Significant correlations included: calprotectin with PMN% (r = 0.471, p = 0.05) and alpha-defensin with WBC (r = 0.830, p < 0.01) in the successful cohort. For septic re-revisions, calprotectin and alpha-defensin were highly correlated (r = 0.969, p < 0.01). ICM correctly diagnosed persistent PJI in 26.7%, while EBJIS diagnosed 24.2%. The microbial spectrum shifted from gram-positive to gram-negative bacteria between reimplantation and re-revision surgeries.

Conclusion: Synovial calprotectin and alpha-defensin demonstrated limited accuracy in ruling out persistent PJI at reimplantation. The low sensitivity of current diagnostic criteria, combined with the observed shift in microbial spectrum, underscores the challenges in diagnosing persistent PJI during 2nd stage of a two-stage revisions arthroplasty.

Keywords: EBJIS criteria; ICM criteria; Periprosthetic joint infection; Reimplantation; Synovial alpha-defensin; Synovial calprotectin.

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Conflict of interest statement

Declarations. Competing interests: Funding statement: The “Michael Ogon Laboratory for Orthopaedic Research” received a research grant from “Lyfstone® BV”. The collection, analysis, and interpretation of data, writing of the report, and the decision to submit the paper for publication were performed by the authors and not influenced by Lyfstone® BV.

References

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