Synovial calprotectin is a reliable biomarker for periprosthetic joint infections in acute-phase inflammation - a prospective cohort study

Abstract

Purpose: Diagnosing periprosthetic joint infections (PJI) are challenging and may be hampered by the presence of other causes of local inflammation. Conventional synovial and serum markers are not reliable under these circumstances. Synovial calprotectin has been recently shown as a promising biomarker for PJI in total hip (THA) and total knee arthroplasty (TKA). The aim of this study is to investigate if calprotectin is reliable for PJI diagnosis in cases with accompanying inflammation due to recent surgery, dislocation or implant breakage in primary and revision TKA and THA.

Methods: Thirty-three patients were included in this prospective study between July 2019 and October 2021 (17 patients undergoing surgery < 9 months, 11 dislocations, five implant breakage, respectively). Synovial white blood cell count (WBC), percentage of polymorphonuclear neutrophils (PMC), serum C-reactive protein (CRP) and synovial calprotectin, using a lateral-flow-assay, were analysed. These parameters were tested against a modified European-Bone-and-Joint-Infection-Society (EBJIS) definition with adjusted thresholds to account for the local inflammation. Statistic quality criteria were calculated and compared using a binary classification test.

Results: Seventeen patients were classified as confirmed infections according to the modified EBJIS definition (13 THA and 4 TKA). The calprotectin assay yielded a sensitivity of 0.88 (0.64, 0.99), a specificity of 0.81 (0.54, 0.96), a positive predictive value (PPV) of 0.83 (0.59, 0.96) and a negative predictive value (NPV) of 0.87 (0.60, 0.98).

Conclusions: Even in the presence of local inflammation due to other, non-infectious causes, calprotectin is a reliable diagnostic parameter for the detection of a PJI in primary and revision THA and TKA.

Keywords: Calprotectin; Dislocation; Implant breakage; Periprosthetic joint infection; Post-operative.

Fig. 1

Area under the receiver operating characteristic curve (AUC) of the calprotectin lateral-flow-test, using the modified EBJIS 2021 definition as gold standard. AUC = 0.89; EBJIS 2021, European Bone and Joint Infection society definition of periprosthetic joint infection published in 2021

Fig. 2

X-rays of dislocated revision THA and implant breakage of distal femur replacement. A A 70-year-old patient with dislocation of revision THA. Last dislocation occurred 5 years before index surgery. The implant was revised due to periprosthetic fracture 10 years ago. Primary arthroplasty was performed 11 years ago due to aseptic necrosis of the femoral head. B A 30-year-old patient with implant breakage of a distal femur replacement 10 years after treatment for osteosarcoma. The breakage in the junction to the socket is enlarged

Fig. 3

Illustration of the photometric readout by the Lyfstone application. A The test cassette is mounted in a frame that permits detection by the mobile application. B Illustrated screenshot of the mobile application: the photometric evaluation of the test lines is performed as soon the test is detected with the mobile phone camera by overlapping the frame on the screen (yellow) with the test cassette mounted in the frame (blue). The concentration of calprotectin is proportional to the colour intensity and can therefore be calculated by the application. The illustrations have been modified based on Lyfstone AS, Tromsø, Norway