Improved diagnostic accuracy with the classification tree method for diagnosing low-grade periprosthetic joint infections by quantitative measurement of synovial fluid alpha-defensin and C-reactive protein
Related Experiment Video
Updated: Jan 24, 2026

Synovial Fluid Analysis to Identify Osteoarthritis
Published on: October 20, 2022
Max Ettinger1, Peter Savov2, Tilman Calliess2
1Department of Orthopaedic Surgery, Hannover Medical School, Anna-von-Borries-Straße 1-7, 30625, Hannover, Germany. max@ettinger.info.
Background:
The diagnosis of low-grade periprosthetic joint infections (PJIs) is challenging, because patients may present with unspecific symptoms, false-negative cultures, or marginally elevated values of serum biomarkers like C-reactive protein (CRP). This may lead to the unintended implantation of a revision prosthesis into an infected surgical site with a repeat risk of short-term failure. Conversely, false diagnosis of joint infection may result in multistage revision procedures, which expose the patient to unnecessary surgical procedures and inappropriate antibiotic treatment. Here, we investigated whether synovial biomarkers can preoperatively distinguish between aseptic prosthesis loosening and low-grade joint infection and the most accurate biomarker combinations.
Methods:
Inclusion criteria for the study were indication for revision arthroplasty due to aseptic implant failure, acute high-grade infection, or (suspected) low-grade infection. We prospectively collected synovial fluid of patients undergoing revision arthroplasty for quantitative measurement of alpha defensin, CRP, interleukin (IL-6), IL-10, and lipopolysaccharide binding protein (LBP).
Results:
The classification tree method revealed alpha defensin and CRP as the most suitable biomarker combination to distinguish between aseptic loosening and low-grade joint infection. The combination of CRP > 2.0 mg/L and alpha defensin > 90.000 pg/mL correctly identified nine of 11 patients with low-grade infection.
Conclusions:
Alpha defensin plus CRP seems to be the most helpful combination for pre-operative discrimination of aseptic loosening vs. low-grade joint infection.
Insights
Diagnosing low-grade periprosthetic joint infections (PJIs) is difficult. A combination of alpha defensin and C-reactive protein (CRP) in synovial fluid shows promise for distinguishing infection from aseptic loosening before surgery.
Area of Science:
- Orthopedic Surgery
- Biomarker Research
- Infectious Diseases
Background:
- Diagnosing low-grade periprosthetic joint infections (PJIs) is challenging due to non-specific symptoms and unreliable biomarkers.
- Misdiagnosis can lead to revision surgery failure or unnecessary procedures and antibiotic use.
- Accurate preoperative differentiation between aseptic loosening and low-grade PJI is crucial.
Purpose of the Study:
- To evaluate the efficacy of synovial fluid biomarkers in distinguishing between aseptic prosthesis loosening and low-grade PJI.
- To identify the most accurate combination of biomarkers for preoperative diagnosis.
Main Methods:
- Prospective collection of synovial fluid from patients undergoing revision arthroplasty.
- Quantitative measurement of alpha defensin, C-reactive protein (CRP), IL-6, IL-10, and lipopolysaccharide binding protein (LBP).
- Utilized classification tree method to analyze biomarker performance.
Main Results:
- The combination of alpha defensin and CRP demonstrated the highest accuracy in differentiating aseptic loosening from low-grade PJI.
- A threshold of CRP > 2.0 mg/L and alpha defensin > 90,000 pg/mL correctly identified 9 out of 11 patients with low-grade infection.
Conclusions:
- Alpha defensin combined with CRP is a highly effective biomarker panel for preoperative diagnosis.
- This biomarker combination aids in differentiating aseptic loosening from low-grade PJI, improving surgical planning.
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