Related Experiment Video
Updated: Sep 4, 2025

Novel Diagnostics in Revision Arthroplasty: Implant Sonication and Multiplex Polymerase Chain Reaction
Published on: December 3, 2017
Cell-free Deoxyribonucleic Acid: A Potential Biomarker of Chronic Periprosthetic Knee Joint Infection
Hugo A de A B Cobra1, Alan P Mozella1, Idemar M da Palma2
1Center for Surgery of Knee, National Institute of Traumatology and Orthopaedics, Rio de Janeiro, Brazil.
Background:
The correct diagnosis of a chronic periprosthetic joint infection (PJI) is a major challenge in clinical practice, with the "gold standard" for diagnosis yet to be established. Synovial fluid analysis has been proven to be a useful tool for that purpose. Cell-free DNA (cf-DNA) levels have been shown to be increased in several conditions such as cancer, trauma, and sepsis. Therefore, this study was designed to evaluate the potential of synovial fluid cf-DNA quantification for the diagnosis of chronic periprosthetic infections following total knee arthroplasty.
Methods:
A prospective study with patients undergoing total knee arthroplasty revision surgery for any indication was performed. PJI diagnosis was defined according to the Second International Consensus Meeting on Musculoskeletal Infection (2018) criteria. The study cohort consisted of 26 patients classified as infected and 40 as noninfected. Synovial fluid cf-DNA direct quantification by fluorescent staining was made. Sensitivity, specificity, and receiver operating characteristic curve were calculated.
Results:
The cf-DNA levels were significantly higher in patients who had PJIs (122.5 ± 57.2 versus 4.6 ± 2.8 ng/μL, P < .0001). With a cutoff of 15 ng/μL, the area under the receiver operating characteristic, sensitivity, and specificity of cf-DNA were 0.978, 96.2%, and 100%, respectively.
Conclusion:
The present study has shown that cf-DNA is increased in synovial fluid of patients who have chronic PJIs. It is a promising biomarker for knee PJI diagnosis and further studies are needed to confirm its utility.
Insights
Diagnosing chronic periprosthetic joint infections (PJI) is challenging. This study found that cell-free DNA (cf-DNA) in synovial fluid is a promising biomarker for detecting knee PJI.
Area of Science:
- Orthopedics
- Infectious Diseases
- Biomarker Discovery
Background:
- Chronic periprosthetic joint infection (PJI) diagnosis remains a clinical challenge, lacking a definitive gold standard.
- Synovial fluid analysis is a valuable diagnostic tool for PJI.
- Elevated cell-free DNA (cf-DNA) levels are observed in various conditions, including sepsis and trauma.
Purpose of the Study:
- To evaluate the diagnostic potential of synovial fluid cf-DNA quantification for chronic periprosthetic infections after total knee arthroplasty.
- To assess cf-DNA as a biomarker for knee PJI.
Main Methods:
- A prospective study involving patients undergoing total knee arthroplasty revision.
- PJI diagnosis followed the 2018 International Consensus Meeting criteria.
- Synovial fluid cf-DNA was quantified using fluorescent staining, with sensitivity, specificity, and ROC curve analysis.
Main Results:
- Synovial fluid cf-DNA levels were significantly higher in infected patients (122.5 ± 57.2 ng/μL) compared to non-infected patients (4.6 ± 2.8 ng/μL).
- A cf-DNA cutoff of 15 ng/μL yielded an area under the ROC curve of 0.978, with 96.2% sensitivity and 100% specificity.
- These findings indicate strong diagnostic performance for cf-DNA in PJI detection.
Conclusions:
- Synovial fluid cf-DNA is elevated in patients with chronic knee PJI.
- cf-DNA shows promise as a diagnostic biomarker for knee PJI.
- Further research is warranted to confirm the clinical utility of cf-DNA for PJI diagnosis.

