Clinical Orthopaedics and Related Research®

, Volume 472, Issue 12, pp 4006–4009 | Cite as

The Alpha Defensin-1 Biomarker Assay can be Used to Evaluate the Potentially Infected Total Joint Arthroplasty

  • Joshua Bingham
  • Henry Clarke
  • Mark Spangehl
  • Adam Schwartz
  • Christopher Beauchamp
  • Brynn Goldberg
Clinical Research



Diagnosing a periprosthetic joint infection (PJI) requires a complex approach using various laboratory and clinical criteria. A novel approach to diagnosing these infections uses synovial fluid biomarkers. Alpha defensin-1 (AD-1) is one such synovial-fluid biomarker. However little is known about the performance of the AD-1 assay in the diagnosis of PJI.


We sought to (1) determine the sensitivity and specificity of the AD-1 assay in a population of patients being evaluated for PJI, using the Musculoskeletal Infection Society (MSIS) criteria as the reference standard, and (2) compare the AD-1 assay with other currently available clinical tests, specifically cell count, culture, erythrocyte sedimentation rate, and C-reactive protein.

Patients and Methods

A retrospective review was performed of all patients undergoing workup for a PJI at our institution from January to June 2013. Sixty-one AD-1 assays were done in 57 patients. The group included 51 patients with 55 painful joints and six patients who underwent aspiration before second-stage reimplantation. Patients were considered to have a PJI if they met the MSIS criteria. We calculated the sensitivity and specificity of the AD-1 synovial fluid assay, and compared it with the sensitivity and specificity of the synovial fluid cell count, culture, erythrocyte sedimentation rate, and C-reactive protein. There were 19 diagnosed infections in the 61 aspirations, with 21 positive and 40 negative AD-1 assays. There were two false positive and no false negatives AD-1 assays.


The sensitivity and specificity for the AD-1 assay were 100% (95% CI, 79%–100%) and 95% (95% CI, 83%–99%), respectively. The sensitivity and specificity of the other tests ranged from 68% to 95% and 66% to 88%, respectively. The AD-1 assay results outperformed the other tests but did not reach statistical significance except for the sensitivity of the erythrocyte sedimentation rate.


The sensitivity and specificity of the synovial fluid AD-1 assay exceeded the sensitivity and specificity of the other currently available clinical tests evaluated here but did not reach significance. The AD-1 assay offers another test with high sensitivity and specificity for diagnosing a PJI especially in the case where the diagnosis of PJI is uncertain, but larger studies will be needed to determine significance and cost effectiveness.

Level of Evidence

Level III, diagnostic study. See the Instructions for Authors for a complete description of levels of evidence.


Synovial Fluid Periprosthetic Joint Infection Joint Arthroplasty Polymorphonuclear Neutrophil Elevated White Blood Cell Count 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We acknowledge CD Diagnostics (Wynnewood, PA, USA) for providing all the testing supplies at no cost to our institution.


  1. 1.
    Costa CR, Johnson AJ, Naziri Q, Maralunda GA, Delanois RE, Mont MA. Efficacy of erythrocyte sedimentation rate and C-reactive protein level in determining periprosthetic hip infections. Am J Orthop (Belle Mead NJ). 2012;41:160–165.PubMedGoogle Scholar
  2. 2.
    Deirmengian C, Hallab N, Tarabishy A, Della Valle C, Jacobs JJ, Lonner J, Booth RE Jr. Synovial fluid biomarkers for periprosthetic infection. Clin Orthop Relat Res. 2010;468:2017–2023.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Deirmengian C, Kardos K, Kilmartin P, Cameron A, Schiller K, Booth RE Jr, Parvizi J. The alpha-defensin test for periprosthetic joint infection outperforms the leukocyte esterase test strip. Clin Orthop Relat Res. 2014 June 19. [Epub ahead of print].Google Scholar
  4. 4.
    Del Pozo JL, Patel R. Clinical practice: infection associated with prosthetic joints. N Engl J Med. 2009;361:787–794.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Dinneen A, Guyot A, Clements J, Bradley N. Synovial fluid white cell and differential count in the diagnosis or exclusion of prosthetic joint infection. Bone Joint J. 2013;95:554–557.PubMedCrossRefGoogle Scholar
  6. 6.
    Ghanem E, Parvizi J, Burnett RS, Sharkey PF, Keshavarzi N, Aggarwal A, Barrack RL. Cell count and differential of aspirated fluid in the diagnosis of infection at the site of total knee arthroplasty. J Bone Joint Surg Am. 2008;90:1637–1643.PubMedCrossRefGoogle Scholar
  7. 7.
    Jacovides CL, Parvizi J, Adeli B, Jung KA. Molecular markers for diagnosis of periprosthetic joint infection. J Arthroplasty. 2011;26(6 suppl):99–103.e1.Google Scholar
  8. 8.
    Newcombe RG. Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998;17:857–872.PubMedCrossRefGoogle Scholar
  9. 9.
    Parvizi J, Jacovides C, Zmistowski B, Jung KA. Definition of periprosthetic joint infection: is there a consensus? Clin Orthop Relat Res. 2011;469:3022–3030.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Parvizi J, Zmistowski B, Berbari EF, Bauer TW, Springer BD, Della Valle CJ, Garvin KL, Mont MA, Wongworawat MD, Zalavras CG. New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res. 2011;469:2992–2994.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Spangehl MJ, Masri BA, O’Connell JX, Duncan CP. Prospective analysis of preoperative and intraoperative investigations for the diagnosis of infection at the sites of two hundred and two revision total hip arthroplasties. J Bone Joint Surg Am. 1999;81:672–683.PubMedGoogle Scholar

Copyright information

© The Association of Bone and Joint Surgeons® 2014

Authors and Affiliations

  • Joshua Bingham
    • 1
  • Henry Clarke
    • 1
  • Mark Spangehl
    • 1
  • Adam Schwartz
    • 1
  • Christopher Beauchamp
    • 1
  • Brynn Goldberg
    • 1
  1. 1.Department of OrthopaedicsMayo Clinic PhoenixPhoenixUSA

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