Biomarkers to discriminate between aseptic loosened and stable total hip or knee arthroplasties: a systematic review

Shaho Hasan*, Peter van Schie, Bart L. Kaptein, Jan W. Schoones, Perla J. Marang-van de Mheen, Rob G.H.H. Nelissen

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Background: Loosening is a major cause for failure of total hip and total knee arthroplasties (THAs/TKAs). Preemptive diagnostics of asymptomatic loosening could open strategies to prevent gross loosening. A multitude of biomarkers may discriminate between loosened and stable implants, but it is unknown which have the best performance. The present systematic review aimed to assess which biomarkers have shown the most promising results in discriminating between stable and aseptic loosened THAs and TKAs.

Methods: PubMed, Embase, Web of Science, Cochrane Library, and Academic Search Premier were systematically searched up to January 2020 for studies including THA/TKA and biomarkers to assess loosening. Two reviewers independently screened records, extracted data, and assessed the risk of bias using the ICROMS tool to classify the quality of the studies.

Results: Twenty-eight (three high-quality) studies were included, reporting on a median of 48 patients (interquartile range 28–69). Serum and urine markers were evaluated in 22 and 10 studies, respectively. Tumor necrosis factor α and osteocalcin were significantly higher in loosened compared with stable implants. Urinary N-terminal telopeptide had significantly elevated levels in loosened prostheses.

Conclusion: Several serum and urine markers were promising in discriminating between loosened and stable implants. We recommend future studies to evaluate these biomarkers in a longitudinal fashion to assess whether progression of loosening is associated with a change in these biomarkers. In particular, high-quality studies assessing the usability of these biomarkers are needed.

Original languageEnglish
Pages (from-to)25-39
Number of pages15
JournalEFORT Open Reviews
Issue number1
Publication statusPublished - 2024


  • arthroplasty
  • biomarkers
  • loosening


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