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J Orthop Res. 2019 Jun 24. doi: 10.1002/jor.24398. [Epub ahead of print]

Chronic, Active Inflammation in Patients With Failed Total Knee Replacements Undergoing Revision Surgery.

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Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom.
Musculoskeletal Unit, Department of Orthopaedics, Freeman Hospital, Newcastle Hospitals, NHS Trust, Newcastle upon Tyne, NE7 7DN, United Kingdom.
School of Mathematics & Statistics, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom.


Chronic pain and restricted knee motion is a significant problem following the total knee arthroplasty (TKA). The molecular pathogenesis of pain post-TKA is not known and no targeted therapeutic intervention is available. The aim of this study was to investigate whether pro-inflammatory mediators are elevated in revision knee patients, indicating an active, ongoing inflammatory process that may contribute to pain. Twelve key markers (pro-inflammatory cytokines granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin 5 [IL-5], IL-8 and IL-10, chemokines CCL2, CCL3, CCL4, and CCL13, mediators of angiogenesis Flt-1, vascular endothelial growth factor, and cell migration vascular cell adhesion molecule 1 and intercellular adhesion molecule 1) were measured in knee tissue and synovial fluid (SF) from primary TKA (n = 29) and revision patients (n = 32). Indications for surgery were osteoarthritis (OA) for primary TKA, and component loosening (n = 11), stiffness (n = 11), laxity pattern (n = 8), or progression of OA in patella resurfacing (n = 3) for revision surgery. Pain levels (WOMAC score) were higher in revision than primary patients ( p ≤ 0.05). Time from primary to revision ranged from 8 months to 30 years (median 10 years). All markers were elevated in revision TKA; there was no trend toward decreasing levels with greater time from primary surgery for any marker studied in SF. Similar results were seen in knee tissue. We found no differences comparing indications for revision surgery (p ≥ 0.05). The elevation of inflammatory mediators in painful post-TKA knees requiring revision suggests active, chronic inflammation. Characterization of upregulated markers provides rationale for targeted therapy, even many years from the primary surgery.


arthroplasty; fibrosis; inflammation; knee; pain


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