title: The Inflammatory Phenotype in Failed Metal-On-Metal Hip Arthroplasty Correlates with Blood Metal Concentrations.
abstract: Hip arthroplasty is the standard treatment of a painful hip destruction. The use of modern metal-on-metal (MOM) bearing surfaces gained popularity in total hip arthroplasties during the last decade. Recently, worrisome failures due to adverse reaction to metal debris (ARMD), including pseudotumor response, have been widely reported. However, the pathogenesis of this reaction remains poorly understood. The aim of the present study was to investigate the ARMD response by flow cytometry approach.
  
  
  
  Sixteen patients with a failed Articular Surface Replacement (ASR) hip prosthesis were included in the study. Samples of pseudotumor tissues collected during revision surgery were degraded by enzyme digestion and cells were typed by flow cytometry. Whole blood chromium and cobalt concentrations were analyzed with mass spectrometry before revision surgery.
  
  
  
  Flow cytometry analysis showed that the peri-implant pseudotumor tissue expressed two principal phenotypes, namely macrophage-dominated and T-lymphocyte-dominated response; the average portions being 54% (macrophages) and 25% (T-lymphocytes) in macrophage-dominated inflammation and 20% (macrophages) and 54% (T-lymphocytes) in T-lymphocyte-dominated response. The percentages of B-lymphocytes and granulocytes were lower in both phenotypes. Interestingly, the levels of blood chromium and cobalt were significantly higher in patients with macrophage-dominated response.
  
  
  
  The results suggest that the adverse tissue reactions induced by MOM wear particles contain heterogeneous pathogeneses and that the metal levels are an important factor in the determination of the inflammatory phenotype. The present results support the hypothesis that higher metal levels cause cytotoxicity and tissue injury and macrophages are recruited to clear the necrotic debris. On the other hand, the adverse response developed in association with lower metal levels is T-lymphocyte-dominated and is likely to reflect hypersensitivity reaction.
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Erja-Leena
authors.initials: EL
authors.lastname: Paukkeri
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Riku
authors.initials: R
authors.lastname: Korhonen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Hämäläinen
authors.affiliation: Immunoregulation, Institute of Biomedical Technology, University of Tampere, Tampere, Finland.|Department of Dermatology, Tampere University Hospital, Tampere, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Pesu
authors.affiliation: Coxa Hospital for Joint Replacement, Tampere, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Eskelinen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.|Coxa Hospital for Joint Replacement, Tampere, Finland.
authors.forename: Teemu
authors.initials: T
authors.lastname: Moilanen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
mesh_terms: D000328:Adult; D000368:Aged; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D002857:Chromium / Q000097:blood*; D003035:Cobalt / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D005547:Foreign Bodies / Q000097:blood*; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D057910:Implant Capsular Contracture / Q000097:blood / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
chemical_list: D002857:Chromium; D003035:Cobalt