title: Tumor necrosis factor-alpha (TNF-alpha) in loosening of total hip replacement (THR).
abstract: OBJECTIVE
  The initially well-fixed implants of total hip replacement (THR) are in the long-term subject to aseptic loosening. Many cytokines can contribute to osteolysis due to osteoclast recruitment and/or activation. However, in this respect tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role, because it upregulates interleukin-1 and 6 and granulocyte-macrophage colony stimulating factor. The aim of this study was to assess the eventual presence, cellular localization and extent of expression of TNF-alpha in the synovial-like membrane at the implant or at the cement to bone interface compared to control synovial membrane.
  
  
  METHODS
  Twenty samples from the synovial-like membrane of the periprosthetic tissues were compared to control samples. TNF-alpha containing cells were visualized using an avidin-biotin-peroxidase complex (ABC) method and analyzed by light microscopy, double labelling and image analysis.
  
  
  RESULTS
  TNF-alpha was found in the periprosthetic tissues in fibroblasts and vascular endothelial cells, but mainly in the macrophages was it found to coincide with areas containing implant-derived debris. TNF-alpha containing cells were more numerous in the synovial-like membrane in the interface tissue from the proximal stem area (2816 +/- 318 cells) than in the control synovial membrane (565 +/- 93 cells, p < 0.01). Interestingly, similarly high TNF-alpha expression (3452 +/- 582 cells) was also seen in the synovial-like membrane of the pseudocapsule.
  
  
  CONCLUSIONS
  These findings suggest that the foreign body-type host reaction caused by THR is characterized by the high expression of TNF-alpha. Because such expression occurred in the interface tissue between the implant and surrounding bone, TNF-alpha, due to its pivotal direct and indirect role in the activation and recruitment of osteoclasts, may contribute to periprosthetic osteolysis and to the loosening of THR.
authors.affiliation: Research Unit of the Orthopaedic Hospital, Invalid Foundation, Helsinki, Finland.
authors.forename: J W
authors.initials: JW
authors.lastname: Xu
authors.forename: Y T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: J
authors.initials: J
authors.lastname: Lassus
authors.forename: S
authors.initials: S
authors.lastname: Natah
authors.forename: A
authors.initials: A
authors.lastname: Ceponis
authors.forename: S
authors.initials: S
authors.lastname: Solovieva
authors.forename: P
authors.initials: P
authors.lastname: Aspenberg
authors.forename: S
authors.initials: S
authors.lastname: Santavirta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006622:Hip Prosthesis; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010014:Osteolysis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011475:Prosthesis Failure; D012086:Reoperation; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha