title: Emerging ideas: Instability-induced periprosthetic osteolysis is not dependent on the fibrous tissue interface.
abstract: BACKGROUND
  Stable initial fixation of a total joint arthroplasty implant is critical to avoid the risk of aseptic loosening and premature clinical failure. With implant motion, a fibrous tissue layer forms at the bone-implant interface, leading to implant migration and periprosthetic osteolysis. At the time of implant revision surgery, proresorptive signaling cytokines are expressed in the periimplant fibrous membrane. However, the exact role of this fibrous tissue in causing periprosthetic osteolysis attributable to instability remains unknown.
  
  
  OBJECTIVE
  We propose an alternative mechanism of periprosthetic osteolysis independent of the fibrous tissue layer, where pressurized fluid flow along the bone-implant interface activates mechanosensitive osteocytes in the periprosthetic bone, causing the release of proresorptive cytokines and subsequent osteoclast differentiation and osteolysis.
  
  
  METHODS
  An animal model for instability-induced osteolysis that mimics the periprosthetic bone-implant interface will be used. In this model, a fibrous tissue membrane is allowed to form in the periprosthetic zone, and pressurized fluid flow transmitted through this membrane reliably creates osteolytic lesions in the periprosthetic bone. In this study, half of the rats will have the fibrous tissue present, while the other half will not. We will determine whether the fibrous tissue membrane is essential for the release of proosteoclastic cytokines, leading to osteoclast differentiation and periprosthetic bone loss, by measuring the volume of bone resorption and presence of proresorptive cytokines at the bone-implant interface.
  
  
  CONCLUSIONS
  We will determine whether the fibrous tissue membrane is crucial for osteoclastogenic signaling in the setting of periimplant osteolysis. In the future, this will allow us to test therapeutic interventions, such as specific cytokine inhibitors or alterations in implant design, which may translate into new, clinically relevant strategies to prevent osteolysis.
authors: Department of Orthopaedic Surgery Adult Reconstruction and Joint Replacement Division, Hospital for Special Surgery, 535 E 70th Street, New York, NY 10021, USA. namd@hss.edu
authors: Denis
authors: D
authors: Nam
authors: Mathias P G
authors: MP
authors: Bostrom
authors: Anna
authors: A
authors: Fahlgren
mesh_terms: D000818:Animals; D019643:Arthroplasty, Replacement / Q000009:adverse effects*; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D010011:Osteocytes / Q000378:metabolism / Q000473:pathology; D010014:Osteolysis / Q000209:etiology* / Q000473:pathology; D011312:Pressure; D011475:Prosthesis Failure / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012107:Research Design; D015398:Signal Transduction
chemical_list: D016207:Cytokines