title: Periprosthetic osteolysis: genetics, mechanisms and potential therapeutic interventions.
abstract: Aseptic loosening and periprosthetic osteolysis occur as a result of the biological response to particulate wear debris and are one of the leading causes of arthroplasty failure. Periprosthetic osteolysis originates from chronic inflammatory responses triggered by implant-derived particulate debris, which cause recruitment of cells, including macrophages, fibroblasts, lymphocytes and osteoclasts. These cells secrete proinflammatory and osteoclastogenic cytokines, exacerbating the inflammatory response. In addition to their direct activation by phagocytosis, there are contributing autocrine and paracrine effects that create a complex milieu within the periprosthetic space, which ultimately governs the development of osteolysis. Chronic cell activation may upset the delicate balance between bone formation and bone resorption leading to periprosthetic osteolysis. This article summarizes the genetic mechanisms underlying periprosthetic loosening and identifies potential therapeutic agents.
authors.affiliation: Department of Orthopaedic Surgery, University of British Columbia, Vancouver, BC. shahryar.noordin@aku.edu
authors.forename: Shahryar
authors.initials: S
authors.lastname: Noordin
authors.forename: Bassam
authors.initials: B
authors.lastname: Masri
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D000818:Animals; D019643:Arthroplasty, Replacement / Q000009:adverse effects*; D001862:Bone Resorption; D006801:Humans; D007595:Joint Prosthesis / Q000009:adverse effects*; D010012:Osteogenesis; D010014:Osteolysis / Q000150:complications / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D019904:Polymethyl Methacrylate; D011475:Prosthesis Failure / Q000209:etiology; D014025:Titanium
chemical_list: D019904:Polymethyl Methacrylate; D014025:Titanium