title: The cellular and molecular biology of periprosthetic osteolysis.
abstract: The generation of prosthetic implant wear after total joint arthroplasty is recognized as the major initiating event in development of periprosthetic osteolysis and aseptic loosening, the leading complication of this otherwise successful surgical procedure. We review current concepts of how wear debris causes osteolysis, and report ideas for prevention and treatment. Wear debris primarily targets macrophages and osteoclast precursor cells, although osteoblasts, fibroblasts, and lymphocytes also may be involved. Molecular responses include activation of MAP kinase pathways, transcription factors (including NFkappaB), and suppressors of cytokine signaling. This results in up-regulation of proinflammatory signaling and inhibition of the protective actions of antiosteoclastogenic cytokines such as interferon gamma. Strategies to reduce osteolysis by choosing bearing surface materials with reduced wear properties should be balanced by awareness that reducing particle size may increase biologic activity. There are no approved treatments for osteolysis despite the promise of therapeutic agents against proinflammatory mediators (such as tumor necrosis factor) and osteoclasts (bisphosphonates and molecules blocking receptor activator of NFkappaB ligand [RANKL] signaling) shown in animal models. Considerable efforts are underway to develop such therapies, to identify novel targets for therapeutic intervention, and to develop effective outcome measures.
authors.affiliation: Hospital for Special Surgery, New York, NY, USA. purduee@hss.edu
authors.forename: P Edward
authors.initials: PE
authors.lastname: Purdue
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Koulouvaris
authors.forename: Hollis G
authors.initials: HG
authors.lastname: Potter
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Nestor
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Sculco
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D019643:Arthroplasty, Replacement / Q000009:adverse effects*; D018450:Disease Progression; D005786:Gene Expression Regulation; D006801:Humans; D008279:Magnetic Resonance Imaging; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010014:Osteolysis / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics; D014057:Tomography, X-Ray Computed
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases