title: The balance between endotoxin accumulation and clearance during particle-induced osteolysis in murine calvaria.
abstract: Bacterial endotoxin may contribute to aseptic loosening of orthopedic implants even in the absence of clinical or microbiological evidence of infection. One potential source of endotoxin during aseptic loosening is systemically circulating endotoxin, derived from intestinal flora, minor infections, or dental procedures, that may bind to wear particles. The current study demonstrates that systemically derived endotoxin accumulates when 'endotoxin-free' titanium and polyethylene particles are implanted on murine calvaria. Time-course experiments and experiments using germ-free mice rule out the possibility that the observed endotoxin accumulation may be due to bacterial contamination. In contrast, endotoxin is cleared from titanium particles that originally carry high amounts of adherent endotoxin. The mechanism of endotoxin clearance is not dependent on induction of a respiratory burst. Taken together, these results indicate that a balance between endotoxin accumulation and endotoxin clearance controls the steady-state level of endotoxin surrounding orthopedic wear particles implanted on murine calvaria. This balance may regulate the rate of osteolysis in the murine calvaria model as well as in patients with aseptic loosening.
authors.affiliation: Department of Orthopadics, Case Western Reserve University and University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, Ohio 44106-5000, USA.
authors.forename: Joscelyn M
authors.initials: JM
authors.lastname: Tatro
authors.forename: Naoya
authors.initials: N
authors.lastname: Taki
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Islam
authors.forename: Victor M
authors.initials: VM
authors.lastname: Goldberg
authors.forename: Clare M
authors.initials: CM
authors.lastname: Rimnac
authors.forename: Claire M
authors.initials: CM
authors.lastname: Doerschuk
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Stewart
authors.forename: Edward M
authors.initials: EM
authors.lastname: Greenfield
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000378:metabolism*; D005260:Female; D005856:Germ-Free Life; D051379:Mice; D008810:Mice, Inbred C57BL; D010014:Osteolysis / Q000209:etiology / Q000378:metabolism*; D020959:Polyethylene / Q000009:adverse effects*; D011475:Prosthesis Failure; D012886:Skull / Q000187:drug effects / Q000378:metabolism; D014025:Titanium / Q000009:adverse effects*
chemical_list: D004731:Endotoxins; D020959:Polyethylene; D014025:Titanium