title: Histomorphometric analysis of the intramedullary bone response to titanium particles in wild-type and IL-1R1 knock-out mice: a preliminary study.
abstract: Aseptic loosening of implants following total joint arthroplasty remains a major cause of implant failure. Particulate debris generated primarily from wear results in inflammatory mediated periprosthetic osteolysis. Titanium is a commonly utilized metal in joint arthroplasty and titanium debris induces the production of the pro-inflammatory cytokine IL-1. To further elucidate the role of IL-1, this study examined the response of murine femora to the presence of titanium particles following implantation of an intramedullary rod in mice lacking the receptor for IL-1. We hypothesized that the inflammatory effects of wear debris on bone would be mitigated in IL-1R1 deficient mice with a resultant decrease in resorption. Femora receiving titanium particles demonstrated a marked inflammatory response in wild-type mice with increased endocortical resorption, periprosthetic membrane formation, and significant histomorphometric changes. Femora exposed to titanium particles in the knockout mice also demonstrated osteolysis with irregular deposition of trabecular bone and increased cortical porosity. The persistence of inflammation and osteolysis, despite the lack of functional IL-1R1, suggests a multi-factorial role for IL-1 in the proinflammatory cascade resulting from wear debris. This intramedullary murine model provides the ability to evaluate and quantify the proinflammatory cascade in an in vivo model approximating prosthesis failure.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA. bragg@stanford.edu
authors.forename: Bill
authors.initials: B
authors.lastname: Bragg
authors.forename: Noah J
authors.initials: NJ
authors.lastname: Epstein
authors.forename: Ting
authors.initials: T
authors.lastname: Ma
authors.forename: Stuart
authors.initials: S
authors.lastname: Goodman
authors.forename: R Lane
authors.initials: RL
authors.lastname: Smith
mesh_terms: D000818:Animals; D001858:Bone Nails; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D005269:Femur / Q000473:pathology / Q000601:surgery; D007375:Interleukin-1 / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D010014:Osteolysis / Q000378:metabolism / Q000473:pathology; D011475:Prosthesis Failure; D053573:Receptors, Interleukin-1 Type I / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D014025:Titanium
chemical_list: D007375:Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D014025:Titanium