title: Cement particles containing radio-opacifiers stimulate pro-osteolytic cytokine production from a human monocytic cell line.
abstract: Proponents of the biological theory of aseptic loosening have in recent years tended to concentrate on the production and distribution of particulate ultra-high-molecular-weight polyethylene (UHMWPE) debris around the potential joint space. However, mechanical loading of cemented implants with the differing elastic moduli of metal stems, polymethylmethacrylate (PMMA) cement and bone can result in relative micromotion, implying the potential for production of metal and PMMA particles from the stem-cement interface by fretting wear. In order to investigate the production and biological reactivity of debris from this interface, PMMA and metal particulate debris was produced by sliding wear of PMMA pins containing barium sulphate and zirconium dioxide against a Vaquasheened stainless steel counterface. This debris was characterised by SEM, energy-dispersive analysis by X-ray (EDAX) and image analysis, then added to cell cultures of a human monocytic cell line, U937, and stimulation of proosteolytic cytokines measured by ELISA. Large quantities of PMMA cement debris were generated by the sliding wear of PMMA pins against Vaquasheened stainless steel plates in the method developed for this study. Both cements stimulated the release of pro-osteolytic TNFalpha from the U937 monocytic cell line, in a dose-dependent fashion. There was a trend towards greater TNFalpha release with Palacos cement than CMW cement at the same dose. Palacos particles also caused significant release of IL-6, another pro-osteolytic cytokine, while CMW did not. The particulate cement debris produced did not stimulate the release of GM-CSF or IL1beta from the U937 cells. These results may explain the cytokine pathway responsible for bone resorption caused by particulate PMMA debris. Radio-opaque additives are of value in surgical practice and clinical studies to quantify the relevance of these in vitro findings are required before the use of cement containing radio-opacifier is constrained.
authors.affiliation: Leeds General Infirmary, University of Leeds, England.
authors.forename: David L
authors.initials: DL
authors.lastname: Shardlow
authors.forename: Martin H
authors.initials: MH
authors.lastname: Stone
authors.forename: Eileen
authors.initials: E
authors.lastname: Ingham
authors.forename: John
authors.initials: J
authors.lastname: Fisher
mesh_terms: D001672:Biocompatible Materials; D001843:Bone Cements; D001858:Bone Nails; D002460:Cell Line; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D017276:Friction; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis / Q000096:biosynthesis; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D007595:Joint Prosthesis; D008855:Microscopy, Electron, Scanning / Q000379:methods; D009000:Monocytes; D010014:Osteolysis; D019904:Polymethyl Methacrylate; D011475:Prosthesis Failure; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
chemical_list: D001672:Biocompatible Materials; D001843:Bone Cements; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019904:Polymethyl Methacrylate