title: Bisphosphonates in bone cement inhibit PMMA particle induced bone resorption.
abstract: OBJECTIVE
  Wear particle induced bone resorption is thought to be one of the mechanisms that contribute to implant loosening. It has previously been shown that macrophages, in response to polymethylmethacrylate (PMMA) particles, differentiate into bone resorbing osteoclasts, and that this process is inhibited by a bisphosphonate, etidronate (EHDP). The aim of this study was to determine whether incorporating EHDP in bone cement could reduce PMMA associated bone resorption.
  
  
  METHODS
  Two concentrations of EHDP were mixed with PMMA monomer before polymerisation. Particles of PMMA (1-10 microns) were generated then added to mouse monocytes cocultured with UMR106 rat osteoblast-like cells and the extent of osteoclast differentiation was determined by assessing the extent of tartrate resistant acid phosphatase (TRAP) staining and measuring the amount of lacunar bone resorption.
  
  
  RESULTS
  The addition of PMMA to monocyte-UMR106 cocultures resulted in a marked increase in the number of TRAP positive osteoclast-like cells and a significant increase in the number of lacunar resorption pits compared with control cultures to which no particles had been added. After the addition of particles of PMMA + 20 mg EHDP, significantly fewer lacunar pits (p = 0.00006) and fewer TRAP positive cells were noted compared with cocultures containing PMMA particles alone.
  
  
  CONCLUSIONS
  These results indicate that by mixing a bisphosphonate with bone cement, it is possible to inhibit PMMA particle induced bone resorption. This bisphosphonate inhibition of PMMA biomaterial wear particle containing macrophage-osteoclast differentiation and bone resorption may provide a possible therapeutic strategy to prevent or to control the osteolysis of aseptic loosening.
authors.affiliation: Nuffield Orthopaedic Centre, University of Oxford.
authors.forename: A
authors.initials: A
authors.lastname: Sabokbar
authors.forename: Y
authors.initials: Y
authors.lastname: Fujikawa
authors.forename: D W
authors.initials: DW
authors.lastname: Murray
authors.forename: N A
authors.initials: NA
authors.lastname: Athanasou
mesh_terms: D000818:Animals; D001843:Bone Cements / Q000494:pharmacology*; D001862:Bone Resorption / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D001842:Bone and Bones / Q000648:ultrastructure; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D012968:Etidronic Acid / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D019904:Polymethyl Methacrylate; D051381:Rats
chemical_list: D001843:Bone Cements; D019904:Polymethyl Methacrylate; D012968:Etidronic Acid