title: Bisphosphonate remains highly localized after elution from porous implants.
abstract: BACKGROUND
  Local elution of zoledronic acid from a porous implant reportedly enhances periimplant bone formation and implant fixation. However, there is no information in the literature on the extent to which eluted bisphosphonate remains localized around the implant or becomes systemically distributed.
  
  
  OBJECTIVE
  We ascertained to what extent eluted zoledronic acid remains local and whether there is systemic exposure after local elution from porous implants.
  
  
  METHODS
  A hydroxyapatite-coated porous tantalum implant dosed with 100 μg (14)C-labeled zoledronic acid was implanted into the left femoral intramedullary canal of six dogs. Bone samples near to and distant from the implant were harvested from three dogs at 6 weeks and three dogs at 52 weeks. The concentration of radiolabeled bisphosphonate in each sample was quantified using liquid scintillation spectrophotometry and its distribution in periimplant bone was revealed by exposing histologic sections to autoradiography film.
  
  
  RESULTS
  In all six dogs, the concentration of zoledronic acid in immediate periimplant bone was two orders of magnitude higher than in any other sampled tissue, averaging 732.6 ng/g at 6 weeks and 377.2 ng/g at 52 weeks. Minute amounts of zoledronic acid (≤ 7.2 ng/g) were detected throughout the skeleton, indicating some escape into the circulation after local elution. Autoradiographs revealed the greatest concentration of zoledronic acid on and within the implant, with rapid decrease short distances away and no uptake within the femoral cortex.
  
  
  CONCLUSIONS
  Zoledronic acid eluted from an implant remains mainly localized with minimal systemic distribution.
  
  
  CONCLUSIONS
  Local bisphosphonate elution reduces the risk of systemic side effects and skeletal bisphosphonate exposure.
authors.affiliation: Jo Miller Orthopaedic Research Laboratory, Montreal General Hospital, Montreal, Canada.
authors.forename: Kimberly
authors.initials: K
authors.lastname: McKenzie
authors.forename: J
authors.initials: J
authors.lastname: Dennis Bobyn
authors.forename: Jacintha
authors.initials: J
authors.lastname: Roberts
authors.forename: Dorota
authors.initials: D
authors.lastname: Karabasz
authors.forename: Michael
authors.initials: M
authors.lastname: Tanzer
mesh_terms: D000818:Animals; D001345:Autoradiography; D050071:Bone Density Conservation Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D004164:Diphosphonates / Q000737:chemistry / Q000493:pharmacokinetics*; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry; D017886:Durapatite / Q000737:chemistry; D005269:Femur / Q000737:chemistry / Q000378:metabolism / Q000601:surgery; D007093:Imidazoles / Q000737:chemistry / Q000493:pharmacokinetics*; D010012:Osteogenesis; D019736:Prostheses and Implants; D019919:Prosthesis Implantation; D012588:Scintillation Counting; D012995:Solubility; D013635:Tantalum / Q000737:chemistry; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D020099:Coated Materials, Biocompatible; D004164:Diphosphonates; D004337:Drug Carriers; D007093:Imidazoles; D013635:Tantalum; D000077211:Zoledronic Acid; D017886:Durapatite
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