title: High dosage treatment of nitrogen-containing bisphosphonate ibandronate is required for osseointegration of cementless metal implants.
abstract: BACKGROUND
  There is evidence that application of a bisphosphonate can improve fixation of cementless metal implants by enhancing the extent of osseointegration, but the required dose regimen is still under discussion. The current preclinical study was designed to determine the optimal treatment dose of the nitrogen-containing bisphosphonate ibandronate to improve osseointegration of cementless metal implants.
  
  
  METHODS
  The study was conducted in 52 female Sprague-Dawley rats in which uncoated and hydroxyapatite-coated titanium implants were surgically inserted into the medullary canal of each femur. The animals were randomly assigned to receive subcutaneous treatment with ibandronate 1 microg/kg body weight (osteoporosis dose) or 25 microg/kg (tumor dose) per day or saline solution for control.
  
  
  RESULTS
  Histomorphometric evaluation revealed a significant enhanced extent of osseointegrated implant surface in the high-dose treatment group for both implants compared to the low-dose group and the control group. No significant differences were observed between the two implants in any group.
  
  
  CONCLUSIONS
  The results of the present study indicate that improved osseointegration of hydroxyapatite-coated and uncoated titanium implants is dose-dependent and requires high-dose application of bisphosphonate ibandronate equivalent to that needed to treat patients with tumor disease. Lower doses equivalent to those for treatment of osteoporosis showed no beneficial effect.
authors.affiliation: Department of Orthopedic Surgery, University Hospital Frankfurt, Marienburgstrasse 2, 60528, Frankfurt, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Eberhardt
authors.forename: Markus
authors.initials: M
authors.lastname: Schwarz
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Kurth
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D020099:Coated Materials, Biocompatible / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006882:Hydroxyapatites / Q000378:metabolism; D000077557:Ibandronic Acid; D020007:Implants, Experimental; D008670:Metals / Q000737:chemistry*; D009584:Nitrogen / Q000378:metabolism*; D016348:Osseointegration / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties
chemical_list: D050071:Bone Density Conservation Agents; D020099:Coated Materials, Biocompatible; D004164:Diphosphonates; D006882:Hydroxyapatites; D008670:Metals; D009584:Nitrogen; D000077557:Ibandronic Acid