title: The bisphosphonate ibandronate accelerates osseointegration of hydroxyapatite-coated cementless implants in an animal model.
abstract: BACKGROUND
  There is evidence that bisphosphonates can improve fixation of cementless metal implants by enhancing the extent of osseointegration. The current preclinical study examined whether the nitrogen-containing bisphosphonate ibandronate can accelerate this process, resulting in early achievement of secondary stability and sealing of the bone-implant interface to prevent wear debris migration.
  
  
  METHODS
  The study was conducted on 88 female Sprague-Dawley rats in which uncoated titanium 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 1.0, 2.5, or 5.0 microg/kg per day ibandronate or saline solution as a control. The extent of osseointegration expressed by the osseointegrated implant surface was quantified by histomorphometry at eleven time points during the study period. To determine the time course of osseointegration, the data were expressed using third-order polynomial regression analysis.
  
  
  RESULTS
  For hydroxyapatite-coated implants, the highest dose of ibandronate (5 microg) reduced the time for a sufficient implant fixation of 60% osseointegrated implant surface to 18 days compared to 38 days in the control group. This reduction of 20 days (52.6%) represents a halving in the time required for sufficient osseointegration of the implant. For hydroxyapatite-coated implants and low-dose ibandronate application (1 microg, 2.5 microg) and for uncoated titanium implants, acceleration of osseointegration was not observed in any of the study arms.
  
  
  CONCLUSIONS
  Continuous treatment with 5 microg/kg per day ibandronate is potent in accelerating osseointegration of hydroxyapatite-coated implants. As a result, improved early secondary stability and prevention of wear debris migration by the sealing of the implant-bone interface can be expected, therefore prolonging the long-term survival of the implant.
authors.affiliation: Department of Orthopaedic Surgery, University Hospital Frankfurt, Marienburgstrasse 2, 60528, Frankfurt, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Eberhardt
authors.forename: Björn
authors.initials: B
authors.lastname: Habermann
authors.forename: Stephan
authors.initials: S
authors.lastname: Müller
authors.forename: Markus
authors.initials: M
authors.lastname: Schwarz
authors.forename: Frieder
authors.initials: F
authors.lastname: Bauss
authors.forename: Andreas H A
authors.initials: AH
authors.lastname: Kurth
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D020099:Coated Materials, Biocompatible; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D017886:Durapatite; D005260:Female; D005264:Femoral Fractures / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D000077557:Ibandronic Acid; D007279:Injections, Subcutaneous; D016348:Osseointegration / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D020099:Coated Materials, Biocompatible; D004164:Diphosphonates; D017886:Durapatite; D000077557:Ibandronic Acid