title: Effect of local zoledronate on implant osseointegration in a rat model.
abstract: BACKGROUND
  An implant coating with poly(D, L-lactide) (PDLLA) releasing incorporated zoledronic acid (ZOL) has already proven to positively effect osteoblasts, to inhibit osteoclasts and to accelerate fracture healing. Aim of this study was to investigate the release kinetics of the chosen coating and the effect of different concentrations of ZOL locally released from this coating on the osseointegration of implants.
  
  
  METHODS
  For release kinetics the release of C14-labled ZOL out of the coating was monitored over a period of six weeks in vitro. For testing the osseointegration, titanium Kirschner wires were implanted into the medullary canal of right femurs of 100 Sprague Dawley rats. The animals were divided into five groups receiving implants either uncoated or coated with PDLLA, PDLLA/ZOL low (1.2% w/w) or PDLLA/ZOL high (2% w/w). Additionally, a group with uncoated implants received ZOL intravenously (i.v.). After 56 days animals were sacrificed, femurs dissected and either strength of fixation or histological bone/implant contacts and newly formed bone around the implants were determined.
  
  
  RESULTS
  Release kinetics revealed an initial peak in the release of C14-ZOL with a slight further progression over the following weeks. There was no significant enhancement of osseointegration for both groups who received ZOL-coated implants or ZOL i.v. compared to the controls in biomechanical or histological analyses, except for a significant raise in strength of fixation of ZOL i.v. versus PDLLA.
  
  
  CONCLUSIONS
  Even though the investigated local ZOL application did not enhance the osseointegration of the implant, the findings might support its application in fracture treatment, since fracture stabilization devices are often explanted after consolidation.
authors.affiliation: Department of Orthopedics and Traumatology, German Armed Forces Hospital Berlin, Berlin, Germany.
authors.forename: David A
authors.initials: DA
authors.lastname: Back
authors.forename: Stephan
authors.initials: S
authors.lastname: Pauly
authors.forename: Lisa
authors.initials: L
authors.lastname: Rommel
authors.forename: Norbert P
authors.initials: NP
authors.lastname: Haas
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schmidmaier
authors.forename: Britt
authors.initials: B
authors.lastname: Wildemann
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Greiner
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000737:chemistry; D001864:Bone Wires; D002626:Chemistry, Pharmaceutical; D020099:Coated Materials, Biocompatible; D004164:Diphosphonates / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers; D004343:Drug Implants; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000601:surgery; D007093:Imidazoles / Q000008:administration & dosage* / Q000737:chemistry; D007275:Injections, Intravenous; D007700:Kinetics; D016348:Osseointegration / Q000187:drug effects*; D011091:Polyesters / Q000737:chemistry; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D020099:Coated Materials, Biocompatible; D004164:Diphosphonates; D004337:Drug Carriers; D004343:Drug Implants; D007093:Imidazoles; D011091:Polyesters; C033616:poly(lactide); D000077211:Zoledronic Acid