title: Early inhibitory effects of zoledronic acid in tooth extraction sockets in dogs are negated by recombinant human bone morphogenetic protein.
abstract: OBJECTIVE
  This study was conducted with 2 purposes. The first was to determine the effect of a single dose of zoledronic acid (ZA) on the healing of a tooth extraction socket in dogs. The second was to determine if placement of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) - INFUSE, (Medtronic, Memphis, TN) into these extraction sockets would inhibit the inhibition on bone healing and remodeling by ZA.
  
  
  METHODS
  Nine adult female beagle dogs (2 to 3 yr old) were placed into 3 groups of 3 dogs each. Group I received 15 mL of sterile saline intravenously; group II received 2.5 mg of ZA intravenously; and group III received 5 mg of ZA intravenously. Forty-five days after treatment, all dogs underwent extraction of noncontiguous right and left mandibular first molars and second premolars. In group I, the right mandibular extraction sockets had nothing placed in them, whereas the left mandibular sockets had only ACS placed in them. In groups II and III, the right mandibular sockets had rhBMP-2/ACS placed in them, whereas the left mandibular sockets had only ACS placed. All extraction sockets were surgically closed. Tetracycline was given intravenously 5 and 12 days later, and all animals were euthanized 15 days after tooth extraction. The extraction sockets and rib and femur samples were harvested immediately after euthanasia, processed, and studied microscopically.
  
  
  RESULTS
  A single dose of ZA significantly inhibited healing and bone remodeling in the area of the tooth extractions. The combination of rhBMP-2/ACS appeared to over-ride some of the bone remodeling inhibition of the ZA and increased bone fill in the extraction sites, and remodeling activity in the area was noted. The effects of rhBMP-2/ACS were confined to the area of the extraction sockets because bone activity at distant sites was not influenced.
  
  
  CONCLUSIONS
  A single dose of ZA administered intravenously inhibits early healing of tooth extraction sockets and bone remodeling in this animal model. The combination of rhBMP-2/ACS significantly increased bone fill and bone remodeling in these areas, negating much of the effect of the ZA.
authors.affiliation: Professor, Department of Oral and Maxillofacial Surgery, University of Tennessee Medical Center, Knoxville, TN.
authors.forename: David A
authors.initials: DA
authors.lastname: Gerard
authors.affiliation: Professor and Chairman, Department of Oral and Maxillofacial Surgery, University of Tennessee Medical Center, Knoxville, TN. Electronic address: ecarlson@mc.utmck.edu.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Carlson
authors.affiliation: Professor, Department of Oral and Maxillofacial Surgery, University of Tennessee Medical Center, Knoxville, TN.
authors.forename: Jack E
authors.initials: JE
authors.lastname: Gotcher
authors.affiliation: Chief Resident, Department of Oral and Maxillofacial Surgery, University of Tennessee Medical Center, Knoxville, TN.
authors.forename: David O
authors.initials: DO
authors.lastname: Pickett
mesh_terms: D000818:Animals; D000880:Anthraquinones; D001641:Bicuspid / Q000601:surgery; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects; D003094:Collagen; D004396:Coloring Agents; D004164:Diphosphonates / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004285:Dogs; D004337:Drug Carriers; D005260:Female; D005269:Femur / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007093:Imidazoles / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007275:Injections, Intravenous; D008963:Molar / Q000601:surgery; D010012:Osteogenesis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012272:Ribs / Q000187:drug effects; D014048:Tolonium Chloride; D014081:Tooth Extraction; D020390:Tooth Socket / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects; D000077211:Zoledronic Acid
chemical_list: D000880:Anthraquinones; D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D004396:Coloring Agents; D004164:Diphosphonates; D004337:Drug Carriers; D007093:Imidazoles; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D014048:Tolonium Chloride; C010078:alizarin; D000077211:Zoledronic Acid; D003094:Collagen