title: The anti-angiogenic substance TNP-470 impairs peri-implant bone formation: a pilot study in the rabbit metaphysis model.
abstract: OBJECTIVE
  To study the osseointegration of dental implants under the conditions of impaired blood vessel formation in a rabbit model.
  
  
  METHODS
  Twenty-four titanium implants were placed in the diaphyses of 12 rabbits, two in each tibia. After 2 days, six animals received TNP-470, an anti-angiogenic substance, 10 mg/kg body weight, three times a week, by subcutaneous injection. The remaining six animals served as controls. All animals were sacrificed 6 weeks post implantation.
  
  
  RESULTS
  The amount of newly formed bone (NFB) within a peri-implant distance of 0.2 mm and the percentage of bone-to-implant contacts (BIC) were determined in undecalcified ground sections. In both groups, appositional bone growth originating from the cortex was associated with a dense network of blood vessels. Within 1 mm apical from the implant shoulder, NFB was 29.3+/-6.7% in TNP-470 treated animals vs. 44.2+/-13.1% in the controls (P=0.03). In the adjacent cortical area NFB was 46.1+/-10.0% in TNP-470 treated animals and 58.4+/-3.0% in the control group (P=0.02). In the endosteal area, 3 mm from the implant shoulder NFB was 24.8+/-11.8% in TNP-470-treated animals and 27.0+/-9.6% in controls (P=0.73) and in the most apical peri-implant area corresponding to the bone marrow cavity 4.3+/-3.2% in TNP-470-treated animals and 10.5+/-5.2% in the controls (P=0.03). No decrease in BIC in response to TNP-470 was observed.
  
  
  CONCLUSIONS
  The data suggest that TNP-470 decreases the formation of peri-implant bone, whereas BIC overall are not affected by it. The rabbit model presented here supports the importance of angiogenesis in the process of peri-implant bone formation.
authors.affiliation: Department of Oral Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Mair
authors.forename: Gabor
authors.initials: G
authors.lastname: Fuerst
authors.forename: Pawel
authors.initials: P
authors.lastname: Kubitzky
authors.forename: Stefan
authors.initials: S
authors.lastname: Tangl
authors.forename: Helga
authors.initials: H
authors.lastname: Bergmeister
authors.forename: Udo
authors.initials: U
authors.lastname: Losert
authors.forename: Georg
authors.initials: G
authors.lastname: Watzek
authors.forename: Reinhard
authors.initials: R
authors.lastname: Gruber
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D003510:Cyclohexanes / Q000494:pharmacology*; D003758:Dental Implantation, Endosseous / Q000379:methods*; D008297:Male; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D016348:Osseointegration / Q000187:drug effects*; D010865:Pilot Projects; D011817:Rabbits; D012717:Sesquiterpenes / Q000494:pharmacology*; D013977:Tibia / Q000098:blood supply / Q000187:drug effects / Q000601:surgery
chemical_list: D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol