The anti-angiogenic substance TNP-470 impairs peri-implant bone formation: a pilot study in the rabbit metaphysis model.

Objectives: To study the osseointegration of dental implants under the conditions of impaired blood vessel formation in a rabbit model.
Material and 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.
Conclusion: 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.