251. DOSE-EFFECT AND PREMATURE FUSION LINKED WITH RH-BMP-2 IN A MODEL OF BONE DISTRACTION

Abstract

Purpose of the study: Little work has been reported on the effects of BMP on bone healing after distraction and the data available in the literature are contradictory. The type of BMP as well as the optimal dose remain to be defined. We present the results and complications linked with the use of different doses of rhBMP-2 in a model of osteogenesis in distraction.

Material and methods: Fifteen subadult New Zealand rabbits were selected at random and divided into three groups. On day 0, a mediodiaphyseal tibial osteotomy was cut and an M103 fixation implanted. In group I (5 rabbits), 750μg of rhBMP-2 with a type I collagen sponge (Inductos, Medtronic) were deposited on the osteotomy site. In group II (5 rabbits), 350 μg were deposited on the collagen sponge and in group III (controls, 5 rabbits), nothing was deposited. After the 7-day latency period, distraction was conducted for 21 days (0.5 mm(12hr). At the second week of distraction, the callus was analysed on the x-rays and ultrasounds and a weekly absorptiometry was obtained. The animals were sacrificed three weeks after healing was confirmed.

Results: Quantitative radiographic assay showed significantly superior grading (Kirker-Head) in groups I and II (p< 0.05) compared with group III. The qualitative analysis showed premature healing of the regenerate preventing completion of the distraction (pin distortion) for 3/5 rabbits in group I and 1/5 in group II. Bone mineral content was superior in groups I and II in all times studied than in group III (p< 0.05). The difference was also significant between groups I and II (p=0.0087) demonstrating an expected dose effect.

Discussion: Premature healing was achieved for the majority of animals in group I, underlining the importance of the dose of BMP used to stimulate bone healing after callotasis. The undesirable effect thus obtained should be taken into account in the clinical context. A dose of 100 μg/kg (350 μg, group III) appears to suffice in this model and defines the upper dose limit. Differed application of the compound (after distraction) should be useful and should be studied.

Conclusion: The dose of rhBMP-2 used to stimulate bone healing is an essential parameter that should be defined for each experimental model. The dose effect of rhBMP-2 is demonstrated in this particular model.