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EXOGENOUS ADMINISTRATION OF RHBMP-7 DURING DISTRACTION OSTEOGENESIS ON TRABECULAR BONE FORMATION; A DOSE-RESPONSE STUDY
Presenter: Ali Izadpanah, MD
Co-Authors: Alsalmi L; Hamdy R; Lessard L
McGill University

Background: Distraction osteogenesis (DO) has provided surgeons with a valuable tool for approach to patients with bony deficiencies. The main limitation of DO remains the long consolidation period. Bone Morphogenetic Proteins (BMPs) have been shown to enhance bone formation during DO with controversial effects at different administrated doses. We sought to determine effects of exogenous BMP-7 (rhBMP-7) on trabecular bone during DO.

Methods: Sixty-eight wild type mice were randomly assigned to be sacrificed at mid- (day 34) or end of consolidation (day 51). Each group was sub-divided into three study groups (n=10) for three different doses of 2g/kg, 4g/kg, and 20g/kg. Eight mice were omitted for analysis secondary to pin tract infections. Four mice had undergone distraction under with no injection serving as controls. On the first day of distraction, study animals were given a single injection of BMP-7. Mice were then sacrificed mid- and end of consolidation. Distracted specimens were examined using micro-CT for trabecular bone characteristics.

Results: Maximal trabecular bone formation with the lowest structure model index, indicating a more sheet-like structure versus a rod-like structure at mid-consolidation was observed in mice injected with the medium dose (4g/kg), this was followed by the highest (20g/kg), and then lowest dose (2g/kg). Anisotropic results at 34 days demonstrated similar osteogenic patterns.
Similar analysis was performed for specimens collected at the end of consolidation demonstrating greatest trabecular bone formation at the lowest dose, followed by the medium and highest dose.

Conclusion: A single injection of rhBMP-7 at all administered doses significantly stimulated trabecular bone generation at both mid- and end of consolidation. Highest dose of 20g/kg had a positive effect on trabecular bone formation during mid-consolidation, however an inhibitory effect by the end of consolidation. Further dose-response studies with closer look at different doses and other animal models are recommended.


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