Comparison of BMP-2 and -4 for rat mandibular bone regeneration at various doses.
OBJECTIVE
To compare mandibular bone regeneration with bone morphogenetic proteins-2 and -4 (BMP-2 and -4) at varying doses.


METHODS
Defects were created in the left hemi-mandibles of 82 Sprague-Dawley rats. The defects were filled with a hyaluronic acid polymer loaded with 0.01, 0.1, 1, or 10 microg of BMP-2 or -4. Control groups consisted of animals with unfilled defects, or with defects filled with the hyaluronic acid sponges loaded with growth factor dilution buffer. Animals were killed after 8 weeks, and the hemi-mandibles were analyzed histologically using stereologic techniques.


RESULTS
Mandibles implanted with carriers containing 10 microg of BMP-2 or -4 differed significantly from controls in terms of new bone area (p = 0.01 and p = 0.0001, respectively). Marrow space development occurred in a dose-dependent fashion (p < 0.0001 for both growth factors), and this effect was more pronounced for BMP-2 at larger doses (p < 0.0001 at 1 and 10 microg doses). New bone areas and volumes did not differ significantly between the growth factors. While defects implanted with BMP-4 tended to have thicker cortical bone and more trabecular bone, at least partial defect bridging was achieved in a greater number of defects implanted with BMP-2 (47%) than with BMP-4 (35%).


CONCLUSIONS
Although similar areas and volumes of new bone were induced with BMP-2 and -4, differences were noted in the quality of bone generated with each growth factor. The results indicate a threshold dose for acute administration between 1 and 10 mug BMP-2 for bony union in this model, and > or =10 microg for BMP-4.


CONCLUSIONS
These findings suggest that differences in bone growth factor osteogenic potential deserve further study and may have an impact on the translation of osteoinductive protein therapy into clinical practice.
Arosarena
O
O
Division of Otolaryngology, Department of Surgery, University of Kentucky Medical Center, Lexington, 40536, USA. oaaros2@pop.uky.edu
Collins
W
W
D000704:Analysis of Variance; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008334:Mandible / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*
C525720:Bmp2 protein, rat; C525811:Bmp4 protein, rat; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta