Comparison of the osteogenesis and fusion rates between activin a / BMP-2 chimera (AB204) and rhBMP-2 in a beagle's posterolateral lumbar spine model

• Published in: The spine journal 2017-10, Vol.17 (10), p.1529-1536
• Main Authors: Zheng, Guang Bin, Yoon, Byung-Hak, Lee, Jae Hyup
• Format: Article
• Language: English
• Subjects: AB204; Activins - pharmacology; Animals; Beagle dog; Biphasic calcium phosphate; Bone Morphogenetic Protein 2 - pharmacology; Chimera; Dogs; Hydroxyapatites - pharmacology; Lumbar Vertebrae - pathology; Male; Models, Animal; Orthopedics; Osteogenesis; Osteogenesis - drug effects; Posterolateral fusion; Recombinant Fusion Proteins - pharmacology; Recombinant Proteins - pharmacology; rhBMP-2; Spinal Fusion - methods; Tomography, X-Ray Computed; Transforming Growth Factor beta - pharmacology
• ISSN: 1529-9430; 1878-1632
• DOI: 10.1016/j.spinee.2017.05.014

Abstract Background Context Activin A/BMP-2 chimera (AB204) could promote bone healing more effectively than recombinant bone morphogenetic protein 2 (rhBMP-2) with much lower dose in rodent model, but there is no report about the effectiveness of AB204 in a large animal model. Purpose The purpose of this study was to compare the osteogenesis and fusion rate between AB204 and rhBMP-2 using biphasic calcium phosphate (BCP) as a carrier in beagle's posterolateral lumbar fusion model. Study Design A randomized control animal study. Methods 17 male beagle dogs were included. Bilateral posterolateral fusion was performed at L1-2 and L4-5 levels. BCP (2cc), rhBMP-2 (50µg) + BCP (2cc) or AB204 (50 µg) + BCP (2cc) were implanted into the intertransverse space randomly. X-ray was performed at 4 and 8 weeks. After 8 weeks, the animals were sacrificed, new bone formation and fusion rate were evaluated by manual palpation, computed tomography and undecalcified histology. Results AB204 group showed significantly higher fusion rate (90%) than rhBMP-2 group (15%) or Osteon group (6.3%) by manual palpation. In X-ray and CT assessment, fusion rate and the volume of newly formed bone were also significantly higher in AB204 group than other groups. In contrast, more osteolysis was found in rhBMP-2 group (40%) than AB204 group (10%) in CT study. In histological results, new bone formation was sufficient between transverse processes in AB204 group, obvious trabeculation and bone remodeling were observed. But in rhBMP-2 group, new bone formation was less than AB204 group and osteolysis was observed between the intertransverse space. Conclusions Low dose of AB204 with BCP as a carrier significantly promote the fusion rate in large animal model when compare to the rhBMP-2. These findings demonstrate that AB204 could be an alternative to rhBMP-2 to improve fusion rate.