565. Acceleration of Fracture Healing with Adenovirally Transduced Human BMP-2 and -6 Genes in Horse Metatarsal Osteotomy and Ostectomy Models

Introduction; Treatment of delayed or nonunion fractures can be challenging. Bone morphogenetic protein-2 (BMP-2) is one of the most studied growth factors associated with bone healing, and successful induction of bone formation by BMP-2 has been demonstrated both in vitro and in vivo. The less investigated member of BMP family, BMP-6, currently received attention because it may contribute bone formation by an alternative mechanism compared to other BMPs. This study was to compare the efficacy of BMP-2 and -6 genes transduced by adenoviral vector (Ad) in an acceleration of bone healing using two different sizes of unstable fracture models using horses.Materials and methods; Transverse osteotomy at fourth metatarsal bones (Mt4) and gap ostectomy at second metatarsal bones (Mt2) were surgically created in 12 horses. Two weeks after surgery, bone defects in one hindlimb had direct injection of Ad-BMP-2 or Ad-BMP-6, and the defects in the contralateral limb had no treatment or marker vector (Ad-LacZ). Six weeks following the injection, the horses were euthanized and fracture healing was assessed by radiographs, quantitative computed tomography, mechanical testing, and histology. Biosafety was assessed by physical examination, blood chemistry, and adenovirus serum neutralization titer assay.Results; For both fracture models, Ad-BMP-2 and Ad-BMP-6 treated bone defects had significantly quicker and larger size of external callus formation (Fig. 1), higher mineral density, greater mechanical strength (Fig. 2), and more mature bony bridging. No physical and hematological signs of systemic infection were detected despite increased serum neutralization antibody titer.Discussion and Conclusion; Single percutaneous injection of adenovirus encoding BMP-2 or BMP-6 gene accelerated the healing of unstable fractures in a large animal model. Ad-BMP-2 treated bone defects had a greater structural integrity compared to Ad-BMP-6 treated defects. No adverse reactions were observed, but systemic antibody to Ad developed. Percutaneous AdBMP2 injection may accelerate fracture repair in horses and other species.