Percutaneous injection of recombinant human bone morphogenetic protein-2 in a calcium phosphate paste accelerates healing of a canine tibial osteotomy.

Abstract

In this study, we evaluated the capacity of a single percutaneous injection of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in a rapidly resorbable calcium phosphate paste (alpha-BSM) to accelerate bone-healing in a canine tibial osteotomy model. We hypothesized that the osteotomy sites would heal faster after percutaneous delivery of rhBMP-2/alpha-BSM than they would after injection of alpha-BSM alone or after no treatment. Bilateral tibial osteotomy was performed and the sites were stabilized with external fixators in sixteen dogs. Four hours after the surgery, one limb of each dog was treated with a single percutaneous injection of rhBMP-2/alpha-BSM paste or an equal volume of alpha-BSM alone. There were eight limbs in each group, and the osteotomy site in the contralateral limb served as an untreated control. The results were evaluated with serial radiography and force-plate analysis at four and eight weeks after surgery and with mechanical testing and histologic examination at eight weeks after the surgery. At four and eight weeks after the osteotomy and treatment, the scores for radiographic union were significantly greater for the rhBMP-2/alpha-BSM-treated limbs than they were for the alpha-BSM-treated or untreated, control limbs (p < 0.05). The callus area in the rhBMP-2/alpha-BSM-treated limbs was significantly greater than that in the alpha-BSM-treated and untreated, control limbs at four and eight weeks postinjection (p < 0.05). The time-integrated vertical force for the rhBMP-2-treated limbs was significantly greater than that for their contralateral controls at four weeks and significantly greater than that for the treated and control limbs of the alpha-BSM-treated dogs at four and eight weeks after the surgery (p </= 0.05). The rhBMP-2-treated limbs were significantly stiffer in bending and in torsion (p < 0.05) compared with the alpha-BSM-treated and control limbs. Histologic analysis demonstrated increased bone formation and more mature bone at the osteotomy site in the rhBMP-2-treated limbs compared with that in the alpha-BSM-treated and control limbs. This study demonstrates the capacity of a single percutaneous injection of rhBMP-2 delivered in a resorbable calcium phosphate paste (alpha-BSM) four hours after surgery to accelerate the healing of tibial osteotomy sites in a canine model.