Background: 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
(a-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/a-BSM than they would after injection of a-BSM
alone or after no treatment.
Methods: 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/a-BSM paste or an equal volume of a-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.
Results: At four and eight weeks after the osteotomy and treatment,
the scores for radiographic union were significantly greater for the
rhBMP-2/a-BSM-treated limbs than they were for the a-BSM-treated
or untreated, control limbs (p < 0.05). The callus area in the
rhBMP-2/a-BSM-treated limbs was significantly greater than that in the
a-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 a-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 a-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 a-BSM-treated and
control limbs.
Conclusions: This study demonstrates the capacity of a single
percutaneous injection of rhBMP-2 delivered in a resorbable calcium phosphate
paste (a-BSM) four hours after surgery to accelerate the healing of
tibial osteotomy sites in a canine model.
Clinical Relevance: A single percutaneous injection of
rhBMP-2/a-BSM may be useful as an adjuvant treatment to accelerate
healing of bone defects similar to those created in this study.