The Journal of Bone and Joint Surgery (American) 86:1425-1438 (2004)
© 2004 The Journal of Bone and Joint Surgery, Inc.
Percutaneous Injection of Recombinant Human Bone Morphogenetic Protein-2 in a Calcium Phosphate Paste Accelerates Healing of a Canine Tibial Osteotomy
Ryland B. Edwards, III, DVM, MS, PhD1,
Howard J. Seeherman, PhD, VMD2,
John J. Bogdanske, BS1,
Jennifer Devitt, BS1,
Ray Vanderby, Jr., PhD3 and
Mark D. Markel, DVM, PhD1
1 Comparative Orthopaedic Research Laboratory, Departments of Surgical Sciences
(R.B.E.III) and Medical Sciences (J.J.B., J.D., and M.D.M.), School of
Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive,
Madison, WI 53706-1102. E-mail address for R.B. Edwards III:
edwardsr{at}svm.vetmed.wisc.edu
2 Wyeth Discovery Research, 200 Cambridge Park Drive, Cambridge, MA 02140
3 Department of Orthopedics and Rehabilitation, Clinical Science Center,
University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI 53792
Investigation performed at the Comparative Orthopaedic Research
Laboratory, School of Veterinary Medicine, University of Wisconsin-Madison,
Madison, Wisconsin
In support of their research or preparation of this manuscript, R.B.
Edwards III, J.J. Bogdanske, J. Devitt, M.D. Markel, and R. Vanderby Jr.
received grants or outside funding from Wyeth. In addition, H.J. Seeherman
received payments or other benefits or a commitment or agreement to provide
such benefits from a commercial entity (Wyeth). Also, a commercial entity
(Wyeth) paid or directed, or agreed to pay or direct, benefits to an
educational institution (University of Wisconsin Regents) with which the
authors are affiliated or associated.
A commentary is available with the electronic versions of this article, on our web site (www.jbjs.org) and on our quarterly CD-ROM (call our subscription department at 781-449-9780, to order the CDM-ROM).
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
( -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/-BSM than they would after injection of -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/-BSM paste or an equal volume of -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/-BSM-treated limbs than they were for the -BSM-treated
or untreated, control limbs (p < 0.05). The callus area in the
rhBMP-2/-BSM-treated limbs was significantly greater than that in the
-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 -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 -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 -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 (-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/-BSM may be useful as an adjuvant treatment to accelerate
healing of bone defects similar to those created in this study.
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