The Journal of Bone and Joint Surgery (American). 2006;88:806-817.
doi:10.2106/JBJS.E.00846
© 2006 The Journal of Bone and Joint Surgery, Inc.
Additive Enhancement of Implant Fixation Following Combined Treatment with rhTGF- 2 and rhBMP-2 in a Canine Model
D.R. Sumner, PhD1,
T.M. Turner, DVM2,
R.M. Urban2,
A.S. Virdi, PhD1 and
N. Inoue, MD, PhD2
1 Department of Anatomy and Cell Biology, Rush University Medical Center, 600 S.
Paulina, Room 507, Chicago IL 60612. E-mail address for D.R. Sumner:
rick_sumner{at}rush.edu
2 Department of Orthopedic Surgery, Rush University Medical Center, 1653 West
Congress Parkway, Chicago IL 60612
Investigation performed at the Department of Anatomy and Cell Biology
and the Department of Orthopedic Surgery, Rush Arthritis and Orthopedics
Institute, Rush Medical College, Rush University Medical Center, Chicago,
Illinois
In support of their research for or preparation of this manuscript, one or
more of the authors received grants or outside funding from the National
Institutes of Health (Grant AR42862) and the Grainger Foundation. None of the
authors received payments or other benefits or a commitment or agreement to
provide such benefits from a commercial entity. Several commercial entities
paid or directed, or agreed to pay or direct, benefits to a research fund,
foundation, educational institution, or other charitable nonprofit
organization with which the authors are affiliated or associated. Implants
were provided by Zimmer, TGF- was provided by Genzyme, and BMP-2 was
provided by Wyeth.
Background: Gaps at the interface between implant and bone increase
the risk of diminished implant fixation and eventual loosening. The purpose of
the present study was to determine if combined use of recombinant human
transforming growth factor-beta 2 (rhTGF-2) and bone morphogenetic
protein 2 (rhBMP-2) led to greater implant fixation strength in the presence
of interface gaps than the use of either growth factor alone.
Methods: Twenty-eight skeletally mature adult male dogs received one
porous-coated titanium implant in the proximal part of each humerus, for a
total of fifty-six implantation sites. Spacers were used to establish an
initial 3-mm gap between the implant and the host bone at all fifty-six sites.
Forty-two implants were coated with hydroxyapatite-tricalcium phosphate and
were used in three growth-factor-treatment groups in which the implants placed
in the left humerus were loaded with 12 µg of rhTGF-2 (Group 1, seven
animals), 25 µg of rhBMP-2 (Group 2, seven animals), or 12 µg of
rhTGF-2 combined with 25 µg of rhBMP-2 (Group 3, seven animals). In
these animals, the twenty-one implants that were placed in the right humerus
were loaded with buffer only to serve as contralateral controls. In Group 4
(seven animals), the implants were not coated with hydroxyapatite-tricalcium
phosphate, the gap in the left humerus was lightly packed with autogenous bone
graft, and the gap in the right humerus was left empty to serve as a
contralateral control. All animals were killed at twenty-eight days. The
primary end points included three mechanical variables: fixation strength,
interface stiffness, and energy to failure. Secondary end points included bone
ingrowth and bone volume and trabecular architecture in the gap and in a
region located 2 mm medial to the implantation site.
Results: The hydroxyapatite-tricalcium phosphate coating had no
effect on implant fixation, bone ingrowth, or bone formation in the 3-mm gap.
Individual growth factor treatments led to 2.3 to 3.2-fold increases in
fixation strength and stiffness as compared with the values for the
contralateral controls (p < 0.05). The combined growth factor treatment led
to 5.7-fold increases in fixation strength and stiffness compared with the
values for the contralateral controls (p < 0.01). Autogenous bone graft
treatment was associated with 4.5 to 6.4-fold increases in implant fixation
strength and stiffness as compared with the values for the contralateral
controls (p < 0.01). Compared with the relevant contralateral controls,
energy to failure was increased 3.5-fold in association with TGF-2 alone
(p < 0.05), 4.5-fold in association with TGF-2 combined with BMP-2 (p
< 0.01), and 2.5-fold in association with autogenous bone-grafting. As much
as 63% of the variance in the mechanical end points was associated with
variance in bone volume and architecture in the 3-mm gap and in the region of
interest located 2 mm medial to the implantation site (p < 0.01).
Conclusions: In this animal model, the combined use of TGF-2
and BMP-2 led to more secure mechanical fixation of the implant than did the
use of either growth factor alone and demonstrated results that were similar
to those associated with the use of autogenous bone graft.
Clinical Relevance: This growth factor cocktail is more useful for
enhancing implant fixation than individual growth factor therapy and may
provide an alternative strategy to autogenous bone-grafting.
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