1. P A R T N E R S O R T H O P A E D I C
Trauma Rounds
Case Reports from the Mass General Hospital and Brigham & Women’s Hospital
A Quarterly Case Study Volume 4, Fall 2012
Healing Critical Defects in the Femur
Chris Evans, PhD
Vaida Glatt, PhD
Large segmental defects heal poorly and often present clinical
challenges. Approaches used to improve healing include auto-
graft and allograft bone, distraction osteogenesis, vascularized
bone grafts and the application of BMP-2 and BMP-7. We
wanted to determine whether modulation of the mechanical Figure 1: Histological appearance at 8 weeks of defects stabilized with
environment could improve bone healing in a rat femoral seg- low, medium and high stiffness fixators and subjected to reverse
mental defect model. dynamization.
The responsiveness of bone to mechanical stimulation has been by rigid fixation. This is called reverse dynamization. We tested
known for well over a century, and there is a considerable body the reverse dynamization process in the study described here.
of literature describing its influence on fracture healing. Sur- Methods
prisingly, we could find no prior literature concerning the re- Five mm, critical-sized, mid-femoral defects were created in
sponses of large segmental defects to their mechanical envi- rats. These do not spontaneously heal, but do heal in response
ronment. To remedy this, we developed customized external to 11 !g recombinant, human BMP-2.
fixators of different stiffness for use in conjunction with a 5 mil-
We maintained groups of rats for 8 weeks with fixators of low
limeter (mm) femoral defect in the rat. The external fixator de-
(114 N/mm), medium (185 N/mm) and high (254 N/mm) stiff-
sign allows the stiffness to be changed on living animals as they
ness. An additional group underwent reverse dynamization,
heal.
where low stiffness fixation was applied for the first 2 weeks,
The concept of modulating the rigidity of fixation to promote after which time we imposed high stiffness fixation. All defects
bone healing goes back to the late 1970’s when Dr. Giovanni de also received BMP-2.
Bastiani of the University of Verona, Italy, proposed the applica- Animals were euthanized at 8 weeks. Healing was assessed by
tion of “dynamization” for external fracture fixation treatment. radiologic evaluation, mechanical testing, histology, dual-
According to Dr. de Bastiani’s concept, the fracture site is ini- energy ray absorptiometry (DXA) and !CT.
tially fixed very rigidly to provide stability and to allow healing
Results
to commence. Once woven bone is laid down, the fixator is
loosened to allow the bone to bear greater load and thus re- Surprisingly, radiologic evaluation suggested that the least stiff
fixator gave the most rapid and complete healing after 8 weeks.
model more rapidly.
Reverse dynamization, however, improved upon this consid-
Based upon certain information from the literature, we won- erably. Histology (figure), confirmed that defects subjected to
dered whether the healing of large segmental defects would reverse dynamization were narrower in cross section, and had
benefit from the opposite strategy – loose fixation first, followed an organized tissue structure with better architecture and well-
Trauma Rounds, Volume 4, Fall 2012
1

2. P A R T N E R S O R T H O P A E D I C T R A U M A R O U N D S
formed evenly distributed neocortices, and only a small amount Funding
of trabecular bone. All other defects had persistent callus, and Supported by the AO Foundation (Grant S-08-42G) and the De-
contained disorganized woven bone with poor cortication. De- partment of Defense (Grant W81XWH-10-1-0888).
fects stabilized for 8 weeks with medium stiffness fixators con- Christopher Evans, PhD, is the Maurice Mueller Professor of Orthopaedic
tained a central gap in the defect surrounded by unmineralized Surgery and Director of the Center for Advanced Orthopaedic Studies in the
soft tissue. Defects stabilized for 8 weeks with the highest stiff- Department of Orthopaedic Surgery at Beth Israel Deaconess Medical Center.
ness fixator contained a prominent band of cartilage, raising the
Vaida Glatt, PhD, is a Senior Research Fellow with the Trauma Research
possibility of developing into a non-union. Cartilage was not
Group of the Institute of Health and Biomedical Innovation at Queensland
seen in any of the other groups at 8 weeks. University of Technology Brisbane, Queensland.
The !CT, DXA and mechanical testing data were in broad References
agreement with the radiological and histological data. 1. This short brief was excerpted from this detailed manuscript: Glatt V, Miller
M, Ivkovic A, Liu F, Parry N, Griffin D, Vrahas M, Evans C. Improved heal-
Discussion
ing of large segmental defects in the rat femur by reverse dynamization in
These data support the concept of reverse dynamization to im- the presence of bone morphogenetic protein-2. J Bone Joint Surg Am. 2012
prove the healing of large segmental defects. Only one regimen Nov 21;94 (22):2063-2073.
of reverse dynamization was evaluated in this study. It is pos- 2. This study was performed in partial fulfillment of a PhD degree from the
University of Warwick, UK, granted to Vaida Glatt.
sible that a different stiffnesses or timing of reverse dynamiza-
tion would provide even better results. Optimization of the New England Regional Fracture Summit, Stowe, VT
strategy remains a future goal.
The annual AO Fracture Summit will be held January 18 – 21, 2013 in
Although these experiments used a rat model, the results are Stowe, VT. The course is chaired by Drs Mark Vrahas, Jesse Jupiter and
relevant to clinical orthopaedics. They show that the healing of Raymond White, and features several Harvard Orthopaedic Faculty.
critical-sized segmental defects is highly responsive to the am- This year’s special guest will be the renowned foot and ankle surgeon,
bient mechanical environment. The use of reverse dynamization Sigvard Hansen, MD, of Harborview Medical Center, Seattle, WA.
runs counter to present clinical practice, where large segmental The course uses an informal, discussion-based, highly interactive format.
defects are subject to immediate rigid fixation. Further study of The chief aim is to educate community orthopaedic surgeons who are
reverse dynamization could lead to improved clinical manage- actively involved in the treatment of patients with fractures. Partici-
ment of patients with these difficult injuries. pants are invited to bring their own cases for discussion.
Future Research Registration is still open!
Using funding from the Department of Defense we are deter- For more information: www.aona.org
mining whether reverse dynamization reduces the need for
BMP-2 to achieve healing, and whether it accelerates the acqui-
sition of mechanical strength. The former would reduce health
care costs and the latter would allow earlier load bearing. We Happy Holidays
have also applied for additional funding to undertake a study On behalf of our entire faculty and staff, I wish you and your
of reverse dynamization in sheep. family a very happy holiday season.
We wish you all the best in 2013.
AchesAndJoints.org/Trauma
Read archives of all previous issues ~ Mark Vrahas, MD
Jesse Jupiter, MD — 617-726-5100 Please share your comments online, or by email:
Trauma Faculty MGH Hand & Upper Extremity Service Mark Vrahas, MD / mvrahas@partners.org
Mark Vrahas, MD — 617-726-2943 jjupiter@partners.org Yawkey Center for Outpatient Care, Suite 3C
Partners Chief of Orthopaedic Trauma 55 Fruit Street, Boston, MA 02114
mvrahas@partners.org David Ring, MD — 617-724-3953
Mitchel B Harris, MD — 617-732-5385
MGH Hand & Upper Extremity Service Editor in Chief
dring@partners.org
Chief, BWH Orthopedic Trauma Mark Vrahas, MD
mbharris@partners.org Brandon E Earp, MD — 617-732-8064
R Malcolm Smith, MD, FRCS — 617-726-2794 BWH Hand & Upper Extremity Service Program Director
bearp@partners.org
Chief, MGH Orthopaedic Trauma Suzanne Morrison, MPH
rmsmith1@partners.org George Dyer, MD — 617-732-6607 (617) 525-8876
BWH Hand & Upper Extremity Service smmorrison@partners.org
David Lhowe, MD — 617-724-2800
MGH Orthopaedic Trauma gdyer@partners.org
dlhowe@partners.org
Editor, Publisher
John Kwon, MD — 617-643-5701 Arun Shanbhag, PhD, MBA
Michael Weaver, MD — 617-525-8088 MGH Foot & Ankle Service
BWH Orthopedic Trauma www.MassGeneral.org/ortho
jkwon@partners.org
mjweaver@partners.org www.BrighamAndWomens.org/orthopedics
2
Trauma Rounds, Volume 4, Fall 2012