Scientific Articles   |    
Transient Soft-Tissue Edema Associated with Implantation of Increasing Doses of rhBMP-2 on an Absorbable Collagen Sponge in an Ectopic Rat Model
Hyun W. Bae, MD1; K. Brandon Strenge, MD2; Nomaan Ashraf, MD2; Jeffrey M. Badura, MS3; Steven M. Peckham, PhD3; William F. McKay, ME3
1 Spine Center, Division of Orthopaedic Surgery, Department of Surgery, Cedars-Sinai Medical Center, 444 South San Vicente Boulevard, Suite 901, Los Angeles, CA 90048. E-mail address: baehw@yahoo.com
2 The Spine Institute, 2811 Wilshire Boulevard, Suite 850, Santa Monica, CA 90403. E-mail address for K.B. Strenge: bstrenge@siumed.edu. E-mail address for N. Ashraf: Nomaan.ashraf@gmail.com
3 Medtronic, Inc., Spinal and Biologics Business, 2600 Sofamor Danek Drive, Memphis, TN 38121. E-mail address for J.M. Badura: Jeffrey.m.badura@medtronic.com. E-mail address for S.M. Peckham: steve.peckham@medtronic.com. E-mail address for W.F. McKay: Bill.mckay@medtronic.com
View Disclosures and Other Information
  • Disclosure statement for author(s): PDF

Investigation performed at the Spine Center, Division of Orthopaedic Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California

Disclosure: One or more of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of an aspect of this work. In addition, one or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. No author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2012 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2012 Oct 17;94(20):1845-1852. doi: 10.2106/JBJS.K.00469
5 Recommendations (Recommend) | 3 Comments | Saved by 3 Users Save Case



Recombinant human bone morphogenetic protein-2 (rhBMP-2) is an osteoinductive protein. However, soft-tissue edema adjacent to the site of rhBMP-2 implantation has been reported. This animal study was designed to examine soft-tissue edema associated with increasing rhBMP-2 doses with implantation on an absorbable collagen sponge (ACS) and with injection directly into muscle.


Thirty-six Lewis rats received intramuscular implantation of rhBMP-2 on an ACS (Part I) or intramuscular injection of rhBMP-2 solution (Part II). Part-I sites received rhBMP-2/ACS at doses of 0 μg, 30 μg (normal), 129 μg (mid), or 450 μg (high). Part-II sites received rhBMP-2/ACS or rhBMP-2 intramuscular injection at doses of 10 μg (normal) or 150 μg (mid). A previous rat model showed 10 μg to be 100% effective at inducing osseous spinal fusion. In our study, T2-weighted magnetic resonance imaging (MRI) was performed at two and seven days to assess edema volume, and statistical comparisons were carried out with analysis of variance (ANOVA). Cellular response, vascularity, and ossification were examined histologically.


Quantitative MRI demonstrated similar peri-implant edema volumes in the control (buffer on an ACS) and normal-dose rhBMP-2 groups. Higher doses resulted in increased edema volume. Edema decreased significantly from two to seven days. Similar capillary densities were observed in all rhBMP-2 groups at two days, and there was dose-dependent increased ossification at seven days. Compared with the rhBMP-2 injection, implantation of the rhBMP-2/ACS resulted in increased edema. This edematous response was transient in all groups. Minimal or no ossification occurred after the rhBMP-2 injections.


Transient peri-implant soft-tissue edema occurred in a dose-dependent manner following implantation of rhBMP-2/ACS in this rat model. The normal dose of rhBMP-2/ACS produced edema similar to that in the controls. Finally, rhBMP-2 solutions injected directly into muscle resulted in minimal soft-tissue edema.

Clinical Relevance: 

This animal study demonstrates a dose-dependent effect of rhBMP-2 on peri-implant soft-tissue edema. Even though the response is transient, these data show the importance of using an appropriate rhBMP-2 dose to limit local soft-tissue edema. Controlled studies are needed to examine the appropriate rhBMP-2 dose for various clinical applications.

Figures in this Article
    Sign In to Your Personal ProfileSign In To Access Full Content
    Not a Subscriber?
    Get online access for 30 days for $35
    New to JBJS?
    Sign up for a full subscription to both the print and online editions
    Register for a FREE limited account to get full access to all CME activities, to comment on public articles, or to sign up for alerts.
    Register for a FREE limited account to get full access to all CME activities
    Have a subscription to the print edition?
    Current subscribers to The Journal of Bone & Joint Surgery in either the print or quarterly DVD formats receive free online access to JBJS.org.
    Forgot your password?
    Enter your username and email address. We'll send you a reminder to the email address on record.

    Forgot your username or need assistance? Please contact customer service at subs@jbjs.org. If your access is provided
    by your institution, please contact you librarian or administrator for username and password information. Institutional
    administrators, to reset your institution's master username or password, please contact subs@jbjs.org


    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
    CME Activities Associated with This Article
    Submit a Comment
    Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
    Comments are moderated and will appear on the site at the discretion of JBJS editorial staff.

    * = Required Field
    (if multiple authors, separate names by comma)
    Example: John Doe

    Related Content
    The Journal of Bone & Joint Surgery
    JBJS Case Connector
    Topic Collections
    Related Audio and Videos
    Clinical Trials
    Readers of This Also Read...
    JBJS Jobs
    WY - Memorial Hospital of Sweetwater County
    MA - The University of Massachusetts Medical School