0
Commentary and Perspective   |    
Rat Study Leaves Unanswered Questions About Using rhBMP-2 for Spinal Cord Injury in HumansCommentary on an article by Anton E. Dmitriev, PhD, et al.: “Alterations in Recovery from Spinal Cord Injury in Rats Treated with Recombinant Human Bone Morphogenetic Protein-2 for Posterolateral Arthrodesis”
S. Tim Yoon, MD, PhD
View Disclosures and Other Information

The author did not receive payments or services, either directly or indirectly (i.e., via his institution), from a third party in support of any aspect of this work. He, or his 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. The author has not had any other relationships, or 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 © 2011 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2011 Aug 17;93(16):e96 1-1. doi: 10.2106/JBJS.K.00624
5 Recommendations (Recommend) | 3 Comments | Saved by 3 Users Save Case
text A A A
This paper investigated the effect of rhBMP-2 use for spinal fusion in a rat model of spinal cord injury. The authors selected the worst-case scenario, in which the dura is lacerated irreparably and a hemisection injury of the spinal cord is performed. A posterolateral fusion was then performed with 43 μg of rhBMP-2 impregnated within an absorbable collagen sponge, and the rats were analyzed for improvement in neurological function. The authors found that the mean BBB score (Basso, Beattie, and Bresnahan scoring system, a neurological outcome measure) was initially worse for the rhBMP-2 group than for the control animals but became similar at later time points. However, there was increased histological evidence of scarring of the spinal cord, and there were subtle deficits in fine motor function in the rats treated with rhBMP-2, even at later time points. On the basis of these findings, the authors raised the question of whether similar negative effects may occur in humans. However, the answer to that question is not so clear.
When trying to translate this rat study to human clinical outcomes, several limitations of this animal model must be recognized. Rats have much better spontaneous recovery rates after spinal cord injury than humans, and therefore mechanisms that inhibit this more “rat-specific” recovery mechanism may not be directly relevant to humans. Rats and humans have very different sensitivities to rhBMP-2, with humans requiring much higher doses of rhBMP-2 than rats to get reliable spinal fusion. Furthermore, the carrier that is used with rhBMP-2 may alter the complication profile. It is known that the rhBMP-2 elution profile over time is highly affected by the carrier, and the current rat study uses an absorbable collagen sponge as opposed to the ceramic carrier used for posterolateral fusions with rhBMP-2 in Food and Drug Administration trials. Finally, this animal study is unable to replicate issues that could have an impact in trauma surgery such as increased length of time or blood loss in obtaining autograft.
Despite the limitations of this rat study, the authors raise important concerns for surgeons treating patients with spinal cord injury, especially in clinical scenarios that are very similar to those used in this study, namely, patients with the dura open and a lacerated spinal cord who have posterior spinal fusion in which rhBMP-2 on an absorbable collagen sponge is used. However, the answer to these concerns cannot be determined without further study. There are just too many unknowns and factors that are hard to simulate in animal studies. Ultimately, clinical studies need to be performed to address the concern raised by this investigation.

Submit a comment

References

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
PubMed Articles
Clinical Trials
Readers of This Also Read...
JBJS Jobs
01/22/2014
Pennsylvania - Penn State Milton S. Hershey Medical Center
03/05/2014
Oklahoma - The University of Oklahoma
11/15/2013
Louisiana - Ochsner Health System
12/31/2013
S. Carolina - Department of Orthopaedic Surgery Medical Univerity of South Carlonina