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Bone Marrow Enhances the Performance of rhBMP-2 in Spinal FusionA Rodent Model
Hyun W. Bae, MD1; Li Zhao, MD, PhD1; Linda E.A. Kanim, MA1; Pamela Wong, MPH2; Deborah Marshall, BA1; Rick B. Delamarter, MD1
1 Tissue Engineering Laboratory (H.W.B., L.Z., L.E.A.K., and R.B.D.) and Biomechanics Laboratory (D.M.), Spine Center, Department of Surgery, Cedars-Sinai Medical Center, 444 South San Vicente Boulevard, Suite 901, Los Angeles, CA 90048
2 Spine Research Foundation, The Spine Institute, 2811 Wilshire Boulevard, Suite 850, Santa Monica, CA 90403
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Investigation performed at the Division of Orthopaedic Surgery, Department of Surgery, Cedars-Sinai Spine Center, Los Angeles, California



Disclosure: None 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 any aspect of this work. 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. Also, one or more of the authors has had another relationship, or has engaged in another activity, 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 © 2013 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2013 Feb 20;95(4):338-347. doi: 10.2106/JBJS.K.01118
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Abstract

Background: 

Reliable and rapid bone formation is the goal of biologics and cell-based spinal fusion technologies. While no cell-based therapy alone has been successful, recombinant human bone morphogenetic protein-2 (rhBMP-2) has been successfully used in a wide spectrum of patients undergoing a variety of spinal fusion procedures since its approval by the United States Food and Drug Administration (FDA) in 2002. However, the question remains how to improve the biologic efficiency, or osteoinductivity, of rhBMP-2 for successful application in the most challenging patients undergoing spinal fusion or to reduce the doses currently required. The present study investigated how varying the cellular environments through the addition of freshly harvested bone marrow aspirate (BMA) modulates rhBMP-2 efficiency.

Methods: 

An L4-L5 posterolateral intertransverse process spinal fusion procedure was performed in Lewis rats. The implants were a subeffective concentration of 0.006 mg/mL of rhBMP-2/two absorbable collagen sponges (ACS) plus directly applied fresh syngeneic BMA transplants (n = 18), 0.006-mg/mL rhBMP-2/two ACS/side (n = 12), 0.006-mg/mL rhBMP-2/one ACS/side (n = 12), or BMA/one ACS/side (n = 6). Rats were killed at eight weeks and were evaluated with use of manual palpation, radiographs, and biomechanical testing.

Results: 

BMA plus 0.006-mg/mL rhBMP-2/ACS significantly increased the L4-L5 fusion rate to 89% (sixteen of eighteen) compared with a base fusion rate of 33% (four of twelve) to 50% (six of twelve) for rats implanted with rhBMP-2/ACS (p < 0.05), with no difference in strength or stiffness between conditions. No fusion or bone formation was observed in the six rats that received BMA/ACS alone.

Conclusions: 

Less rhBMP-2 was needed for effect when mixed with BMA. A nearly twofold increase in the fusion rate was found when BMA was mixed with a deliberate subeffective concentration of rhBMP-2. There was no improvement in terms of fusion strength or stiffness.

Clinical Relevance: 

Adjuvants such as BMA with rhBMP-2 may improve fusion success, allow marked dose reduction per segment in multilevel spinal surgery, result in cost savings, and/or decrease dose-related complications. This warrants further study prior to clinical implementation.

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    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.
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