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Effect of Recombinant Human Bone Morphogenetic Protein-2 in an Experimental Model of Spinal Fusion in a Radiated Area

Ames, Christopher P. MD*; Smith, Justin S. MD, PhD*; Preul, Mark C. MD†; Crawford, Neil R. PhD†; Kim, Grace E. MD‡; Nottmeier, Eric MD†; Chamberlain, Robert MS†; Speiser, Burton MD§; Sonntag, Volker K. H. MD†; Dickman, Curtis A. MD†

Basic Science

Study Design. An animal model of posterolateral intertransverse process spine fusion was used.

Objectives. To investigate whether recombinant human bone morphogenetic protein-2 (rhBMP-2) can overcome the adverse effects of radiation treatment (RT) on spine fusion.

Summary of Background Data. Spinal metastases are common. Some of these patients are candidates for spinal cord decompression and vertebral reconstruction; however, radiation has significant adverse effects on bone healing.

Methods. A posterolateral fusion model was used with rhBMP-2 or iliac crest bone graft (ICBG). Eighty one-year-old rabbits were divided into eight groups: 1) RT 14 days before surgery, rhBMP-2; 2) RT 14 days before surgery, ICBG; 3) RT 2 days after surgery, rhBMP-2; 4) RT 2 days after surgery, ICBG; 5) RT 14 days after surgery, rhBMP-2; 6) RT 14 days after surgery, ICBG; 7) no RT, rhBMP-2; 8) no RT, ICBG. Animals were killed approximately 35 days after surgery. Manual palpation was the definitive test of fusion. Biomechanical and histologic assessments were also performed.

Results. All rhBMP-2 groups had significantly greater fusion rates versus respective ICBG control groups: 1 (86%) versus 2 (0%) (P = 0.005), 3 (100%) versus 4 (0%) (P < 0.0001), 5 (100%) versus 6 (0%) (P < 0.0001), and 7 (100%) versus 8 (60%) (P = 0.003). Stiffness and ultimate strength did not differ significantly between the experimental and control groups. Histologic assessment confirmed new bone formation in the fusion masses from rhBMP-2 groups.

Conclusions. Use of rhBMP-2 produced a significantly greater rate of fusion compared with ICBG in a previously radiated area in an animal model, without the morbidity of ICBG harvesting and without the risk of inadvertently using autograft contaminated by micrometastases.

Radiation is often first-line therapy for spinal metastases. Some of these patients may subsequently need surgical decompression and reconstruction. Recombinant human bone morphogenetic protein-2 is shown to overcome the adverse effects of radiation on spine fusion in a rabbit model, producing significantly greater rates of fusion compared with iliac crest bone graft alone.

From the *Comprehensive Spine Center, Department of Neurological Surgery, and ‡Department of Pathology, University of California, San Francisco School of Medicine, San Francisco, CA; †Spinal Biomechanics Research Laboratory, Department of Neurosurgery Research, and §Department of Radiation Oncology, Barrow Neurological Institute, Phoenix, AZ.

Acknowledgment date: October 14, 2004. First revision date: March 2, 2005. Second revision date: March 21, 2005. Acceptance date: March 23, 2005.

Supported by the Newsome Endowed Chair of Neurosurgery Research, Barrow Neurologic Institute, and Medtronic Sofamor Danek (Memphis, TN).

The device(s)/drug(s) that is/are the subject of this manuscript is/are not FDA-approved for this indication and is/are not commercially available in the United States.

Corporate/Industry funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Address correspondence and reprint requests to Christopher P. Ames, MD, Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Avenue, Room M-779, Box 0112, San Francisco, CA 94143-0112; E-mail: amesc@neurosurg.ucsf.edu

© 2005 Lippincott Williams & Wilkins, Inc.