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Cancer After Spinal Fusion: The Role of Bone Morphogenetic Protein

Lad, Shivanand P. MD, PhD*,‡; Bagley, Jacob H. BS*,‡; Karikari, Isaac O. MD; Babu, Ranjith MS; Ugiliweneza, Beatrice PhD, MSPH§; Kong, Maiying PhD§; Isaacs, Robert E. MD; Bagley, Carlos A. MD; Gottfried, Oren N. MD; Patil, Chirag G. MD; Boakye, Maxwell MD

doi: 10.1227/NEU.0000000000000018
Research-Human-Clinical Studies: Editor's Choice
Editor's Choice
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BACKGROUND: Bone morphogenetic protein (BMP) is used in tens of thousands of spinal fusions each year. A trial evaluating a high-dose BMP formulation demonstrated that its use may be associated with an increased risk of cancer.

OBJECTIVE: To evaluate whether BMP, as commonly used today, is associated with an increased risk of cancer or benign tumors.

METHODS: We performed a retrospective study using the Thomson Reuter MarketScan database. We retained all patients who had no previous diagnosis of cancer or benign tumor and had at least 2 years of uninterrupted enrollment in the database before and after their operations. A propensity score--matched cohort was created to ensure greater covariate balance between treatment groups.

RESULTS: Within the propensity score--matched cohort (n = 4698), BMP-exposed patients had a nonsignificant increase in the rate of cancer diagnosis (9.37% vs 7.92%; P = .08). After adjustment for covariates, BMP exposure was associated with a 31% increased risk of benign tumor diagnosis (odds ratio, 1.31; 95% confidence interval, 1.02-1.68; P < .05). When the benign tumor diagnoses were stratified by organ type, BMP patients had significantly more diagnoses of benign nervous system tumors (0.81% vs 0.34%; P = .03), and within this group, benign tumors of the spinal meninges were much more common in the BMP-treated group (0.13% vs 0.02%; P = .002).

CONCLUSION: The results of this large, independent, propensity-matched study suggest that the use of BMP in lumbar fusions is associated with a significantly higher rate of benign neoplasms but not malignancies.

ABBREVIATIONS: aOR, adjusted odds ratio

BMP, bone morphogenetic protein

CI, confidence interval

CPT-4, Current Procedural Terminology, Fourth Edition

ICD-9-CM, International Classification of Disease, Ninth Revision, Clinical Modification

Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina

§Department of Bioinformatics and Biostatistics and

Department of Neurosurgery, University of Louisville, Louisville, Kentucky

Center for Neurosurgical Outcomes Research, Maxine Dunitz Neurosurgical Institute, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California

Correspondence: Shivanand P. Lad, Division of Neurosurgery, Department of Surgery, Duke University Medical Center 3807, 200 Trent Dr, Blue Zone–Room 4529, Durham, NC 27710. E-mail:

* These authors have contributed equally to this article.

Received October 24, 2012

Accepted May 31, 2013

Copyright © by the Congress of Neurological Surgeons