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Complications of Spinal Fusion With Utilization of Bone Morphogenetic Protein: A Systematic Review of the Literature

Singh, Kern MD*; Ahmadinia, Kasra MD*; Park, Daniel K. MD; Nandyala, Sreeharsha V. BA*; Marquez-Lara, Alejandro MD*; Patel, Alpesh A. MD, FACS; Fineberg, Steven J. MD*

doi: 10.1097/BRS.0000000000000004
Literature Review

Study Design. Systematic review.

Objective. A systematic review was performed to identify the types of complications and complication rates associated with the use of bone morphogenetic protein (BMP) in both anterior and posterior cervical and lumbar spine surgery.

Summary of Background Data. There has been an increase in BMP use in various clinical situations typically in an “off-label” fashion. Associated with its use, however, have been reports of various complications.

Methods. A MEDLINE search was conducted. All articles involving complications after spine surgery in patients receiving BMP were included. Articles were excluded on the basis of the following criteria: Non-English manuscripts and nonhuman subjects. A total of 29 articles met the inclusion and exclusion criteria and were used in the analysis. For each complication identified, the incidence was calculated by pooling the subjects from the studies that reported the complication. χ2 tests were used to compare the incidence rates between those that had received BMP and the control groups.

Results. Of the 29 articles included, 7 reported complication rates in anterior cervical fusions, 3 in posterior cervical fusions, 4 in anterior lumbar interbody fusions (ALIF), 9 in posterior/transforaminal lumbar interbody fusions (PLIF/TLIF), and 6 in posterolateral lumbar fusions. Individual complication rates when BMP was used was in the range from 0.66% to 20.1% in anterior cervical fusions, 3.5% to 14.6% in posterior cervical fusions, 2.0% to 7.3% in ALIFs, 1.5% to 21.8% in PLIF/TLIFs, and 1.4% to 8.2% in posterolateral lumbar fusions. Pseudarthrosis rates were statistically significantly lower with the utilization of BMP in all procedures except for PLIF/TLIFs, which only approached significance (P = 0.07). The only individual complication that was statistically significantly greater with BMP utilization was retrograde ejaculation in ALIFs (7.3 vs. 2.3%; P = 0.03). The rate of dysphagia/swelling in anterior cervical fusions was greater with BMP (20.1 vs. 15.6%), however this only approached statistical significance (P = 0.07).

Conclusion. The body of literature reports complication rates with BMP ranging from 0.66% to 21.8%. However, the only statistically significant adverse complication rate was retrograde ejaculation in the ALIF population (7.3%). Despite the increased awareness of complications associated with BMP, complication rates remain spine site specific and low. Thorough patient education should be done with the physician to make an informative use regarding BMP utilization in spinal surgery.

Level of Evidence: 3

A systematic review of the literature was performed to assess complications rates associated with the utilization of bone morphogenetic protein (BMP) in both cervical and lumbar spinal fusions. Complication rates were in the range from 0.66% to 21.8% depending upon the specific complication and procedure. Retrograde ejaculation was statistically increased with BMP use in anterior lumbar fusions.

*Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, IL

Department of Orthopaedic Surgery, William Beaumont Hospital, Royal Oak, MI; and

Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL.

Address correspondence and reprint requests to Kern Singh, MD, Department of Orthopaedic Surgery, Rush University Medical Center, 1611 W. Harrison St, Suite 300, Chicago, IL 60612; E-mail:

Acknowledgment date: June 13, 2013. First revision date: July 30, 2013. Acceptance date: August 24, 2013.

The device(s)/drug(s) is/are FDA-approved or approved by corresponding national agency for this indication.

The manuscript includes unlabeled/investigational uses of the products/devices listed hereafter and the status of these is disclosed in the manuscript: Utilization of rhBMP-2/ACS as well as rhBMP-7 for non-ALIF spinal procedures.

No funds were received in support of this work.

Relevant financial activities outside the submitted work: board membership, consultancy, royalties, and stock/stock options.

© 2014 by Lippincott Williams & Wilkins