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Commentary and Perspective   |    
Is Off-Label Use of BMP in Pediatric Spine Surgery Now a Standard of Care?Commentary on an article by Amit Jain, MD, et al.: “Factors Associated with Use of Bone Morphogenetic Protein During Pediatric Spinal Fusion Surgery. An Analysis of 4817 Patients”
Geoffrey F. Haft, MD1
1 Sanford Orthopedics and Sports Medicine, Sanford Children’s Hospital, Sioux Falls, South Dakota
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The author received no payments or services, either directly or indirectly (i.e., via his institution), from a third party in support of any aspect of this work. Neither the author nor his institution has had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, 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 © 2013 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2013 Jul 17;95(14):e103 1-2. doi: 10.2106/JBJS.M.00320
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I was recently involved in a battle with an adult patient’s private insurance company over hospital payment for the off-label use of bone morphogenetic protein (BMP) during a routine L5-S1 anterior lumbar interbody fusion procedure. The U.S. Food and Drug Administration (FDA) indication for use of BMP at the L5-S1 level mandates utilization of a specific threaded titanium interbody cage; I had instead used a polyetheretherketone (PEEK) cage1. The insurance company insisted that any use of BMP outside of the strict FDA criteria was experimental and there would be no reimbursement. I argued that the widespread off-label use of BMP in adult spine fusion surgery, by definition, makes such use a standard of care in the U.S. One recent study, I pleaded, suggested that up to 85% of BMP use in 2009 was off-label2. The insurance company countered with recent studies that suggested high complication rates with the use of BMP in spine surgery. Even if lots of surgeons are using BMP, they wrote, its use is still experimental. Needless to say, the insurance company refused to pay the bill.
The article by Jain et al. provides clear evidence that surgeons in the U.S. are frequently using BMP in pediatric spine fusions. In 2009, the most recent year for which data were available, nearly 10% of pediatric spine fusions involved use of BMP. From such data, one might reasonably infer that many expert pediatric spine surgeons have concluded, on the basis of the existing literature and personal experience, that the benefits of BMP outweigh any risks. Such touted benefits include higher fusion rates and avoidance of the morbidity reported to be associated with iliac crest bone graft harvest. Indeed, the lure of a growth factor that reliably induces bone formation can be irresistible in the setting of complex spinal surgery. It is not surprising that, in the study by Jain et al., the highest rate of BMP use was in the setting of spondylolisthesis, a condition associated with higher rates of pseudarthrosis following fusion surgery3.
On the other hand, as mentioned by Jain et al., a recent FDA report has outlined a concerning association between BMP use and high rates of complications including heterotopic ossification, radiculopathy, local tissue reactions, and infection4. In a systematic review of published studies on complications associated with BMP use, Carragee et al. also highlighted risks of adverse events related to both FDA-approved and off-label BMP use5. In the face of such reports, increasing use of BMP in pediatric spine surgery ought to still be considered experimental. With few published pediatric spine outcome studies involving BMP, success and complication rates remain unknown. As such, the increasing use of BMP in pediatric spine surgery should still be approached with considerable caution. Families and patients should be thoroughly informed of the risks and potential benefits of such use, and this discussion should be carefully documented in the medical record. Any planned use of BMP should also be preapproved by the insurance company to ensure the patient does not get stuck with an unexpected bill.
Surgeons and insurance companies will continue to debate what constitutes a standard of care. The point at which a medication, device, or procedure crosses the line from “experimental” to “standard” is hard to define. While there is no widely accepted medical definition, the legal profession defines a standard of care as “the watchfulness, attention, caution and prudence that a reasonable person in the circumstances would exercise.”6 In the case of pediatric spine surgery, Jain et al. revealed that many expert surgeons have exercised their prudent judgment to use BMP. However, before surgeons can confidently recommend BMP for routine use in their patients, more published outcome studies in the pediatric realm are mandatory. If >9% of pediatric spine surgical procedures involve use of BMP, a flood of published outcome studies, hopefully, will soon be forthcoming.
U.SFood and Drug Administration. InFUSE Bone Graft/LT-Cage Lumbar Tapered Fusion Device - P000058.  http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm083423.htm. Accessed 2013 Feb 18.
 
Ong  KL;  Villarraga  ML;  Lau  E;  Carreon  LY;  Kurtz  SM;  Glassman  SD. Off-label use of bone morphogenetic proteins in the United States using administrative data. Spine (Phila Pa 1976).  2010 Sep 1;35(  19):1794-800.[CrossRef]
 
Cheung  EV;  Herman  MJ;  Cavalier  R;  Pizzutillo  PD. Spondylolysis and spondylolisthesis in children and adolescents: II. Surgical management. J Am Acad Orthop Surg.  2006 Aug;14(  8):488-98.
 
Woo  EJ. Recombinant human bone morphogenetic protein-2: adverse events reported to the Manufacturer and User Facility Device Experience database. Spine J.  2012 Oct;12(  10):894-9.  Epub 2012 Oct 22.[CrossRef]
 
Carragee  EJ;  Hurwitz  EL;  Weiner  BK. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J.  2011 Jun;11(  6):471-91.[CrossRef]
 
Legal dictionary. Standard of care.  http://dictionary.law.com/Default.aspx?selected=2002. Accessed 2013 Feb 18.
 

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References

U.SFood and Drug Administration. InFUSE Bone Graft/LT-Cage Lumbar Tapered Fusion Device - P000058.  http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm083423.htm. Accessed 2013 Feb 18.
 
Ong  KL;  Villarraga  ML;  Lau  E;  Carreon  LY;  Kurtz  SM;  Glassman  SD. Off-label use of bone morphogenetic proteins in the United States using administrative data. Spine (Phila Pa 1976).  2010 Sep 1;35(  19):1794-800.[CrossRef]
 
Cheung  EV;  Herman  MJ;  Cavalier  R;  Pizzutillo  PD. Spondylolysis and spondylolisthesis in children and adolescents: II. Surgical management. J Am Acad Orthop Surg.  2006 Aug;14(  8):488-98.
 
Woo  EJ. Recombinant human bone morphogenetic protein-2: adverse events reported to the Manufacturer and User Facility Device Experience database. Spine J.  2012 Oct;12(  10):894-9.  Epub 2012 Oct 22.[CrossRef]
 
Carragee  EJ;  Hurwitz  EL;  Weiner  BK. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J.  2011 Jun;11(  6):471-91.[CrossRef]
 
Legal dictionary. Standard of care.  http://dictionary.law.com/Default.aspx?selected=2002. Accessed 2013 Feb 18.
 
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