Complications due to the use of BMP/INFUSE in spine surgery: The evidence continues to mount

Increasingly, adverse events (AE) attributed to utilizing BMP/INFUSE (Bone Morphogenetic Protein, Medtronic, Memphis, TN, USA) “off-label” in spine surgery are being reported. In 2008, the Food and Drug Administration (FDA) issued a warning that in anterior cervical spine surgery, the “off-label” use of BMP/INFUSE contributed to marked dysphagia, hematoma, seroma, swelling, and/or the need for intubation/tracheostomy. Subsequent studies have cited the following AE; heterotopic ossification (HO), osteolysis, infection, arachnoiditis, increased neurological deficits, retrograde ejaculation, and cancer. Furthermore, in 2011, Carragee et al. noted that 13 of the original industry-sponsored BMP/INFUSE spinal surgery studies failed to acknowledge multiple AE. Additionally, in 2012, Comer et al. observed that the frequency of retrograde ejaculation reported for BMP/INFUSE used “on-label” to perform Anterior Lumbar Interbody Fusion/Lumbar Tapered Fusion-Cage Device (ALIF/LT-Cage) was also largely “under-reported.” To summarize, there is mounting evidence in the spinal literature that utilizing BMP/INFUSE in spinal fusions contributes to major perioperative and postoperative morbidity.

[1]  P. Tortolani,et al.  Transforaminal lumbar interbody fusion and posterior lumbar interbody fusion utilizing BMP-2 in treatment of degenerative spondylolisthesis: neither safe nor cost effective , 2013, Surgical neurology international.

[2]  David S Baskin,et al.  A Prospective, Randomized, Controlled Cervical Fusion Study Using Recombinant Human Bone Morphogenetic Protein-2 With the CORNERSTONE-SR™ Allograft Ring and the ATLANTIS™ Anterior Cervical Plate , 2003, Spine.

[3]  Alpesh A. Patel,et al.  Complications Associated With Posterior and Transforaminal Lumbar Interbody Fusion , 2012, The Journal of the American Academy of Orthopaedic Surgeons.

[4]  D. Long,et al.  Off-label use of drugs and devices: role of medical professionals in the establishment of parameters for their use. , 2013, Neurosurgery.

[5]  N. Epstein,et al.  Costs and frequency of “off-label” use of INFUSE for spinal fusions at one institution in 2010 , 2011, Surgical neurology international.

[6]  E. Hurwitz,et al.  Retrograde ejaculation after anterior lumbar interbody fusion using rhBMP-2: a cohort controlled study. , 2011, The spine journal : official journal of the North American Spine Society.

[7]  N. Epstein,et al.  Pros, cons, and costs of INFUSE in spinal surgery , 2011, Surgical neurology international.

[8]  H. Deutsch.  High-dose bone morphogenetic protein-induced ectopic abdomen bone growth. , 2010, The spine journal : official journal of the North American Spine Society.

[9]  H. An,et al.  Update on bone morphogenetic proteins and their application in spine surgery. , 2005, Journal of the American College of Surgeons.

[10]  John R. Johnson,et al.  The perioperative cost of Infuse bone graft in posterolateral lumbar spine fusion. , 2008, The spine journal : official journal of the North American Spine Society.

[11]  N. Epstein.  Spine surgery in geriatric patients: Sometimes unnecessary, too much, or too little , 2011, Surgical neurology international.

[12]  M. Maltenfort,et al.  Impact of bone morphogenetic proteins on frequency of revision surgery, use of autograft bone, and total hospital charges in surgery for lumbar degenerative disease: review of the Nationwide Inpatient Sample from 2002 to 2008. , 2014, The spine journal : official journal of the North American Spine Society.

[13]  E. Woo.  Recombinant human bone morphogenetic protein-2: adverse events reported to the Manufacturer and User Facility Device Experience database. , 2012, The spine journal : official journal of the North American Spine Society.

[14]  Bradley K Weiner,et al.  A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. , 2011, The spine journal : official journal of the North American Spine Society.

[15]  L. Aledort.  Off-label use of recombinant activated factor VII--safe or not safe? , 2010, The New England journal of medicine.

[16]  James Kang,et al.  Bone morphogenetic protein in spine surgery: current and future uses. , 2012, The Journal of the American Academy of Orthopaedic Surgeons.

[17]  K. Baker,et al.  Molecular and genetic advances in the regeneration of the intervertebral disc , 2013, Surgical neurology international.

[18]  J. Dettori,et al.  The use of rhBMP in spine surgery: is there a cancer risk? , 2012, Evidence-Based Spine-Care Journal.

[19]  F. Gamache.  The value of “another” opinion for spinal surgery: A prospective 14-month study of one surgeon's experience , 2012, Surgical neurology international.

[20]  R. Juniper,et al.  Trigeminal neuralgia and multiple sclerosis. , 1995, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[21]  M. Arts,et al.  Clinical outcome of instrumented fusion for the treatment of failed back surgery syndrome: a case series of 100 patients , 2012, Acta Neurochirurgica.

[22]  Donald C. Hood,et al.  “Unnecessary” spinal surgery: A prospective 1-year study of one surgeon's experience , 2011, Surgical neurology international.

[23]  E. Hurwitz,et al.  Retrograde ejaculation after anterior lumbar interbody fusion with and without bone morphogenetic protein-2 augmentation: a 10-year cohort controlled study. , 2012, The spine journal : official journal of the North American Spine Society.

[24]  Jeffrey C. Wang,et al.  The Effect of Corticosteroid Administration on Soft-Tissue Inflammation Associated With rhBMP-2 Use in a Rodent Model of Inflammation , 2013, Spine.

[25]  R. Vaidya,et al.  Complications of anterior cervical discectomy and fusion using recombinant human bone morphogenetic protein-2 , 2007, European Spine Journal.

[26]  R. Stafford,et al.  Regulating off-label drug use--rethinking the role of the FDA. , 2008, The New England journal of medicine.

[27]  N. Epstein.  Commentary on research of bone morphogenetic protein discussed in review article: Genetic advances in the regeneration of the intervertebral disc , 2013, Surgical neurology international.