June Issue Examines Controversial rhBMP-2 Research and Publications 

EMBARGOED FOR RELEASE         

June 28, 2011 at 5:00 p.m. EST
 
(Burr Ridge, IL)— In a bold move, the nation's leading spine journal is shining a critical light on the limitations of industry-sponsored research and is bolstering transparency initiatives to protect the integrity of scientific publishing. The June issue of The Spine Journal is dedicated to a review of recombinant bone morphogenetic protein-2 (rhBMP-2), a controversial synthetic bone growth product often used in spine fusion surgeries.

"The history of rhBMP-2 research is a cautionary tale for all medical professionals, researchers and patients," said Christopher M. Bono, MD of Brigham & Women's Hospital in Boston, MA and acting editor in chief of this issue of The Spine Journal.  "As this matter demonstrates, the spine care field is currently at a precarious intersection of professionalism, morality and public safety. As physicians and journal editors, we felt an obligation to present a thorough examination of this controversial issue."

Early industry-sponsored clinical research on rhBMP-2, published in a variety of orthopedic and spine-related medical journals, reported no adverse events or complications in hundreds of patients. However, in recent years, the use of rhBMP-2 has been associated with various early inflammatory reactions, cancer, osteolysis, infection, implant dislodgement and occasional life-threatening complications.  A separate study also in the June issue of The Spine Journal suggests that rhBMP-2 usage could cause a higher incidence of male sterility than previously described by industry-sponsored researchers.

"Despite the growing list of complications associated with this product, rhBMP-2 still may be of great benefit to a small group of patients who have serious problems in healing bone," said Dr. Bono. "In fact, this special issue features several interesting basic science and clinical studies exploring alternative dosing and delivery methods of rhBMP-2 that could prove to have fewer complications and adverse events in the future."  

Highlights:
1) Main Editorial
After reviewing the findings and articles in this special issue, a blue-ribbon panel of spine experts wrote a compelling editorial, "A challenge to integrity in spine publications: years of living dangerously with the promotion of bone growth factors." The authors provide an overview of the current spine care research climate, the clinical trial history of rhBMP-2, and imperatives for protecting the scientific publishing process. The authors state that "the core of our professional faith is to first do no harm. It harms patients to have biased and corrupted research published. It harms patients to have unaccountable special interests permeate medical research. It harms patients when poor publication practices become business as usual. Yet harm has been done. And that fact creates a basic moral obligation." In the spirit of that obligation, the authors vow to continue and improve on The Spine Journal's already-stringent disclosure and transparency practices.

The editorial's authors are: Eugene J. Carragee, MD of the Stanford University School of Medicine, Redwood City, CA; Alexander J. Ghanayem, MD of Loyola University Medical Center, Maywood, IL; Bradley K. Weiner, MD of The Methodist Hospital, Houston, TX; David J. Rothman, PhD of Columbia University College of Physicians and Surgeons, New York, NY and Christopher M. Bono, MD of Brigham & Women's Hospital, Boston, MA.

2) Review Article: "A critical review of rhBMP-2 trials in spinal surgery: emerging safety concerns and lessons learned"
This comprehensive review of the 13 original industry-sponsored rhBMP-2 studies found that authors—many with financial ties to the sponsor—reported 10 to 50 times fewer complications with rhBMP-2 than were found in the original FDA summaries or other documents. Prompted by complaints to journal editors and media reports of questionable research and publishing practices, this exhaustive review was led by Eugene J. Carragee, MD of the Stanford University School of Medicine, Redwood City, CA and the editor in chief of The Spine Journal.

3) Clinical Study: Posterior iliac crest pain after posterolateral fusion with or without iliac crest graft harvest
Proponents of rhBMP-2 frequently cite "less patient pain" as a justification for using bone growth products versus the traditional strategy of harvesting a patient's own hip bone to use in the spine fusion procedure. This study disputes the severity and frequency of this complaint and puts it in the perspective of the general pain experienced by patients after any posterior lumbar fusion. The lead author of this study is Jennifer M. Howard, MPH of the University of the Louisville School of Medicine in Louisville, KY. Serena S. Hu, MD of the University of California in San Francisco, CA offers the commentary "Iliac crest bone graft: are the complications overrated?"

4) Review Article: "Bone morphogenetic protein-2 and spinal arthrodesis: the basic science perspective on protein interaction with the nervous system"
This study is one of the first reviews to highlight some of the deleterious effects, at the cellular level, of rhBMP-2 on the central and peripheral nervous system. Their findings of possible direct injury to the sensory ganglion of nerve by BMP-2, may help explain the high rates of root irritation seen in clinical practice with this drug. The lead author of the study is Anton E. Dmitriev, PhD of the Uniformed Services University of Health Sciences in Bethesda, MD. In an accompanying commentary, "Important considerations on bone morphogenetic protein-2 and neuroinflammation," Michael H. Heggeness, MD, PhD of the Baylor College of Medicine in Houston, TX, cautions that BMP-2 interaction with neurologic tissues is complex, involves a potent inflammatory response, and that the downstream effects are not yet well understood.

5) Clinical Study: "Adjacent vertebral body osteolysis with bone morphogenetic protein use in transforaminal lumbar interbody fusion"
This study is among the first to determine the incidence and resolution of osteolysis, a common side-effect of rhBMP-2 use in spinal fusion. Osteolysis, when bone is reabsorbed by the body, can impact the success of the spinal fusion, including subsidence or migration of the implanted intervertebral cage. This study found that the early incidence of osteolysis after a spinal fusion utilizing rhBMP-2 was 54 percent compared with 41 percent at one to two years. The area/rate of osteolysis did not appear to significantly affect the rate of fusion or final outcome with an overall union rate of 83 percent. However, only 24 percent of the vertebral bodies with evidence of osteolysis at 3 to 6 months completely resolved. The lead author of this study is Melvin D. Helgeson, MD of the Walter Reed Army Medical Center in Washington, DC.

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The Spine Journal is the scientific, peer-reviewed journal of the North American Spine Society (NASS).  NASS is a multidisciplinary medical organization dedicated to fostering the highest quality, evidence-based and ethical spine care by promoting education, research and advocacy. NASS is comprised of more than 6,200 members from several disciplines including orthopedic surgery, neurosurgery, physiatry, neurology, radiology, anesthesiology, research, physical therapy and other spine care professionals. http://www.spine.org/. Find NASS on: NASS Facebook and NASS Twitter.

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