PHILADELPHIA, PA – September 2005 - One of the major advances in spine surgery in recent decades has been the development of a man-made protein that allows surgeons to control bone formation and bony healing in the spine. The FDA approved the protein for use only in the lumbar spine, and at a precise dose. A new report shows that off-label use at a different dose in the cervical spine may pose problems for patients.
The study says that some patients suffer swallowing and breathing difficulties after they undergo cervical spinal fusions augmented by a collagen sponge laden with recombinant human morphogenetic protein (rhBMP-2). The problem appears to be swelling in the throat caused by a high dose of the rhBMP-2 product known as Infuse.
“The swelling is not completely understood,” said Steven Glassman, MD, one of the study’s coauthors. “The soft tissues in the throat react as if it is an allergic or vascular response.”
The findings were reported on Thursday, September 29, at the 20th annual meeting of the North American Spine Society in Philadelphia.
Recombinant human morphogenetic protein is a highly purified human growth factor. It is widely employed as a substitute for a patient’s own bone graft, which is usually harvested from the patient’s iliac crest, or hip, to augment spinal fusions. Randomized trials in the lumbar spine show that rhBMP-2 significantly increases radiographic fusion rates when compared to fusions using the patient’s own bone. The compound also enables patients to avert a bone-harvesting operation.
After investigators performed extensive testing of the optimum rhBMP-2 dose in the lumbar spine, the Food and Drug Administration approved Infuse for use in lumbar fusions with interbody cages. However, surgeons increasingly employ the compound off-label in the cervical spine as well, unsure of how much to stuff into its tight disc spaces. One group of researchers reported no throat swelling or breathing problems in a small pilot study of 18 cervical fusions augmented with 0.6 mg of rhBMP-2. (See Baskin DS et al., Spine, 2003; 28:1219-25.) In the absence of other trials, however, spine specialists continue to experiment.
The current retrospective review looked at what happened when surgeons packed as much rhBMP-2 into the vertebral space as possible.
Lisa B.E. Shields, MD, with Glassman and others from the University of Louisville in Kentucky, analyzed the records of 151 consecutive patients who underwent anterior cervical fusions augmented with Infuse during a nine-month period in 2003-2004. The Louisville researchers placed about 2.1 mg into the disc space, or three to four times more than previously studied.
“We thought more would be better,” said Glassman. Instead, “We began to see patients with a disproportionate number of problems.”
Rather than see hematomas immediately after surgery, when swallowing problems typically occur if they occur at all, said Glassman, the researchers found the problems surfaced four or five days later. They also observed another complication—soft tissue swelling in the absence of hematomas that interfered with breathing and swallowing.
“We think that the dose of Infuse was too big,” said Glassman.
The authors believe two changes to their protocol might prevent these complications. In the future, they believe surgeons should use a dose of rhBMP-2 that is less than 2.1 mg. And they recommend that surgeons confine the dose within a fibular graft, cage, or similar constraint.
“No one knows the optimal dose,” said Glassman. “It may lie somewhere between 0.6 mg and 2.1 mg. We really need more research.”
As with so much in medicine and life, said Glassman, “More isn’t necessarily better.”
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NASS is a multidisciplinary medical organization dedicated to fostering the highest quality, evidence-based, and ethical spine care by promoting education, research, and advocacy. Since its start in 1985, NASS has grown to nearly 4,000 members in 22 spine-related specialties. NASS members are MDs, DOs, and PhDs, including orthopedics, neurosurgery, physiatry, pain management, and other disciplines. Nurse practitioners, physician’s assistants, chiropractors, physical therapists, practice administrators, and other allied health care professionals involved in spine care are also represented as affiliate members.
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North American Spine Society
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Kathleen Hansen
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