Study Finds BMP-2 Could Hamper Neurologic Recovery After Spinal Cord Injury

Researchers have known for years that bone morphogenetic protein-2 (BMP-2) promotes bone growth. But a new study indicates this protein could cause swelling and glial scarring when it is used to repair a spinal cord injury.

Results of the in vivo animal study were presented Wednesday at the North American Spine Society’s (NASS) 25th Annual Meeting in Orlando, Fla. The study is a follow-up to research presented at last year’s event by Anton E. Dmitriev, Ph.D., assistant professor, Department of Surgery, at Uniformed Services University in Bethesda, Md. The research Dmitriev and his colleagues conducted showed that BMP-2 infiltrates the damaged meninges (the system of membranes enveloping the central nervous system) and activates a direct signaling response within the spinal cord.

“Despite the fact that this project was performed in a rodent model, our findings could have significant clinical implications and it’s imperative that surgeons understand the risks and benefits of every product they use during a surgery,” Dmitriev said.

Researchers evaluated the acute inflammatory response and long-term functional recovery in 68 Sprague Dawley rats. The rodents underwent a T10 dorsal hemisection spinal cord injury and were divided into two groups: a one-week follow-up (n=20) and a six-week follow-up (n=32), according to a news release issued by NASS. Thirty minutes after the spinal cord injury, researchers placed 43ug of rhBMP-2 (per side) or carrier alone over T9-11 on a collagen sponge. At one week, researchers added another control group (n=4) that received 43ug of rhAlbumin to adjust for cross-species inflammatory response, the NASS release stated.

Each week, researchers assessed postoperative locomotor function using a BBB open field scale and digital footprint analysis equipment. At the one-week and six-week marks, researchers examined the rodents’ spinal cords for inflammatory markers, gliosis and extracellular matrix proteins.

At the one-week interval, researchers noticed significant changes in spinal cord lesion morphology in the BMP-2 group. In addition, they saw increases in reactive gliosis (284 percent), inflammatory response (250 percent) and ECM protein (186 percent) compared with the control group (P<0.05), the NASS release said. Researchers associated the increases with functional deterioration at seven days (as seen on the BBB open field scale) and in the increased change in the paw rotation angle compared with the animals that did not receive BMP-2 (P<0.05). At one-day post lesion, all groups had the same functional scores.

At six weeks, microCT analyses showed the BMP group had a 100 percent fusion rate, without spinal canal encroachment. While both groups had similar open field locomotion scores, the BMP-2-treated animals had better fine motor skill deficits. The researchers noticed morphologic differences between the two groups during the acute phase at the six-week survival follow-up.

Researchers urged orthopedic surgeons to be cautious about using BMP-2. “Many things have been espoused as being ‘great’ about this product, but nothing is as good as or as bad as it seems,” Dmitriev said. “As the original indications for this product are being continuously stretched, more work has to be done evaluating potential interactions of BMP with the surrounding tissues, particularly the spinal cord and the exiting nerve roots.” Perhaps most importantly though, the various applications for BMP-2 make its directed use (according to packaging) critical, he added.

Dmitriev and his colleagues currently are working on several projects to outline the effects of BMP-2 on the spinal cord after blunt contusion injury without a direct meningeal tear. They also are trying to reproduce in an animal model the clinical reports of radiculitis after posterior lumbar fusion with BMP; their goal is to understand the mechanisms behind this phenomenon, he said.