A bone morphogenetic protein used to treat spinal cord injuries may also cause inflammation and glial scarring, according to a study released today.
The substance, BMP-2 does promote bone growth, but the rats used in the in vivo animal study developed neurological damage, according to results presented at the North American Spine Society’s 25th annual meeting in Orlando, Fla.
"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," said Uniformed Services University assistant professor Anton Dimitriev, who conducted the study.
Dimitriev’s research is a follow-up to another study of his that showed that BMP-2 infiltrates the damaged meninges and activates a direct signaling response within the spinal cord.
One week after doctors treated rats with the biologic substance, they observed significant changes in spinal cord lesion morphology versus the control group. The group of rats in the study that received BMP-2 posted a 284 percent increase in reactive gliosis, a 250 percent increase in inflammatory response and a 186 percent increase in ECM protein. Six weeks after BMP-2 treatment, the rats exhibited fine motor skill defects.
The researcher urged orthopedic surgeons to use cautious when 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. 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," Dimitriev said.
In July, the FDA cleared Medtronic Inc.’s (NYSE:MDT) Amplify spinal implant, which uses BMP-2, despite concerns over higher cancer rates associated with the substance.
The FDA’s Orthopaedic and Rehabilitation Devices panel had delayed the device’s clearance because it wanted more information on whether the higher number of cancer cases among patients treated with the Fridley, Minn.-based medical device monolith’s device warrant further investigation.
The Centers for Medicare and Medicaid Services held a meeting Sept. 22 to discuss on- and off-label uses of BMP used in several orthopedic implants and procedures. The panel voted on a series of questions about its members’ confidence in using the protein in a variety of orthopedic applications. The committee gave the protein a lukewarm reception, voting on a scale of 1 through 5, with 1 denoting "low confidence" and 5 denoting "high confidence:"
- How confident are you that there is adequate evidence to determine whether or not the use of BMPs in each of the following indications improves at least one of the clinically meaningful health outcomes?
- On-label use in
- Lumbar spine ( FDA Ref. LS and LS HDE) Panel — Average score: 3.63
- Open tibial fracture ( FDA Ref. T) — Average score: 3.31
- Recalcitrant long bone nonunions (FDA Ref. LB) — Average score: 1.94
- Off-label use in
- Cervical spine — Average score: 2.63
- Lumbar spine — Average score: 2.81
- All other — Average score: 1.06
- On-label use in
- How confident are you that there is adequate evidence to determine that the use of BMPs in the lumbar spine for each of the indications identified below improves at least one of the clinically meaningful health outcomes?
- FDA PMA on-label use (FDA Ref. LS) — Average score: 3.5
- FDA HDE on-label use (FDA Ref. LS HDE) — No vote – question not asked
- Off-label use — Average score: 2.06
- How confident are you that the evidence is adequate to conclude that the use of BMPs for FDA PMA approved on-label use for the treatment of acute, open tibial fractures improves at least one of the clinically meaningful health outcomes? (FDA Ref. T ) — Average score: 3.6
- How confident are you that the evidence is adequate to conclude the off-label use of BMPs in the cervical spine improves at least one of the clinically meaningful health outcomes? — Average score: 1.13
- How confident are you that these conclusions are generalizable to:
- the Medicare patient population? — Average score: 2.25
- community based settings? — Average score: 2.44