Even with BMPs, osteoinductive matrices still play a role in spine restoration cases

Osteolysis, radiculitis and excess bone formation are among the risks of using large doses of BMP.

Issue: September 2008

While osteoinductive factors and matrices may be advantageous for spinal fusion, a leading spine surgeon warns about the consequences of using bone morphogenetic proteins in large doses and calls for a re-examination of iliac crest bone grafting.

“Lumbar spine fusion, especially posterior lumbar spine [fusion], continues to present a difficult clinical problem,” Harvinder S. Sandhu, MD, said. “Although BMPs are powerful and useful biologic tools, do not underestimate the risks when using supraphysiologic doses. There is an inflammatory and osteolytic host response in some cases and, in the spine, chronic radiculitis. Well-designed osteoconductive matrices and local bone graft and bone marrow still have an important role.

“I think that we have to revisit the whole issue of iliac crest bone grafting, particularly in light of the newer, less invasive bone harvesting methods that are now available. It ultimately may be a safer and more cost effective method, even when combined with osteoconductive matrices,” he said.

Osteoinductive matrices

Despite the enthusiasm for bone morphogenetic proteins (BMPs), osteoinductive matrices continue to play a significant role in spine surgery, Sandhu said. “In fact, we have practically given up on harvesting iliac crest cortical bone graft for the cervical spine,” he said during his presentation at the American Academy of Orthopaedic Surgeons 75th Annual Meeting. “A combination of a good, machined allograft spacer with an appropriate osteoconductive matrix with marrow has a very high fusion rate.” While he noted that few Level I studies and limited prospective clinical data exist on osteoconductive materials, anecdotal evidence shows promising results.

“Although BMPs are powerful and useful biologic tools, do not underestimate the risks when using supraphysiologic doses.”
— Harvinder S. Sandhu, MD

“The most popular of the osteoconductive matrices for the spine are the calcium phosphates and among those Vitoss (Orthovita), seems to presently be the most popular,” Sandhu said.

BMPs

BMPs have grabbed the attention of many surgeons and Sandhu estimates that recombinant human bone morphogenetic protein-2 (rhBMP-2, Infuse, Medtronic Sofamor Danek) is the single most-successful product in spinal device history.

The results of several Level I studies on rhBMP-2 for anterior lumbar fusion with titanium cages suggest shorter surgical times and length of hospital stay, less blood loss, better fusion rates and faster return to work compared to iliac crest bone graft in that specific application.

The results also indicate better Oswestry Pain and Disability Index scores at various time points with compared to iliac crest bone graft. Research combining rhBMP-2 with allograft for anterior lumbar fusion also indicates accelerated bone formation, resorption and remodeling, Sandhu said.

A subgroup analysis of a larger series investigating the use of rhBMP-2 in patients undergoing single-level instrumented posterolateral fusion revealed about a 15% higher fusion rate in patients who received 40 mg of rhBMP-2 compared to those who had iliac crest bone grafts.

However, investigators found no significant differences between the groups regarding clinical outcomes at 2-year follow-up.

“From an economic analysis standpoint, you have to really look at this carefully,” Sandhu said. “You’ve spent the equivalent of more than three kits of Infuse at a cost of $5,000 per kit on one group and clinically haven’t made much of an impact.

“Is it surprising that the molecule works so well? Not really. If you think about what we are giving to our patients, 1.5 mg/cc, compare that to how much BMP is contained in processed DBM allograft. This is, in fact, far more BMP-2 than exists in an entire human skeleton. These are supraphysiologic doses we are using.”

Risks

Sandhu warned that using such high doses can pose significant complications. Some surgeons using rhBMP-2 in the cervical spine have noticed an intense seroma formation 4 to 5 days postoperatively which appears to be an inflammatory response related to compaction and concentration of the Infuse device.

“A number of these patients required reintubation and tracheostomies,” he said. “This was a very serious complication that was noted with off-label use and, in fact, at our institution we don’t allow the use of BMP-2 for cervical fusion surgery due to this unjustifiable risk.”

Investigators reported the first cases of excess bone formation associated with rhBMP-2 in patients who underwent posterior lumbar interbody fusions.

Osteolysis linked with rhBMP-2 use was first noted in an allograft series and later in off-label use cases where surgeons appeared to have aggressively decorticated the vertebral endplates.

“One of the more recent findings is this problem of radiculitis that does not seem to be caused by a mass effect or a mechanical pressure, but simply irritation of the nerve [root],” Sandhu said. While initial reports estimated a 20% incidence of the condition, recent research from investigators at the Rothman Institute reports up to a 23% rate of radiculitis when rhBMP-2 is used. “The mean duration surprised us,” Sandhu said. “[It was] 13 months.”

For more information:

Harvinder S. Sandhu, MD, can be reached at The Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021; 212-606-1798; e-mail: sandhuh@hss.edu. He received financial compensation from Kyphon/Medtronic, Osteotech and Orthovita, and was not a consultant for any of these companies at the time he presented this data.

Reference:

Sandhu HS. Assessment and use of new and existing technologies for bone restoration in spine surgery. Presented at the American Academy of Orthopaedic Surgeons 75th Annual Meeting. March 5-9, 2008. San Francisco.