Study Weighs Risks Versus Benefits in Use of rhBMP-2 for Minimally Invasive TLIF

Terry Stanton

The use of human bone morphogenetic protein-2 (rhBMP-2) in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) was effective for arthrodesis in a prospective nonrandomized study, but the study authors warn that complications of neuroforaminal bone growth, osteolysis, and pseudarthrosis may arise with this off-label use.

The study, which was presented yesterday by Kern Singh, MD, of Rush University Medical Center, is the largest to address the issue of neuroforaminal bone growth and the first to address the additional hospital costs of treating such growth occurring with MIS-TLIF.

The 4-year study included 573 patients, 39 of whom (6.8 percent) required reoperation for clinically symptomatic pseudarthrosis. In addition, 10 patients (1.7 percent) required 15 additional procedures based on recalcitrant radiculopathy and CT evidence of neuroforaminal bone growth (Fig. 1), vertebral body osteolysis, and/or cage migration. All 10 of these cases were single-level fusions.

Fig 1 Axial CT scan demonstrating neuroforaminal bone growth.
Courtesy of Kern Singh, MD

Bone overgrowth was associated with nerve impingement and radiculopathy in all 10 patients. Nine patients received a small packet of rhBMP-2 (4.2 mg), whereas the other patient received a large packet (12 mg). Two patients experienced osteolysis and cage migration.

In the initial surgery, the surgeon employed a unilateral approach through a paramedian skin incision using the Wiltse technique under fluoroscopy. Unilateral pedicle screws were placed percutaneously over a guide wire. The laminectomy, bilateral facetectomy, and TLIF were performed through a unilateral 21-mm non-expandable tube retractor. No posterolateral fusion was performed. Midline muscular and ligamentous structures were all preserved during the procedure. Local bone graft that had been harvested from the laminectomy and facetectomy was collected in a bone trap and mixed with either the small or large kit of rhBMP-2.

The rhBMP-2 product used has been approved by the U.S. Food and Drug Administration (FDA) for use in anterior lumbar interbody fusion (ALIF). The authors note that in ALIF, rhBMP-2 is applied to a collagen sponge that serves as a biologic carrier. During clinical trials, no adverse events were reported, and the group treated with rhBMP-2 reported improved outcomes. After rhBMP-2 was approved by the FDA for ALIF, however, physician-directed (off-label) use began in clinical practice in both the anterior and the posterior cervical spine and in the posterolateral lumbar spine in an effort to improve fusion rates.

Caution issued
Complications in the cervical spine—local swelling, hematoma, dysphagia, and airway compromise—have surfaced in the past. As a result, in 2008 the FDA issued a public health warning regarding off-label use of BMP-2 in the cervical spine. Ectopic bone formation has been reported in both the epidural space as well as in the insertional track when rhBMP-2 was used in posterior lumbar interbody fusions. A case series of four patients reported neural compromise after the physician-directed use of rhBMP-2 following MIS-TLIF.

In Dr. Singh’s study, the 10 patients with neuroforaminal bone growth underwent 15 procedures. Most revision surgeries (13) were laminoforaminotomies with neurolysis and excision of the bone growth from the ventral aspect of the canal. Intraoperative inspection in these patients revealed adherence of the neural structures to the surface of the ectopic bone, requiring microscopic dissection to free the dura and nerve root sheath.

An absence of trabecular bone within the vertebral body as well as graft subsidence and loss of endplate integrity was noted in the two patients with osteolysis. One patient also required a lumbar dural repair and an additional procedure for irrigation and débridement of a subsequent lumbar wound infection.

The 39 patients with clinically symptomatic pseudarthrosis were treated with contralateral MIS-TLIF, pedicle screw instrumentation, and the use of local bone graft augmented with a small kit of rhBMP-2.

According to Dr. Singh, some clinical studies have speculated that the complications associated with rhBMP-2 use relates mainly to the dosage, whereas others have found that BMP-2–related complications are dose-independent. Studies that had no instances of heterotopic bone formation generally used doses of approximately 1.5 mg/mL. Dr. Singh’s study found no connection between increased dosages and increased clinical complications.

“Moreover, our analysis suggests that it is concentrations of BMP-2 relative to local bone graft that seem to be more involved with complications, rather than absolute dosage measurements of rhBMP-2 alone,” he reported.

Although the 1.7 percent rate of primary complication in this study is low, it does incur additional hospital costs—an average of $14,785 per encounter.

“This increase in cost, however, should be evaluated in the context of a potential decreased need for reoperation secondary to pseudarthrosis,” said Dr. Singh. “Costs to treat pseudarthrosis in general are much more expensive, time-consuming, and debilitating to patients.

“Patients should be educated regarding the 1.7 percent rate of neuroforaminal growth that may occur with BMP-2. A discussion should be had with patients regarding the risk of bone growth versus the increased risk of nonunions that occur when other biologic agents are used. Ultimately this is a patient-directed decision,” he concluded. “In terms of cost and patient recovery, it is less expensive and time-consuming to deal with neuroforaminal bone growth resulting in stenosis than to revise a nonunion.”

Dr. Singh’s coauthors for Scientific Presentation 241, “Clinical Complications Following rhBMP-2 Use in a Minimally Invasive Transforaminal Lumbar Interbody Fusion,” were Miguel Pelton, BS; Tom D. Cha, MD; and Safdar N. Khan, MD.

Disclosure information: Dr. Singh—Pioneer, Zimmer, DuPuy, Stryker, Globus Medical, Thieme, Lippincott Williams & Wilkins, Vital 5. Mr. Pelton and Drs. Cha and Khan reported no conflicts.

2013 Annual Meeting News
Tuesday through Friday, February 19 – 23, 2013.
http://www.aaos.org/news/acadnews/2013/AAOS7_3_21.asp