Formation of Abdominal Heterotopic Bone Following the Utilization of Bone Morphogenetic Protein in Anterior Lumbar Spinal Fusion

Abstract

INFUSE (Medtronic), or recombinant human bone morphogenetic protein-2 (rhBMP-2), was introduced in 2002 as an osteoinductive material to increase spinal fusion rates with the potential to eliminate the morbidity associated with bone-grafting of the iliac crest. This U.S. Food and Drug Administration (FDA)-approved indication is to use INFUSE as an adjuvant in achieving fusion with the LT-Cage Lumbar Tapered Fusion Device (Medtronic) in anterior lumbar interbody fusion (ALIF). Off-label use is widespread and includes implementation in anterior cervical fusion, anterior lumbar fusion with implants other than the LT-Cage, and posterior lumbar fusion1. Epstein and Schwall reported that 96% of their institution’s use of rhBMP-2 was off-label, with an estimated cost of $4,547,822 for one year2. A number of reports have recently cited complications, including hematoma and seroma formation; soft-tissue swelling; heterotopic bone formation; vertebral osteolysis; bowel, bladder, and sexual dysfunction; and neurologic deficit3. Another major concern is the potential association of malignancy arising in patients in whom rhBMP-2 has been used4-6. More studies are needed to further our understanding of this association. Formation of heterotopic bone with the use of rhBMP-2 has been well documented in posterior interbody procedures. An FDA investigational study by Haid et al. on the use of rhBMP-2 in posterior lumbar interbody fusion suspended enrollment early when an alarming rate of heterotopic bone formation was discovered posterior to the cages. At the two-year follow-up, nearly 75% of patients who had received rhBMP-2 were found to have such heterotopic bone formation7. Joseph and Rampersaud described epidural bone formation in 20.8% of their rhBMP-2 study group, but no associated neurological deficits8. Wong et al. reported five cases of neurologic impairment from the development of epidural heterotopic bone following the use of rhBMP-29. …