BMP-2 with anterior lumbar interbody fusion: Clinical usage and recent controversies
Introduction
Since discovery of the osteogenic potential of bone morphogenetic protein (BMP) in the 1960s, there has been interest in its potential for clinical application in orthopedic surgery.1 BMP-2, in its recombinant human form (rhBMP), has been approved by the United States Food and Drug Administration (FDA) for use in anterior lumbar interbody fusion (ALIF) with a titanium metallic cage. However, off-label application has spread widely to a variety of cervical and lumbar interventions.2
Given initial positive results and the reported low risk of adverse effects, the use of the BMP-2 increased significantly during the 2000s. It was used in less than 1% of all spine surgery in 2002 and greater than 50% of ALIFs and 40% of posterolateral lumbar fusions in 2007.3 Since then, however, greater awareness of potential complications associated with its use has led to judicious reassessment of the role of BMP-2 in ALIF, and in spine surgery as a whole.4, 5 Decision-making regarding the use of BMP-2 continues to evolve with greater understanding of its benefits and complications. The goal of the current review is to characterize the best case use of rhBMP-2 in ALIF and to explore some of the more commonly associated complications: retrograde ejaculation, heterotopic ossification, and radiculitis.
Section snippets
Review of best use case
The introduction of rhBMP-2 into spine surgery began with its very specific FDA approval in 2002 for application in a single-level ALIF using a titanium, threaded, tapered interbody cage at L4-5 or L5-S1. Several studies have evaluated the radiographic outcomes of ALIF with use of rhBMP-2. Figure 1 shows postoperative radiograph of patient who underwent single-level ALIF with a cage. In a small prospective randomized trial of 14 patients undergoing ALIF, Boden et al.6 showed a 100% fusion rate
Retrograde ejaculation
Manipulation of the superior hypogastric plexus during ALIF can lead to development of retrograde ejaculation (RE) with rates reported from 0.5% to 10%.18, 22, 23, 24 Initial studies showed no adverse RE events with use of rhBMP-2. However, FDA reports did acknowledge a slightly higher but statistically insignificant higher risk of RE. BMP-2 is postulated to increase risk of RE by promoting a local inflammatory response near the disc space or by formation of ectopic bone in the region of the
Radiculitis
Postoperative radiculitis is defined as worsening leg pain in a dermatomal distribution that is not necessarily associated with nerve compression. Although limited by the scope and quality of previous studies, in a meta-analysis of five randomized trials of BMP-2 in ALIF as part of the Yale Open Data Access (YODA) project, Fu et al.18 found no difference in worsening leg pain or radiculitis in the immediate and later postoperative period. They appropriately noted that, “adverse events
Heterotopic ossification
In patients undergoing ALIF with BMP-2, heterotopic ossification (HO) can occur presumably when the biological agent leaks from the collagen carrier into the extradiscal space. The formation of heterotopic ossification is usually triggered by an inducing trauma to bone or musculature, formation of a hematoma containing mesenchymal progenitor cells, and an environment conducive to osteogenesis.41 BMP induces the undifferentiated mesenchymal cells to enter a pathway for the development of bone,
Conclusions
The introduction and adoption of BMP-2 with ALIF (and spine surgery in general) has led to increased scrutiny of its benefits and risks. Although harvesting iliac crest bone graft (ICBG) has been portrayed as a potentially painful and disabling procedure, a review of prospective randomized control studies have shown no clinical difference in health-related functional outcome measures in patients treated with BMP-2 and ICBG.48 The best available evidence does suggest increased fusion rates with
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