The Spine Blog

Friday, February 14, 2014

In Search of a Bone Graft Substitute for MIS-TLIF

While minimally invasive approaches to spinal fusion have gained popularity, one of the challenges is obtaining fusion in the absence of a traditional posterolateral fusion and without iliac crest or local bone graft obtained from the procedure. One solution to this in MIS-TLIF has been the use of BMP-2 in the interbody space, however, risks of subsidence, ectopic bone formation in the epidural space, increased post-operative pain, and potentially cancer have raised concern over this off-label use.1 To address these issues, Dr. Singh and his colleagues from Chicago performed a randomized controlled trial comparing MIS-TLIF with unilateral percutaneous pedicle screw fixation using either BMP-2 or silicate-substituted calcium phosphate (Si-CaP) with bone marrow aspirate as  bone graft substitutes. They randomized 52 patients with one level degenerative spondylolisthesis to the two groups and then compared fusion rates and clinical outcomes between the two groups. Computed tomography at 6 and 12 months was used to define fusion, and the visual analog scale for low back pain was the clinical outcome measure. At 1 year, patients treated with Si-CaP had a pseudarthrosis rate of 35% compared to only 8% in the BMP-2 group. Somewhat surprisingly, all patients with a pseudarthrosis were symptomatic, had significantly worse VAS scores, and underwent revision surgery, either with ALIF or contralateral MIS-TLIF. The only BMP-2 related complication reported was ectopic bone formation in the neuroforamen in one patient who also had a pseudarthrosis and went onto revision surgery.


The authors should be congratulated on performing this high quality, Level 1 study addressing an important clinical question. Based on these results, it is clear that Si-CaP does not lead to acceptable rates of fusion and is associated with a high rate of revision surgery. While the fusion rates observed for BMP-2 are consistent with those in the literature, concerns about its use are what prompted investigation of alternative bone graft substitutes. The fact that 100% of the pseudarthrosis patients had symptoms severe enough to warrant revision surgery in the short term is surprising, as prior literature has suggested that pseudarthrosis was not associated with clinical outcomes in the first two years. In their classic study comparing instrumented and uninstrumented decompression and fusion for degenerative spondylolisthesis, Fischgrund et al. found that radiographic pseduarthrosis did not affect outcomes in either group out to 2 years.2 Subsequent work did demonstrate worse outcomes for uninstrumented patients who went onto pseudarthrosis in the long-term, though this was at an average follow-up of seven years.3 It is possible that the unilateral instrumentation used in this study did not provide sufficient stability to limit symptoms even in the absence of solid fusion. This study highlights the challenges facing MIS fusion techniques. While pedicle screws and interbody devices can be safely placed through small incisions, there remains to be a safe and reliable method to obtain fusion with MIS approaches. BMP-2 does yield high fusion rates, however, its use in either TLIF or posterolateral fusion remains controversial. Until a bone graft substitute is developed that yields high fusion rates without causing unwanted side-effects, open fusion techniques will likely remain the gold standard.

Please read Dr. Singh’s article on this topic in the February 1 issue. Does this change how you view the use of bone graft substitutes in MIS-TLIF? Let us know by leaving a comment on The Spine Blog.

Adam Pearson, MD, MS

Associate Web Editor



1.            Carragee EJ, Hurwitz EL, Weiner BK. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. The spine journal : official journal of the North American Spine Society 2011;11:471-91.

2.            Fischgrund JS, Mackay M, Herkowitz HN, Brower R, Montgomery DM, Kurz LT. 1997 Volvo Award winner in clinical studies. Degenerative lumbar spondylolisthesis with spinal stenosis: a prospective, randomized study comparing decompressive laminectomy and arthrodesis with and without spinal instrumentation. Spine 1997;22:2807-12.

3.            Kornblum MB, Fischgrund JS, Herkowitz HN, Abraham DA, Berkower DL, Ditkoff JS. Degenerative lumbar spondylolisthesis with spinal stenosis: a prospective long-term study comparing fusion and pseudarthrosis. Spine 2004;29:726-33; discussion 33-4.