The search for a highly efficacious, safe, and low cost bone graft substitute continues. While iliac crest bone graft is considered the gold standard, it has been largely abandoned due to concerns about donor site morbidity. Surgeons also prefer to avoid the time-consuming procedure which is hardly reimbursed. BMP-2 was widely adopted prior to 2011, then its use markedly decreased after safety concerns were published by Carragee et al.1 Hospitals have also pressured surgeons to avoid its use due to cost concerns. Local bone graft has been shown to be effective for one and two level instrumented fusions, though cases that do not yield sufficient local bone graft and longer fusions require other bone graft options.2-4 Bone graft substitutes have been developed to fill this void, one of which is silicate calcium phosphate (SiCaP, marketed by Baxter Healthcare as Actifuse). This compound serves as an osteoconductive scaffold but has no osteoinductive properties. To better assess the efficacy of SiCaP, Dr. Coughlan and colleagues from Australia and the Netherlands performed an RCT in which 103 one or two level fusion patients were randomized to SiCaP or BMP-2, which was placed across the transverse processes. All patients also received pedicle screw instrumentation and PLIF, which included an interbody device and local bone graft in the disk space. The primary outcome was radiographic fusion at 12 months, based on evaluation of the intertransverse fusion on CT scans and motion on flexion-extension radiographs. Fusion status at 24 months, back and leg VAS, ODI, and SF-36 scores were also recorded. At 12 months, 78 patients had imaging available to assess fusion. The authors did not report the fusion rate for these 78 patients but instead included the patients without imaging and classified them as not fused. Using this approach, the fusion rate was 53% for the SiCaP patients and 56% for the BMP-2 patients. At 24 months, 92 of the patients had radiographic data available, and the same analysis yielded a fusion rate of 80% for both groups. A separate per protocol analysis excluded patients without radiographs and also eliminated 21 patients with protocol violations, 13 of which were related to not using Mastergraft granules in the BMP-2 patients. Sixty-two patients were included in this analysis at 12 months, with a fusion rate of 71% for SiCaP and 74% for BMP-2. In the per protocol analysis, the 24 month fusion rate increased to 79% for the SiCaP group and 85% for the BMP-2 group. Clinical outcomes and adverse events were similar, with some clinical outcomes favoring the SiCaP group at 6 months.
This is a complex study that is challenging to interpret. The major limitation is the peculiar study design in which the interbody fusion using local bone graft was not considered when evaluating fusion status, and fusion across the facet joints was also apparently ignored. Additionally, no local bone graft was used for the intertransverse fusion, though this would typically be performed when local bone graft was available. The comparison of SiCaP to BMP-2 is also questionable, as BMP-2 is generally not indicated for one and two level fusions when local bone graft is available. A more compelling study design would have been SiCaP + local bone graft vs. local bone graft in single level decompression and posterolateral instrumented fusion, as that is a common procedure for which surgeons need to decide about adding a bone graft extender to the local bone graft. The inclusion of an interbody fusion using an interbody device with local bone graft confounds the current analysis as it is not clear what effect an interbody fusion or nonunion would have on the intertransverse fusion. Patients with instrumented fusions frequently fuse across the facet joints, and this was apparently not considered in the current analysis. Additionally, the blinding of the radiologists interpreting the studies is questionable as the SiCaP is radiodense and remains present even in the absence of bone formation. Finally, the study was underpowered due to protocol violations, loss to follow-up, and a relatively low number of patients initially enrolled. Given these limitations, it is difficult to draw any conclusions from the current study. Hopefully higher quality studies evaluating the efficacy of bone graft extenders will be forthcoming. However, given the widespread use of these products despite a lack of evidence supporting their efficacy, companies that produce them may not be motivated to fund studies that could yield a negative result.
Please read Dr. Coughlan's article on this topic in the August 1 issue. Does this change your opinion about SiCaP as a bone graft substitute? 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. Inage K, Ohtori S, Koshi T, et al. One, two-, and three-level instrumented posterolateral fusion of the lumbar spine with a local bone graft: a prospective study with a 2-year follow-up. Spine 2011;36:1392-6.
3. Kang J, An H, Hilibrand A, Yoon ST, Kavanagh E, Boden S. Grafton and local bone have comparable outcomes to iliac crest bone in instrumented single-level lumbar fusions. Spine 2012;37:1083-91.
4. Sengupta DK, Truumees E, Patel CK, et al. Outcome of local bone versus autogenous iliac crest bone graft in the instrumented posterolateral fusion of the lumbar spine. Spine (Phila Pa 1976) 2006;31:985-91.