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The Spine Blog

Friday, January 11, 2019

Does teriparatide improve fusion rate?

While the role of fusion in the surgical treatment of degenerative spondylolisthesis remains controversial, most spine surgeons agree that a solid fusion is preferable to a pseudarthrosis.1-3 Investigators have demonstrated that pedicle screw instrumentation, iliac crest bone graft, and BMP-2 increase fusion rates. Unfortunately, these are all associated with increased morbidity, increased cost, or both. As such, researchers have made an effort to identify lower risk alternatives to increase fusion rates. Teriparatide (synthetic parathyroid hormone, marketed as Forteo) has shown to be a promising medication that has improved fusion rate and quality in animal models. A non-randomized Japanese study compared fusion rate in osteoporotic women with degenerative spondylolisthesis treated with either teriparatide or risedronate around the time of lumbar laminectomy and instrumented fusion with local bone graft. The patients received the medication for two months pre-operatively and for eight months post-operatively. There was no control group that received placebo or no medication. They found that the 12-month fusion rate as determined by CT scan was higher in the teriparatide group (82% vs. 68%). Given these promising findings, Dr. Jespersen and colleagues from Denmark performed an RCT in which 101 degenerative spondylolisthesis patients over 60 years old undergoing one or two level decompression and uninstrumented fusion using local bone graft and allograft were randomized to 90 days of teriparatide or placebo. At one year, all patients underwent a CT scan to determine fusion rate, fusion mass volume, and fusion mass density. Overall, the fusion rate was 33%, and there were no significant differences between the two groups (29% teriparatide vs. 37% placebo). There were no differences in fusion mass volume or density. Based on these findings, the authors concluded that 90 days of teriparatide did not change the fusion rate or quality in this population.

The authors should be congratulated on successfully performing a Level 1 study that was well-designed to answer a specific clinical question. While RCTs provide the highest level evidence, they can only answer one specific question. Teriparatide seemed promising in animal models, and it may be helpful in different scenarios than the one studied here. This investigation looked at a specific dose, duration, and fusion technique, and it is reasonable to conclude that teriparatide was not helpful in this specific situation. It is possible that longer duration therapy, starting it months pre-operatively, using it with instrumented fusion, or using it strictly in a population of osteoporotic women would result in a different outcome, though these specific scenarios would need to be studied to answer the question. One of the striking findings of this study is that the overall fusion rate was only 33% with an uninstrumented fusion using local bone graft and allograft. Patient reported outcomes were not included in this study, but there is some evidence suggesting that long-term outcomes are worse in uninstrumented fusion patients who go onto nonunion.3 Given that many degenerative spondylolisthesis patients do well without fusion, it may be that nonunion does not have a markedly negative impact on their outcomes. It will be interesting to see the patient reported outcomes in this study population to determine if the patients with nonunion have worse outcomes. The role of teriparatide in lumbar fusion remains unclear, though this study makes it clear that it is not beneficial at this dose and for this duration in this population. The bigger question about the best surgical technique for degenerative spondylolisthesis patients remains unanswered. It seems likely that degenerative spondylolisthesis represents a disease spectrum and that patients with different characteristics do best with different operations, though how to determine the best operation for an individual patient remains unknown.

Please read Dr. Jespersen’s article on this topic in the February 1 issue. Does this change your view of teriparatide in lumbar fusion? Let us know by leaving a comment on The Spine Blog.

Adam Pearson, MD, MS

Associate Web Editor

REFERENCES

1.            Forsth P, Olafsson G, Carlsson T, et al. A Randomized, Controlled Trial of Fusion Surgery for Lumbar Spinal Stenosis. The New England journal of medicine 2016;374:1413-23.

2.            Ghogawala Z, Dziura J, Butler WE, et al. Laminectomy plus Fusion versus Laminectomy Alone for Lumbar Spondylolisthesis. The New England journal of medicine 2016;374:1424-34.

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.