Tag Archive | Bone morphogenetic protein

What’s New in Spine Surgery

Spine for O'Buzz.jpegEvery month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz Specialty Update summaries.

This month, OrthoBuzz asked Theodore Choma, MD, co-author of the June 21, 2017 Specialty Update on spine surgery, to select the five most clinically compelling findings from among the more than 40 studies cited in the article.

Biomaterials and Biologics

A multicenter randomized prospective trial compared osteogenic protein-1 (OP-1, also known as bone morphogenetic protein [BMP]-7) combined with local autograft to iliac crest autograft combined with local autograft in posterolateral lumbar fusion. Based on computed tomography (CT) scan assessments, the authors found a 54% fusion rate in the OP-1 group and a 74% fusion rate in the iliac crest group. OP-1 appears to be a poor substitute for iliac crest autograft for achieving posterolateral lumbar fusion.

Adult Spinal Deformity (ASD)

We continue to elucidate the risks and morbidity of adult degenerative spinal deformity surgery. The Scoli-Risk-1 study,1 a Level-III multicenter, prospective observational study, reported on 272 patients with ASD treated surgically. Twenty-two percent of the patients were discharged from the hospital with a decline in the lower-extremity motor score, while only 13% demonstrated improvement. However, by 6 months postoperatively, 21% demonstrated improvement, 69% demonstrated maintenance, and 11% continued to demonstrate lower-extremity motor decline.

Spinal Cord Injury

A Level-I, randomized, crossover trial2 examined whether the character of neuropathic pain following spinal cord injury determined the response to 300 mg/day of either pregabalin or oxcarbazepine. Both anticonvulsant medications significantly improved neuropathic pain in these patients. A subgroup analysis demonstrated that oxcarbazepine was more effective in patients without evoked pain and pregabalin was more effective in patients with evoked pain.

Lumbar Degenerative Spondylolisthesis

To address the consequences of fusion along with decompression in degenerative lumbar spondylolisthesis, a Level-I, randomized controlled trial3 specifically compared laminectomy only with laminectomy plus fusion among 66 patients with stable degenerative spondylolisthesis and symptomatic lumbar stenosis. Patients in the fusion group had significantly higher SF-36 scores at 2, 3, and 4 years, but the groups did not differ with respect to ODI scores at 2 years. The authors reported a significantly higher reoperation rate (34% compared with 14%) in the decompression-only group over the 4-year follow-up, but patients who underwent decompression with fusion began to have an increase in the probability of reoperation 36 months after surgery.

Osteoporotic Injuries

We have more evidence of the effectiveness of vertebral cement augmentation for osteoporotic thoracolumbar compression fractures. The authors of a level-I systematic review and meta-analysis examined randomized controlled trials comparing vertebroplasty with conservative treatment or placebo/sham and identified 11 relevant studies involving 1,048 subjects. The meta-analysis found that patients receiving percutaneous vertebroplasty (n = 531) had lower pain ratings at 1 to 2 weeks, 2 to 3 months, and 1 year. The effect size of vertebroplasty was significant and close to the minimal clinically important difference (MCID).

References

  1. Lenke LG, Fehlings MG, Shaffrey CI, Cheung KM, Carreon L, Dekutoski MB, Schwab FJ, Boachie-Adjei O, Kebaish KM, Ames CP, Qiu Y, Matsuyama Y, Dahl BT, Mehdian H, Pellis´e-Urquiza F, Lewis SJ, Berven SH. Neurologic outcomes of complex adult spinal deformity surgery: results of the prospective, multicenter Scoli-RISK- 1 study. Spine (Phila Pa 1976). 2016 Feb;41(3):204-12.
  2. Min K, Oh Y, Lee SH, Ryu JS. Symptom-based treatment of neuropathic pain in spinal cord-injured patients: a randomized crossover clinical trial. Am J Phys Med Rehabil. 2016 ;95(5):330–8
  3. Ghogawala Z, Dziura J, Butler WE, Dai F, Terrin N, Magge SN, Coumans JV, Harrington JF, Amin-Hanjani S, Schwartz JS, Sonntag VK, Barker FG 2nd, Benzel EC. Laminectomy plus fusion versus laminectomy alone for lumbar spondylolisthesis. N Engl J Med. 2016 Apr 14;374(15):1424-34.

No BMP–Cancer Link Found in Older Patients After Lumbar Arthrodesis

The July 6, 2016, edition of The Journal of Bone & Joint Surgery features a large case-cohort study that may help older patients and clinicians decide whether to use bone morphogenetic protein (BMP) as an adjunct to lumbar arthrodesis. Among Medicare patients aged 65 years and older, Beachler et al. found that BMP use was not associated with the following:

  • Overall cancer risk
  • Increased risk of individual cancer types
  • Increased risk of cancer in people who had cancer prior to undergoing lumbar arthrodesis
  • Increased mortality after a cancer diagnosis

BMP was used in 30.7% of >3,600 lumbar-arthrodesis patients analyzed, and the lack of association between BMP use and cancer held whether patients received the growth factor as part of an FDA-approved anterior lumbar interbody fusion or as an off-label application.
BMP-Cancer.gif
In an accompanying commentary, Singh et al. laud the authors for designing a study that was not only well-powered but also analyzed risk among those with a medical history of cancer. The commentators emphasize, however, that the median follow-up in this study was 2.4 years, leading them to wonder “whether this time frame is sufficient to evaluate the impact of BMPs on carcinogenesis.”

Until a large, prospective, randomized trial on this subject is conducted, Singh et al. say, “the decision to use BMPs should be made on the basis of sound clinical judgment by the treating physician after a full disclosure of the potential risks to the patient.”

BMP vs Autograft for Instrumented Posterolateral Lumbar Fusion

In diligent efforts to improve osseous bridges when performing spinal fusion surgery, orthopaedists have been using harvested allograft bone for more than a century and bone morphogenetic protein (BMP) for nearly a half century. Now, a European multicenter, randomized trial by Delawi et al., in the March 16, 2016 Journal of Bone & Joint Surgery, has compared overall success (defined as a combination of CT-determined fusion rates and clinical results at 12 months) between the two approaches among 113 patients.

This was a non-inferiority trial, and the BMP formulation used (Osigraft BMP-7, known commonly as OP-1 and available in the US in a similar formulation known as OP-1 Putty) was not non-inferior to iliac crest autograft. To clarify the potentially confusing double negative: OP-1 was less successful than autograft, due primarily to lower fusion rates. There were no significant between-group differences in clinical outcomes as measured by scores on the Oswestry Disability Index, although the authors added that “our follow-up period of one year may have been too short to show differences in clinical results.”

Delawi et al. conclude that, based on their findings, “use of OP-1 in place of autologous iliac crest bone graft in instrumented posterolateral lumbar fusions cannot be recommended.” That conclusion is echoed by commentator Jeffrey Coe, MD, who sees these findings as “another bit of evidence against the use of rhBMP-7 as a substitute for [iliac crest bone grafts] in posterolateral spinal fusion.”

Is Bone Regeneration Possible in Humans?

It’s a known fact that zebra fish have innate abilities to regenerate lost appendages and organs, but will researchers be able to crack the code that would make the same thing possible for humans? A recent paper published in Cell Reports shows how the two molecular pathways—the Wnt signaling pathway and the bone morphogenetic protein (BMP) pathway– work together in zebra fish to regenerate fins when they are amputated. University of Oregon (UO) researchers believe that understanding these signaling mechanisms in zebra fish could support the design of regenerative therapies that direct human cells to behave similarly.

According to a UO press release, “The researchers found that cell-to-cell signaling mediated by the Wnt pathway helps existing mature bone cells become progenitor cells after fin amputation.” Then the BMP pathway directs the newly formed cells to develop into functional bone cells. Humans have these same pathways, and defects in them are linked to human bone diseases.  Lead author Scott Stewart, PhD, said, “As we discover the cellular and molecular roles of the signals in zebra fish and pinpoint the missing network connections in mammals, maybe we could coax human bones to repair themselves equally as well.”

Read more here