Fusion rates in multilevel, instrumented anterior cervical fusion for degenerative disease with and without the use of bone morphogenetic protein

Frenkel, Mark B.; Cahill, Kevin S.; Javahary, Ramin J.; Zacur, George M.; Green, Barth A.; Levi, Allan D.

doi:10.3171/2012.12.spine12607

Cited by 29 publications

(42 citation statements)

References 20 publications

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“…While some studies exist about the effectiveness of growth factor treatment for vertebral body fusion and IVD implants [29-31]; to our knowledge nothing is known about the effect of growth factor injection during discectomy. Our broad aim is to improve knowledge of how discectomy procedures influence IVD physiology and assess the potential of growth factor injection at the time of surgery, and we specifically evaluate the effects of TGFβ3 injection into the discectomy site during surgery using a bovine organ culture model.…”

Section: Introductionmentioning

confidence: 99%

Detrimental effects of discectomy on intervertebral disc biology can be decelerated by growth factor treatment during surgery: a large animal organ culture model

Illien-Jünger

Purmessur

et al. 2014

The Spine Journal

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BACKGROUND CONTEXT Lumbar discectomies are common surgical interventions that treat radiculopathy by removing herniated and loose intervertebral disc (IVD) tissues. However, remaining IVD tissue can continue to degenerate resulting in long-term clinical problems. Little information is available on the effects of discectomy on IVD biology. Currently no treatments exist that can suspend or reverse the degeneration of the remaining IVD. PURPOSE To improve knowledge how discectomy procedures influence IVD physiology and to assess the potential of growth-factor treatment as an augmentation during surgery STUDY DESIGN To determine effects of discectomy on IVDs with and without TGFβ3 augmentation using bovine IVD organ culture. METHODS This study determined effects of discectomy with and without TGFβ3 injection using 1, 6, and 19 days organ culture experiments. Treated IVDs were injected with 0.2μg TGFβ3 in 20μl PBS+BSA into several locations of the discectomy site. Cell viability, gene expression, nitric-oxide release, IVD height, aggrecan degradation, and proteoglycan content were determined. RESULTS Discectomy significantly increased cell death, aggrecan degradation and nitric-oxide release in healthy IVDs. TGFβ3 injection treatment prevented or mitigated those effects for the 19 days culture period. CONCLUSIONS Discectomy procedures induced cell death, catabolism and nitric-oxide production in healthy IVDs, and we conclude that post-discectomy degeneration is likely to be associated with cell death and matrix degradation. TGFβ3 injection augmented discectomy procedures by acting to protect IVD tissues by maintaining cell viability, limiting matrix degradation and suppressing nitric-oxide. We conclude that discectomy procedures can be improved with injectable therapies at the time of surgery although further in vivo and human studies are required.

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Section: Introductionmentioning

confidence: 99%

Detrimental effects of discectomy on intervertebral disc biology can be decelerated by growth factor treatment during surgery: a large animal organ culture model

Illien-Jünger

Purmessur

et al. 2014

The Spine Journal

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“…Is a major limitation of multilevel anterior cervical fusion, traditional techniques have a 20% of patients who develop pseudarthrosis, one strategy used to help decrease the rate of it is to have posterior instrumentation to increase the rigidity of the construct, however it adds morbidity by increase the time of surgery. Frenkel et al 16 demonstrate that BMP usage in anterior cervical approach has almost 100% rate of solid arthrodesis regardless of level, but its study does not have statistical significance.…”

Section: Discussionmentioning

confidence: 98%

The use of bone morphogenetic proteins (BMP) and pseudarthrosis, a literature review

Oliveira

Martins

Lima

et al. 2017

Revista Brasileira de Ortopedia (English Edition)

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Bone morphogenetic proteins (BMP) are multi-functional growth factors to promote bone healing with the proposal of less morbidity compared to the usual methods of bone graft harvest. Pseudoarthrosis occur when the fusion attempt fails, a solid fusion is not achieved, or there is motion across the segment leading to it, and it can be clinically symptomatic as pain, deformity, neurocompression, or hardware failure. BMPs are used at spinal fusion as a tool for the treatment of degenerative, traumatic, neoplastic and infectious conditions of the spine. This review shows that the use of BMPS is effective and secure when compared with iliac crest bone graft (ICGB); however, depending of the location of usage (cervical spine, lumbar spine or sacrum) and the medical status of the patient (presence of comorbidities, tobacco usage), it is more likely to exhibit complications. Therefore, the use of these proteins must be an informed decision of patient and physician preferences.

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“…Similarly, Stachniak et al reported a 95 % fusion rate at 6-months and a 100 % fusion rate at 9-months following a 2-or 3-level ACDF with rhBMP-2 in a group with substantial risk factors for pseudarthrosis (33 % smoking, 13 % diabetes, and 43 % obesity) [53]. In another retrospective cohort study comparing multilevel ACF with and without rhBMP-2, the authors demonstrated a 100 % fusion rate in the rhBMP-2 cohort vs an 82.6 % fusion rate in the group without rhBMP-2 [44]. Lastly, Lu et al demonstrated lower rates of pseudarthrosis with the application of BMP in multilevel ACF, especially in patients who underwent a 4-level ACDF and in smokers [56].…”

Section: Arguments In Favor Of Bmp Utilization In the Anterior Cervicmentioning

confidence: 93%

“…Controversy still exists regarding the administration of BMP in ACF. Some groups maintain that it is safe and efficacious [43,44] while others report multiple serious complications [45,46]. Argument against BMP utilization in the anterior cervical spine On July 1, 2008 the FDA issued a public health notification warning about the utilization of rhBMP-2 in cervical spine fusion procedures.…”

Section: Discussionmentioning

confidence: 99%

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Point-counter-point debate: the association between recombinant human bone morphogenetic protein utilization and complications in spine surgery

Siemionow

Sundberg

Tyrakowski³

et al. 2014

Curr Rev Musculoskelet Med

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Bone morphogenetic proteins (BMPs) have been utilized in spine surgery for over 10 years as a bone graft substitute. Potential BMP-related adverse effects including retrograde ejaculation and heterotopic neuroforaminal bone formation have been described. Additionally, some studies have suggested an association between BMP and cancer. Inconsistencies exist in the published spine literature with regards to the incidence and association of complications with BMP utilization. In a point-counterpoint format, this article discusses the current evidence concerning the relationship between the utilization of BMP in spinal fusion and the risk of cancer, retrograde ejaculation (RE), neuroforaminal bone formation, and its role in anterior cervical spine surgery and adolescents.Keywords Bone morphogenetic protein . Retrograde ejaculation . Anterior cervical fusion . Neuroforaminal bone growth . Cancer Point-counterpointRetrograde Ejaculation (RE) RE occurs secondary to impaired function of the internal vesicle sphincter muscle. Anterior lumbar approaches, particularly at the L5-S1 level, carry a greater potential for damage to the superior hypogastric sympathetic plexus, which innervates the internal vesicle sphincter muscle. Other etiologies of RE including diabetes, benign prostate hypertrophy and its treatment, multiple sclerosis, pelvic trauma, and pelvic or rectal surgery [1][2][3][4][5][6]. RE following anterior lumbar spine surgery is also purported to be related to the surgical approach [7][8][9].Burkus et al first published a prospective, randomized, nonblinded FDA-approved study concerning the use of rhBMP-2 in ALIF [8]. Six males (4.1 %; 6/146) reported RE following surgery, of which 4 underwent a transperitoneal approach (TPA) (13.3 %; 4 of all 30 males that underwent TPA) and 2 underwent a retroperitoneal approach (RPA) (1.8 %; 2 of 116 males that underwent RPA). Since the difference in RE between the TPA and RPA groups was statistically significant the authors concluded that a TPA was associated with a higher risk of RE. No comparison in RE between the investigational and control group was performed. The reported differences between the 2 approaches persisted at the 2-year follow-up period [10]. However, in 2010 Smoljanovic et al reviewed the data by Burkus et al [11] and reported that all 6 patients with RE had received rhBMP-2. Thus, the prevalence of RE in the investigational group (rhBMP-2) would have been 7.7 % (6/78 males), which was significantly greater than the control group (ICBG). The reason for ignoring the relationship between RE and rhBMP-2 was questioned, which sparked an intense debate over the potential association between the utilization of rhBMP-2 and RE.Correlation between rhBMP-2 utilization and RE Curr Rev Musculoskelet Med (2014) 7:200-207 DOI 10.1007/s12178-014-9219-x patients (7.2 %) in the rhBMP-2 group developed RE while only 1 of 174 patients (0.6 %; 1/69) reported RE in the control group. Significant differences in RE were also evident among patients that underwent a singl...

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Fusion rates in multilevel, instrumented anterior cervical fusion for degenerative disease with and without the use of bone morphogenetic protein

Cited by 29 publications

References 20 publications

Detrimental effects of discectomy on intervertebral disc biology can be decelerated by growth factor treatment during surgery: a large animal organ culture model

Detrimental effects of discectomy on intervertebral disc biology can be decelerated by growth factor treatment during surgery: a large animal organ culture model

The use of bone morphogenetic proteins (BMP) and pseudarthrosis, a literature review

Point-counter-point debate: the association between recombinant human bone morphogenetic protein utilization and complications in spine surgery

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