Abstract
Study design
Systematic Review of the Literature.
Objective
The purpose of this study was to perform a systematic review describing fusion rates for anterior cervical discectomy and fusion (ACDF) using autograft vs various interbody devices augmented with different osteobiologic materials.
Methods
A systematic review limited to the English language was performed in Medline, Embase and Cochrane library using Medical Subject Heading (MeSH) terms. Studies that evaluated fusion after ACDF using autografts and osteobiologics combined with PEEK, carbon fibre, or metal cages were searched for. Articles in full text that met the criteria were included in the review. The main outcomes evaluated were the time taken to merge, the definition of the fusion assessment, and the modality of the fusion assessment. The risk of bias of each article was assessed by the MINORS score or ROB 2.0 depending on the randomisation process.
Results
The total number of references reviewed was six hundred and eighty-two. After applying the inclusion criteria, 54 were selected for the retrieval of the full text. Eight studies were selected and included for final analysis in this study. Fusion rates were reported between 83.3% and 100% for autograft groups compared to 46.5% and 100% for various interbody device/osteobiological combinations. The overall quality of the evidence in all radiographic fusion studies was considered insufficient due to a serious risk of bias.
Conclusion
Mechanical interbody devices augmented with osteobiologics performed similarly to autografts in terms of reliability and efficacy. Their time to fusion and fusion rate were comparable to autografts at the end of the final follow-up.
Keywords: osteobiologics, anterior cervical discectomy and fusion, fusion, interbody devices, autograft
Introduction
Anterior cervical discectomy and fusion is 1 of the most successful surgical procedures for the treatment of degenerative cervical disc disease.1,2 The anterior approach to ACDF was first described by Cloward 3 and Robinson and Smith 4 in the 1950s. In both of these procedures, fusion was achieved with an autologous bone graft obtained from the iliac crest. Many studies demonstrated successful clinical and radiological outcomes following ACDF using an iliac crest graft with fusion rates up to 100%. Iliac crest bone grafts have been considered almost perfect because they are relatively easy to harvest, cost-free, and meet all the requirements of the ideal graft: osteogenesis, osteoinduction, and osteoconduction. Furthermore, there is no possibility of foreign tissue reaction or allergy at the recipient site. In addition, it is easier to radiologically assess the fusion rate because there are less artefacts on the imaging. Follow-up computerized tomography can be a powerful tool for assessment of fusion but only if visualisation of the endplate – graft interface is not obscured by artefacts produced by the foreign material. This concern is somewhat mitigated by the use of nonmetal interbody spacers. 5 However, the disadvantages and complications associated with the harvesting of bone from the iliac crest are not uncommon. Although there are disadvantages associated with autograft usage, especially donor site morbidity, it is still considered the gold standard due to reliably high fusion rates.6,7 Other potential complications associated with autografts include superficial infections, herniated abdominal contents, neurovascular injuries, seromas, minor haematomas, and iliac wing fractures.8,9
To overcome these complications associated with autografts, alternative materials have been developed and are currently being used. These include mechanical interbody spacers (made of PEEK, carbon fiber or metal) or allografts (corticocancellous or composite). The choice of structural graft material to be used typically depends on the surgeon’s preference and local availability. There is worldwide variation among surgeons when selecting the graft material for ACDF. According to a survey conducted in 2017, 64.1% of spine surgeons around the world preferred mechanical interbody fusion devices, while 20% preferred the autologous iliac crest as a structural component used in ACDF. 10 This survey among spine surgeons observes that there are 2 different schools of practice when it comes to performing ACDF.
To enhance fusion rates, interbody devices are combined with a variety of nonstructural graft materials such as osteobiologic materials or bone graft substitutes. 11 The most common bone graft substitutes that are used in conjunction with these interbody devices are autografts, allografts, calcium sulphate, tricalcium phosphate followed by synthetic materials like such as bone morphogenic protein (BMP), demineralised bone matrix (DBM), ceramics and other synthetic materials.12-16 Fusion rates vary with each osteobiologic, as every combination with the interbody device is unique in itself, leading to variations in radiological outcomes. Although ACDF commonly requires short hospital admission and is well tolerated by most patients, surgical delays, complications, and increased length of stay can be influenced by identifiable risk factors such as preoperative altered functional status, high comorbidity burden, and chronic steroid use. 17 Furthermore, high creatinine values, anemia, hyponatremia, and leukocytosis were found to be associated with any complications of 30 days and unplanned readmissions after the ACDF procedure, but no long-term impact on the fusion rate associated with these risk factors was observed. 18
Given the numerous osteobiologics and interbody devices available for use in ACDF, there is a pressing need for a critical review of fusion rates across different combinations of these treatments. To date, there is no real objective rationale for the preference for 1 type of osteobiologic over another. Complicating the issue even further, there is currently no evidence on the cost effect between osteobiologics and autologous bone graft. Not all osteobiologics are available at every spinal point of care and, therefore, in many circumstances, the choice made by the surgeon is mandated by availability and cost.
The purpose of this present review is to analyse whether osteobiologics increase fusion in ACDF surgery performed with mechanical interbody devices and to compare its fusion rates with structural autograft.
Materials and Methods
Search Strategy
The literature search and review were carried out in accordance with the PRISMA guidelines. A comprehensive literature search was performed using the Medline, Embase, and Cochrane library to identify studies that evaluated fusion rates with the use of mechanical interbody spacers with ostebiologics and compared with that with autografts. The search was limited to the English language and was searched until October 2020.
Inclusion and Exclusion Criteria
Studies are included when mechanical interbody devices (PEEK, carbon fiber, metal cages) augmented with osteobiologics were used for ACDF and were compared to structural autografts. The studies excluded were case reports, ACDF surgery using allografts, patients with spinal cord injury, fracture, or infection, studies in skeletally immature patients, case series with fewer than 10 patients per group, animal, in vitro, and biomechanical studies.
Data Extraction
The following data were extracted. 1) study design, 2) patient characteristics, 3) interventions, 4) inclusion and exclusion criteria, 5) fusion rates, 6) modality of fusion evaluation, 7) time to fusion, 8) definition of fusion, 9) follow-up of each treatment group, 10) various clinical outcomes, 11) type of osteobiologics used, 12) adverse events, 13) level of incidence, funding, and conflict of interest. Fusion rates were compared at different intervals of final follow-up, as follow-up times were inconsistently reported in the included studies. All data extracted were examined for possible pooling.
Study Selection
Two independent reviewers (MS,CC) screened the title and abstracts for eligibility, and the third independent reviewer (VA) resolved the disagreements between the 2. Rayyan QCRI software was used for screening and selection.
Study Quality and Overall Strength
The risk of bias was assessed for each article using the MINORS score for nonrandomised control trials (non-RCT) and ROB 2.0 for randomised control trials (RCT). In the case of RCT, the initial strength of the evidence was considered high and could be downgraded based on the randomisation process, deviations from the intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result.
Data Analysis
The extracted data were summarised in tables and classified according to the graft tissue used. For the available continuous variables, the mean differences and variance between baseline and follow-up values were calculated, while the percentages (risk proportions) were determined for dichotomous variables by adding risks in case the patient experiences an event. The collected data were not pooled due to the heterogeneity of the studies.
Results
Total number of citations reviewed was six hundred and eighty two (Figure 1). One hundred forty-nine duplicates were removed and after applying the inclusion criteria, 54 articles were retrieved for full texts. Of these 54 full texts, 46 were excluded due to the absence of a comparator group (n = 19, comparator other than autograft (n = 9), no osteobiologic was used (n = 7), no radiological assessment of fusion (n = 5) and the comparator group using local autograft (n = 6). Eight studies were selected and included for the final analysis in this study (Table 1).
Figure 1.
Flow chart showing the literature search and article selection process.
Table 1.
Study Characteristics and Risk of Bias Assessment for Studies of Fusion Rates Who Underwent Anterior Cervical Decompression and Fusion.
| First Author, Year | Study Design | Type of Interbody Device | Osteobiologic Used | Comparator | Sample Size (a = Interbody Device; b = Autograft) | Mean Age (years) | Levels (No. of Patients) | Indications | MINORS Score | Overall Bias |
|---|---|---|---|---|---|---|---|---|---|---|
| Christian B. Barlocher (2002) | Prospective, RCT | Titanium cage (BAK/C; Sulzer medica, spine tech, münsingen, Switzerland) | Human cancellous allograft (tutoplast; neutromedics AG, Cham, Switzerland) | Autograft | a = 36; b = 30 | a = 50.5 ± 13.4; b = 47.3 ± 11.5 | 1 (66) | Cervical pain (%) - 97.2:86.6 Radicular pain (%) - 94.4:93.3 Neurological deficits (%) - 77.7:73.3 |
NA | Some concerns |
| Ayush Sharma (2018) | Retrospective | PEEK | Tricalcium phosphate (ChronOS - synthetic b-tricalcium phosphate;DePuy Synthes) | Autograft | a = 60; b = 60 | a = 47.3 ± 9.3; b = 51.07 ± 9.39 | 1 (94) 2 (26) |
Myelopathy - 18:22; Myelopathy with radiculopathy - 42:38 | 16/24 | High |
| Petr Vanek (2012) | Prospective cohort | PEEK (Cornerstone; medtronic) with anterior plate (premier, medtronic) | Tricalcium phosphate (Chronos; Synthes, oberdorf, Switzerland) | Autograft b1) without plate b2) with plate (premier; medtronic, memphis, Tennessee) |
a = 29; b1 = 28; b2 = 18 | a = 51.3 ± 10.1; b1 = 52.1 ± 11.1; b2 = 57.8 ± 10.0 | 1 (14/20/9) 2 (15/8/9) |
NR | 21/24 | Low |
| Yu-Cheng Chou (2008) | Retrospective | a1) non-threaded titanium cage (Advanced spine technology, inc, oakland, CA, USA) a2) PEEK cage (Solis; Stryker, Allendale, NJ, US) |
Triosite, 40% β-tricalcium phosphate [β-TCP] and 60% hydroxyapatite (Zimmer, Berlin, Germany) |
Autograft | a1 = 27; a2 = 9; b = 19 | a1 = 55.2 (range 37-77 years) a2 = 54.2 (range 42-66 years) b = 47.6 (range 15-83 years) |
1 (14/3/10) 2 (10/6/4) 3 (3/0/5) |
Traumatic = 1:2:6 Cervical spondylosis = 10:0:10 OPLL = 1:0:0 Herniated disc = 15:7:3 |
16/24 | High |
| Robert J. Hacker (2000) | RCT | Titanium cage (BAK/C; Sulzer spine- Tech, Minneapolis,MN) | Hydroxyapatite coating | Autograft | a = 167 b = 142 |
Single:Double level a = 43 ± 8: 47 ± 7 b = 44 ± 9: 48 ± 8 |
1 (129/119) 2 (38/23) |
Single level: Herniation = 85%:86% Disc degeneration = 29%:27% Decreased disc height = 26%:25% Double level: Herniation = 74%:74% Disc degeneration = 53%:48% Decreased disc height = 34%:44% |
NA | Low |
| Jae sung Ahn (2011) | Retrospective | Interbody cage (type - not mentioned) | Tricalcium phosphate (Cervios ChronOS - synthetic b-tricalcium phosphate;DePuy Synthes) | Autograft | a = 25; b = 59 | a = 56 ± 6.31; b = 54 ± 9.72 | 1 (84) | NR | 14/24 | High |
| Arup K. Bhadra (2009) | Prospective cohort | PEEK cage with AO plate | Allograft mixed with blood and marrow aspirated from the iliac crest | Autograft | a = 15 b = 15 |
a = 37 (range 24-72) b = 35 (range 30-75) |
1 (30) | Cervical radiculopathy owing to single-level degenerative disease | 16/24 | High |
| Joon Huh (2011) | Retrospective | PEEK | Tricalcium phosphate (Cervios-chronOS Synthes, Mathys medical, Bettlach, Switzerland) | Autograft | a = 15; b = 13 | a = 49.9±10.3; b = 55.07±9.9 | 1 (18) | Traumatic- 1:1; Cervical spondylosis - 10:8; HIVD - 4:4 |
14/24 | High |
Abbrevations – NR, Not reported; TCP, tricalcium phosphate; PEEK, Polyetheretherketone.
Fusion Rates of Mechanical Interbody Devices Augmented With Tricalcium Phosphate vs Autograft
A total of 5 cohorts (n = 362) compared the tricalcium phosphate fusion rates used with PEEK or titanium and compared with autograft. Most of the participants included were male (M: F = 213: 149). Ayush Sharma et al (2018) in the retrospective cohort compared PEEK with TCP and autograft. Fusion rates were determined by flexion-extension radiographs at 3,6,12 months and CT at 1 year. At the end of 1 year, they did not observe significant differences in the fusion rate between the PEEK and autograft groups (93.3% vs 96.6%). In general, the fusion rates were better for single-level ACDF (95.74%) compared to two-level ACDF (76%). Petr Vanek et al (2012) in the prospective study observed 100% fusion rates determined by CT at the end of 2 years of follow-up comparing PEEK with TCP and autograft. They did not observe differences in terms of fusion with or without additional plate application. Joon Huh et al (2011) had similar observations in their retrospective study comparing PEEK with TCP and autograft at the end of 1 year with no significant differences (93.3% vs 100%) as assessed by CT scan. Chou et al (2008) in the retrospective study compared the fusion rates of titanium cage and PEEK with Triosite (40% TCP and 60% hydroxyapatite) with autograft. They concluded that the radiographic results were better in the PEEK and autograft groups where 100% fusion was achieved at the end of 12 months, but the titanium group with triosite achieved only 46.51% fusion determined by x-rays at the end of 12 months. In a study by Ahn et al (2011) comparing TCP and autograft, the type of interbody device was not mentioned. Fusion rates were evaluated by flexion-extension radiographs at the end of 1 year, and the autograft group performing better with 100% fusion compared to TCP with 88%.
Fusion Rates of Mechanical Interbody Device Augmented With Human Cancellous Allograft vs Autograft
Two cohorts with a sample size of 96 compared PEEK and titanium cages augmented with allograft to autograft. Barlocher et al (2002), in their prospective trial, observed that titanium-implanted patients and allograft-implanted patients had significantly better fusion rates at 6 months compared to the autograft group (86.1% vs 65.3%; P-value <.05). However, there were no major differences in terms of fusion at the end of 1 year (97.2% vs 93.3%). Bhadra et al (2009), compared PEEK cage augmented with allograft mixed with blood and marrow aspirated from the iliac crest and concluded that there were no differences in radiographic fusion rates between the groups at the end of 1 year (both at 100%).
Fusion Rates of Mechanical Interbody Device Augmented With Hydroxyapatite vs Autograft
A retrospective study on fusion rates was reviewed that compared autograft and mechanical interbody devices augmented with hydroxyapatite. Hacker et al (2000) in their randomised control trial comparing titanium cage with hydroxyapatite coating and autograft found that single-level fusions had better radiographic union compared to double-level fusions. The titanium with the hydroxyapatite coating group had a better union rate at 6 months (97.9% vs 80.5%) but there were no significant differences between them at the end of 2 years (100% vs 93%). They observed that titanium with hydroxyapatite coating in single-level ACDF achieved faster union than autograft. Fusion was assessed by lateral flexion-extension radiographs at 6,12 and 24 months (Table 2).
Table 2.
Fusion Rates of Studies Included in the Review.
| First Author, Year | Level of Evidence | Follow up (months) | Modality of Fusion Assessment | Who Assessed Fusion | Fusion Rates (Interbody Device vs Autograft) | Power Calculation |
|---|---|---|---|---|---|---|
| Christian B. Barlocher (2002) | 1 | 12 | CT scan at 1 year and flexion-extension X-ray films at 6 months and 12 months | NR | 97.2 vs 93.3 | NR |
| Ayush Sharma (2018) | 3 | 12 | CT scan at 1 year in PEEK group and flexion-extension radiographs at 3,6 and 12 months | Blinded authors | 93.3 vs 96 | NR |
| Petr Vanek (2012) | 2 | 24 | CT scan | Independent observer | 100 vs 100 | NR |
| Yu-Cheng Chou (2008) | 3 | 12 | Standard, flexion-extension and bilateral oblique X-rays at 6 and 12 months | NR | 46.5 (titanium cage with TCP) vs 100 (PEEK with TCP) vs 100 (autograft) | NR |
| Robert J. Hacker (2000) | 1 | 24 | Lateral flexion/Extension radiographs at 6,12 and 24 months | Independent orthoradiologist | 98.9 vs 89.7 (single level) 87.5 vs 83.3 (double level) |
NR |
| Jae sung Ahn (2011) | 3 | 12-30 | Lateral flexion/Extension radiographs at 1,3 and 6 months | Treating surgeons and authors | 88 vs 100 | NR |
| Arup K. Bhadra (2009) | 2 | 28-43 | Lateral flexion/Extension radiographs at 6 and 12 months | NR | 100 vs 100 | NR |
| Joon Huh (2011) | 3 | 12-24 | CT scan at 1 year | Two independent surgeons | 93.3 vs 100 | NR |
Abbrevations - PEEK, Polyetheretherketone; RCT, Randomised control trial; NA, Not applicable.
Assessment of Bias
Non-RCT articles were evaluated for risk of bias using the MINORS score, and RCTs were evaluated using the ROB 2.0 method. The overall risk of bias was high in 5 cohorts and low in a prospective cohort by Petr Vanek et al. The total score ranged between 14 and 21 for non-RCTs. When the RCT by Christian Barlocher was evaluated for risk of bias, there were some concerns, whereas the risk was low in the RCT by Robert J Hacker.
Discussion
The purpose of this review was to determine whether osteobiologics enhance fusion when combined with mechanical interbody devices and to compare their fusion rates with those of standard structural autografts. In general, fusion rates were reported to be high in both comparative arms, allowing us to comment that mechanical interbody devices filled with biomaterials such as tricalcium phosphate, human cancellous allograft, and hydroxyapatite performed similarly in terms of radiological results compared to structural autografts. A total of 8 studies were included in the final analysis, with fusion rates ranging from 46.5% to 100%. Four out of 8 were retrospective studies, 2 were prospective cohorts, and 2 were randomised control trials. Due to the heterogeneity of the data, a quantitative reporting meta-analysis could not be performed. The overall quality of the evidence for radiographic fusion in all studies was insufficient. Most non-RCT studies demonstrated a high risk of bias due to a wrong patient enrolment method, lack of follow-up, and improper statistical analysis.
The fusion rates at the end of 1 year were high for human cancellous allograft (97.2% - 100%), tricalcium phosphate (88% - 100%), hydroxyapatite (98.9%) and were comparable to structural autograft (89.7% - 100%). However, Yu-Cheng Chou et al reported that PEEK cages had higher fusion rates (100%) compared to titanium cages (46.5%) when combined with TCP. The lower fusion rates could be attributed to the sample size of the titanium group, which had a large number of multilevel ACDF procedures, which has previously been observed to have lower fusion rates compared to single-level ACDF procedures. This shows that future randomised control trials are needed that directly compare PEEK and titanium combined with various osteobiologics are needed.
Since the introduction of surgical fusion in 1911, many methods have been used to assess it. From static radiographs to dynamic magnetic resonance imaging. Dynamic radiographs improve the accuracy of fusion assessment when compared to static radiographs but still have few limitations such as two-dimensional assessment, disagreement on allowable motion, etc. With the advent of fine-cut imaging and 3D reconstruction, CT is widely used for fusion assessment. However, there are significant concerns about the high radiation exposure due to CT. 27 The gold standard for the assessment of fusion is described by Rhee et al as <1-mm of interspinous motion on flexion-extension radiographs, with computed tomography (CT) follow-up if fusion status was indeterminate regardless of graft or instrumentation type. 28 In this review, CT alone is observed to be used to assess fusion in 2 of 8 studies, while 6/8 preferred dynamic radiographs as a modality to assess fusion rates at long-term follow-up and was defined by the presence of bony trabeculation throughout the graft.
The structural autograft has been widely used for the ACDF procedure for many decades and is considered the ‘gold standard’ to achieve consistent fusion. 29 However, a literature search showed that the number of articles on the use of structural tricortical iliac crest graft for ACDF has decreased in the last decade. There is a paradigm change, where the number of publications on mechanical interbody devices and other osteobiologics in ACDF has increased in the recent past. This change can be attributed in part to the preferences of surgeons and patients. Osteobiologics are the key to successful spinal fusion procedures, including ACDF, and the variability in their use reflects the uncertainty with respect to their effectiveness and potential risks. 30 Patient satisfaction is a factor that is almost neglected when it comes to ACDF graft choices. One such study examined patient satisfaction after ACDF surgery and found that 95.4% of patients who underwent revision ACDF surgery preferred synthetic bone graft substitute over structural autograft. Ninety-one percent of the patients rated the incision at the graft site as more painful than at the index anterior cervical surgical site. 31 The authors were also against the traditional recommendation that autograft is the ‘gold standard’ for ACDF. The statement that autograft should not be considered as the “gold standard” but merely 1 of several options for ACDF in this modern era of graft substitutes merits further discussion among peers.
Historically, iliac crest is considered to be the best source of autologous bone graft. In an effort to avoid morbidity, surgeons have explored various other sites of autologous graft harvest which included ribs and cervical lamina.32,33 However in any of these methods, the need for second surgical incision could not be avoided. Hence, local autograft obtained after removing osteophytes was used to fill the interbody spacer in order to avoid complications of second surgical site. But the main concern with this method is the volume of local graft obtained. In a study by O. Neill et al, only 20% of patients had enough volume of local graft which could be filled completely inside the interbody spacer. 34 In majority of the patients, volume of local graft was not enough to fill the interbody spacer and had to be supplemented by demineralised bone matrix.
Although ACDF is generally an effective procedure, it does carry a significant risk of morbidity. A recent review showed 13.2% to 19.3% overall morbidity rate, including but not limited to complications such as dysphagia, postoperative hematoma with and without epidural hematoma, exacerbation of myelopathy, symptomatic recurrent laryngeal nerve palsy, cerebrospinal fluid leak, wound infection, increased radiculopathy, Horner’s syndrome, respiratory insufficiency, esophageal perforation, and instrument failure. 35 As many of these complications could be caused by several factors, each individually lends itself to the dilemma between correlation and causation. There is a possibility that the biologics used in isolation and/or contingent on a patient’s specific comorbidities could have more influence on such morbidities than we currently suspect. Proving or disproving this would be very difficult given the multitude of factors that could potentially influence said morbidities and the inherent difficulty of producing a truly controlled experiment in the setting of surgery.
This review has its own set of limitations. The combination of synthetic cage filled with local bone chips from the osteophytes, a commonly practiced economic option, was not included in this search. Additionally, the effect of adding a plate to the fusion could not be separated. Yet, the most important limitation in this study was the heterogeneity of the included studies where meta-analysis could not be performed. Therefore, quantitative conclusions could not be drawn when all of these groups were compared. We believe that radiological results should not be the only comparative parameter when the ‘gold standard’ structural autograft is paired with other alternative biomaterials. Clinical outcomes play a major role in evaluating their long-term efficacy, a parameter that was not included in this systematic review.
Conclusion
In summary, we observed that there is very high incidence of bias in almost all studies. Although this systematic review had its own limitations, individual analysis allowed us to show with certainty that mechanical interbody devices augmented with osteobiologics performed similarly to autografts. The time to fusion may be longer for certain osteobiologics, but the fusion rate was comparable to autografts at the end of the final follow-up. Future studies should focus on minimising bias by performing a blinded assessment of fusion status, having adequate follow-up of 2 years, patient randomisation, and following a standardised protocol for evaluating radiological fusion. Surgeons performing the ACDF procedure may also consider patient satisfaction/preference when selecting grafts.
Supplemental Material
Supplemental Material for Do Osteobiologics Augment Fusion in Anterior Cervical Discectomy and Fusion Surgery Performed With Mechanical Interbody Devices (PEEK, Carbon Fiber, Metal Cages) and is the Fusion Rate Comparable to that With Autograft? – A Systematic Review by Viswanadha Arun-Kumar, Stipe Corluka, Zorica Buser, Yabin Wu, Mohammad El-Sharkawi, Charles André Carazzo, Nikhil Ponugoti, Jeffrey Wang and Hans Jörg Meisel in Global Spine Journal
Supplemental Material for Do Osteobiologics Augment Fusion in Anterior Cervical Discectomy and Fusion Surgery Performed With Mechanical Interbody Devices (PEEK, Carbon Fiber, Metal Cages) and is the Fusion Rate Comparable to that With Autograft? – A Systematic Review by Viswanadha Arun-Kumar, Stipe Corluka, Zorica Buser, Yabin Wu, Mohammad El-Sharkawi, Charles André Carazzo, Nikhil Ponugoti, Jeffrey Wang and Hans Jörg Meisel in Global Spine Journal
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This supplement was organized and financially supported by AO Spine through the AO Spine Knowledge Forum Degenerative, a focused group of international spine experts.
Supplemental Material: Supplemental material for this article is available online.
ORCID iDs
Viswanadha Arun-Kumar https://orcid.org/0000-0002-6322-4357
Stipe Corluka https://orcid.org/0000-0002-5732-1150
Zorica Buser https://orcid.org/0000-0002-5680-0643
Yabin Wu https://orcid.org/0000-0002-1836-7674
Mohammad El-Sharkawi https://orcid.org/0000-0001-6177-7145
Hans Jörg Meisel https://orcid.org/0000-0003-3838-1489
References
- 1.Cauthen JC, Kinard RE, Vogler JB. Outcome analysis of noninstrumented anterior cervical discectomy and interbody fusion in 348 patients. Spine. 1998;23:188–192. [DOI] [PubMed] [Google Scholar]
- 2.Heidecke V, Rainov NG, Marx T, et al. Outcome in Cloward anterior fusion for degenerative cervical spinal disease. Acta Neurochir (Wien). 2000;142:283–291. [DOI] [PubMed] [Google Scholar]
- 3.Song KJ, Lee KB. A preliminary study of the use of cage and plating for single-segment fusion in degenerative cervical spine dis- ease. J Clin Neurosci. 2006;13:181–187. [DOI] [PubMed] [Google Scholar]
- 4.Liao JC, Niu CC, Chen WJ, Chen LH. Polyetheretherketone (PEEK) cage filled with cancellous allograft in anterior cervical discectomy and fusion. Int Orthop. 2008;32:643–648. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Epstein N. Iliac crest autograft versus alternative constructs for anterior cervical spine surgery: pros, cons, and costs. Surg Neurol Int. 2012;3(4):143. doi: 10.4103/2152-7806.98575. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Goulet JA, Senunas LE, DeSilva GL, et al. Autogenous iliac crest bone graft: complications and functional assessment. Clin Orthop. 1997;339:76–81. [DOI] [PubMed] [Google Scholar]
- 7.Janssen E, Nguyen C, Beckham R. Biological cages. Eur Spine J. 2000;9:S102–S109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Samartzis D, Shen FH, Goldberg EJ, An HS. Is autograft the gold standard in achieving radiographic fusion in one-level anterior cervical discectomy and fusion with rigid anterior plate fixation? Spine (Phila Pa 1976). 2005;30:1756–1761. [DOI] [PubMed] [Google Scholar]
- 9.Samartzis D, Shen FH, Matthews DK, Yoon ST, Goldberg EJ, An HS.Comparison of allograft to autograft in multilevel anterior cervical discectomy and fusion with rigid plate fixation. Spine J. 2003;3:451–459. [DOI] [PubMed] [Google Scholar]
- 10.Yoon ST, Konopka JA, Wang JC, et al. ACDF graft selection by surgeons: survey of AOspine members. Global Spine J. 2017;7(5):410-416. doi: 10.1177/2192568217699200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Chau AMT, Xu LL, Wong JHY, Mobbs RJ. Current status of bone graft options for anterior interbody fusion of the cervical and lumbar spine. Neurosurg Rev. 2014;37(1):23-37. doi: 10.1007/s10143-013-0483-9. [DOI] [PubMed] [Google Scholar]
- 12.Dai LY, Jiang LS. Anterior cervical fusion with interbody cage containing beta-tricalcium phosphate augmented with plate fixation: a prospective randomized study with 2-year follow-up. Eur Spine J. 2008;17:698–705. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Cho DY, Lee WY, Sheu PC, Chen CC. Cage containing a biphasic calcium phosphate ceramic (Triosite) for the treatment of cervical spondylosis. Surg Neurol. 2005;63:497–503, discussion 503–494. [DOI] [PubMed] [Google Scholar]
- 14.Topuz K, Colak A, Kaya S, Simsek H, Kutlay M, Demircan MN, et al. Two-level contiguous cervical disc disease treated with peek cages packed with demineralized bone matrix: results of 3- year follow-up. Eur Spine J. 2009;18:238–243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Scholz M, Schleicher P, Eindorf T, Friedersdorff F, Gelinsky M, Konig U, et al. Cages augmented with mineralized collagen and platelet-rich plasma as an osteoconductive/inductive combination for interbody fusion. Spine (Phila Pa 1976). 2010;35:740–746. [DOI] [PubMed] [Google Scholar]
- 16.Dickerman RD, Reynolds AS, Morgan B. Polyetheretherketone (PEEK) cage filled with bone morphogenic protein and demineralised bone matrix in anterior cervical discectomy and fusion. Int Orthop. 2008;32:717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Renfree SP, Makovicka JL, Chung AS. Risk factors for delay in surgery for patients undergoing elective anterior cervical discectomy and fusion. J Spine Surg. 2019;5(4):475-482. doi: 10.21037/jss.2019.10.09. PMID: 32042998; PMCID: PMC6989940. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Suresh KV, Wang K, Sethi I, Zhang B, Margalit A, Puvanesarajah V, et al. Spine surgery and preoperative hemoglobin, hematocrit, and hemoglobin A1c: A Systematic review. Global Spine J. 2022;12(1):155-165. doi: 10.1177/2192568220979821. Epub 2021 Jan 21. PMID: 33472418; PMCID: PMC8965292. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Bärlocher CB, Barth A, Krauss JK, Binggeli R, Seiler RW. Comparative evaluation of microdiscectomy only, autograft fusion, polymethylmethacrylate interposition, and threaded titanium cage fusion for treatment of single-level cervical disc disease: a prospective randomized study in 125 patients. Neurosurg Focus. 2002;12(1):E4. doi: 10.3171/foc.2002.12.1.5. PMID: 16212331. [DOI] [PubMed] [Google Scholar]
- 20.Sharma A, Kishore H, Singh V, et al. Comparative study of functional outcome of anterior cervical decompression and interbody fusion with tricortical stand-alone iliac crest autograft versus stand-alone polyetheretherketone cage in cervical spondylotic myelopathy. Global Spine J. 2018;8(8):860-865. doi: 10.1177/2192568218780345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Vanek P, Bradac O, DeLacy P, Saur K, Belsan T, Benes V. Comparison of 3 fusion techniques in the treatment of the degenerative cervical spine disease. Is stand-alone autograft really the “gold standard?”: prospective study with 2-year follow-up. Spine (Phila Pa 1976). 2012;37(19):1645-1651. doi: 10.1097/BRS.0b013e31825413fe. PMID: 22433506. [DOI] [PubMed] [Google Scholar]
- 22.Chou YC, Chen DC, Hsieh WA, Chen WF, Yen PS, Harnod T, et al. Efficacy of anterior cervical fusion: comparison of titanium cages, polyetheretherketone (PEEK) cages and autogenous bone grafts. J Clin Neurosci. 2008;15(11):1240-1245. doi: 10.1016/j.jocn.2007.05.016. Epub 2008 Sep 17. PMID: 18801658. [DOI] [PubMed] [Google Scholar]
- 23.Hacker RJ, Cauthen JC, Gilbert TJ, Griffith SL. A prospective randomized multicenter clinical evaluation of an anterior cervical fusion cage. Spine (Phila Pa 1976). 2000;25(20):2646-2654; discussion 2655. doi: 10.1097/00007632-200010150-00017. PMID: 11034651. [DOI] [PubMed] [Google Scholar]
- 24.Ahn JS, Lee JK, Kim JH. Comparative study of clinical outcomes of anterior cervical discectomy and fusion using autobone graft or cage with bone substitute. Asian Spine J. 2011;5(3):169-175. doi: 10.4184/asj.2011.5.3.169. Epub 2011 Aug 12. PMID: 21892389; PMCID: PMC3159065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Bhadra AK, Raman AS, Casey AT, Crawford RJ. Single-level cervical radiculopathy: clinical outcome and cost-effectiveness of four techniques of anterior cervical discectomy and fusion and disc arthroplasty. Eur Spine J. 2009;18(2):232-237. doi: 10.1007/s00586-008-0866-8. Epub 2009 Jan 9. PMID: 19132413; PMCID: PMC2899334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Huh J, Oh J, Chough C, Cho CB, Joo W, Park H. Polyetheretherketone cage filled with beta-tricalcium phosphate versus autogenous tricortical iliac bone graft in anterior cervical discectomy and fusion. Korean Journal of Spine. 2011;8:165. 10.14245/kjs.2011.8.3.165. [DOI] [Google Scholar]
- 27.Jacobs W, Willems PC, van Limbeek J, et al. Single or double-level anterior interbody fusion techniques for cervical degenerative disc disease. Cochrane Database Syst Rev 2011;19(1):CD004958. doi: 10.1002/14651858.CD004958.pub2. PMID: 21249667. [DOI] [PubMed] [Google Scholar]
- 28.Selby MD, Clark SR, Hall DJ, Freeman BJ. Radiologic assessment of spinal fusion. J Am Acad Orthop Surg. 2012;20(11):694-703. doi: 10.5435/JAAOS-20-11-694. PMID: 23118135. [DOI] [PubMed] [Google Scholar]
- 29.Rhee JM, Chapman JR, Norvell DC, Smith J, Sherry NA, Riew KD. Radiological determination of postoperative cervical fusion: a systematic review. Spine (Phila Pa 1976). 2015;40(13):974-991. doi: 10.1097/BRS.0000000000000940. PMID: 25893344. [DOI] [PubMed] [Google Scholar]
- 30.Hsu WK, Hashimoto RE, Berven SH, Nassr A. Biological substitutes/extenders for spinal arthrodesis: which agents are cost-effective? Spine (Phila Pa 1976). 2014;39(22 suppl 1):S86-S98. doi: 10.1097/BRS.0000000000000548. PMID: 25299264. [DOI] [PubMed] [Google Scholar]
- 31.Maharaj MM, Phan K, Mobbs RJ. Anterior cervical discectomy and fusion (ACDF) autograft versus graft substitutes: what do patients prefer?-A clinical study. J Spine Surg. 2016;2(2):105-110. doi: 10.21037/jss.2016.05.01. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Sawin PD, Traynelis VC, Menezes AH. Acomparativeanalysisof fusion rates and donor-site morbidity for autogeneic rib and iliac crest bone grafts in posterior cervical fusions. J Neurosurg. 1998;88:255-265. [DOI] [PubMed] [Google Scholar]
- 33.Liu J, Xiong X, Long X, Shu Y, Huang S, Yang D, et al. A new source of structural autograft for ACDF surgery: cervical laminae. Int J Clin Exp Med. 2015;8:9100-9106. [PMC free article] [PubMed] [Google Scholar]
- 34.O'Neill CN, Walterscheid ZJ, Carmouche JJ. A novel local cancellous autograft source for anterior cervical discectomy with fusion. Global Spine J. 2022;12(2):190-197. doi: 10.1177/2192568220947741. Epub 2020 Sep 29. PMID: 32990036; PMCID: PMC8907638. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Epstein NE. A review of complication rates for anterior cervical diskectomy and fusion (ACDF). Surg Neurol Int. 2019;10:100. doi: 10.25259/SNI-191-2019. PMID: 31528438; PMCID: PMC6744804. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplemental Material for Do Osteobiologics Augment Fusion in Anterior Cervical Discectomy and Fusion Surgery Performed With Mechanical Interbody Devices (PEEK, Carbon Fiber, Metal Cages) and is the Fusion Rate Comparable to that With Autograft? – A Systematic Review by Viswanadha Arun-Kumar, Stipe Corluka, Zorica Buser, Yabin Wu, Mohammad El-Sharkawi, Charles André Carazzo, Nikhil Ponugoti, Jeffrey Wang and Hans Jörg Meisel in Global Spine Journal
Supplemental Material for Do Osteobiologics Augment Fusion in Anterior Cervical Discectomy and Fusion Surgery Performed With Mechanical Interbody Devices (PEEK, Carbon Fiber, Metal Cages) and is the Fusion Rate Comparable to that With Autograft? – A Systematic Review by Viswanadha Arun-Kumar, Stipe Corluka, Zorica Buser, Yabin Wu, Mohammad El-Sharkawi, Charles André Carazzo, Nikhil Ponugoti, Jeffrey Wang and Hans Jörg Meisel in Global Spine Journal

