Symptomatic myelopathy and/or radiculopathy are common indications for surgical intervention in the cervical spine. Anterior cervical decompression and fusion (ACDF) is considered to be the “gold standard” to treat these conditions with adjacent-level degeneration-free rates of 86% at 5 years. 1 Although successful, the incidence of symptomatic adjacent segment disease (ASD) has been widely accepted as 2.9% per year and 25.6% for 10 years after cervical fusion. 1 ASD is the occurrence of symptoms of radiculopathy or myelopathy referable to segments adjacent to a successful spinal arthrodesis severe enough to warrant treatment. 1 The cause for this, however, remains widely debated. Some authors think the incidence represents a natural progression of cervical disc disease, whereas others suggest altered biomechanics at levels adjacent to a fusion accelerate this process. 2,3 Concern for adjacent levels has been the rationale for development of motion-preserving interventions as a substitute for fusion, such as total disc arthroplasty (TDA). Previous studies have demonstrated the biomechanical and clinical outcome advantages of TDA compared with ACDF. 4,5 However, we believe that the majority of the improvement in clinical outcome after cervical surgery occurs as a result of a successful decompression, particularly in the 1- to 2-year follow-up period after surgery. The purpose of TDA and motion preservation is ostensibly to reduce stresses and breakdown at adjacent spinal segments. Conclusion. From a meta-analysis of prospective studies, there is no difference in the rate of ASD for ACDF versus TDA.
We also report an overall lower rate of follow-up for patients with ACDF than for those with TDR. Future prospective studies should continue to focus on excellent patient follow-up and accurate assessment of patient symptoms that are attributable to an adjacent level as this has been an under-reported fi nding in prospective studies. Key words: cervical disc replacement , total disc replacement , total disc arthroplasty , TDR , CDR , ACDF , cervical fusion , adjacent segment disease , ASD , motion sparing techniques , cervical fusion , anterior cervical discectomy and fusion . Level of Evidence: 1 Spine 2013;38:2253–2257 Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. SPINE130649.indd 2253 PINE130649.indd 2253 11/18/13 8:52 PM 1/18/13 8:52 PM CERVICAL SPINE Rate of ASD in TDR vs. ACDF • Verma et al 2254 www.spinejournal.com December 2013 However, few previous studies have investigated the effect of TDA on incidence of ASD. The purpose of this meta-analysis review is to review the current literature comparing the reported incidence of ASD requiring surgical intervention between ACDF and TDA. 6
The null hypothesis is that there is no statistical difference between these 2 groups. This study also aims to highlight the importance of reporting ASD as an outcome in future prospective studies. MATERIALS AND METHODS Inclusion and Exclusion Criteria For our analysis, all prospective, randomized, comparative studies (level I, level II, or level III) comparing a population of patients who underwent ACDF versus a population who underwent TDA for single and 2-level degenerative cervical disease (myelopathy or radiculopathy) were obtained. Other primary outcomes ( i. e. clinical outcome scores, radiographical fi ndings, device safety, and/or effi cacy) other than symptomatic ASD requiring reoperation were not evaluated in this review. Measures were taken to avoid repetition of data, such as excluding single-site data part of a multicenter trial and only including articles with the longest follow-up from a single trial. The inclusion and exclusion criteria are listed in Table 1 . The methodology for the systematic review has been previously published 7 ( Table 1 ). MEDLINE (PubMed) The evidence based method, PICO 8 (P: population of interest, I: intervention, C: comparison intervention, O: outcome of Interest) was used to create the following search in PubMed: ((“Cervical Vertebrae”[Mesh] AND “Radiculopathy”[Mesh]) OR “Spinal Cord Diseases”[Mesh]) AND (“Arthrodesis”[Mesh] OR “Arthroplasty, Replacement”[Mesh]). Also, a simple MEDLINE text search for “cervical disc arthroplasty,” “cervical disc replacement,” “total disc replacement,” and “total disc arthroplasty” was also used to produce additional results.
The details of the selection process can be found in Figure 1A and our previously published systematic review. 7 The Cochrane Library In a similar fashion, the Cochrane Library was searched for “cervical disc arthroplasty,” “cervical disc replacement,” “total disc replacement,” and “total disc arthroplasty” with all studies published before 2001 being excluded. No additional unique studies were captured by this method ( Figure 1B ). Eight studies were ultimately selected for this review and 6 were used to estimate an overall reported rate of ASD ( Figure 2 ). Statistical Analysis A meta-analysis of ASD incidence as reported by randomized controlled studies was performed on the basis of the number of patients available for follow-up 2 to 5 years from surgery in the ACDF and TDA group. The analysis was repeated again taking into consideration all patients initially enrolled into the study regardless of follow-up rate of each group. Both these meta-analyses were performed using the Rev Man software from the Cochrane Collaboration (version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.) Published data are available for the occurrence of ASD as function of follow-up year. 1 These data, with the number of patients available in each study, were used to predict the number of patients in each group with symptomatic ASD.
RESULTS Of the 8 studies specifi cally addressing adjacent surgery for ASD after ACDF versus TDA, only 6 (4 IDE trials and 2 nonIDE trials) were randomized controlled trials with at least 2 years of follow-up. Each of these randomized controlled trial was broken up by the number of patients in the ACDF versus TDA group both at the start of the study and at the fi nal follow-up. Pooling these studies, the overall sample size at baseline was 1586 (ACDF = 777, TDA = 809) and at the TABLE 1. Inclusion and Exclusion Criteria Inclusion Exclusion Prospective study design Animal studies Greater than or equal to 2 years of follow-up Retrospective studies, meta-analyses, biomechanical or kinematic studies, review articles, or in vitrostudies Comparative study of cervical arthroplasty and cervical arthrodesis Single site results as a part of multicenter trial (to avoid repetition of data) Examines adjacent-level degeneration or secondary surgery for adjacent-level degeneration Noncomparative studies Nonprospective studies Less than 2 years of follow-up Does not address adjacent-level degeneration or secondary surgery for adjacent-level degeneration Published in languages other than English Studies that examine lumbar disc replacement Copyright © 2013 Lippincott Williams & Wilkins.
Unauthorized reproduction of this article is prohibited. SPINE130649.indd 2254 PINE130649.indd 2254 11/18/13 8:52 PM 1/18/13 8:52 PM CERVICAL SPINE Rate of ASD in TDR vs. ACDF • Verma et al Spine www.spinejournal.com 2255 Figure 2. Reported ASD data from prospective, randomized controlled trials included in this meta-analysis. ASD indicates adjacent segment diseases; ACDF, anterior cervical decompression and fusion; TDA, total disc arthroplasty. fi nal follow-up was 1110 giving an overall follow-up of 70% at 2 to 5 years (3 ± 1.3, mean ±SE) (column A, Figure 2 ). Overall, there was a signifi cantly higher rate of follow-up for patients undergoing TDR (72.6%, n = 587) than for those undergoing ACDF (67.3%, n = 523) ( P = 0.01, column B, Figure 2 ). Overall, at 2 to 5 years of follow-up, a total of 36 patients from all studies required surgery at an adjacent level after an ACDF (6.9%) compared with 30 patients after TDA (5.1%) (column C, Figure 2 ).
The first meta-analysis included only patients who were available for follow-up, whereas the second analysis included all patients in the original cohort. In the initial analysis, there was no signifi cant difference in rate of ASD related surgery between the ACDF and TDR groups ( Figure 3 , P = 0.19). However, when all patients in the original cohort were included, there was a lower rate of ASD in the TDR group than the ACDF group ( Figure 4 , P = 0.01, odds ratio 0.74). Using historical data for the rate of ASD for a given follow-up year, we predicted 48 patients in the ACDF group and 55 patients in the ADF group would have new symptoms of myelopathy or radiculopathy attributable to an adjacent level at the fi nal follow-up 1 (column C, Figure 2 ). DISCUSSION In this meta-analysis, we selected 6 randomized controlled studies comparing ACDF versus TDR that specifi cally reported on the rate of reoperation for ASD at 2 to 5 years of follow-up.
On the basis of an initial sample size of 1586 patients with 70% follow-up, there was no detectable difference in the reoperation rate between these groups. The mean reoperation rate for all patients with TDR and ACDF was 1.8% ± 1.6% per year for both groups, which correlates with historical data reporting a 2.9% yearly incidence of symptomatic ASD after ACDF. 1 Notably, patients who underwent an ACDF had a tendency to have poorer follow-up rates than those who had TDR (67.3 vs. 72.6%). The reasons for this bias are not clear and are likely multifactorial as patients, although randomized, were not blinded to the treatment groups for a majority of the trials. Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Figure 1. Schematic diagram depicting search results in Medline (PubMed) ( A) and Cochrane Library ( B). SPINE130649.indd 2255 PINE130649.indd 2255 11/18/13 8:52 PM 1/18/13 8:52 PM CERVICAL SPINE Rate of ASD in TDR vs. ACDF • Verma et al 2256 www.spinejournal.com December 2013 Figure 3. Forest plot comparing ASD in TDR versus ACDF in patients available for follow-up.
ASD indicates adjacent segment diseases; ACDF, anterior cervical decompression and fusion; TDA, total disc arthroplasty; CI, confi dence interval. Figure 4. Forest plot comparing ASD in TDR versus ACDF in all patients in cohorts. ASD indicates adjacent segment diseases; ACDF, anterior cervical decompression and fusion; TDA, total disc arthroplasty; CI, confi dence interval. Biomechanical models have shown TDA to better mimic native cervical range of motion at adjacent levels than the models of ACDF. 4,5,9,10 Coric et al11 have shown improved radiological outcomes at adjacent levels with TDA versus ACDF. 12 Overall, patient satisfaction and pain relief may also be improved with TDA over ACDF. 13–15 Burkus et al13 reported improved clinical outcomes in the Neck Disability Index as well as neurological status with TDA versus ACDF. The need for supplemental fi xation either with posterior fi xation or external bone stimulators was also signifi cantly higher for ACDF versus TDR (3.4% vs. 0.0%). At the 4-year follow-up, Sasso et al15 reported statistically higher overall success rates for arthroplasty (85.1%) versus fusion group (72.5%). However, none of these studies specifi cally reported on the onset of new symptomatic disease at an adjacent level to the fusion.
Two studies have aimed to report the relative rate of symptomatic ASD from clinical trials. Jawahar et al16 collected data at the 3-year follow-up from 93 patients enrolled into 3 separate clinical trials. That study found a 16% and 18% incidence of ASD for TDR versus ACDF. 16 Most recently, Nunley et al17 reported a 3.1% yearly incidence of ASD after TDR, which mirrored data from the Hilibrand study. 1 Data were gathered from 167 patients at the 4-year follow-up with 96% follow-up. A few meta-analyses have been published recently comparing ACDF versus TDR. Jiang et al18 reported a lower rate of ASD for TDR versus ACDF. However, this analysis included radiographical assessments of ASD that do not correlate with reoperation rate. In addition, the analysis was heavily infl uenced by the 2-year follow-up data from Mummaneni et al. 19 The 5-year data from this same author, however, showed equivalent ASD rates for ACDF versus TDR. 12 Also, a recently published meta-analysis by Gao et al20 found that arthroplasty was associated with fewer secondary surgical procedures.
However the indications for these secondary procedures was unclear. From the 2-year follow-up data, Phillips et al21 reported an equivalent rate of secondary procedures for ASD versus TDR (5.4% vs. 5.2%). The study does not specifi cally report, however, the number of reoperations for ASD alone. In a recent Cochrane Review, Boselie et al22 reported an equivalent rate of reoperation for ASD between ACDF versus TDR. Although our fi ndings are in agreement with this study, the Cochrane Review included only 3 studies in the analysis of ASD. Similarly, Yang et al23 reported no difference in the incidence of ASD (radiographical features and reoperation rate) comparing ACDF versus TDR in a meta-analysis. Although the conclusion of the authors was similar to that of this study, there were methodological differences worth nothing. The analysis by Yang et al23 included data from Jawahar et al, 16 which was a radiographical evaluation of adjacent segment degeneration rather than reoperation rate. Radiographical signs of ASD are known to not directly correlate with symptomology. In addition, Yang et al23 included only 140 patients in the meta-analysis, whereas this study included more than 1500 patients at baseline and 1100 patients at the fi nal follow-up.
Lastly, the meta-analysis by Yang et al23 was current up to 2011 (same as this study), but their selection of studies was notably different than that of this study. Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. SPINE130649.indd 2256 PINE130649.indd 2256 11/18/13 8:52 PM 1/18/13 8:52 PM CERVICAL SPINE Rate of ASD in TDR vs. ACDF • Verma et al Spine www.spinejournal.com 2257 ➢ Key Points A meta-analysis of prospective randomized studies comparing TDR and ACDF shows no signifi - cant diff erence with respect to revision surgery for ASD. No prior prospective study has had ASD as a primary outcome. In addition, patient symptoms related to a degenerative adjacent level are not well reported.
Patients with ACDF have lower follow-up rates than patients with TDR. Future studies should focus on excellent patient follow-up. CONCLUSION From an analysis of 1110 patients, our meta-analysis supports the hypothesis that ACDF and TDR result in equivalent rates of reoperation for ASD. Meta-analyses have inherent limitations and this study may be prone to type 2 error. It can be argued, however, that any statistical difference in ASD detected in a larger cohort of ACDF versus patients with TDR is unlikely to be of practical signifi cance. It is worth noting as well, that ASD had not been a main outcome in any randomized clinical trial. 24 There is also a bias favoring patients with TDR to follow-up more reliability compared with patients with ACDF. Although we report the reoperation rates at adjacent levels, the onset of symptomatic disease, levels at greatest risk, and progression of patient symptoms have not been well reported in clinical trials. The anticipated benefi t of motion preservation technology is to prevent the onset of symptomatic disease at an adjacent level. To this end, future prospective studies should continue to focus on excellent patient follow-up and accurate assessment of patient symptoms that are attributable to an adjacent level.
9. Cunningham BW , Hu N , Zorn CM , et al. Biomechanical comparison of single- and two-level cervical arthroplasty versus arthrodesis: effect on adjacent-level spinal kinematics . Spine J 2010 ; 10 : 341 – 49 .
10. Auerbach JD , Anakwenze OA , Milby AH , et al. Segmental contribution toward total cervical range of motion: a comparison of cervical disc arthroplasty and fusion . Spine (Phila Pa 1976) 2011 ; 36 : E1593 – 9 .
11. Coric D , Nunley PD , Guyer RD , et al. Prospective, randomized, multicenter study of cervical arthroplasty: 269 patients from the Kinefl ex|C artifi cial disc investigational device exemption study with a minimum 2-year follow-up: clinical article . J Neurosurg Spine 2011 ; 15 : 348 – 8 .
12. Robertson JT , Papadopoulos SM , Traynelis VC . Assessment of adjacent-segment disease in patients treated with cervical fusion or arthroplasty: a prospective 2-year study . J Neurosurg Spine 2005 ; 3 : 417 – 23 .
13. Burkus JK , Haid RW , Traynelis VC , et al. Long-term clinical and radiographic outcomes of cervical disc replacement with the Prestige disc: results from a prospective randomized controlled clinical trial . J Neurosurg Spine 2010 ; 13 : 308 – 18 .
14. Murrey D , Janssen M , Delamarter R , et al. Results of the prospective, randomized, controlled multicenter Food and Drug Administration investigational device exemption study of the ProDisc-C total disc replacement versus anterior discectomy and fusion for the treatment of 1-level symptomatic cervical disc disease . Spine J 2009 ; 9 : 275 – 86 .
15. Sasso RC , Anderson PA , Riew KD , et al. Results of cervical arthroplasty compared with anterior discectomy and fusion: four-year clinical outcomes in a prospective, randomized controlled trial . J Bone Joint Surg Am 2011 ; 93 : 1684 – 92 .
16. Jawahar A , Cavanaugh DA , Kerr EJ 3rd , et al. Total disc arthroplasty does not affect the incidence of adjacent segment degeneration in cervical spine: results of 93 patients in three prospective randomized clinical trials . Spine J 2010 ; 10 : 1043 – 8 .
17. Nunley PD, Jawahar A, Kerr EJ, 3rd, et al. Factors affecting the incidence of symptomatic adjacent-level disease in cervical spine after total disc arthroplasty: 2- to 4-year follow-up of 3 prospective randomized trials. Spine (Phila Pa 1976). 2012;37:445–451.
18. Jiang H, Zhu Z, Qiu Y, et al. Cervical disc arthroplasty versus fusion for single-level symptomatic cervical disc disease: a metaanalysis of randomized controlled trials. Arch Orthop Trauma Surg. 2012;132:141–151.
19. Mummaneni PV, Burkus JK, Haid RW, et al. Clinical and radiographic analysis of cervical disc arthroplasty compared with allograft fusion: a randomized controlled clinical trial. J Neurosurg Spine. 2007;6:198–209.
20. Gao Y , Liu M , Li T , et al. A meta-analysis comparing the results of cervical disc arthroplasty with anterior cervical discectomy and fusion (ACDF) for the treatment of symptomatic cervical disc disease . J Bone Joint Surg Am 2013 ; 95 : 555 – 61 .
21. Phillips FM , Lee JY , Geisler FH , et al. A prospective, randomized, controlled clinical investigation comparing PCM(r) cervical disc arthroplasty to anterior cervical discectomy and fusion: 2 year results from the us IDE clinical trial . Spine (Phila Pa 1976) 2013 .
22. Boselie TF , Willems PC , van Mameren H , et al. Arthroplasty versus fusion in single-level cervical degenerative disc disease . Cochrane Database Syst Rev 2012 ; 9 : CD009173 .
23. Yang B , Li H , Zhang T , et al. The incidence of adjacent segment degeneration after cervical disc arthroplasty (CDA): a meta analysis of randomized controlled trials . PloS One 2012 ; 7 : e35032 .
24. Botelho RV , Moraes OJ , Fernandes GA , et al. A systematic review of randomized trials on the effect of cervical disc arthroplasty on reducing adjacent-level degeneration . Neurosurg Focus 2010 ; 28 : E5 .
25. Nabhan A, Steudel WI, Nabhan A, et al. Segmental kinematics and adjacent level degeneration following disc replacement versus fusion: RCT with three years of follow-up. J Long Term Eff Med Implants. 2007;17:229–236.
26. Porchet F, Metcalf NH. Clinical outcomes with the Prestige II cervical disc: preliminary results from a prospective randomized clinical trial. Neurosurg Focus. 2004;17:E6.