RASP was variably defined and reported in 4 studies, including 1 RCT, comparing arthroplasty with fusion.10,15,16,18 Across studies, risk of RASP were lower for arthroplasty, with risk differences ranging from 1.7% to 23.8%, but statistical significance was reached only in RCT (Figure 2).
Findings From Randomized Controlled Trials
An industry-funded FDA Investigational Device Exemption (IDE) RCT involved 21 sites and compared the clinical and radiographical outcomes of subjects with single-level symptomatic cervical degenerative disc disease or spondylosis who underwent TDR with the Kineflex/C compared with fusion.10 RASP was evaluated by quantitative analysis of disc height and an independent radiologist's subjective assessments of the extent of osteophyte formation and degree of endplate sclerosis, classified as none, mild, moderate, or severe. For cases with pre-existing moderate ASP, a 1-grade change was required for classification as ASP; for other cases, a 2-grade increase in pathology was required to be classified as ASP. Unfortunately, it does not seem that there was blinding of the treatment (i.e., blocking out the operative level on the radiograph) to these radiologists. The 24-month follow-up rate was 87.0% (234/269). RASP rates were 10.1% (12/119) for the Kineflex/C group and 28.7% (33/115) for fusion subjects (R = 0.35, 95% CI: 0.19, 0.65). These RASP rates differ from those published in the article because the rates reported here are based upon 24-month subject numbers.
Findings From Cohort Studies
A prospective cohort study evaluated changes at the adjacent level in subjects with symptomatic single- or double-level cervical disc disease who underwent TDR with the Bryan disc or fusion surgery.15 This article reported on 105 participants, though the follow-up rate of the subject population was not reported. The mean follow-up time for the study population was 19 (range 12–40) months. The presence of RASP was defined as the presence of new anterior or enlarging osteophytes, increase or new (≥30%) narrowing of disc space, and/or calcification of the anterior longitudinal ligament in the adjacent segment(s). For subjects who underwent single-level procedures, the rate of RASP was 12.8% (5/39) in subjects who received the Bryan disc and 23.1% (6/26) in those who underwent fusion (RR = 0.56, 95% CI: 0.19, 1.63). For double-level procedures, RASP was reported in 33.3% (4/12) of subjects in the Bryan group and 57.1% (16/28) of the fusion group (RR = 0.58, 95% CI: 0.25, 1.38). Taken together, the authors reported that radiological evidence of ASP was 3.5 times more likely for the fusion group at the time of the last follow-up compared with those who received the Bryan disc. Unfortunately, the observers rating the radiographs were not blinded at the treatment level (i.e., blocking out the operative level on the radiograph) regarding whether a fusion or TDR was performed.
Another prospective cohort study evaluated the incidence of ASP in patients with cervical degenerative disc disease who underwent cervical disc arthroplasty (CDA) compared with fusion surgery.16 At 36 months, the follow-up rate was 91.3% (190/208). RASP was assessed by an independent evaluator and was defined as the development of new anterior osteophyte formation or enlargement of existing osteophytes, increased or new narrowing of a disc space (>30%), and/or new or increased calcification of the anterior longitudinal ligament and formation of radial osteophytes. RASP was found in 8.8% (7/85) of subjects in the CDA group and 10.5% (11/105) in the fusion group (RR = 0.79, 95% CI: 0.32, 1.94).
A cohort of consecutive subjects who underwent cervical ADR or fusion was followed prospectively for the effects of treatment on spinal alignment and other changes, including ASP.18 The follow-up rate was 100% (33/33), with a mean length of follow-up of 28 ± 5 months for the ASP group and 30 ± 6 months for fusion subjects. RASP was defined as the development of new spondylotic changes in the adjacent vertebral bodies or a decrease of more than 10% in the height of adjacent discs. Further, reoperation due to ASP was also reported. The rate of RASP was 26.7% (4/15) in ADR subjects and 44.4% (8/18) in those who underwent fusion (P = NS).
CASP and Treatment for CASP
Six RCTs9–14 and 2 prospective cohort studies17,18 reported on reoperation at adjacent segments following index arthroplasty or fusion. Risk differences between treatment groups ranged from 1.0% to 4.8%. Risks of requiring surgery for ASP were lower for arthroplasty across 6 of the 8 studies, and higher for arthroplasty in the other 2 studies, but no statistical differences were seen in any study (Figure 3). Characteristics of individual studies are described below; the 2 studies10,18 that reported RASP as well as CASP are described in the section above.
Findings From Randomized Controlled Trials
In a 31-site FDA IDE RCT, subjects underwent TDR and insertion of the Bryan disc or fusion surgery in subjects with single-level symptomatic degenerative disc disease, and ASP rates were compared between the two groups.13 Reoperation at adjacent levels was reported; however, if reoperation procedures involved both index and adjacent levels, they were reported for the index level only. At 48 months, the follow-up rate was 68.9% (319/463), and the reoperation rate in the Bryan group was 5.5% (10/181), while that of the fusion group was 6.5% (9/138; R = 0.85, 95% CI: 0.35, 2.03). The index report of the same population at the 24-month follow-up has been published.21
A 3-site RCT in a Chinese population reported reoperation due to ASP in subjects who underwent TDR with the Bryan disc or fusion surgery.14 The study investigators commented that they attempted to use the same inclusion and exclusion criteria as in the US FDA IDE. At 24 months, the follow-up rate was 90.8% (109/120). Reoperation due to ASP in this population was 1.8% (1/56) for the Bryan disc and 5.7% (3/53) in the fusion group (R = 0.23, 95% CI: 0.03, 2.94).
Another FDA IDE study was a 32-site RCT that assessed the long-term safety and efficacy of TDR with the Prestige cervical disc prosthesis compared with fusion in subjects with single-level symptomatic degenerative disc disease.9 At 60 months, the follow-up rate was 50.1% (271/541); however, at the time of publication, not all subjects had reached the 60-month follow-up examination. Reoperation at adjacent levels due to ASP was 5.6% (8/144) in the Prestige group and 10.2% (13/127) in subjects who underwent fusion (R = 0.54, 95% CI: 0.23, 1.27). The index report of the same population at the 24-month follow-up has been published.2
A FDA IDE RCT evaluated the safety and efficacy of TDR and insertion of the ProDisc-C disc compared with fusion surgery in subjects who underwent single-level treatment for symptomatic cervical disc disease.11 This 13-site study reported adjacent-level reoperation at the 24-month follow-up. The rate of follow-up was 96.5% (this follow-up reported on 209 subjects, but the number of subjects in the total study population was not reported), and rates of reoperation due to ASP were 0% (0/101) for the ProDisc-C group and 1.0% (1/100) in fusion subjects (RR = not able to calculate).
Nabhan et al12 performed a RCT in which they assessed segmental motion following implantation of the ProDisc-C disc compared with fusion surgery in subjects who underwent single-level treatment for symptomatic cervical disc disease. The follow-up rate at 36-months was 83.7% (41/49). Reoperation at the adjacent level was reported to be 0% (0/20) for subjects who received the ProDisc-C and 4.8% (1/21) for fusion subjects (RR = not able to calculate). The index report of the same population at the 12-month follow-up has been published; however, the definition of ASP was not clearly defined in this study with less follow-up.22
In the study by Coric et al,10 treatment for CASP was performed in 7.6% (9/119) for Kineflex/C subjects and 6.1% (7/115) in those who underwent fusion (R = 1.24, 95% CI: 0.48, 3.23).
Findings From Prospective Cohort Studies
The cohort study by Park et al18 reported no reoperations due to ASP for either group (RR = 0.60, 95% CI: 0.22, 1.61).
Nunley et al17 evaluated a cohort of subjects from 2 collaborating institutions who had participated in 1 of 3 different FDA IDE RCTs. Participating subjects had 1- or 2-level cervical degenerative disease and received either TDA with implantation of the Kineflex-C, Mobi-C or Advent cervical disc or fusion surgery. This prospective cohort study reported on subjects who were followed for a median of 38 (range 32–54) months and reported a follow-up rate of 93.4% (170/182). ASP was assessed through a multistep process in which RASP was first assessed radiographically and was rated as no, mild, moderate, or severe disease, followed by clinical assessment with electrophysiologic (electromyography and nerve conduction velocity) studies to rule out peripheral nerve pathologies. Once the existence of ASP was established, medical and/or surgical management of ASP was carefully recorded. Only those subjects who demonstrated clinical-radiological stigmata of ASP and received active intervention for its management were reported as having treatment for ASP. Given this definition of ASP, the rate for CASP and treatment for CASP were higher for arthroplasty, and were reported to be 17.6% (20/113) for subjects who underwent TDR and 14.0% (8/57) for the fusion group (RR = 1.26, 95% CI: 0.59, 2.69). We also note this is the only 1 of these 8 studies cited which was not industry funded.
Risk of Adjacent Segment Disease Comparing Motion-Sparing Devices
One prospective cohort study (LoE III) directly compared 2 different artificial discs for development of RASP,19 and the characteristics of this study are summarized in Table 2. The study population for this study was 58% male, age ranged from 29 to 62 years. The risks of RASP were similar between groups, with a risk difference of 0.9%.
In this study, Ryu et al19 evaluated consecutive patients with single-level degenerative cervical spine diseases who underwent TDR using a Bryan disc (N = 19) or a ProDisc-C (N = 17), with all procedures performed by a single surgeon. The mean follow-up time was 27.3 ± 4.9 (range 24–40) months, and the rate of follow-up was 78.3% (36/46). Radiographical assessments were performed twice by 2 independent observers on high-resolution CTs, and RASP was defined as degenerative changes, spur formation and/or progression of facet arthrosis at adjacent levels. RASP was reported by level, though not for subjects. For the Bryan disc group, the risk of RASP was 7.9% (3/38 levels) and was 8.8% (3/34 levels) for subjects who received the ProDisc-C (R = 0.90, 95% CI: 0.19, 4.14).
Controversy remains whether RASP and CASP requiring treatment is due to fusion-altered biomechanics and kinematics versus the underlying natural history of the patient's degenerative disease. Our systematic review focused on a high-quality literature with specific inclusion and exclusion criteria (Table 1 and Figures 1A–C) comparing ACDF with alternative motion preservation techniques or devices regarding the development of RASP or CASP. Variability in reported risk for both RASP and CASP is likely due, at least in part, to significant differences in the definitions used. For studies reporting reoperation for CASP, various methods of calculating risks were reported by the authors.
Regarding question 1 (in Table 5), we found that the overall strength of the body of literature is moderate based on the GRADE criteria.7 Many studies were excluded due to not reporting ASP as an outcome or overlapping data with shorter follow-up than included studies. Initial baseline level of evidence was graded as high given 6 RCTs (LoE II) in addition to 4 LoE III cohort studies comparing TDR versus ACDF (Table 5). One major methological problem with all studies except Coric et al10 and Maldonado et al16 was lack of blinded assessment of ASP, raising the question of potential bias in favor of motion-sparing devices and procedures (particularly for radiographical evaluation). Also, in industry-funded studies, frequency of reoperation for ASP in different treatment groups may have been influenced by investigators. Bias in the cohort studies related to treatment allocation, comparable evaluation, and treatment of study groups are possible.
Additionally, in 1 study, reoperations at adjacent levels did not include participants who had reoperation at both the index level and adjacent levels.13 Using previously described calculated risk ratios (RR), risk differences (RD), and confidence intervals (CI), comparison of TDR versus fusion RASP (Table 2, Figure 2) and CASP requiring treatment (Figure 3) was performed. Six of these 8 studies reported a nonsignificant lower overall risk of ASP with TDR compared with fusion. Imprecision in results reporting drove our 1-level final downgrade to a moderate strength of evidence. Additionally, 2 of the studies reported that TDR has a nonsignificant higher overall risk of ASP, including the only nonindustry funded study by Nunley et al.17 It is not clear from these studies that radiographic pathological changes at segments adjacent to fusion or motion-sparing devices are related to patient symptoms or function. Small sample sizes in some studies may have contributed to lack of statistical significance for differences between treatment groups. We are unable to determine whether the current evidence reflects the true effect. Independently funded, blinded long-term follow-up studies would be able to delineate the true effect of TDR versus fusion regarding incidence of RASP and CASP and treatment of CASP.
Regarding question 2 (in Table 5), our final overall strength of the body of literature is insufficient based on the GRADE criteria.7 We approached this topic with broad aims to compare ACDF with nonarthroplasty motion-sparing operations including posterior foraminotomy with or without discectomy, anterior discectomy alone without fusion, and laminoplasty regarding risk of RASP or CASP (Table 1). Unfortunately, literature is sparse (3 studies) with none fitting inclusion criteria due to lack of reporting of ASP or no direct comparison of treatment groups. Likewise, there were no studies directly comparing different fusion techniques with the development of ASP.
Regarding question 3 (in Table 5), our final overall strength of the body of literature is insufficient based on the GRADE criteria.7 A flow diagram of the literature search (Figure 1C) details the paucity of true direct comparable reports of various motion-sparing devices primarily due to lack of reporting of ASP. Initial baseline level of evidence was graded as low given only a single prospective cohort study comparing Bryan TDR to ProDisc-C TDR (LoE III).19 No significant RASP difference was noted (7.9% [Bryan] vs. 8.8% [Prodisc-C]) and CASP was not reported (Table 4). Given only 1 report available, we downgraded our overall strength of evidence to insufficient.
The strength of this report is the use of a structured rigorous systematic search and review of numerous full-text articles to identify comparison studies that measured RASP and CASP. Unfortunately, a paucity of high-quality literature comparing motion-preserving devices or treatment methods to fusion or other motion-preserving techniques or devices (with ASP as an outcome using consistent definitions) exists. Independently funded, blinded long-term follow-up prospective studies would be able to delineate the true effects regarding incidence or RASP and CASP and treatment of CASP.
CONSENSUS STATEMENTS AND CLINICAL RECOMMENDATIONS
- There is no significant difference in development of RASP and CASP after C-TDR versus ACDF at short- to mid-term follow-up.
Level of Evidence: Moderate
Strength of Statement: Strong
Recommendation 1: No recommendation can be made from comparative literature of nonarthroplasty motion preservation device or techniques compared with fusion regarding the risk of RASP or CASP.
Level of Evidence: Insufficient
Strength of Statement: Strong
Recommendation 2: No recommendation can be made from direct comparative literature of various motion preservation devices or techniques regarding the risk of RASP or CASP.
Level of Evidence: Insufficient
Strength of Statement: Strong
- Reported rates of radiographical and clinical adjacent segment pathology seem to be comparable in patients treated with total disc replacement versus arthroplasty for cervical disc disease with radiculopathy or myelopathy.
- Studies have significant variation in follow-up, definitions of radiographical and clinical ASP.
- Clarification of ASP definitions and classification is needed to optimally compare different interventions, devices, and patient populations.
Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal's Web site (www.spinejournal.com).
1. 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.
2. 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.
3. Riew KD, Schenk-Kisser JM, Skelly AC. Adjacent segment disease and C-ADR: promises fulfilled? EBSJ 2012;3:39–46.
4. Wright JG, Swiontkowski MF, Heckman JD. Introducing levels of evidence to the journal. J Bone Joint Surg Am 2003;85-A:1–3.
5. Norvell DC, Dettori JR, Skelly AC, et al. Methodology for the systematic reviews on adjacent segment pathology. Spine (Phila Pa 1976) 2012;37:E342–8.
6. StataCorp. Stata Statistical Software: Release 9 ed. College Station, TX:StataCorp LP, 2005.
7. Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendations. BMJ 2004;328:1490.
8. West S, King V, Carey TS, et al. Systems to rate the strength of scientific evidence. Evidence Report/Technology Assessment No. 47 (Prepared by the Research Triangle Institute-University of North Carolina Evidence-based Practice Center, Contract No. 290-97-0011): Agency for Healthcare Research and Quality, Rockville, MD, 2002.
9. 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.
10. Coric D, Nunley PD, Guyer RD, et al. Prospective, randomized, multicenter study of cervical arthroplasty: 269 patients from the Kineflex/C artificial disc investigational device exemption study with a minimum 2-year follow-up: clinical article. J Neurosurg Spine 2011;15:348–58.
11. 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.
12. 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;17:229–36.
13. 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.
14. Zhang X, Zhang X, Chen C, et al. Randomized, controlled, multicenter, clinical trial comparing BRYAN cervical disc arthroplasty
with anterior cervical decompression and fusion in China. Spine (Phila Pa 1976) 2011;15:433–8.
15. Kim SW, Limson MA, Kim SB, et al. Comparison of radiographic changes after ACDF versus Bryan disc arthroplasty in single and bi-level cases. Eur Spine J 2009;18:218–31.
16. Maldonado CV, Paz RD, Martin CB. Adjacent-level degeneration after cervical disc arthroplasty
versus fusion. Eur Spine J 2011;20 (Suppl 3):403–7.
17. Nunley PD, Jawahar A, Kerr EJ III. Factors affecting the incidence of symptomatic adjacent level disease in cervical spine after total disc arthroplasty: 2–4 years follow-up of 3 prospective randomized trials. Spine (Phila Pa 1976) 201115:445–51.
18. Park SB, Jahng TA, Chung CK. Remodeling of adjacent spinal alignments following cervical arthroplasty and anterior discectomy and fusion. Eur Spine J 2012;21:322–7.
19. Ryu KS, Park CK, Jun SC, et al. Radiological changes of the operated and adjacent segments following cervical arthroplasty after a minimum 24-month follow-up: comparison between the Bryan and Prodisc-C devices. J Neurosurg Spine 2010;13:299–307.
20. Walraevens J, Liu B, Meersschaert J, et al. Qualitative and quantitative assessment of degeneration of cervical intervertebral discs and facet joints. Eur Spine J 2009;18:358–369.
21. Anderson PA, Sasso RC, Riew KD. Comparison of adverse events between the Bryan artificial cervical disc and anterior cervical arthrodesis. Spine (Phila Pa 1976) 2008;33:1305–12.
22. Nabhan A, Ahlhelm F, Shariat K, et al. The ProDisc-C prosthesis: clinical and radiological experience 1 year after surgery. Spine (Phila Pa 1976) 2007;32:1935–41.
cervical spondylotic myelopathy; cervical radiculopathy; cervical adjacent segment disease; cervical disc arthroplasty
Supplemental Digital Content
© 2012 Lippincott Williams & Wilkins, Inc.