Anterior cervical discectomy and fusion (ACDF) is a

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1 SPINE Volume 41, Number 12, pp E733 E741 ß 2016 Wolters Kluwer Health, Inc. All rights reserved CERVICAL SPINE Bryan Cervical Disc Arthroplasty Versus Anterior Cervical Discectomy and Fusion for Treatment of Cervical Disc Diseases A Meta-analysis of Prospective, Randomized Controlled Trials Yuhang Zhu, MD, Zhishen Tian, MD, Bitao Zhu, MD, y Wenjing Zhang, MD, z Youqiong Li, MD, PhD, and Qingsan Zhu, MD, PhD Study Design. A meta-analysis of randomized controlled trials (RCTs). Objective. The purpose of this study is to evaluate the effectiveness and safety of Bryan cervical disc arthroplasty (BCDA) as compared with anterior cervical discectomy and fusion (ACDF) for treatment of cervical disc diseases (CDDs). Summary of Background Data. Previous meta-analyses focused on the comparison of effectiveness and safety between ACDF and CDA, which consisted of various types of disc prostheses. No meta-analysis has been conducted up to present to compare ACDF with a specialized type of artificial cervical disc. Methods. We comprehensively searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trails for prospective RCTs that compared BCDA with ACDF. The retrieved results were last updated on October 1, 2015, without language restrictions. We classified the trials into subgroups by short-term and midterm follow-up. Results. Eight relevant RCTs involving 1816 individuals were included in the meta-analysis. In overall-term follow-up, the clinical outcomes indicated that BCDA was superior to ACDF considering lower NDI scores (P ¼ ), greater range of motion at the index level (P ¼ 0.02), and fewer adverse events From the Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, China; y Department of Orthopedics, The First Hospital of Jilin University, Changchun, China; z Department of Anaesthesia, China-Japan Union Hospital of Jilin University, Changchun, China; and Department of the Human Anatomy, College of Basic Medicine of Jilin University, Changchun, China. Acknowledgment date: May 8, First revision date: June 11, Acceptance date: December 11, The manuscript submitted does not contain information about medical device(s)/drug(s). No funds were received in support of this work. No relevant financial activities outside the submitted work. Address correspondence and reprint requests to Qingsan Zhu, MD, PhD, Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun , China; zhuqingsan1@foxmail.com (P ¼ 0.004), but inferior to ACDF considering operation time (P < ). There was no significant difference between two groups regarding blood loss (P ¼ 0.43), length of hospital stay (P ¼ 0.12), and secondary surgical procedures (P ¼ 0.20). Conclusion. BCDA presented better NDI improvement, greater range of motion at the index level, and fewer adverse events. However, the benefits of BCDA considering blood loss, length of hospital stay, and secondary surgical procedures are still incapable to be proved. More well design studies with longer term follow-up are needed to provide a better evaluation of the effectiveness and safety of the two procedures. Key words: anterior cervical discectomy and fusion, Bryan cervical disc arthroplasty, meta-analysis, randomized controlled trial. Level of Evidence: 1 Spine 2016;41:E733 E741 Anterior cervical discectomy and fusion (ACDF) is a conventional and well accepted surgical procedure as the gold standard to treat symptomatic cervical disc diseases (CDDs). 1,2 Clinical studies have reported high success rates, favorable outcomes, and relief of symptoms. 3 6 However, there is evidence showing that ACDF may result in complications such as dysphagia and adjacent segment degeneration. 7,8 And some biomechamics studies have indicated that the adjacent levels of fusion may suffer higher articular surface load and kinematic strain leading to mechanical instability and disc degeneration, 9,10 for which additional operations are often needed. The Bryan cervical disc prosthesis (Medtronic Sofamor Danek, Memphis, TN) was the first cervical prosthesis to be implanted in the United States in May and Bryan cervical disc arthroplasty (BCDA) has become a progressively popular surgical procedure to substitute ACDF The purposes of BCDA are to accomplish the same neural decompression as that of conventional fusion surgery and to restore disc height and maintain the motion of joint. Thus, it can normalize the kinematics of cervical spine in theory and DOI: /BRS Spine E733

2 possibly retard degeneration of adjacent segments. Nevertheless, cervical arthroplasty may also be companied with complications such as kyphosis and heterotopic ossification (HO). 14,15 So, the clinical effect and safety of Bryan disc prostheses are still disputed. There have already been some meta-analyses focusing on the comparison between cervical disc arthroplasty (CDA) and fusion. However, the CDA groups in all these reviews contained different types of cervical disc prostheses, and the different device types may affect the comparing outcomes between the interventions. So, we performed a metaanalysis to compare the effectiveness and safety of treating CDDs between cervical fusion and a specialized type of disc prosthesis (Bryan disc prosthesis). MATERIALS AND METHODS Search Strategy To make an exhaustive search of all relevant literatures, two independent reviewers (YHZ and BTZ) conducted a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-compliant search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trails (CENTRAL) for randomized controlled trials (RCTs). The following search of (Anterior cervical decompression and fusion OR anterior cervical arthrodesis OR cervical fusion OR ACDF) AND (Artificial cervical disc replacement OR Cervical arthroplasty OR disc implants OR disc prostheses OR CTDR OR CDA) AND Clinical Trial [ptyp] AND Bryan was used. Meanwhile, a mesh search of ( Arthrodesis [Mesh] OR Arthroplasty, Replacement [Mesh]) AND Cervical Vertebrae [Mesh] AND Clinical Trial [ptyp] AND Bryan was also used to provide additional results. The retrieved results were last updated on October 1, 2015, without language restrictions. References cited in the relevant literatures were also reviewed. Criteria for Selected Trials We included studies that were eligible for the following criteria: (1) the study is a RCT; (2) the target individuals had symptomatic CDDs and underwent BCDA or ACDF; (3) the individuals were older than 18 years; (4) the article with a minimum of 2-year follow-up. The exclusion criteria were as follows: (1) the researches were case reports, reviews, or observational studies. (2) The outcomes were descriptive or graphic with no numerical values. (3) The arthroplasty group contained other types of prostheses and the outcomes were mixed together. (4) The same data had been published repeatedly. Two reviewers (YHZ and BTZ) independently selected the potentially qualified trials according to the inclusion and exclusion criteria. Any disagreement was resolved by discussion and a conformity was reached. Data Extraction Two independent reviewers (YHZ and ZST) extracted the data from eligible studies. Any discrepancy was either resolved by discussion or by involving a third reviewer (WJZ) when necessary until a consensus for all items was achieved. The indispensable data extracted from eligible researches included the study design, sample size, age, sex distribution, intervention details, duration of follow-up, missing size, and outcomes. The outcome parameters pooled in this analysis included surgical parameters (operation time, blood loss, and length of hospital stay), and clinical indexes [neck disability index (NDI), range of motion (ROM), adverse events, and secondary surgical procedures]. Quality Assessment Two reviewers (YHZ and YQL) independently used the 12 criteria recommended by the Cochrane Back Review Group 16 to assess the risk of bias of the included studies. If at least six of the criteria went through without serious flaws, studies were defined as meeting low risk of bias. If not, we defined the studies as having high risk of bias. Moreover, the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach was used to rate the strength of evidence for all pooled outcomes. According to the assessment of study design, risk of bias, consistency, directness and precision, the quality of outcomes was categorized as very low, low, moderate, or high. 17 Statistical Analysis The standardized mean difference (SMD) and its 95% confidence interval (CI) were calculated for the continuous data, and the risk ratio (RR) and its 95% CI were calculated for the dichotomous data. The Chi-square test and I-square test were used to assess the statistical heterogeneity. 18,19 It demonstrated significant heterogeneity when a P value of the Chi-square test was less than 0.10 or I 2 values exceeded 50%. A random effects model was used when significant heterogeneity was observed among the included studies. Otherwise, a fixed effects model was used for no significant heterogeneity. The possibility of publishing bias was not researched because of the limited number of included studies. This meta-analysis was performed by RevMan 5.3 software (Cochrane Collaboration, Copenhagen, Denmark). The statistically significant level was set at P < RESULTS Search Results A total of 151 relevant researches were initially inspected from PubMed (N ¼ 63), EMBASE (N ¼ 30), CENTRAL (N ¼ 47), and reference lists (N ¼ 11). Forty-five trials were remained after excluding the duplicates. After reviewing the titles and abstracts, 26 trials were excluded because they did not reach the standard of inclusion criteria. A full-text review was accessed in the retaining 19 studies, and finally, eight RCTs (six IDE trials and two non-ide trials) with 1816 individuals (BCDA ¼ 925, ACDF ¼ 891) were included in this meta-analysis (Fig. 1). The duration of follow-up was classified as short-term (2 3 years) or midterm (4 years). We recorded the characteristics of the E734 June 2016

3 The operation time of the BCDA group was significantly longer than that of the ACDF group (SMD, 1.17; 95% CI: , P < ) (Fig. 3). However, the amount of blood loss showed no significant difference between two groups (SMD, -0.37; 95% CI: to 1.55, P ¼ 0.43). Also, there was no significant difference in the length of hospital stay (SMD, 0.35; 95% CI: to 0.79, P ¼ 0.12) (Fig. 4). Outcome Analysis of Clinical Indexes Neck Disability Index In short-term follow-up, there was no significant difference in Neck Disability Index (NDI) scores between BCDA and ACDF groups (SMD, 0.15; 95% CI: 0.32 to 0.02, P ¼ 0.09). Nevertheless, the BCDA group presented statistically lower NDI scores in the medium term (SMD, 0.37; 95% CI: 0.59 to 0.14, P ¼ 0.001). And NDI scores of BCDA were statistically lower than those of ACDF in overall term follow-up (SMD, 0.23; 95% CI: 0.36 to 0.09, P ¼ ) (Fig. 5). Figure 1. The flow diagram of selecting relevant studies according to a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-compliant search. included papers (Table 1), as well as recruitment characteristics and details of clinical outcomes (Table 2). Quality Assessment Regarding the 12 criteria of assessing the risk of bias recommended by the Cochrane Back Review Group, seven studies with low risk of bias and one study with high risk of bias were indicated (Figure 2). According to the GRADE approach, two-fifths of clinical indexes in short-term follow-up and two-thirds in the medium term were moderate quality evidences (Table 3). Outcome Analysis of Surgical Parameters Three studies reported the data of operation time and blood loss, and two studies reported the length of hospital stay. Range of Motion The flexion-extension range of motion at the index level was determined by the tangential lines drawn between the superior endplate of the cephalad vertebral body and the inferior endplate of the caudal body. 28 The Range of Motion (ROM) information was supplied by three short-term studies. The BCDA group had statistically better range of motion at the index level than the ACDF group (SMD, 9.83; 95% CI: , P ¼ 0.02) (Figure 6). Adverse Events No significant difference was found in the occurrence of adverse events between two groups in short-term follow-up (RR, 0.58; 95% CI: , P ¼ 0.08). However, the BCDA group presented statistically fewer adverse events than the ACDF group in both midterm follow-up (RR, 0.44; 95% CI: , P ¼ 0.02) and overall term follow-up (RR, 0.51; 95% CI: , P ¼ 0.004) (Figure 7). TABLE 1. Characteristics of the Studies in the Analysis Studies Published Year Sample Size (BCDA/ACDF) Mean Age (yr) (BCDA/ACDF) Sex (BCDA/ACDF) (male/female) Missing Size (BCDA/ACDF) Sasso et al (56/59) 42.5/41.6 (30/26)/(32/27) 20/24 Sasso et al (242/221) 44.4/44.7 (110/132)/(113/108) 12/27 Heller et al (242/221) 44.4/44.7 (110/132)/(113/108) 12/27 Coric et al (21/41) NR/46.3 NR/(16/21) NR/4 Zhang et al (60/60) 44.8/45.6 (35/25)/(32/28) 4/7 Garrido et al (21/26) 40/43 (13/8)/(17/9) 3/6 Cheng et al (41/42) 47.2/47.7 (21/20)/(23/19) 0/2 Sasso et al (242/221) 44/44.7 (110/132)/(113/108) 61/83 ACDF indicates anterior cervical discectomy and fusion; BCDA, Bryan cervical disc arthroplasty; NR, not reported. Spine E735

4 TABLE 2. Characteristics and Clinical Outcomes of the Studies in the Analysis Studies Number of Cervical Levels Follow-up (yr) US FDA IDE Trial Secondary Surgical Procedures procedures were described as revisions, removals, supplemental fixations, or reoperations. 29 In both short-term and midterm follow-up, there was no significant difference between two groups no matter whether secondary surgical procedures happened at the index level or at the adjacent level. Although the total rate of secondary surgical procedures of the BCDA group (2.92%) was lower than that of the ACDF group (4.03%), it was not statistically significant (RR, 0.75; 95% CI: , P ¼ 0.20) (Figure 8). The pooled results of surgical parameters and clinical indexes are displayed in Table 4. DISCUSSION Some meta-analyses have reported that CDA showed equivalent or superior efficacy and reliability compared Number of Centers Outcomes Sasso et al Yes 3 Operation time, Blood loss, Hospital stay Sasso et al Yes 31 ROM Heller et al Yes 30 NDI, Reoperations, Complications Coric et al Yes 21 Reoperations, Complications Zhang et al No 3 Operation time, Blood loss, Hospital stay, NDI, ROM, Reoperations Garrido et al Yes 1 Complications, Reoperations Cheng et al 26 1, 2 or 3 3 No 1 Operation time, Blood loss, ROM, Complications Sasso et al Yes 30 NDI, Reoperations, Complications IDE indicates investigational device exemption; NDI, neck disability index; ROM, range of motion. Figure 2. The risk of bias of the included studies was evaluated in our meta-analysis. with ACDF for the treatment of CDDs. A recent systematic review by Luo et al 34 also indicated that CDA was superior to ACDF regarding reducing adjacent segment disease (ASD). However, the CDA group of these reviews consisted of various types of prostheses, which are mainly divided into three types, minimally constrained/unconstrained (Bryan, Mobi-C), semi-constrained (PCM, Prestig-LP), and constrained (Prodisc-C). 30 Quite a few meta-analyses indicated that different device types might affect the comparing outcomes between the interventions. Moreover, some recent studies demonstrated that biomechanical characteristics and clinical outcomes of different cervical disc prostheses were diverse. 35,36 Nevertheless, few meta-analyses have been conducted up to present to compare ACDF with a specialized type of artificial cervical disc. The Bryan cervical disc is an unconstrained, metal-on-polymel device utilizing a unique polyurethane nucleus and milling-based convex porous ingrowth surfaces for fixation. 37 It has been used widely as a surgical procedure to substitute ACDF. But the effectiveness and safety of BCDA are still controversial. That is why we performed a meta-analysis of eight RCTs to determine whether BCDA was superior to ACDF. Some basic epidemiological information of individuals is summarized in Table 1. The sex ratio of two groups was almost 1:1 and it suggested that CDDs might not be related to sex. And most patients were at their 40s or older, which indicated that cervical disc degeneration accelerated at the middle age. Two previous meta-analyses 31,38 have compared the surgical parameters between CDA and ACDF. They both indicated that ACDF was associated with shorter operation time and similar length of hospital stay than CDA, but blood loss was not consistent in the reviews. The operation time and length of hospital stay in our meta-analysis were consistent with the previous studies, and we found that BCDA was equivalent to ACDF considering the blood loss. Compared with fusion, lower NDI scores and better NDI improvement of CDA were reported by some meta-analyses. 32,33,39 Although our meta-analysis showed that patients treated with BCDA acquired better NDI improvement in overall-term follow-up, only one study with 4-year follow-up was included in the medium term. Hence, E736 June 2016

5 TABLE 3. Summary of Strength of Evidence With Regard to the Outcome Parameters Outcomes Studies Risk of Bias Inconsistency Indirectness Imprecision Quality Surgical parameters Operation time, min 3 Serious No No Serious Low Blood loss, ml 3 Serious Serious z No Serious Very low Length of hospital stay, d 2 Serious Serious z No Serious Very low Clinical indexes in short-term follow-up NDI scores 2 Serious No No No Moderate ROM (deg) 3 Serious y Serious z No No Low Adverse events 3 Serious y No No Serious Low 3 Serious No No No Moderate procedures (index level) 3 Serious No No Serious Low procedures (adjacent level) Clinical indexes in midterm follow-up Adverse events 2 Serious No No No Moderate 2 Serious No No Serious Low procedures (index level) 2 Serious No No No Moderate procedures (adjacent level) Serious risk of performance and attrition bias. y Serious risk of performance bias, detection bias, and attrition bias. z Significant heterogeneity existed across the trials. Wide confidence intervals are around the estimate of the effect or total population size is less than 400. NDI indicates neck disability index; ROM, range of motion. the NDI scores should be researched more strictly with the emergence of more high-quality studies with longer followup. BCDA resulted in better range of motion than ACDF at the index level, which agreed with the outcomes of previous studies. 33,39 It was reported that worse segmental motion at the index level would increase the load of articular surface and expedite the degeneration of adjacent segments. 9 It remains under debate whether the adjacent segment disease caused by spinal fusion attributes to iatrogenic motion restriction. Some scholars hypothesized that altered biomechanics at adjacent segments accelerated the nature history of spinal segmental degeneration. 40,41 However, Sasso et al 21 found that compared with fusion, although BCDA gained better segmental motion at the treated level, the ROM at cranial and caudal adjacent segments of two procedures had no significant difference. So, further studies should still pour attention into the biomechanical and kinematic change at adjacent levels of two procedures. The advantage of fewer adverse events began to manifest at the medium term in the BCDA group. The main adverse events of the Bryan disc included kyphosis, HO, spontaneous fusion, and subsidence. Segmental kyphosis after Bryan disc arthroplasty was reported as a common postoperative complication at the initial stage of its clinical use. 15 However, some modified techniques were utilized to prevent postoperative kyphosis such as change of the Bryan disc insertion depth and insertion angle, and the results have shown successful improvement. 35,42 Yi et al 43 indicated that different device types showed significantly different HO occurrence rates, and the HO occurrence rate of the Bryan disc (21.0%) was significantly lower than that of Mobi-C (52.5%) or ProDisc C (71.4%), respectively. The relatively lower HO occurrence rate may attribute to the unique polyurethane membrane that reduces friction, wear debris and ingrowth of soft tissue or bone, as well as the unconstrained motion inducing less stress at the bone to Figure 3. Forest plot comparing operation time (min) between Bryan cervical disc arthroplasty (BCDA) and cervical fusion (ACDF). CI indicates confidence interval; df, degrees of freedom; IV, inverse variance. Spine E737

6 Figure 4. Forest plot comparing blood loss (ml) and length of hospital stay (d) between Bryan cervical disc arthroplasty (BCDA) and cervical fusion (ACDF). CI indicates confidence interval; df, degrees of freedom; IV, inverse variance. Figure 5. Forest plot comparing NDI scores between Bryan cervical disc arthroplasty (BCDA) and cervical fusion (ACDF). CI indicates confidence interval; df, degrees of freedom; IV, inverse variance. implant interface in the Bryan disc. 43 Besides, we noted that some patients with osteoporosis, severe facet joint arthrosis, or cervical instability were not involved in the arthroplasty group. These above reasons may contribute to fewer adverse events in the BCDA group. For fusion group, the adverse events mainly included dysphagia, pseudarthrosis, hoarseness, and adjacent segment diseases. Dysphagia was described as the most frequent complication of anterior fusion, which accounted for almost 40% of total complications. 7 Dysphagia is far less common in arthroplasty because BCDA demands less esophageal retraction and consequently reduces the intra-esophageal pressure. 33 It was reported that the most frequent secondary surgical procedures at the operated level were supplemental fixations for ACDF, as well as removal and reoperations for BCDA. 27 Some patients with severe complications in the arthroplasty group were ultimately addressed with arthrodesis. Although BCDA suffered fewer adverse events in total, there was no significant difference between two groups in secondary surgical procedures, regardless of the duration of follow-up or involved segments. We suppose that the complications of BCDA are more in need of secondary surgeries and patients with arthroplasty may be more compliant to accept secondary surgical procedures to get functional improvement. Figure 6. Forest plot comparing range of motion (ROM) (degrees) at the index level between Bryan cervical disc arthroplasty (BCDA) and cervical fusion (ACDF) in short-term follow-up. CI indicates confidence interval; df, degrees of freedom; IV, inverse variance. E738 June 2016

7 Figure 7. Forest plot comparing the number of adverse events between Bryan cervical disc arthroplasty (BCDA) and cervical fusion (ACDF). CI indicates confidence interval; df, degrees of freedom; MH, Mantel-Haenszel. Figure 8. Forest plot comparing the number of secondary surgical procedures between Bryan cervical disc arthroplasty (BCDA) and cervical fusion (ACDF). CI indicates confidence interval; df, degrees of freedom; MH, Mantel-Haenszel. Spine E739

8 TABLE 4. The Pooled Results of Meta-analysis Outcomes Sample Size Model SWD/RR (95% CI) P heterogeneity /I 2 P Favor Surgical parameters Operation time, min 318 Fixed 1.17(0.93 to 1.41) 0.49/0% ACDF Blood loss, ml 318 Random 0.37( 0.28 to 1.55) /94% 0.43 None Length of hospital stay, d 235 Random 0.35( 0.09 to 0.79) 0.09/66% 0.12 None Clinical indexes in short-term follow-up NDI scores 533 Fixed 0.15( 0.32 to 0.02) 0.81/0% 0.09 None ROM, deg 506 Random 9.83(1.57 to 18.08) /99% 0.02 BCDA Adverse events 608 Fixed 0.58(0.32 to 1.08) 0.35/5% 0.08 None 630 Fixed 0.79(0.32 to 1.93) 0.42/0% 0.61 None procedures (index level) procedures (adjacent level) 630 Fixed 0.67(0.26 to 1.72) 0.46/0% 0.41 None Clinical indexes in midterm follow-up Adverse events 510 Fixed 0.44(0.22 to 0.88) 0.55/0% 0.02 BCDA 510 Fixed 0.67(0.29 to 1.53) 0.31/2% 0.35 None procedures (index level) procedures (adjacent level) 510 Fixed 0.88(0.39 to 1.98) 0.45/0% 0.76 None Clinical indexes in overall-term follow-up NDI scores 852 Fixed 0.23( 0.36 to 0.09) 0.30/17% BCDA Adverse events 1118 Fixed 0.51(0.32 to 0.81) 0.59/0% BCDA procedures 2280 Fixed 0.75(0.49 to 1.16) 0.83/0% 0.20 None ACDF indicates anterior cervical discectomy and fusion; BCDA, Bryan cervical disc arthroplasty; NDI, neck disability index; None, no statistical differences; ROM, range of motion; RR, risk ratio; SWD, standardized mean difference. There are some strengths in our study. First, this is the first meta-analysis to evaluate the effectiveness and safety between Bryan disc arthroplasty and ACDF. Second, we used Cochrane risk of bias and GRADE approach to assess the quality of evidence. Additional strengths contained a rigorous search strategy, only RCTs included, no language limitations, and subgroups of outcomes into short and medium terms to guarantee the consistency and accuracy. However, the validness of our study is limited by several factors. First, several pooled outcomes showed low-quality evidences because of inadequate blinding, significant heterogeneity, or imprecision. Second, we did not assess the publication bias due to the limited number of included studies. Third, no studies with more than 4-year followup were available to assess long-term outcomes. Fourth, it is inadequate to compare other specialized types of disc prostheses with ACDF because of the absence of sufficient articles. In summary, BCDA presented longer operation time, better NDI improvement, greater range of motion at the index level, and fewer adverse events than ACDF. However, BCDA was equivalent to ACDF regarding the outcomes of blood loss, length of hospital stay, and secondary surgical procedures. More high-quality studies with longer term follow-up are needed to provide a better evaluation of the effectiveness and safety between the two procedures. Key Points This is the first meta-analysis of prospective randomized controlled studies comparing BCDA and ACDF for treatment of cervical disc diseases. Compared with ACDF, BCDA presented noninferior effectiveness and safety in both short-term and medium-term follow-up. More high-quality studies with longer follow-up are needed to explore long-term effectiveness and safety of the two procedures. References 1. Lied B, Roenning PA, Sundseth J, et al. Anterior cervical discectomy with fusion in patients with cervical disc degeneration: a prospective outcome study of 258 patients (181 fused with autologous bone graft and 77 fused with a PEEK cage). BMC Surg 2010;10: Eastlack RK, Garfin SR, Brown CR, et al. Osteocel Plus cellular allograft in anterior cervical discectomy and fusion: evaluation of clinical and radiographic outcomes from a prospective multicenter study. Spine 2014;39:E E740 June 2016

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Is cervical disc arthroplasty superior to fusion for treatment of symptomatic cervical disc disease? A metaanalysis. Clin Orthop Relat Res 2013;471: Nunley PD, Jawahar A, Kerr EJ, 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 2012;37: Hilibrand AS, Robbins M. Adjacent segment degeneration and adjacent segment disease: the consequences of spinal fusion? Spine J 2004;4:190s 4s. 42. Xu JX, Zhang YZ, Shen Y, et al. Effect of modified techniques in Bryan cervical disc arthroplasty. Spine 2009;34: Yi S, Shin DA, Kim KN, et al. The predisposing factors for the heterotopic ossification after cervical artificial disc replacement. Spine J 2013;13: Spine E741