钛笼与聚醚醚酮椎间融合器在颈前路减压椎间融合中的应用

doi:10.3969/j.issn.2095-4344.2014.04.023

摘要/Abstract

摘要：

背景：目前颈椎前路手术常用的两种椎间融合器为钛笼和聚醚醚酮椎间融合器，但两者在影像学及临床疗效评价上仍然存在争议。

目的：系统评价钛笼与聚醚醚酮椎间融合器应用于颈前路减压椎间融合后影像学及临床疗效。

方法：计算机检索Cochrane Library(2013年第5期)、MEDLINE、EMBASE、CNKI、万方数据库，收集至2013年6月1日国内外公开发表的在颈前路手术中对钛笼与聚醚醚酮椎间融合器的使用进行比较的对照研究，由2位研究者独立评价文献，采用Cochrane协作网提供的RevMan 5.2软件进行Meta分析。

结果与结论：最终纳入文献4篇，共235例患者，其中钛笼组128例，聚醚醚酮椎间融合器组107例。Meta分析结果示：在融合率方面及临床疗效方面，两组差异无显著性意义(P > 0.05)，在融合器下沉移位率方面，两组在短期差异无显著性意义(P > 0.05)，但是在长期方面聚醚醚酮组下沉移位率要小于钛笼组，差异具有显著性意义(P < 0.05)。在颈椎曲度和椎间隙高度的维持方面，聚醚醚酮组要优于钛笼组。在颈前路减压椎间融合术中应用聚醚醚酮椎间融合器可以获得较好的融合率和临床疗效，相比钛笼可以更好的长期维持颈椎曲度和椎间隙高度，并且拥有更小的下沉移位率。

中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程

全文链接：

关键词: 植入物, 脊柱植入物, 钛笼, 聚醚醚酮椎间融合器, 颈前路减压椎间融合术, 颈椎病, 髂骨, 融合, 颈椎曲度, 下沉, 移位, 系统评价

Abstract:

BACKGROUND: The two main cages used in anterior cervical surgery are titanium cages and poly(ether-ether-ketone) cages, but it is still controversial in imaging performances and clinical outcomes.

OBJECTIVE: To systematically evaluate imaging performances and clinical outcomes between titanium cages and poly(ether-ether-ketone) cages in anterior cervical discectomy and fusion surgery.

METHODS: The Cochrane library (issue 5, 2013), Medline database, EMBASE, CNKI and Wanfang database were retrieved by computer. The deadline of all the retrieves concerning control study of uses of titanium cages and poly(ether-ether-ketone) cages was June 1^st, 2013. Two reviewers assessed literatures independently, and the meta-analysis was conducted by RevMan 5.2 software.

RESULTS AND CONCLUSION: A total of four literatures including 235 patients, 128 of titanium cages and 107 of poly(ether-ether-ketone) cages, were included. Meta-analysis results showed that there was no statistically significant difference between the groups in fusion rates, subsidence and dislocation rates of short-term follow-up and clinical outcomes (all P > 0.05). There were statistically significant differences between the groups in subsidence and dislocation rates of long-term follow-up (P < 0.05). Poly(ether-ether-ketone) cage group was superior to titanium cages group in maintenance of cervical curvature and intervertebral height. This meta-analysis showed that poly(ether-ether-ketone) cages had good fusion rates and clinical outcomes, less subsidence and dislocation rates, and can better maintain cervical curvature and intervertebral height compared with titanium cages.

中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程

全文链接：

Key words: cervical vertebrae, spinal fusion, titanium, evidence-based medicine

中图分类号:

R318

段文，孔荣，黄威，周冉. 钛笼与聚醚醚酮椎间融合器在颈前路减压椎间融合中的应用[J]. 中国组织工程研究, 2014, 18(4): 625-630.

Duan Wen1, Kong Rong1, Huang Wei1, Zhou Ran2. Application of titanium cages and poly(ether-ether-ketone) cages in anterior cervical discectomy and fusion surgery[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(4): 625-630.

图/表（结果） 2

2.1 检索结果分析 共检索出文献188篇，通过阅读文献标题及摘要，初步筛选出22篇文献可能符合纳入标准，再通过阅读全文后，最终纳入4篇研究^[34-37]，均为英文文献。

2.2 基线分析及质量评价 表1为纳入研究的基本情况。

通过“随机方法、分配隐藏、盲法、失访/推出、选择性报告结果、其他偏倚”6个方面对纳入研究进行系统评价(表2)。

2.3 系统评价结果

2.3.1 融合率 4项研究均报道了融合率，其中3项研究对短期融合率进行比较^[34-36]，1项研究为长期研究^[37]。对3项短期研究进行Meta分析，其中钛笼组124个节段，聚醚醚酮组91个节段，对研究结果进行异质性分析，结果存在异质性(P=0.01， I²=78%)，因此采用随机效应模型进行分析。结果显示钛笼组与聚醚醚酮组短期融合率差异无显著性意义(P > 0.05)(图1)。在这项长期研究中钛笼组与聚醚醚酮组均达到骨性融合。

2.3.2 颈椎曲度由于纳入研究对颈椎前凸角度的指标不一，因此未进行Meta分析。Niu等^[35]经过2年的随访认为术后对颈椎病变节段前凸的纠正角度钛笼组与聚醚醚酮组差异无显著性意义(P > 0.05)，在随访结束时两组颈椎病变节段前凸角度的丢失程度差异同样无显著性意义(P > 0.05)。Cabraja等^[36]的研究认为钛笼组与聚醚醚酮组术后较术前颈椎曲度均有明显恢复，但两组之间术后及2年随访结束时颈椎曲度差异均无显著性意义(P > 0.05)。Chen等^[37]的研究认为两组术后颈椎曲度差异无显著性意义 (P > 0.05)，7年随访后聚醚醚酮组颈椎曲度要优于钛笼组，差异有显著性意义(P < 0.05)，在颈椎曲度丢失方面，聚醚醚酮组要小于钛笼组，差异有显著性意义(P < 0.05)。

2.3.3 融合节段椎间隙高度由于纳入研究评价椎间隙高度的指标不一，因此未进行Meta分析。Niu等^[35]的研究发现经过2年的随访，聚醚醚酮组术后椎间隙前缘及后缘高度的丢失要明显小于钛笼组，差异具有显著性意义(P < 0.05)。Chen等^[37]的研究发现，经过7年的随访，聚醚醚酮组术后椎间隙高度的丢失要明显小于钛笼组，差异有显著性意义(P < 0.05)。

2.3.4 下沉移位率 4篇研究对椎间融合器下沉及移位均有描述，对3篇短期研究进行Meta分析^[34-36]，其中钛笼组108个节段，聚醚醚酮组85个节段，对研究结果进行异质性分析，结果不存在异质性(P=0.35，I²= 4%)，因此采用固定效应模型进行分析。结果显示钛笼组与聚醚醚酮组下沉移位率差异无显著性意义(P > 0.05) (图2)。但是在这项长期研究中^[11^，^37]结果显示聚醚醚酮组的下沉移位率要小于钛笼组，差异有显著性意义(P < 0.05)。

2.3.5 临床疗效有3项研究采用Odom标准对临床疗效进行评价^[35-37]，其中2篇为短期^[35-36]，1篇为长期^[37]，但考虑临床疗效短期长期变化不大，因此纳入这3项研究进行Meta分析，其中钛笼组101例患者，聚醚醚酮组98例患者，对研究结果进行异质性分析，结果不存在异质性(P= 0.17，I² = 44%)，因此采用固定效应模型进行分析。结果显示钛笼组与聚醚醚酮组的临床疗效差异无显著性意义(P > 0.05) (图3)。

参考文献

[1] Cloward RB.The anterior approach for removal of ruptured cervical disks.J Neurosurg. 1958;15(6):602-617.

[2] Smith GW, Robinson RA.The treatment of certain cervical-spine disorders by anterior removal of the intervertebral disc and interbody fusion.J Bone Joint Surg Am. 1958;40-A(3):607-624.

[3] Zdeblick TA, Ducker TB.The use of freeze-dried allograft bone for anterior cervical fusions.Spine (Phila Pa 1976). 1991;16(7): 726-729.

[4] Young WF, Rosenwasser RH. An early comparative analysis of the use of fibular allograft versus autologous iliac crest graft for interbody fusion after anterior cervical discectomy.Spine (Phila Pa 1976). 1993;18(9):1123-1124.

[5] Baba H, Furusawa N, Tanaka Y,et al.Anterior decompression and fusion for cervical myeloradiculopathy secondary to ossification of the posterior ligament.Int Orthop. 1994;18(4): 204-209.

[6] An HS, Simpson JM, Glover JM,et al.Comparison between allograft plus demineralized bone matrix versus autograft in anterior cervical fusion. A prospective multicenter study.Spine (Phila Pa 1976). 1995;20(20):2211-2216.

[7] Malloy KM, Hilibrand AS.Autograft versus allograft in degenerative cervical disease.Clin Orthop Relat Res. 2002; (394):27-38.

[8] Truumees E, Demetropoulos CK, Yang KH,et al. Effects of disc height and distractive forces on graft compression in an anterior cervical discectomy model.Spine (Phila Pa 1976). 2002;27(22):2441-2445.

[9] Kaiser MG, Haid RW Jr, Subach BR,et al.Anterior cervical plating enhances arthrodesis after discectomy and fusion with cortical allograft.Neurosurgery. 2002;50(2):229-36.

[10] Thomé C, Krauss JK, Zevgaridis D.A prospective clinical comparison of rectangular titanium cages and iliac crest autografts in anterior cervical discectomy and fusion. Neurosurg Rev. 2004;27(1):34-41.

[11] Jagannathan J, Shaffrey CI, Oskouian RJ,et al.Radiographic and clinical outcomes following single-level anterior cervical discectomy and allograft fusion without plate placement or cervical collar.J Neurosurg Spine. 2008;8(5):420-428.

[12] Francke EI, Demetropoulos CK, Agabegi SS,et al.Distractive force relative to initial graft compression in an in vivo anterior cervical discectomy and fusion model.Spine (Phila Pa 1976). 2010;35(5):526-530.

[13] Younger EM, Chapman MW.Morbidity at bone graft donor sites.J Orthop Trauma. 1989;3(3):192-195.

[14] Zdeblick TA, Phillips FM.Interbody cage devices.Spine (Phila Pa 1976). 2003;28(15 Suppl):S2-7.

[15] Schmieder K, Wolzik-Grossmann M, Pechlivanis I,et al. Subsidence of the wing titanium cage after anterior cervical interbody fusion: 2-year follow-up study.J Neurosurg Spine. 2006;4(6):447-453.

[16] Arrington ED, Smith WJ, Chambers HG,et al.Complications of iliac crest bone graft harvesting.Clin Orthop Relat Res. 1996; (329):300-309.

[17] Goulet JA, Senunas LE, DeSilva GL,et al.Autogenous iliac crest bone graft. Complications and functional assessment.Clin Orthop Relat Res. 1997;(339):76-81.

[18] Brooke NS, Rorke AW, King AT,et al.Preliminary experience of carbon fibre cage prostheses for treatment of cervical spine disorders.Br J Neurosurg. 1997;11(3):221-227.

[19] Cho DY, Liau WR, Lee WY,et al.Preliminary experience using a polyetheretherketone (PEEK) cage in the treatment of cervical disc disease.Neurosurgery. 2002;51(6):1343-1349.

[20] Wang X, Chen Y, Chen D,et al.Anterior decompression and interbody fusion with BAK/C for cervical disc degenerative disorders.J Spinal Disord Tech. 2009;22(4):240-245.

[21] Moreland DB, Asch HL, Clabeaux DE,et al.Anterior cervical discectomy and fusion with implantable titanium cage: initial impressions, patient outcomes and comparison to fusion with allograft.Spine J. 2004;4(2):184-191.

[22] Matgé G.Cervical cage fusion with 5 different implants: 250 cases.Acta Neurochir (Wien). 2002;144(6):539-549.

[23] Hwang SL, Lin CL, Lieu AS,et al.Three-level and four-level anterior cervical discectomies and titanium cage-augmented fusion with and without plate fixation.J Neurosurg Spine. 2004;1(2):160-167.

[24] van Jonbergen HP, Spruit M, Anderson PG,et al. Anterior cervical interbody fusion with a titanium box cage: early radiological assessment of fusion and subsidence.Spine J. 2005;5(6):645-649.

[25] Kao FC, Niu CC, Chen LH,et al.Maintenance of interbody space in one- and two-level anterior cervical interbody fusion: comparison of the effectiveness of autograft, allograft, and cage.Clin Orthop Relat Res. 2005;(430):108-116.

[26] Hwang SL, Hwang YF, Lieu AS,et al.Outcome analyses of interbody titanium cage fusion used in the anterior discectomy for cervical degenerative disc disease.J Spinal Disord Tech. 2005;18(4):326-331.

[27] Katzer A, Marquardt H, Westendorf J,et al. Polyetheretherketone- cytotoxicity and mutagenicity in vitro.Biomaterials. 2002;23(8):1749-1759.

[28] Toth JM, Wang M, Estes BT,et al.Polyetheretherketone as a biomaterial for spinal applications.Biomaterials. 2006;27(3): 324-334.

[29] Boakye M, Mummaneni PV, Garrett M,et al.Anterior cervical discectomy and fusion involving a polyetheretherketone spacer and bone morphogenetic protein.J Neurosurg Spine. 2005;2(5):521-525.

[30] Dorai Z, Morgan H, Coimbra C.Titanium cage reconstruction after cervical corpectomy.J Neurosurg. 2003;99(1 Suppl):3-7.

[31] Cutler AR, Siddiqui S, Mohan AL,et al.Comparison of polyetheretherketone cages with femoral cortical bone allograft as a single-piece interbody spacer in transforaminal lumbar interbody fusion.J Neurosurg Spine. 2006;5(6): 534-539.

[32] Chiang CJ, Kuo YJ, Chiang YF,et al.Anterior cervical fusion using a polyetheretherketone cage containing a bovine xenograftp: three to five-year follow-up.Spine (Phila Pa 1976). 2008;33(23):2524-2528.

[33] Lemcke J, Al-Zain F, Meier U, et al. Polyetheretherketone (PEEK) Spacers for Anterior Cervical Fusion: A Retrospective Comparative Effectiveness Clinical Trial.Open Orthop J. 2011; 5:348-353.

[34] Chou YC, Chen DC, Hsieh WA,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.

[35] Niu CC, Liao JC, Chen WJ,et al.Outcomes of interbody fusion cages used in 1 and 2-levels anterior cervical discectomy and fusion: titanium cages versus polyetheretherketone (PEEK) cages.J Spinal Disord Tech. 2010;23(5):310-316.

[36] Cabraja M, Oezdemir S, Koeppen D,et al.Anterior cervical discectomy and fusion: comparison of titanium and polyetheretherketone cages.BMC Musculoskelet Disord. 2012; 13:172.

[37] Chen Y, Wang X, Lu X,et al.Comparison of titanium and polyetheretherketone (PEEK) cages in the surgical treatment of multilevel cervical spondylotic myelopathy: a prospective, randomized, control study with over 7-year follow-up.Eur Spine J. 2013;22(7):1539-1546.

[38] Odom GL, Finney W, Woodhall B.Cervical disk lesions.J Am Med Assoc. 1958;166(1):23-28.

[39] Barsa P, Suchomel P.Factors affecting sagittal malalignment due to cage subsidence in standalone cage assisted anterior cervical fusion.Eur Spine J. 2007;16(9):1395-1400.

[40] Wilke HJ, Kettler A, Goetz C,et al.Subsidence resulting from simulated postoperative neck movements: an in vitro investigation with a new cervical fusion cage.Spine (Phila Pa 1976). 2000;25(21):2762-2770.

[41] Gercek E, Arlet V, Delisle J,et al.Subsidence of stand-alone cervical cages in anterior interbody fusion: warning.Eur Spine J. 2003;12(5):513-516.

[42] Hacker RJ.A randomized prospective study of an anterior cervical interbody fusion device with a minimum of 2 years of follow-up results.J Neurosurg. 2000;93(2 Suppl):222-226.

[43] Profeta G, de Falco R, Ianniciello G,et al.Preliminary experience with anterior cervical microdiscectomy and interbody titanium cage fusion (Novus CT-Ti) in patients with cervical disc disease.Surg Neurol. 2000;53(5):417-426.

[44] Bärlocher CB, Barth A, Krauss JK,et al.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.

[45] Toth JM, Wang M, Estes BT,et al.Polyetheretherketone as a biomaterial for spinal applications.Biomaterials. 2006;27(3): 324-334.

[46] Mastronardi L, Ducati A, Ferrante L.Anterior cervical fusion with polyetheretherketone (PEEK) cages in the treatment of degenerative disc disease. Preliminary observations in 36 consecutive cases with a minimum 12-month follow-up.Acta Neurochir (Wien). 2006;148(3):307-312.

[47] Vadapalli S, Sairyo K, Goel VK,et al.Biomechanical rationale for using polyetheretherketone (PEEK) spacers for lumbar interbody fusion-A finite element study.Spine (Phila Pa 1976). 2006;31(26):E992-998.

[48] Yang JJ, Yu CH, Chang BS,et al.Subsidence and nonunion after anterior cervical interbody fusion using a stand-alone polyetheretherketone (PEEK) cage.Clin Orthop Surg. 2011; 3(1):16-23.

[49] Kulkarni AG, Hee HT, Wong HK.Solis cage (PEEK) for anterior cervical fusion: preliminary radiological results with emphasis on fusion and subsidence.Spine J. 2007;7(2): 205-209.

[50] Dufour T, Huppert J, Louis C,et al.Radiological analysis of 37 segments in cervical spine implanted with a peek stand-alone device, with at least one year follow-up.Br J Neurosurg. 2010; 24(6):633-640.

[51] Ha SK, Park JY, Kim SH,et al.Radiologic Assessment of Subsidence in Stand-Alone Cervical Polyetheretherketone (PEEK) Cage.J Korean Neurosurg Soc. 2008;44(6):370-374.

[52] Kolstad F, Nygaard ØP, Andresen H,et al.Anterior cervical arthrodesis using a "stand alone" cylindrical titanium cage: prospective analysis of radiographic parameters.Spine (Phila Pa 1976). 2010;35(16):1545-1550.

[53] Shousha M, Ezzati A, Boehm H.Four-level anterior cervical discectomies and cage-augmented fusion with and without fixation.Eur Spine J. 2012;21(12):2512-2519.

[54] Song KJ, Yoon SJ, Lee KB.Three- and four-level anterior cervical discectomy and fusion with a PEEK cage and plate construct.Eur Spine J. 2012;21(12):2492-2497.

引言

材料方法

讨论

颈前路椎间盘切除椎间融合术(anterior cervical discectomy with interbody fusion，ACDF)是治疗神经根型颈椎病及脊髓型颈椎病的常用方法。从髂骨取三皮质骨作为椎间融合材料具有良好的临床疗效及影像学结果。但是髂骨取骨也会产生骨质破损及一系列取骨处并发症，同时第二道切口也可能会延长手术时间。在临床中作者发现患者对髂骨取骨处疼痛的主诉要高远高于颈部切口疼痛的主诉，因此这也会增加患者的住院时间。而椎间融合器的出现则避免了这些问题的发生。

目前应用于颈前路椎间盘切除椎间融合手术的椎间融合器材料有很多种，包括金属、碳纤维、聚醚醚酮等。本次研究主要对钛笼与聚醚醚酮椎间融合器在影像学及临床疗效上给予对比分析。

3.1 钛笼的特点 钛笼具有较好的融合率，但是部分报道钛笼的下沉率稍高，所以钛笼的长期应用可能会出现椎间隙高度丢失致再次出现神经症状，进而需要二次手术翻修^[39-44]。Hwang等^[26]的研究对78例行颈前路椎间盘切除椎间融合手术的患者使用钛笼椎间融合器，在影像学上，患者术后神经根孔高度增加，颈椎后凸得以纠正，最终融合率为95%。临床疗效上神经根型颈椎病患者的临床优良率为92%，脊髓型颈椎病患者的临床优良率为69%。 Schmieder等^[15]报道融合率为98%。但是许多研究认为钛笼也具有其劣势。Gercek等^[41]的研究报道了9个融合节段有5个出现钛笼下沉。Schmieder等^[15]报道，经过2年的随访67个融合节段有30个节段出现钛笼下沉。Barsa等^[39]的研究中下沉率为13.2%，在下沉的节段中伴随颈椎前凸的丢失，但颈椎整体曲度无明显改变。

导致钛笼下沉的风险因素包括终板的准备、融合器与终板接触面的大小、椎体的骨密度等^{[8, 16-17, 39]}，但对下沉率影响最大的因素是椎间融合器的材料。

3.2 聚醚醚酮椎间融合器特点 聚醚醚酮材料已经被证明无细胞毒性及致突变性^[27]，并且具有很好的生物相容性、非可吸收性及抗腐蚀性^{[27, 45]}，除此之外聚醚醚酮的弹性模量还与骨相似。因此许多研究认为聚醚醚酮的这些特性可以预防椎间融合器的下沉^[45-54]。Chou等^[34]对9例颈前路椎间盘切除椎间融合手术置入聚醚醚酮椎间融合器，1年后融合率为100%。Niu等^[35]对34个节段置入聚醚醚酮椎间融合器，经过1年的随访，融合率为100%，无一例融合器下沉。Cabraja等^[36]对42个节段置入聚醚醚酮椎间融合器，经过2年的随访，融合率为88.1%，融合器下沉率为14.28%。Chen等^[37]对93个节段置入聚醚醚酮椎间融合器，7年的随访后全部节段均融合，融合器下沉率为5.4%。在临床疗效方面，Niu等^[35]的研究优良率为80%，Cabraja等^[36]为64.3%，Chen等^[37]为74.2%。

在此次研究中，钛笼与聚醚醚酮椎间融合器在融合率方面差异无显著性意义。在下沉移位率方面，短期钛笼与聚醚醚酮差异无显著性意义，但在长期随访中聚醚醚酮下沉移位率要低于钛笼。在临床疗效方面，钛笼与聚醚醚酮差异无显著性。因此作者认为，虽然之前的研究在融合率上有争议，但本次研究未发现统计学差异，因此在融合率方面聚醚醚酮并不占优势。但是在下沉移位率方面，虽然短期二者无明显差异，但是聚醚醚酮对于长期维持椎间隙高度效果更好。在临床疗效上，钛笼和聚醚醚酮都能达到较好的优良率。聚醚醚酮具有好的融合率及临床疗效，并且可以长期维持椎间隙高度，因此是较为理想的颈椎前路椎间融合植入材料。

但是研究仍有一定局限性：①仅纳入4项研究，供235例患者，395个节段，样本量较少。②纳入的4项研究仅有1项研究采用随机方法，并且文献总体质量不高。③4项研究对单一患者椎间融合器使用数量不一，有的仅仅对单节段使用进行对比，有的只对多节段使用进行对比，而有的研究纳入的人群部分需单节段使用，部分需多节段使用。而置入融合器数量的不同对术后影像学及临床疗效均有一定影响。这些均会影响到结论的稳定性。因此今后仍然需要开展高质量的随机大样本对照研究，并对椎间融合器置入节段及置入数量进行限定，以期对临床工作提供更好的指导作用。

中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程
全文链接：