The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year follow-up of a pilot study
The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year follow-up of a pilot study
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DOI：
10.1016/j.spinee.2007.03.012
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发表时间：
2008-05-01
期刊：
影响因子：
4.5
通讯作者：
Fischgrund, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Vaccaro, Alexander R.;Whang, Peter G.;Fischgrund, Jeffrey S.
背景情况：虽然自体骨仍然被认为是促进脊柱融合的金标准移植材料，但已开发出其他骨移植替代品，以提高关节融合率并避免与自体移植物采购相关的并发症。骨形态发生蛋白（BMPs）是一个骨诱导生长因子家族，已知其可刺激骨细胞的成骨分化。成骨蛋白-1（OP-1）腻子是一种商业上可获得的BMP制剂，已被批准用于人类。既往的退行性腰椎滑脱患者临床研究报告称，OP-1腻子的疗效和安全性在1年和2年随访时与自体移植物相当。目的：本研究的目的是通过比较4年的影像学、临床、研究设计/背景：一项前瞻性、随机、对照、多中心临床试验研究。36例接受椎板减压术和单-退行性腰椎滑脱和症状性椎管狭窄的节段非内固定融合，以2：1的比例随机接受OP-1腻子（24例患者）或自体髂嵴植骨（12名患者）。患者报告的结局指标，包括奥斯韦斯特里残疾指数和医学结局研究36项健康调查简表（SF-36）评分用于评价临床疗效。还记录了每次手术的围手术期数据，包括手术时间、估计失血量和住院时间。术后，在每次随访访视时进行神经系统检查和供体部位疼痛评估（如适用）。影像学融合成功定义为在滑脱节段的横突之间存在连续的桥接骨形成，动态侧位X线片显示活动最小。主要有效性终点是总体成功率，这是一个来自影像学和临床参数的复合指标。OP-1油灰的安全性得到证实，通过比较的性质和频率的所有不良事件和并发症，前瞻性地观察在任何group.METHODS：36例退行性脊椎前移和症状的神经源性跛行进行减压椎板切除术和单级非仪器融合OP-1油灰或自体移植。在6周和3、6、9、12和24个月时对所有患者进行评价，之后指导他们每年返回一次。多名神经放射科医生对分配的治疗设盲，使用数字卡尺审查静态和动态X线片，根据横突上是否存在连续桥接骨以及感兴趣节段明显的残余活动量评估融合状态。奥斯韦斯特里残疾指数调查和SF-36问卷被用来评估临床outcome.Results：在48个月的时间点，完整的影像学和临床数据，分别为22 36例（16 OP-1油灰和6自体移植）和25 36例（18 OP-1油灰和7自体移植）。16名OP-1 Putty患者中有11名（68.8%）和6名自体移植物患者中有3名（50%）存在牢固关节融合术的影像学证据。19例OP-1油灰患者中有14例（73.7%）和7例自体移植患者中有4例（57.1%）获得了临床成功结局（定义为术前奥斯韦斯特里评分至少改善20%）; SF-36评分的相似增加证实了这些临床结果。OP-1油灰和自体移植物组的总体成功率分别为62.5%和33.3%。在这项研究中，没有发生局部或全身毒性、异位骨生成或其他与OP-1腻子的使用直接相关的不良事件。尽管在退行性腰椎滑脱患者中获得坚固的非内固定融合存在挑战，但影像学融合率、临床改善，手术后至少48个月内，与使用OP-1油灰相关的总体成功至少与自体移植对照相当。这些结果似乎验证了先前报告的OP-1油灰的短期结果，并表明该材料可能代表某些融合应用的可行骨移植替代品。(C)2008年爱思唯尔公司All rights reserved.
BACKGROUND CONTEXT: Although autogenous bone is still considered to be the gold standard graft material for promoting spinal fusion, other bone graft substitutes have been developed in an attempt to improve arthrodesis rates and avoid the complications associated with the procurement of autograft. The bone morphogenetic proteins (BMPs) represent a family of osteoinductive growth factors that are known to stimulate the osteoblastic differentiation of stein cells. Osteogenic protein-1 (OP-1) Puttyis a commercially available BMP preparation that is already approved for use in humans. Previous clinical studies involving patients with degenerative spondylolisthesis have reported that the efficacy and safety of OP-1 Putty is comparable to that of autograft at both 1- and 2-year follow-up.PURPOSE: The purpose of this study was to evaluate the intermediate-term efficacy and safety of OP-1 Putty as an alternative to autogenous bone by comparing the 4-year radiographic, clinical, and safety data of these same patients who underwent decompression and uninstrumented fusion with either OP-1 Putty or iliac crest autograft.STUDY DESIGN/SETTING: A prospective, randomized, controlled, multicenter clinical pilot study.PATIENT SAMPLE: Thirty-six patients undergoing decompressive laminectomy and single-level uninstrumented fusion for degenerative spondylolisthesis and symptomatic spinal stenosis were randomized in a 2:1 fashion to receive either OP-1 Putty (24 patients) or autogenous iliac crest bone graft (12 patients).OUTCOME MEASURES: Patient-reported outcome measures consisting of Oswestry Disability Index and Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) scores were used to evaluate clinical efficacy. Perioperative data including operative time, estimated blood loss, and duration of hospital stay were also recorded for each surgery. Postoperatively, a neurological examination and an assessment of donor-site pain (if applicable) were performed at every follow-up visit. Radiographic fusion success was defined as the presence of continuous bridging bone formation between the transverse processes at the level of the spondylolisthesis with minimal motion evident on dynamic lateral x-ray films. The primary efficacy endpoint was the overall success rate, a composite measure derived from both radiographic and clinical parameters. The safety of OP-1 Putty was confirmed by comparing the nature and frequency of all adverse events and complications that were prospectively observed in either of the groups.METHODS: Thirty-six patients with degenerative spondylolisthesis and symptoms of neurogenic claudication underwent decompressive laminectomy and single-level uninstrumented fusion with either OP-1 Putty or autograft. All patients were evaluated at 6 weeks and 3, 6, 9, 12, and 24 months, after which time they were instructed to return on a yearly basis. Multiple neuroradiologists blinded to the assigned treatment reviewed static and dynamic X-ray films with digital calipers to assess fusion status according to the presence of continuous bridging bone across the transverse processes as well as the amount of residual motion evident at the level of interest. Oswestry Disability Index surveys and SF-36 questionnaires were used to assess clinical outcomes.RESULTS: At the 48-month time point, complete radiographic and clinical data were available for 22 of 36 patients (16 OP-1 Putty and 6 autograft) and 25 of 36 patients (18 OP-1 Putty and 7 autograft), respectively. Radiographic evidence of a solid arthrodesis was present in 11 of 16 OP-1 Putty patients (68.8%) and 3 of 6 autograft patients (50%). Clinically successful outcomes defined as at least a 20% improvement in preoperative Oswestry scores were experienced by 14 of 19 OP-1 Putty patients (73.7%) and 4 of 7 autograft patients (57.1%); these clinical findings were corroborated by similar increases in SF-36 scores. The respective overall success rates of the OP-1 Putty and autograft group were 62.5% and 33.3%. In this study, there were no incidents of local or systemic toxicity, ectopic bone production, or other adverse events directly related to the use of OP-1 Putty.CONCLUSION: Despite the challenges associated with obtaining a solid uninstrumented fusion in patients with degenerative spondylolisthesis, the rates of radiographic fusion, clinical improvement, and overall success associated with the use of OP-1 Putty were at least comparable to that of the autograft controls for at least 48 months after surgery. These results appear to validate the short-term results previously reported for OP-1 Putty and suggest that this material may potentially represent a viable bone graft substitute for certain fusion applications. (C) 2008 Elsevier Inc. All rights reserved.