Vaccaro Alexander R, Patel Tushar, Fischgrund Jeffrey, Anderson D Greg, Truumees Eeric, Herkowitz Harry, Phillips Frank, Hilibrand Alan, Albert Todd J
Department of Orthopaedic Surgery, Thomas Jefferson University, The Rothman Institute, 925 Chestnut St, 5th Floor, Philadelphia, PA 19107, USA.
Eur Spine J. 2003 Oct;12(5):495-500. doi: 10.1007/s00586-003-0561-8. Epub 2003 Aug 8.
The ability of bone morphogenetic proteins (BMPs) to induce bone formation has led to an increasing interest in the potential for their use in fusion surgery. The purpose of this multi-center clinical pilot study was to evaluate the safety of one such BMP-osteogenic protein 1, in the form of OP-1 putty-combined with autograft for intertransverse process fusion of the lumbar spine in patients with symptomatic spinal stenosis and degenerative spondylolisthesis following spinal decompression. Twelve patients with spinal stenosis and degenerative lumbar spondylolisthesis underwent laminectomy and partial or complete medial facetectomy as required for decompression of the neural elements followed by intertransverse process fusion by placing iliac crest autograft and OP-1 putty between the decorticated transverse processes. No instrumentation was used. Patients were followed clinically using the Oswestry scale and radiographically using static and dynamic radiographs to assess their fusion status. Independent and blinded radiologists assessed the films for the presence of bridging bone between the transverse processes and measured translation and angulation on dynamic films using digital calipers. In addition to bridging bone, less than or equal to 5 degrees of angular motion and less than or equal to 2 mm of translation were required to classify the patients as successfully fused, as per the definition of successful fusion provided by the FDA for use in clinical trials involving investigational devices to attain spinal fusion. Radiographic outcome was compared to a historical control (autograft alone fusion without instrumentation for the treatment of degenerative spondylolisthesis). All adverse events were recorded prospectively. The results showed 9 of the 12 patients (75%) obtained at least a 20% improvement in their preoperative Oswestry score, while 6 of 11 patients (55%) with radiographic follow-up achieved a solid fusion by the criteria used in this study. Bridging bone on the anteroposterior film was observed in 10 of the 11 patients (91%). No systemic toxicity, ectopic bone formation, recurrent stenosis or other adverse events related to the OP-1 putty implant were observed. A successful fusion was observed in slightly over half the patients in this study, using stringent criteria without adjunctive spinal instrumentation. This study did not demonstrate the superiority of OP-1 combined with autograft over an autograft alone historical control, in which the fusion rate was approximately 45%. The lack of adverse events related to the OP-1 putty implant in this study is in agreement with other studies supporting the safety of bone morphogenetic proteins in spinal surgery.
骨形态发生蛋白（BMPs）诱导骨形成的能力，使得人们对其在融合手术中的应用潜力越来越感兴趣。这项多中心临床试点研究的目的是评估一种这样的BMP——成骨蛋白1（以OP-1油灰的形式）与自体骨移植相结合，用于有症状的椎管狭窄和减压术后退行性腰椎滑脱患者腰椎横突间融合的安全性。12例患有椎管狭窄和退行性腰椎滑脱的患者接受了椎板切除术，并根据需要进行部分或完全内侧小关节切除术，以减压神经组织，随后通过在去皮质的横突之间放置髂嵴自体骨和OP-1油灰进行横突间融合。未使用内固定器械。使用Oswestry量表对患者进行临床随访，并使用静态和动态X线片进行影像学随访，以评估其融合状态。独立且不知情的放射科医生评估X线片上横突之间是否存在桥接骨，并使用数字卡尺测量动态X线片上的移位和角度。根据美国食品药品监督管理局（FDA）为涉及研究性器械以实现脊柱融合的临床试验提供的成功融合定义，除了桥接骨外，患者角度运动小于或等于5度且移位小于或等于2毫米才能被分类为成功融合。将影像学结果与历史对照（仅自体骨移植融合，未使用内固定器械治疗退行性腰椎滑脱）进行比较。前瞻性记录所有不良事件。结果显示，12例患者中有9例（75%）术前Oswestry评分至少提高了20%，而11例接受影像学随访的患者中有6例（55%）根据本研究使用的标准实现了牢固融合。11例患者中有10例（91%）在前后位X线片上观察到桥接骨。未观察到与OP-1油灰植入物相关的全身毒性、异位骨形成、再狭窄或其他不良事件。在本研究中，使用严格标准且无辅助脊柱内固定器械的情况下，略超过一半的患者观察到了成功融合。本研究未证明OP-1与自体骨移植联合使用优于仅自体骨移植的历史对照，后者的融合率约为45%。本研究中未观察到与OP-1油灰植入物相关的不良事件，这与其他支持骨形态发生蛋白在脊柱手术中安全性的研究一致。
