Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans - A prospective, randomized clinical pilot trial - 2002 Volvo Award in clinical studies
Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans - A prospective, randomized clinical pilot trial - 2002 Volvo Award in clinical studies
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DOI：
10.1097/00007632-200212010-00005
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发表时间：
2002-12-01
期刊：
影响因子：
3
通讯作者：
Heller, JG
中科院分区：
文献类型：
--
作者：
Boden, SD;Kang, J;Heller, JG
研究设计。这是一项前瞻性随机临床研究。确定在恒河猴身上成功的剂量和载体是否可以在人类体内诱导一致的放射学脊柱融合。临床前研究表明，重组人骨形态发生蛋白-2(rhBMP-2)是一种骨诱导性骨形态发生蛋白，可成功地在兔和猕猴体内诱导脊柱融合。在这项研究中，25名接受腰椎融合术的患者被随机分为三组：自体植骨/德克萨斯苏格兰礼特医院椎弓根螺钉内固定组(n=5)、重组人骨形态发生蛋白-2/TSRHG组(n=11)和单纯重组骨形态发生蛋白-2内固定组(n=9)。每侧各20 mg，载体由60%羟基磷灰石和40%磷酸三钙颗粒组成(10 cm(3)/侧)。患者有单节段腰椎退变、2级及以下滑脱、机械性下腰痛伴或不伴小腿疼痛、非手术治疗失败至少6个月。所有25例患者均可进行随访评估(平均17个月，范围12-27个月)。放射学融合率分别为40%(2/5)和100%(20/20)(P=0.004)。在移植后6周，单纯应用重组人骨形态发生蛋白-2组(-17.6；P=0.009)和移植后3个月组(-17.9；P=0.003)有统计学意义的改善，而自体移植+促性腺激素释放激素组直到6个月(-17.3；P=0.041)才有显著改善。在最终的随访评估中，仅使用重组人骨形态发生蛋白-2组的OSwestry改善最大(-28.7，P<；0.001)。SF-36疼痛指数和PCS分量表也有类似的变化。这项初步研究是第一次进行至少一年的随访评估，证明了使用基于BMP的骨移植替代品成功地进行了后外侧脊柱融合，并以X线片和CT扫描为决定因素。无论是否使用内固定，当给药剂量为每侧20 mg时，rhBMP-2始终能够在腰椎后外侧诱导成骨。滑脱分级高于Meyerding 1级或平移运动超过5 mm的患者仍需内固定。术后部分患者吸烟，rhBMP-2组所有患者仍获得固体融合。在腰椎滑脱不超过1级的患者中，rh BMP-2加双相磷酸钙颗粒可诱导放射学腰椎后外侧融合，内固定或不内固定均可。在统计学上，rh BMP-2组患者的临床结果有更大和更快的改善。
Study Design. A prospective randomized clinical study was conducted.Objective. To determine whether the dose and carrier that were successful in rhesus monkeys could induce consistent radiographic spine fusion in humans.Summary of Background Data. Preclinical studies have demonstrated that recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive bone morphogenetic protein, is successful at generating spine fusion in rabbits and rhesus monkeys.Methods. For this study, 25 patients undergoing lumbar arthrodesis were randomized (1:2:2 ratio) based on the arthrodesis technique: autograft/Texas Scottish Rite Hospital (TSRH) pedicle screw instrumentation (n = 5), rhBMP-2/TSRHG (n = 11), and rhBMP-2 only without internal fixation (n = 9). n each side, 20 mg of rhBMP-2 were delivered on a carrier consisting of 60% hydroxyapatite and 40% tricalcium phosphate granules (10 cm(3)/side). The patients had single-level disc degeneration, Grade 2 or less spondylolisthesis, mechanical low back pain with or without leg pain, and at least 6 months failure of non-operative treatment.Results. All 25 patients were available for follow-up evaluation (mean, 17 months; range 12-27 months). The radiographic fusion rate was 40% (2/5) in the autograft/TSRH group and 100% (20/20) with rhBMP-2 group with or without TSRH internal fixation (P = 0.004). A statistically significant improvement in Oswestry score was seen at 6 weeks in the rhBMP-2 only group (-17.6; P = 0.009), and at 3 months in the rhBMP-2/TSRH group (-17.9; P = 0.003), but not until 6 months in the autograft/TSRH group (-17.3; P = 0.041). At the final follow-up assessment, Oswestry improvement was greatest in the rhBMP-2 only group (-28.7, P < 0.001). The SF-36 Pain Index and PCS subscales showed similar changes.Discussion. This pilot study is the first with at least 1 year of follow-up evaluation to demonstrate successful posterolateral spine fusion using a BMP-based bone graft substitute, with radiographs and CT scans as the determinant. Consistently, rhBMP-2 was able to induce bone in the posterolateral lumbar spine when delivered at a dose of 20 mg per side with or without the use of internal fixation. Patients with spondylolisthesis classified higher than Meyerding Grade 1 or with more than 5 mm of translational motion may still require internal fixation. Some patients did smoke during the postoperative period, and all in the rhBMP-2 groups still obtained solid fusions.Conclusions. consistently, rhBMP-2 with the biphasic calcium phosphate granules induced radiographic posterolateral lumbar spine fusion with or without internal fixation in patients whose spondylolisthesis did not exceed Grade 1. Statistically greater and quicker improvement in patient-derived clinical outcome was measured in the rhBMP-2 groups.