骨形成蛋白-2/7在腰椎融合中效果的META分析
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摘要
目的
应用骨形成蛋白(BMP-2及BMP-7)进行腰椎融合与单纯应用传统植骨(包括自体骨、异体骨及人工骨)材料进行腰椎融合的效果进行系统评价。
方法
计算机及手工检索相关的中英文杂志,检索相关文献的参考文献。收集所有关于应用骨形成蛋白进行腰椎融合与应用传统植骨方法进行腰椎融合术后临床效果比较的随机及类随机对照研究,并评价纳入研究的方法学质量。统计软件应用Cochrane协作网提供的RevMan5.0.18。
结果
共纳入符合标准的相关文献14篇。Meta分析表明：1.在腰椎前路及后路的椎间融合和后外侧融合中应用BMP-2比传统植骨融合方式有更好的融合率；在后外侧融合中应用BMP-7与传统植骨融合方式相比融合率没有差别；2.与传统植骨融合方式相比,应用BMP-2／7进行腰椎融合的术后疗效没有差别。
结论
应用BMP-2进行腰椎融合可提高术后融合率,但与疗效无关。
Objective
To evaluate the effectiveness of bone morphogenetic proteins-2/7(BMP-2/7) versus traditional standard treatment (include autograft, allograft and artificial material graft) in lumbar fusion.
Methods
Randomized and quasi-randomized controlled trials were identified from Pubmed, EBSCO, Springer and CBM(Chinese Biological and Medical database).We handsearch the relative reference, Chinese and English orthopaedic journals. The data of the articles were evaluated by Jadad form. RevMan 5.0.18 were used to analysis the data.
Results
Fourteen randomized or quasi-randomized controlled trials were included. The combined results showed that compare with the traditional standard treatment, using the BMP-2/7 in lumbar fusion proved:1. the higher fusion rate in the cases which used BMP-2 in anterior or posterior lumbar interbody fusion and posterolateral lumbar fusion, but using BMP-7 could not lead to higher fusion rate in posterolateral lumbar fusion,2. There is no better outcome when using BMP-2/7.
Conclusion
Compared with traditional standard treatment, the outcome of fusion with BMP-2/7 is similar but with higher fusion rate when using BMP-2 in lumbar fusion.
应用骨形成蛋白(BMP-2及BMP-7)进行腰椎融合与单纯应用传统植骨(包括自体骨、异体骨及人工骨)材料进行腰椎融合的效果进行系统评价。
方法
计算机及手工检索相关的中英文杂志,检索相关文献的参考文献。收集所有关于应用骨形成蛋白进行腰椎融合与应用传统植骨方法进行腰椎融合术后临床效果比较的随机及类随机对照研究,并评价纳入研究的方法学质量。统计软件应用Cochrane协作网提供的RevMan5.0.18。
结果
共纳入符合标准的相关文献14篇。Meta分析表明：1.在腰椎前路及后路的椎间融合和后外侧融合中应用BMP-2比传统植骨融合方式有更好的融合率；在后外侧融合中应用BMP-7与传统植骨融合方式相比融合率没有差别；2.与传统植骨融合方式相比,应用BMP-2／7进行腰椎融合的术后疗效没有差别。
结论
应用BMP-2进行腰椎融合可提高术后融合率,但与疗效无关。
Objective
To evaluate the effectiveness of bone morphogenetic proteins-2/7(BMP-2/7) versus traditional standard treatment (include autograft, allograft and artificial material graft) in lumbar fusion.
Methods
Randomized and quasi-randomized controlled trials were identified from Pubmed, EBSCO, Springer and CBM(Chinese Biological and Medical database).We handsearch the relative reference, Chinese and English orthopaedic journals. The data of the articles were evaluated by Jadad form. RevMan 5.0.18 were used to analysis the data.
Results
Fourteen randomized or quasi-randomized controlled trials were included. The combined results showed that compare with the traditional standard treatment, using the BMP-2/7 in lumbar fusion proved:1. the higher fusion rate in the cases which used BMP-2 in anterior or posterior lumbar interbody fusion and posterolateral lumbar fusion, but using BMP-7 could not lead to higher fusion rate in posterolateral lumbar fusion,2. There is no better outcome when using BMP-2/7.
Conclusion
Compared with traditional standard treatment, the outcome of fusion with BMP-2/7 is similar but with higher fusion rate when using BMP-2 in lumbar fusion.
引文
1 Schilephake H. Bone growth factors in maxillofacial skeletal reconstruction. Int J Oral Maxillofac Surg.2002; 31:469-84.
2 Nakashima M, Reddi AH. The application of bone morphogenetic proteins to dental tissue engineering. Nat Biotechnol.2003; 21:1025-32.
3 Salata LA, Franke-Stenpart V, Rasmusson L. Recent outcomes and perspectives of the application of bone morphogenetic proteins in implantd entistry. Clin Implant Dent Relat Res.2002; 4:27-32.
4 Urist MR. Bone formation by autoinduction. Science.1965; 150:893-9.
5 Urist MR, Strates BS. Bone morphogenetic protein. J Dent Res.1971; 50:1392-406.
6 van der Horst G, Van Bezooijen RL, Deekers MM, et al. Differentiation ofmurine preosteoblastic KS483 cells depends on autocrine bone morphogenetic protein signaling during all phases of osteoblast formation. Bone.2002; 31:661-9.
7 Vaccaro AR, Patel T, Fischgrund J, et al. A pilot study evaluating the safety and efficacy of OP-1 putty (rhBMP-7) as a replacement for iliac crest autograft in posterolateral lumbar arthrodesis for degenerative spondylolisthesis. Spine.2004; 29:1885-92.
8 Vaccaro AR, Whang PG, Patel T, et al. 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. Spine.2008; 8:457-65.
9 Boden SD, Zdeblick TA, Sandhu HS, et al. The use of rhBMP-2 in interbody fusion cages. Definitive evidence of osteoinduction in humans:A preliminary report. Spine.2000; 25:376-81.
10 Burkus JK, Transfeldt EE, Kitchel SH, et al. Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bonemorphogenetic protein-2. Spine.2002; 27:2396-408.
11 Burkus JK, Gornet MF, Dickman CA, et al. Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages. J Spinal Disord Tech.2002; 15:337-49.
12 Boden SD, Kang J, Sandhu H, et al. 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. Spine.2002; 27:2662-73.
13 Johnsson R, Stromqvist B, Aspenberg P. Randomized radiostereometric studycomparing osteogenicprotein 1(BMP-7) and autograft bone in human noninstrumented posterolateral lumbar fusion:2002 Volvo Award in clinical studies. Spine.2002; 27:2654-61.
14 Burkus JK, Dorchak JD, Sanders DL. Radiographic assessment of interbody fusion using recombinant human morphogenetic protein type 2. Spine.2003; 28:372-7.
15 Haid RW, Branch CL, Alexander JT, et al. Posterior lumbar interbody fusion using recombinant human bone morphogenetic protein type 2 with cylindrical interbody cages. Spine.2004; 4:527-39.
16 Burkus JK, Sandhu HS, Gornet MF, et al. Use of rhBMP-2 in combination with structural cortical allografts:Clinical and radiographic outcomes in anterior lumbar spinal surgery. J Bone Joint Surg Am.2005; 87:1205-12.
17 Kanayama M, Hashimoto T, Shigenobu K, et al. A prospective randomized study of posterolateral lumbar fusion using osteogenic protein-1(OP-1) versus local autograft with ceramic bone substitute. Spine.2006; 31:1067-74.
18 Glassman SD, Dimar JR, Carreon LY, et al. Initial fusion rates with recombinant human bone morphogenetic protein-2/compression resistant matrix and a hydroxyapatite and tricalcium phosphate/collagen carrier in posterolateral spinal fusion. Spine.2005; 30:1694-98.
19 Dimar JR, Glassman SD, Burkus KJ, et al. Clinical outcomes and fusion success at 2 years of single-Level instrumented posterolateral fusions with recombinant human bone morphogenetic protein-2/compression resistant matrix versus iliac crest bone graft. Spine.2006; 31:2534-39.
20 Dimar JR, Glassman SD, Burkus JK, et al. Clinical and radiographic analysis of an optimized rhBMP-2 formulation as an autograft replacement in posterolateral lumbar spine arthrodesis. J Bone Joint Surg Am.2009; 91:1377-86.
21 Dawson E, Bae HW, Burkus KJ, et al. Recombinant human bone morphogenetic protein-2 on an absorbable collagen sponge with an osteoconductive bulking agent in posterolateral arthrodesis with instrumentation. A prospective randomized trial. J Bone Joint Surg Am.2009; 91:1604-13.
22 Kurz LT, Garfin SR, Booth RE. Harvesting autogenous iliac bone grafts:A review of complications and techniques. Spine.1989; 14:1324-31.
23 Fernyhough JC, Schimandale JJ, Weigel MC, et al. Chronic donor site pain complicating bone graft harvesting from the posterior iliac crest for spinal fusion. Spine.1992; 17:1474-80.
24 Solomon L. Bone grafts. J Bone Joint Surg Br.1991; 73:706-7.
25 Carlisle E, Fischgrund JS. Bone morphogenetic proteins for spinal fusion. Spine J.2005; 5:240-249.
26 Burkus JK, Heim SE, Gornet MF, et al. Is INFUSE bone graft superior to autograft bone? An integrated analysis of clinical trials using the LT-CAGE lumbar tapered frsion device. J Spinal Disord Tech.2003; 16:113-122.
27 Mussano F, Ciccone G, Ceccarelli M, et al. Bone morphogenetic proteins and bone defects. A systematic review. Spine.2007; 32:824-830.
28 Martin TJ, Boden SD, Marone MA, et al. Posterolateral intertransverse process spinal arthrodesis with rhBMP-2 in non-human primate:important lessons learned regarding dose, carrier and safety. J Spinal Disord.1999; 12:179-86.
29 Vaccaro AR, Anderson DG, Toth CA. Recombinant human osteogenic protein-1 (bone morphogenetic protein-7) as an osteoinductive agent in spinal fusion. Spine.2002; 27:59-65.
30 Sandhu HS. Bone morphogenetic proteins and spinal surgery. Spine.2003; 28:64-73.
1 Samartzis D. Does rigid instrumentation increase the fusion rate in onelevel anterior cervical discectomy and fusion. Spine.2004; 4:636-643.
2 Kurz LT, Garfin SR, Booth RE. Harvesting autogenous iliac bone grafts:A review of complications and techniques. Spine.1989; 14:1324-31.
3 Fernyhough JC, Schimandale JJ, Weigel MC, et al. Chronic donor site pain complicating bone graft harvesting from the posterior iliac crest for spinal fusion. Spine.1992; 17:1474-80.
4 Solomon L. Bone grafts. J Bone Joint Surg Br.1991; 73:706-7.
5 Urist MR. Bone formation by autoinduction. Science.1965; 150:893-9.
6 Urist MR, Strates BS. Bone morphogenetic protein. J Dent Res.1971; 50:1392-406.
7 Wozney JM, Rosen V, Celeste AJ, et al. Novel regulators of bone formation:Molecular clones and activities. Science.1998; 242:1528-34.
8 Reddi AH. Role of morphogenetic proteins in skeletal tissue engineering and regeneration. Nat Biotechnol.1998; 16:247-52.
9 van der Horst G, van Bezooijen RL,Deekers MM, et al. Differentiation of murine preosteoblastic KS483 cells depends on autocrine bone morphogenetic protein signaling during all phases of osteoblast formation. Bone.2002; 31:661-9.
10 Cheng H, Jiang W, Phillips FM, et al. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am.2003; 85:1544-52.
11 Sandhu HS, Toth JM, Diwan AD, et al. Histologic evaluation of theefficacy of rhBMP-2 compared with autograft bone in sheep spinalanterior interbody fusion. Spine.2002; 27:567-75.
12 Sandhu HS, Kabo JM, Turner AS, et al. rhBMP-2 augmentation of titanium fusion cages for experimental anterior lumbar fusion. Annual Meeting of the North American Spine Society.1996; New York, NY.
13 Sidhu KS, Prochnow TD, Schmitt P, et al. Anterior cervical interbody fusion with rhBMP-2 andtantalum in a goat model. Spine.2001; 1:331-40.
14 Boden SD, Martin GJ, Horton WC. Laparoscopic anterior spinal arthrodesis with rhBMP-2 in a titanium interbody threaded cage. J Spinal Disord.1998; 11:95-101.
15 Hecht BP, Fischgrund JS,Herkowitz HN, et al. The use of recombinant human bone morphogenetic protein2 (rhBMP-2) to promote spinal fusion in a nonhuman primate anterior interbody fusion model. Spine.1999; 24:629-36.
16 Schimandle JH,Boden SD,Hutton WC. Experimental spinal fusion with recombinant human bone morphogenetic protein-2. Spine.1995; 20:1326-37.
17 Sandhu HS,Kanim LE, Kabo JM, et al. Effective doses of recombinant human bone morphogenetic protein-2:an experimental spinal fusion. Spine.1996; 21:2115-22.
18 Sandhu HS, Kanim LE, Toth JM, et al. Experimental spinal fusion with recombinant human bone morphogenetic protein-2,without decortication of osseous elements. Spine 1997; 22:1171-80.
19 Fischgrund JS, James SB, Chabot MS, et al. Augmentation of autograft using rhBMP-2 and different carrier media in the canine spinal fusion model. J Spinal Disord.1997; 10:467-72.
20 Martin TJ Jr, Boden SD, Marone MA, et al. Posterolateral intertransverse process spinal arthrodesis with rhBMP-2 in non-human primate:important lessons learned regarding dose, carrier and safety. J Spinal Disord.1999; 12:179-86.
21 Boden SD, Martin GJ, Morone MA, et al. Posterolateral intertransverse process spinal arthrodesis with rhBMP-2/hydroxyapatite-tricalcium phosphate after laminectomy in the non human primate. Spine.1999; 24:1179-85.
22 Boden SB,Zdeblick TA, Sandhu HS, et al. The use of rhBMP-2in interbody fusion cages. Definitive evidence of osteoinduction inhumans:a preliminary report. Spine.2000; 25:376-81.
23 Burkus JK,Gornet MF, Dickman CA, et al. Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages. J Spinal Disord Tech.2002; 15:337-49.
24 Gornet MF, Burkus K,Dickman CA. rhBMP-2 with tapered cages:a prospective, randomized lumbar fusion study. Paper presented at:Annual Meeting of the North American Spine Society.2001; Seattle, WA.
25 Burkus JK, Transfeldt EE, Kitchel SH, et al. Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bone morphogenic protein-2. Spine.2002; 27:2396-406.
26 Burkus JK, Dorchak JD, Sanders DL. Radiographic assessment of interbody fusion using recombinant human morphogenetic protein type 2. Spine.2003; 28:372-7.
27 Burkus JK, Sandhu HS, Gornet MF, et al. Use of rhBMP-2 in combination with structural cortical allografts:Clinical and radiographic outcomes in anterior lumbar spinal surgery. J Bone Joint Surg Am.2005; 87:1205-12.
28 Haid RW, Branch CL,Alexander JT, et al. Posterior lumbar interbody fusion using recombinant human bone morphogenetic protein type 2 with cylindrical interbody cages. Spine.2004; 4:527-39.
29 Boden SD, Kang J, Sandhu H, et al. Use of recombinant bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans:a prospective randomized clinical pilot trial:2002 Volvo Award in clinical studies. Spine.2002; 27: 2662-73.
30 Glassman SD, Dimar JR, Carreon LY, et al. Initial fusion rates with recombinant human bone morphogenetic protein-2/compression resistant matrix and a hydroxyapatite and tricalcium phosphate/collagen carrier in posterolateral spinal fusion. Spine.2005; 30:1694-98.
31 Dimar JR, Glassman SD, Burkus KJ, et al. Clinical outcomes and fusion success at 2 years of single-Level instrumented posterolateral fusions with recombinant human bone morphogenetic protein-2/compression resistant matrix versus iliac crest bone graft. Spine.2006; 31:2534-39.
32 Baskin DS, Ryan P, Sonntag V, et al. A prospective, randomized, controlled cervical fusion study using recombinant human bone morphogenetic protein-2 with the CORNE-STONE-SR allograft ringand the ATLANTIS anterior cervical plate. Spine.2003; 28:1210-25.
33 Cook SD, Dalton JE, Tan EH, et al. In vivo evaluation of recombinant human osteogenic protein (rhOP-1) implants as a bone graft substitute for spinal fusion. Spine.1994; 19:1655-63.
34 Magin M,Delling G. Improved lumbar vertebral interbody fusion using rhOP-1. Spine.2001; 26:469-78.
35 Grauer JN, Patel TC, Erulkar JS, et al. Evaluation of OP-1 as a graft substitute for the intertransverse process lumbar fusion. Spine.2000; 6:127-33.
36 Cunningham BW, Shimanoto I, Sefter JC, et al. Posterolateral spinal arthrodesis using osteogenic protein-1:an in vivo time-course study using a canine model. Paper presented at the 15th Annual Meeting of the North American Spine Society.2000; New Orleans, LA.
37 Patel TC, Vaccaro AR, Truumees E, et al. A safety and efficacy study of OP-1 (rhBMP-7) as an adjunct to posterolateral lumbar fusion. Paper presented at the 16th Annual Meeting of the North American Spine Society.2001; Seattle, WA.
38 Vaccaro AR, Patel T, Fischgrund J, et al. A pilot safety and efficacy study of OP-1 putty (rh-BMP-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions. Eur Spine J.2003; 12:495-500.
39 Johnsson R, Stromqvist B, Aspenberg P. Randomized radiostereometric studycomparing osteogenicprotein 1 (BMP-7) and autograft bone in human noninstrumented posterolateral lumbar fusion:2002 Volvo Award in clinical studies. Spine.2002; 27:2654-61.
40 Kanayama M,Hashimoto T,Shigenobu K,et al. A prospective randomized study of posterolateral lumbar fusion using osteogenic protein-1(OP-1) versus local autograft with ceramic bone substitute. Spine.2006; 31:1067-74.
41 Vaccaro AR, Whang PG, Patel T, et al. 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. Spine.2008; 18:457-65.
42 Burkus JK, Heim SE, Gornet MF, et al. Is INFUSE bone graft superior to autograft bone? An integrated analysis of clinical trials using the LT-CAGE lumbar tapered fusion device. J Spinal Disord.2003; 16:113-122.
43 Mussano F, Ciccone G,Ceccarelli M, et al. Bone morphogenetic proteins and bone defects. A systematic review. Spine.2007; 32:824-830.
44 Polly DW Jr, Ackerman S J, Shaffrey CI, et al. A cost analysis of bone morphogenetic protein versus autogenous iliac crest bone graft in single-level anterior lumbar fusion. Orthopedics.2003; 26:1027-1037.
45 Hansen SM, Sasso RC. Resorptive response of rhBMP2 simulating infection in an anterior lumbar interbody fusion with a femoral ring. J Spinal Disord Tech.2006; 19:130-134.
46 Pradhan BB, Bae HW,Dawson EG, et al. Graft resorption with the use of bone morphogenetic protein:lessons from anterior lumbar interbody fusion using femoral ring allografts and recombinant human bone morphogenetic protein-2. Spine.2006; 31 (10):277-284.
2 Nakashima M, Reddi AH. The application of bone morphogenetic proteins to dental tissue engineering. Nat Biotechnol.2003; 21:1025-32.
3 Salata LA, Franke-Stenpart V, Rasmusson L. Recent outcomes and perspectives of the application of bone morphogenetic proteins in implantd entistry. Clin Implant Dent Relat Res.2002; 4:27-32.
4 Urist MR. Bone formation by autoinduction. Science.1965; 150:893-9.
5 Urist MR, Strates BS. Bone morphogenetic protein. J Dent Res.1971; 50:1392-406.
6 van der Horst G, Van Bezooijen RL, Deekers MM, et al. Differentiation ofmurine preosteoblastic KS483 cells depends on autocrine bone morphogenetic protein signaling during all phases of osteoblast formation. Bone.2002; 31:661-9.
7 Vaccaro AR, Patel T, Fischgrund J, et al. A pilot study evaluating the safety and efficacy of OP-1 putty (rhBMP-7) as a replacement for iliac crest autograft in posterolateral lumbar arthrodesis for degenerative spondylolisthesis. Spine.2004; 29:1885-92.
8 Vaccaro AR, Whang PG, Patel T, et al. 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. Spine.2008; 8:457-65.
9 Boden SD, Zdeblick TA, Sandhu HS, et al. The use of rhBMP-2 in interbody fusion cages. Definitive evidence of osteoinduction in humans:A preliminary report. Spine.2000; 25:376-81.
10 Burkus JK, Transfeldt EE, Kitchel SH, et al. Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bonemorphogenetic protein-2. Spine.2002; 27:2396-408.
11 Burkus JK, Gornet MF, Dickman CA, et al. Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages. J Spinal Disord Tech.2002; 15:337-49.
12 Boden SD, Kang J, Sandhu H, et al. 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. Spine.2002; 27:2662-73.
13 Johnsson R, Stromqvist B, Aspenberg P. Randomized radiostereometric studycomparing osteogenicprotein 1(BMP-7) and autograft bone in human noninstrumented posterolateral lumbar fusion:2002 Volvo Award in clinical studies. Spine.2002; 27:2654-61.
14 Burkus JK, Dorchak JD, Sanders DL. Radiographic assessment of interbody fusion using recombinant human morphogenetic protein type 2. Spine.2003; 28:372-7.
15 Haid RW, Branch CL, Alexander JT, et al. Posterior lumbar interbody fusion using recombinant human bone morphogenetic protein type 2 with cylindrical interbody cages. Spine.2004; 4:527-39.
16 Burkus JK, Sandhu HS, Gornet MF, et al. Use of rhBMP-2 in combination with structural cortical allografts:Clinical and radiographic outcomes in anterior lumbar spinal surgery. J Bone Joint Surg Am.2005; 87:1205-12.
17 Kanayama M, Hashimoto T, Shigenobu K, et al. A prospective randomized study of posterolateral lumbar fusion using osteogenic protein-1(OP-1) versus local autograft with ceramic bone substitute. Spine.2006; 31:1067-74.
18 Glassman SD, Dimar JR, Carreon LY, et al. Initial fusion rates with recombinant human bone morphogenetic protein-2/compression resistant matrix and a hydroxyapatite and tricalcium phosphate/collagen carrier in posterolateral spinal fusion. Spine.2005; 30:1694-98.
19 Dimar JR, Glassman SD, Burkus KJ, et al. Clinical outcomes and fusion success at 2 years of single-Level instrumented posterolateral fusions with recombinant human bone morphogenetic protein-2/compression resistant matrix versus iliac crest bone graft. Spine.2006; 31:2534-39.
20 Dimar JR, Glassman SD, Burkus JK, et al. Clinical and radiographic analysis of an optimized rhBMP-2 formulation as an autograft replacement in posterolateral lumbar spine arthrodesis. J Bone Joint Surg Am.2009; 91:1377-86.
21 Dawson E, Bae HW, Burkus KJ, et al. Recombinant human bone morphogenetic protein-2 on an absorbable collagen sponge with an osteoconductive bulking agent in posterolateral arthrodesis with instrumentation. A prospective randomized trial. J Bone Joint Surg Am.2009; 91:1604-13.
22 Kurz LT, Garfin SR, Booth RE. Harvesting autogenous iliac bone grafts:A review of complications and techniques. Spine.1989; 14:1324-31.
23 Fernyhough JC, Schimandale JJ, Weigel MC, et al. Chronic donor site pain complicating bone graft harvesting from the posterior iliac crest for spinal fusion. Spine.1992; 17:1474-80.
24 Solomon L. Bone grafts. J Bone Joint Surg Br.1991; 73:706-7.
25 Carlisle E, Fischgrund JS. Bone morphogenetic proteins for spinal fusion. Spine J.2005; 5:240-249.
26 Burkus JK, Heim SE, Gornet MF, et al. Is INFUSE bone graft superior to autograft bone? An integrated analysis of clinical trials using the LT-CAGE lumbar tapered frsion device. J Spinal Disord Tech.2003; 16:113-122.
27 Mussano F, Ciccone G, Ceccarelli M, et al. Bone morphogenetic proteins and bone defects. A systematic review. Spine.2007; 32:824-830.
28 Martin TJ, Boden SD, Marone MA, et al. Posterolateral intertransverse process spinal arthrodesis with rhBMP-2 in non-human primate:important lessons learned regarding dose, carrier and safety. J Spinal Disord.1999; 12:179-86.
29 Vaccaro AR, Anderson DG, Toth CA. Recombinant human osteogenic protein-1 (bone morphogenetic protein-7) as an osteoinductive agent in spinal fusion. Spine.2002; 27:59-65.
30 Sandhu HS. Bone morphogenetic proteins and spinal surgery. Spine.2003; 28:64-73.
1 Samartzis D. Does rigid instrumentation increase the fusion rate in onelevel anterior cervical discectomy and fusion. Spine.2004; 4:636-643.
2 Kurz LT, Garfin SR, Booth RE. Harvesting autogenous iliac bone grafts:A review of complications and techniques. Spine.1989; 14:1324-31.
3 Fernyhough JC, Schimandale JJ, Weigel MC, et al. Chronic donor site pain complicating bone graft harvesting from the posterior iliac crest for spinal fusion. Spine.1992; 17:1474-80.
4 Solomon L. Bone grafts. J Bone Joint Surg Br.1991; 73:706-7.
5 Urist MR. Bone formation by autoinduction. Science.1965; 150:893-9.
6 Urist MR, Strates BS. Bone morphogenetic protein. J Dent Res.1971; 50:1392-406.
7 Wozney JM, Rosen V, Celeste AJ, et al. Novel regulators of bone formation:Molecular clones and activities. Science.1998; 242:1528-34.
8 Reddi AH. Role of morphogenetic proteins in skeletal tissue engineering and regeneration. Nat Biotechnol.1998; 16:247-52.
9 van der Horst G, van Bezooijen RL,Deekers MM, et al. Differentiation of murine preosteoblastic KS483 cells depends on autocrine bone morphogenetic protein signaling during all phases of osteoblast formation. Bone.2002; 31:661-9.
10 Cheng H, Jiang W, Phillips FM, et al. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am.2003; 85:1544-52.
11 Sandhu HS, Toth JM, Diwan AD, et al. Histologic evaluation of theefficacy of rhBMP-2 compared with autograft bone in sheep spinalanterior interbody fusion. Spine.2002; 27:567-75.
12 Sandhu HS, Kabo JM, Turner AS, et al. rhBMP-2 augmentation of titanium fusion cages for experimental anterior lumbar fusion. Annual Meeting of the North American Spine Society.1996; New York, NY.
13 Sidhu KS, Prochnow TD, Schmitt P, et al. Anterior cervical interbody fusion with rhBMP-2 andtantalum in a goat model. Spine.2001; 1:331-40.
14 Boden SD, Martin GJ, Horton WC. Laparoscopic anterior spinal arthrodesis with rhBMP-2 in a titanium interbody threaded cage. J Spinal Disord.1998; 11:95-101.
15 Hecht BP, Fischgrund JS,Herkowitz HN, et al. The use of recombinant human bone morphogenetic protein2 (rhBMP-2) to promote spinal fusion in a nonhuman primate anterior interbody fusion model. Spine.1999; 24:629-36.
16 Schimandle JH,Boden SD,Hutton WC. Experimental spinal fusion with recombinant human bone morphogenetic protein-2. Spine.1995; 20:1326-37.
17 Sandhu HS,Kanim LE, Kabo JM, et al. Effective doses of recombinant human bone morphogenetic protein-2:an experimental spinal fusion. Spine.1996; 21:2115-22.
18 Sandhu HS, Kanim LE, Toth JM, et al. Experimental spinal fusion with recombinant human bone morphogenetic protein-2,without decortication of osseous elements. Spine 1997; 22:1171-80.
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