{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:46:46Z","timestamp":1791258406915,"version":"4.1.0"},"reference-count":47,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["SPI"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:sec>\n<jats:title>Object<\/jats:title>\n<jats:p>Autograft and allograft, the standard approaches for lumbar fusion procedures, have important disadvantages. Bone graft substitutes such as recombinant human bone morphogenetic proteins (rhBMP-2 and rhBMP-7) have emerged as viable alternatives. The authors conducted a systematic review to compare the efficacy and safety of osteoinductive bone graft substitutes using autografts and allografts in lumbar fusion.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>A search for prospective controlled trials was conducted on MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases. Data were extracted for key outcomes including radiographically demonstrated nonunion, Oswestry Disability Index, operating time, blood loss, and length of hospital stay. The quality of randomized controlled trials was assessed using the Jadad scale. Meta-analyses were performed when feasible, and heterogeneity was assessed using the Q statistic and the I<jats:sup>2<\/jats:sup> statistic.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Seventeen of 732 potential studies met the inclusion criteria, with 9 examining rhBMP-2, 3 examining rhBMP-7, 3 examining demineralized bone matrix, and 2 examining autologous growth factor. Recombinant human BMP-2 significantly decreased radiographic nonunion when compared with autologous iliac crest bone graft (AIBG) in a meta-analysis (relative risk 0.27, 95% CI 0.16\u20130.46). Stratification of meta-analyses by the type of surgical procedure performed yielded similar results. Funnel plots suggested publication bias. Trials of rhBMP-2 suggested reductions in the operating time and surgical blood loss, with less effect on the length of hospital stay. There was no difference in radiographic nonunion with the use of rhBMP-7 when compared with AIBG (relative risk 1.02, 95% CI 0.52\u20131.98). Neither rhBMP-2 nor rhBMP-7 demonstrated a significant improvement on the Oswestry Disability Index when compared with AIBG. The limited data on demineralized bone matrix and autologous growth factor showed no significant improvement in radiographic outcomes.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Recombinant human BMP-2 may be an effective alternative to AIBG in lumbar fusion. Data are limited for other bone graft substitutes.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2009.6.spine08669","type":"journal-article","created":{"date-parts":[[2011,2,23]],"date-time":"2011-02-23T21:42:35Z","timestamp":1298497355000},"page":"729-740","source":"Crossref","is-referenced-by-count":65,"title":["Osteoinductive bone graft substitutes for lumbar fusion: a systematic review"],"prefix":"10.3171","volume":"11","author":[{"given":"Rajender","family":"Agarwal","sequence":"first","affiliation":[{"name":"Center for Evidence-Based Practice, University of Pennsylvania Health System;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendal","family":"Williams","sequence":"additional","affiliation":[{"name":"Center for Evidence-Based Practice, University of Pennsylvania Health System;"},{"name":"Department of Medicine;"},{"name":"Center for Clinical Epidemiology and Biostatistics; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig A.","family":"Umscheid","sequence":"additional","affiliation":[{"name":"Center for Evidence-Based Practice, University of Pennsylvania Health System;"},{"name":"Department of Medicine;"},{"name":"Center for Clinical Epidemiology and Biostatistics; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Welch","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-0110729","series-title":"Biometrics","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.2307\/2533446","article-title":"Operating characteristics of a rank correlation test for publication bias","volume":"50","author":"Begg","year":"1994"},{"key":"b2-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"S26","DOI":"10.1097\/00007632-200208151-00007","article-title":"Overview of the biology of lumbar spine fusion and principles for selecting a bone graft substitute","volume":"27","author":"Boden","year":"2002"},{"key":"b3-0110729","series-title":"Spine (Phila Pa 1976)","doi-asserted-by":"publisher","first-page":"2662","DOI":"10.1097\/00007632-200212010-00005","article-title":"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","volume":"27","author":"Boden","year":"2002"},{"key":"b4-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1097\/00007632-200002010-00020","article-title":"The use of rhBMP-2 in interbody fusion cages. definitive evidence of osteoinduction in humans: A preliminary report","volume":"25","author":"Boden","year":"2000"},{"key":"b5-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1097\/01.BRS.0000048469.45035.B9","article-title":"Radiographic assessment of interbody fusion using recombinant human bone morphogenetic protein type 2","volume":"28","author":"Burkus","year":"2003"},{"key":"b6-0110729","series-title":"J Spinal Disord Tech","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1097\/00024720-200210000-00001","article-title":"Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages","volume":"15","author":"Burkus","year":"2002"},{"key":"b7-0110729","series-title":"J Bone Joint Surg Am","first-page":"1205","article-title":"Use of rhBMP-2 in combination with structural cortical allografts: Clinical and radiographic outcomes in anterior lumbar spinal surgery","volume":"87","author":"Burkus","year":"2005"},{"key":"b8-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.1097\/00007632-200211010-00015","article-title":"Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2","volume":"27","author":"Burkus","year":"2002"},{"key":"b9-0110729","series-title":"Spine (Phila Pa 1976)","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1097\/01.BRS.0000116588.17129.B9","article-title":"Two-year fusion rate equivalency between grafton DBM gel and autograft in posterolateral spine fusion: A prospective controlled trial employing a side-by-side comparison in the same patient","volume":"29","author":"Cammisa","year":"2004"},{"key":"b10-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"E243","DOI":"10.1097\/01.brs.0000160846.85397.44","article-title":"Platelet gel (AGF) fails to increase fusion rates in instrumented posterolateral fusions","volume":"30","author":"Carreon","year":"2005"},{"key":"b11-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1097\/BRS.0b013e3181642a49","article-title":"Adverse events in patients re-exposed to bone morphogenetic protein for spine surgery","volume":"33","author":"Carreon","year":"2008"},{"key":"b12-0110729","series-title":"J Spinal Disord Tech","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1097\/01.bsd.0000110342.54707.19","article-title":"Role of activated growth factors in lumbar spinal fusions","volume":"17","author":"Castro","year":"2004"},{"key":"b13-0110729","series-title":"Stat Med","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1002\/sim.4780060308","article-title":"Avoidance of large biases and large random errors in the assessment of moderate treatment effects: The need for systematic overviews","volume":"6","author":"Collins","year":"1987"},{"key":"b14-0110729","series-title":"N Engl J Med","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1056\/NEJMsb031771","article-title":"Spinal-fusion surgery\u2014the case for restraint","volume":"350","author":"Deyo","year":"2004"},{"key":"b15-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"2534","DOI":"10.1097\/01.brs.0000240715.78657.81","article-title":"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","volume":"31","author":"Dimar","year":"2006"},{"key":"b16-0110729","series-title":"Biometrics","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1111\/j.0006-341X.2000.00455.x","article-title":"Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in metaanalysis","volume":"56","author":"Duval","year":"2000"},{"key":"b17-0110729","series-title":"BMJ","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1136\/bmj.316.7124.61","article-title":"Bias in location and selection of studies","volume":"316","author":"Egger","year":"1998"},{"key":"b18-0110729","series-title":"Systematic Reviews in Health Care: Meta-Analysis in Context","author":"Egger","year":"2001"},{"key":"b19-0110729","series-title":"Physiotherapy","first-page":"271","article-title":"The oswestry low back pain disability questionnaire","volume":"66","author":"Fairbank","year":"1980"},{"key":"b20-0110729","series-title":"Health Technol Assess","first-page":"1","article-title":"Clinical effectiveness and cost-effectiveness of bone morphogenetic proteins in the non-healing of fractures and spinal fusion: A systematic review","volume":"11","author":"Garrison","year":"2007"},{"key":"b21-0110729","series-title":"Spine J","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.spinee.2007.03.004","article-title":"The perioperative cost of infuse bone graft in posterolateral lumbar spine fusion","volume":"8","author":"Glassman","year":"2008"},{"key":"b22-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.1097\/01.brs.0000172157.39513.80","article-title":"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","volume":"30","author":"Glassman","year":"2005"},{"key":"b23-0110729","series-title":"Spine J","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.spinee.2004.03.025","article-title":"Posterior lumbar interbody fusion using recombinant human bone morphogenetic protein type 2 with cylindrical interbody cages","volume":"4","author":"Haid","year":"2004"},{"key":"b24-0110729","series-title":"Curr Opin Rheumatol","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1097\/01.bor.0000198003.80944.4c","article-title":"Modern biologics used in orthopaedic surgery","volume":"18","author":"Hidaka","year":"2006"},{"key":"b25-0110729","series-title":"BMJ","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003"},{"key":"b26-0110729","series-title":"Control Clin Trials","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0197-2456(95)00134-4","article-title":"Assessing the quality of reports of randomized clinical trials: Is blinding necessary?","volume":"17","author":"Jadad","year":"1996"},{"key":"b27-0110729","series-title":"Spine J","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.spinee.2005.08.014","article-title":"A prospective study of autologous growth factors (AGF) in lumbar interbody fusion","volume":"6","author":"Jenis","year":"2006"},{"key":"b28-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"2654","DOI":"10.1097\/00007632-200212010-00004","article-title":"Randomized radiostereometric study comparing osteogenic protein-1 (BMP-7) and autograft bone in human noninstrumented posterolateral lumbar fusion: 2002 Volvo award in clinical studies","volume":"27","author":"Johnsson","year":"2002"},{"key":"b29-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1097\/01.brs.0000216444.01888.21","article-title":"A prospective randomized study of posterolateral lumbar fusion using osteogenic protein-1 (OP-1) versus local autograft with ceramic bone substitute: Emphasis of surgical exploration and histologic assessment","volume":"31","author":"Kanayama","year":"2006"},{"key":"b30-0110729","series-title":"J Orthop Trauma","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.1097\/00005131-200511101-00006","article-title":"Bone morphogenic protein science and studies","volume":"19","author":"Lane","year":"2005"},{"key":"b31-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1097\/01.brs.0000259227.51180.ca","article-title":"Bone morphogenetic proteins and bone defects: A systematic review","volume":"32","author":"Mussano","year":"2007"},{"key":"b32-0110729","series-title":"Orthopedics","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.3928\/0147-7447-20031001-12","article-title":"A cost analysis of bone morphogenetic protein versus autogenous iliac crest bone graft in single-level anterior lumbar fusion","volume":"26","author":"Polly","year":"2003"},{"key":"b33-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"E277","DOI":"10.1097\/01.brs.0000216442.12092.01","article-title":"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","volume":"31","author":"Pradhan","year":"2006"},{"key":"b34-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"S15","DOI":"10.1097\/BRS.0b013e318053d4b4","article-title":"Evidence-based spine surgery","volume":"32","author":"Resnick","year":"2007"},{"key":"b35-0110729","series-title":"J Neurosurg Spine","doi-asserted-by":"publisher","first-page":"733","DOI":"10.3171\/spi.2005.2.6.0733","article-title":"Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 16: Bone graft extenders and substitutes","volume":"2","author":"Resnick","year":"2005"},{"key":"b36-0110729","series-title":"J Am Coll Surg","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.jamcollsurg.2004.09.046","article-title":"Update on bone morphogenetic proteins and their application in spine surgery","volume":"200","author":"Samartzis","year":"2005"},{"key":"b37-0110729","series-title":"Orthopedics","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.3928\/0147-7447-20001001-17","article-title":"Augmenting local bone with grafton demineralized bone matrix for posterolateral lumbar spine fusion: Avoiding second site autologous bone harvest","volume":"23","author":"Sassard","year":"2000"},{"key":"b38-0110729","series-title":"J Spinal Disord Tech","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1097\/00024720-200608000-00008","article-title":"Use of recombinant human bone morphogenetic protein-2 as an adjunct in posterolateral lumbar spine fusion: A prospective CT-scan analysis at one and two years","volume":"19","author":"Singh","year":"2006"},{"key":"b39-0110729","series-title":"Spine J","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.spinee.2006.10.015","article-title":"Accelerating lumbar fusions by combining rhBMP-2 with allograft bone: a prospective analysis of interbody fusion rates and clinical outcomes","volume":"7","author":"Slosar","year":"2007"},{"key":"b40-0110729","series-title":"BMJ","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1136\/bmj.320.7249.1574","article-title":"Empirical assessment of effect of publication bias on metaanalyses","volume":"320","author":"Sutton","year":"2000"},{"key":"b41-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"2709","DOI":"10.1097\/01.brs.0000190812.08447.ba","article-title":"Comparison of OP-1 putty (rhBMP-7) to iliac crest autograft for posterolateral lumbar arthrodesis: A minimum 2-year follow-up pilot study","volume":"30","author":"Vaccaro","year":"2005"},{"key":"b42-0110729","series-title":"Eur Spine J","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1007\/s00586-004-0845-7","article-title":"A 2-year follow-up pilot study evaluating the safety and efficacy of op-1 putty (rhbmp-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions","volume":"14","author":"Vaccaro","year":"2005"},{"key":"b43-0110729","series-title":"Eur Spine J","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s00586-003-0561-8","article-title":"A pilot safety and efficacy study of OP-1 putty (rhBMP-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions","volume":"12","author":"Vaccaro","year":"2003"},{"key":"b44-0110729","series-title":"Spine","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1097\/01.brs.0000137062.79201.98","article-title":"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","volume":"29","author":"Vaccaro","year":"2004"},{"key":"b45-0110729","series-title":"J Bone Joint Surg Br Proceedings","first-page":"89","article-title":"One year follow up on patients in a pilot safety and efficacy study of OP-1 (RHBMP-7) in posterolateral lumbar fusion as a replacement for iliac crest autograft","volume":"86B","author":"Vaccaro","year":"2004"},{"key":"b46-0110729","series-title":"Orthopedics","doi-asserted-by":"publisher","first-page":"567","DOI":"10.3928\/01477447-20070701-06","article-title":"Demineralized bone matrix composite grafting for posterolateral spinal fusion","volume":"30","author":"Vaccaro","year":"2007"},{"key":"b47-0110729","series-title":"Spine J","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.spinee.2007.03.012","article-title":"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","volume":"8","author":"Vaccaro","year":"2008"}],"container-title":["Journal of Neurosurgery: Spine"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-spine\/11\/6\/article-p729.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-spine\/11\/6\/article-p729.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-spine\/11\/6\/article-p729.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,15]],"date-time":"2023-04-15T21:40:18Z","timestamp":1681594818000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-spine\/11\/6\/article-p729.xml"}},"subtitle":["Clinical article"],"short-title":[],"issued":{"date-parts":[[2009,12]]},"references-count":47,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.3171\/2009.6.spine08669","relation":{},"ISSN":["1547-5654"],"issn-type":[{"value":"1547-5654","type":"print"}],"subject":[],"published":{"date-parts":[[2009,12]]}}}