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Volume:3 Issue:8 Number:53 ISSN#:2563-5476
ACE Report #6671

Bone morphogenetic protein vs. autologous iliac crest bone graft in lumbar fusion surgery

How to Cite

OrthoEvidence. Bone morphogenetic protein vs. autologous iliac crest bone graft in lumbar fusion surgery. ACE Report. 2014;3(8):53. Available from: https://myorthoevidence.com/AceReport/Report/6671

Study Type:Meta-analysis/Systematic Review
OE Level Evidence:1
Journal Level of Evidence:N/A

A meta analysis of lumbar spinal fusion surgery using bone morphogenetic proteins and autologous iliac crest bone graft

PLoS One. 2014 Jun 2;9(6):e97049. doi: 10.1371/journal.pone.0097049. eCollection 2014.

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19 randomized controlled trials (n=1852) were included in this meta-analysis comparing bone morphogenetic protein (BMP) to autogenous iliac crest bone graft (ICBG) in lumbar fusion for patients with lumbar degenerative disease. Results demonstrated a significantly higher fusion rate, significantly lower reoperation rate, and a significantly shorter operation time favouring BMP over ICBG. Hospital stay was borderline significant in favour of BMP, while clinical success, complication rate, blood loss, patient satisfaction, work status, return to work were not significantly different between patient cohorts.

Publication Funding Details +
None disclosed

Risk of Bias


Reporting Criteria


Fragility Index


Were the search methods used to find evidence (original research) on the primary question or questions stated?

Was the search for evidence reasonably comprehensive?

Were the criteria used for deciding which studies to include in the overview reported?

Was the bias in the selection of studies avoided?

Were the criteria used for assessing the validity of the included studies reported?

Was the validity of all of the studies referred to in the text assessed with use of appropriate criteria (either in selecting the studies for inclusion or in analyzing the studies that were cited)?

Were the methods used to combine the findings of the relevant studies (to reach a conclusion) reported?

Were the findings of the relevant studies combined appropriately relative to the primary question that the overview addresses?

Were the conclusions made by the author or authors supported by the data and or analysis reported in the overview?

How would you rate the scientific quality of this evidence?

Yes = 1

Uncertain = 0.5

Not Relevant = 0

No = 0

The Reporting Criteria Assessment evaluates the transparency with which authors report the methodological and trial characteristics of the trial within the publication. The assessment is divided into five categories which are presented below.




Accessing Data


Analysing Data





Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. J Clin Epidemiol. 1992;45:255-65

The Fragility Index is a tool that aids in the interpretation of significant findings, providing a measure of strength for a result. The Fragility Index represents the number of consecutive events that need to be added to a dichotomous outcome to make the finding no longer significant. A small number represents a weaker finding and a large number represents a stronger finding.

Why was this study needed now?

In lumbar fusion surgery, autogenous iliac crest bone (ICBG) is primarily used as a graft. Nonetheless, well-documented complications have included morbidity of the donor site and a high incidence of nonunion. In light of this, bone morphogenetic proteins (BMPs) have been developed as an alternative. Large scale production was achieved following advancements in gene sequencing and recombinant techniques. Both rhBMP-2 and rhBMP-7 have been approved by the FDA. This meta-analysis was needed to evaluate the comparative efficacy of BMPs to ICBG in spinal fusion surgery.

What was the principal research question?

How does the safety and efficacy of bone morphogenetic proteins compare to autogenous iliac crest bone grafts in lumbar fusion surgery?

Study Characteristics -
Data Source:
An electronic search was performed up to November 2013 in PubMed, The Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE and EMBASE, CINAHL, the China Biological Medicine Database (CBM), International Clinical Trials Registry Platform (ICTRP), Current Controlled Trials, and ClinicalTrials.gov. Relevant systematic reviews, RCTs identified from search, meeting abstracts, and expert opinion communications were additionally searched.
Index Terms:
Key search terms included: 'lumbar degenerative disease', 'low back pain', 'lumbar fusion, 'bone morphogenetic protein-2', 'bone morphogenetic protein-7', 'osteogenic protein-1', and 'randomized controlled trial'.
Study Selection:
Randomized controlled trials (RCTs) were included if BMPs were compared to ICBG for the treatment of systematic lumbar degenerative disease (LDD) in adults (>18 years) requiring lumbar fusion. Studies were excluded if included patients had a spinal column fracture, spondylolisthesis (> Meyerding Grade 2), or were taking medication with potential interference of fusion. Two reviewers performed the selection which was then checked by principal reviewer. Disagreements were resolved through discussion. 19 RCTs (15 BMP-2 and 4 BMP-7), totaling 1852 patients were included.
Data Extraction:
Two independent reviewers extracted data. The primary outcomes extracted included: solid fusion rate, clinical outcomes, compilations, and reoperation rate. The secondary outcomes extracted included: operation time, blood loss, hospital stay, patient satisfaction, and return to work.
Data Synthesis:
Dichotomous outcomes were measured with risk ratios (RR) and 95% confidence intervals while continuous outcomes were measured with mean differences (MD) and 95% CIs and standardized mean differences (SMDs) as necessary. A random-effects model was used for analysis. Publication bias was assessed with a funnel plot and statistic tests (Egger's test and Begg's test). Heterogeneity was assessed using the chi-square test and I-squared statistic; significant heterogeneity was defined as I-squared >/=50%. RevMan 5.1.0 and R project 3.0.1 was used to analyze data. Clinical relevance was assessed by criteria of the Cochrane Back Review Group. Methodological quality was assessed using criteria by the Cochrane Back Review Group by two independent reviewers, and quality of evidence was assessed with the GRADE Working Group criteria.

What were the important findings?

  • Fusion rate was reported in 17 studies (BMP: n=610, ICBG: n=523). Pooled analysis indicated a significant difference, in favour of BMP over ICBG, although with moderate heterogeneity (RR: 1.13 [95% CI 1.05-1.23]; p=0.003; I^2=52%). Subgroup analysis of BMP-2 only demonstrated similar results (RR: 1.16 [95% CI 1.06–1.27]; P = 0.001; I^2=62%). The BMP-7 subgroup indicated contrasting results (RR: 0.90 [95% CI 0.69-1.17]; p=0.43; I^2=0%).
  • Clinical success was assessed in 8 studies (BMP: n=431, ICBG: n=265). Pooling of data demonstrated no significant difference between groups (RR: 1.04 [95% CI 0.95-1.13]; p=0.38; I^2=2%).
  • Complication rate was pooled from 9 studies (BMP: n=605, ICBG: n=444) and results indicated no significant between group difference (RR: 0.96 [95% CI 0.85-1.09]; p=0.54; I^2=0%).
  • Reoperation rate from 14 studies were pooled for analysis (BMP:n=1004, ICBG: n=766). Results demonstrated a significantly lower rate for BMP over ICBG (RR: 0.57 [95% CI 0.42-0.77]; p=0.0002; I^2=0.66).
  • Pooled results favoured BMP over ICBG significantly, with respect to operating time (RR: -0.32 [95% CI -0.55 to -0.08]; p=0.009; I^2=79%), and hospital stay (RR: -0.56 [95% CI -1.12 to -0.01]; p=0.05; I^2=70%), whereas comparable results were observed for blood loss (RR: -50.24 [95% CI -117.38 to 16.90]; p=0.14; I^2=77%).
  • Patient satisfaction, work status, and return to work were not significantly different between groups (p=0.58, p=0.63, and p=0.68, respectively) when pooled.

What should I remember most?

Pooled analyses demonstrated significantly higher fusion rates, lower reoperation rates, and shorter operation times with bone morphogenetic protein (BMP) when compared to autogenous iliac crest bone graft. Additionally, difference in hospital stay was borderline significant in favour of BMP, whereas clinical success, complication rate, blood loss, patient satisfaction, work status, return to work were comparable between groups.

How will this affect the care of my patients?

The results suggest that bone morphogenetic protein increases fusion rate while reducing reoperation rates and operation times for lumbar fusion in patients with systematic lumbar degenerative disease. Clinical success and complication rates, however, were similar to those of the standard autogenous iliac crest bone grafting procedure. Additional high-quality randomized controlled trials are needed to determine the long-term effects of bone morphogenetic protein, and whether it is superior to autogenous iliac crest bone grafting.

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