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Bone morphogenetic proteins may benefit rates of union for open tibial fractures
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February 2016
Bone morphogenetic proteins may benefit rates of union for open tibial fractures
Study Type:Meta analysis
OE Level Evidence:1
Journal Level of Evidence:N/A
Bone Morphogenetic Protein for the Healing of Tibial Fracture: A Meta-Analysis of Randomized Controlled Trials
PLoS One. 2015 Oct 28;10(10):e0141670.Did you know you're eligible to earn 0.5 CME credits for reading this report? Click Here
Synopsis
8 RCTs (1113 patients) comparing the use of bone morphogenetic proteins (BMPs) to conventional treatment methods for acute tibial fractures or tibial non-unions were included in this meta-analysis. The purpose of the study was to determine if BMPs improved the rate of union or decreased surgical revision rate compared to various standard practices. BMPs were found to significantly increase union rates and decrease revision rates when used for the treatment of acute tibial fractures but provided no additional benefit to treatment of tibial non-unions. The use of BMPs had no significant influence on the rate of infection for either type of injury when compared to standard care practices. It should be noted that majority of studies included in the acute fracture analyses only evaluated BMPs in open fractures and that both analyses for acute and non-union fractures were limited by the number of available randomized controlled trials.
Publication Funding Details
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Funding:
Non-funded
Conflicts:
None disclosed
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.
4/4
Introduction
3/4
Accessing Data
3/4
Analysing Data
4/4
Results
1/4
Discussion
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?
Tibial fractures most commonly result from high-energy trauma and are associated with high rates of delayed union and nonunion. Conventional treatment methods, including intramedullary nailing or locking plate fixation, have previously been combined with biological substances, such as bone morphogenetic proteins (BMPs), in order to accelerate healing and decrease disability. BMPs play a role in bone formation/repair and have been found to hasten bone union and decrease revision rates in previous studies. While prior meta-analyses evaluating the efficacy of BMPs for tibial fracture healing have been conducted, they were limited by the quality and quantity of existing studies. The current meta-analysis was needed to combine large, high-quality randomized trials to overcome the limitations of previous reviews.
What was the principal research question?
Does the use of bone morphogenetic protein (BMP) in the treatment of tibial fractures improve the rate of union/revision when compared to the use of standard care in both acute and non-union fractures?
Study Characteristics
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Data Source:
An electronic search of MEDLINE, EMBASE, BIOSIS, Cochrane central and Google Scholar databases was conducted without language restrictions for all articles from database inception to January 31, 2014. Reference lists of extracted studies were manually searched to retrieve any articles missed by the electronic search.
Index Terms:
Search terms with BMP and tibial were used to retrieve titles, abstracts, and Medical Subject Headings. Further information not provided
Study Selection:
Three independent reviewers assessed studies for adherence to inclusion criteria, and disagreements were resolved by discussion with a senior reviewer. Randomized control trials (RCTs) with adult patients, a sample size >10 patients, a follow-up period of at least 6 months, and comparing the use of BMP to conventional treatments for healing of acute tibial fracture or tibial nonunion were included (8 RCTs [1113 patients], 4 RCTs (868 patients) involved patients with acute tibial fractures | 4 RCTs (245 patients) involved patients with tibial fracture nonunion).
Data Extraction:
Two reviewers independently extracted data from the included studies, with any disagreements being resolved via discussion. Authors were contacted for additional information where necessary. Outcomes of interest included union rate, revision rate, hardware failure, and infection.
Data Synthesis:
Statistical analyses were performed using RevMan 5.0 software. Heterogeneity between trials was assessed using the I2 statistic, and a random effects model was employed for all analyses to account for assumed heterogeneity due to low statistical power. Heterogeneity was considered significant when I2>50%. Data was presented as weighted mean difference (WMD) and standardized mean difference (SMD) for continuous outcomes, or relative risk (RR) for dichotomous outcomes, both with corresponding 95% CIs.
What were the important findings?
- 4 RCTs (868 patients) involved patients with acute tibial fractures (3 studies included open fractures/ 1 study included both open and closed fractures). 4 RCTs (245 patients) involved patients with tibial fracture non-union.
- In acute tibial fracture patients, rate of bone union was significantly higher in the BMP group (65%) compared to standard care alone (58.8%) (4 studies [868 patients], RR=1.16 [95% CI 1.04 to 1.30]; I2=14%).
- In acute tibial fracture patients, rate of revision surgery was significantly lower in the BMP group (23%) compared to standard care alone (29.4%) (5 studies [853 patients], RR=0.68 [95% CI 0.54 to 0.85]; I2= 5%).
- In acute tibial fracture patients, rate of hardware failure was not significantly different (4 studies [744 patients], RR=0.77 [95% CI 0.50 to 1.18]; I2=32%), and there were no differences in infection rate between groups (4 studies [744 patients], RR= 1.07 [95% CI 0.66 to 1.74]; I2=54%).
- In tibial non-union patients, rate of bone union was similar between treatment groups (4 studies [245 patients], RR=0.98 [95% CI 0.86 to 1.13]; I2=53%).
- In tibial non-union patients, rate of surgical revision was lower in the BMP group compared to standard care alone but the difference was not significant (1 study [124 patients], RR=0.48 [95% CI 0.13 to 1.85]; I2=NA).
- In tibial nonunion patients, infection rate was lower in the BMP group compared to standard care alone but not significantly different (2 studies [154 patients], RR= 0.61 [95% CI 0.37 to 1.02]; I2=0%).
What should I remember most?
When used to treat acute tibial fractures, bone morphogenetic proteins were found to significantly improve union rate and reduce surgical revision rate compared to standard practice alone. It should be noted that the majority of patient included in this analyses came from studies only investigating open fractures, so findings may not be representative of a closed fracture population. Results from analyses investigating treatment of tibial non-unions found no significant effects between groups. Additionally, bone morphogenetic proteins had no significant influence on infection rate for either type of injury.
How will this affect the care of my patients?
The findings from this study suggest the use bone morphogenetic proteins (BMP) may be beneficial for the treatment of acute tibial fractures, improving union rate and reducing the need for surgical revision. However, these finding may only be applicable to open fractures. The use of bone morphogenetic proteins in the treatment of tibial non-unions suggests that they may not provide any additional benefit over standard care. While this study presents supportive evidence for the benefits of BMP in the treatment of tibial fractures, results should be interpreted with caution due to the low number of studies included and the assumed high heterogeneity as a result of the low statistical power. Therefore, additional high-quality studies utilizing larger sample sizes and longer follow-up times should be undertaken to further verify the efficacy of this treatment practice.
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