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Meta-Analysis
. 2010 Jun 16;2010(6):CD006950.
doi: 10.1002/14651858.CD006950.pub2.

Bone morphogenetic protein (BMP) for fracture healing in adults

Kimberly R Garrison  1 , Ian Shemilt, Simon Donell, Jonathan J Ryder, Miranda Mugford, Ian Harvey, Fujian Song, Volker Alt
Affiliations
Meta-Analysis

Bone morphogenetic protein (BMP) for fracture healing in adults

Kimberly R Garrison et al. Cochrane Database Syst Rev. .

Abstract

Background: Delay in fracture healing is a complex clinical and economic issue for patients and health services.

Objectives: To assess the incremental effectiveness and costs of bone morphogenetic protein (BMP) on fracture healing in acute fractures and nonunions compared with standards of care.

Search strategy: We searched The Cochrane Library (2008, Issue 4), MEDLINE, and other major health and health economics databases (to October 2008).

Selection criteria: Randomised controlled trials (RCTs) and full or partial economic evaluations of BMP for fracture healing in skeletally mature adults.

Data collection and analysis: All clinical and economic data were extracted by one author and checked by another.

Main results: Eleven RCTs, all at high risk of bias, and four economic evaluations were included. Apart from one study, the times to fracture healing were comparable between the BMP and control groups. There was some evidence for increased healing rates, without requiring a secondary procedure, of BMP compared with usual care control in acute, mainly open, tibial fractures (risk ratio (RR) 1.19, 95% CI 0.99 to 1.43). The pooled RR for achieving union for nonunited fractures was 1.02 (95% CI 0.90 to 1.15). One study found no difference in union for patients who had corrective osteotomy for radial malunions. Data from three RCTs indicated that fewer secondary procedures were required for acute fracture patients treated with BMP versus controls (RR 0.65, 95% CI 0.50 to 0.83). Adverse events experienced were infection, hardware failure, pain, donor site morbidity, heterotopic bone formation and immunogenic reactions. The evidence on costs for BMP-2 for acute open tibia fractures is from one large RCT. This indicates that the direct medical costs associated with BMP would generally be higher than treatment with standard care, but this cost difference may decrease as fracture severity increases. Limited evidence suggests that the direct medical costs associated with BMP could be offset by faster healing and reduced time off work for patients with the most severe open tibia fractures.

Authors' conclusions: This review highlights a paucity of data on the use of BMP in fracture healing as well as considerable industry involvement in currently available evidence. There is limited evidence to suggest that BMP may be more effective than controls for acute tibial fracture healing, however, the use of BMP for treating nonunion remains unclear. The limited available economic evidence indicates that BMP treatment for acute open tibial fractures may be more favourable economically when used in patients with the most severe fractures.

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Conflict of interest statement

Simon Donell is currently involved in two clinical trials of BMP‐2 for Wyeth. Two co‐authors of this Cochrane review (FS and IS) had direct involvement in developing the revised economic model (this was undertaken independently of the original model's developers and sponsors, using funds provided by the UK National Coordinating Centre for Health Technology Assessment), and along with others (KG, SD, JR, MM and IH) are also co‐authors of the parallel UK Health Technology Assessment report (Garrison 2007). Two co‐authors of this Cochrane review (VA and SD) had direct involvement in conducting one of the included cost analysis studies (Alt 2006a). VA is an external consultant for Medtronic. Since completing this Cochrane review, four co‐authors (KG, SD, IS and FS) have provided research consultancy to Medtronic on the efficacy, safety costs and cost‐effectiveness of BMP2 in spinal fusion.

Figures

1
1
Classification scheme for economic evaluations
2
2
Garrison 2007: Basic model structure for the model‐based cost utility analysis
3
3
van Engen 2003: Basic model structure for the model‐based cost‐effectiveness analysis (AE = adverse event)
4
4
Methodological quality summary: review authors' judgements about each methodological quality item for each included study. The review of economics studies based on RCTs has led us to question data presented in at least one of the RCT reports (Govender 2002).
5
5
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies. The review of economics studies based on RCTs has led us to question data presented in at least one of the RCT reports (Govender 2002).
6
6
Forest plot of comparison: BMP versus bone graft substitutes, outcome: 1.1 Participants with tibial fracture attaining union without secondary procedure
7
7
Forest plot of comparison: BMP versus bone graft substitutes, outcome: 1.2 Participants with prior nonunion of the long bones attaining union
8
8
Forest plot of comparison: BMP versus bone graft substitutes, outcome: 1.3 Participants attaining union without secondary intervention after osteotomy for radial malunion
9
9
Forest plot of comparison: BMP versus bone graft substitutes, outcome: 1.4 Acute fracture: participants requiring secondary procedure to attain union
10
10
Forest plot of comparison: BMP versus bone graft substitutes, outcome: 1.5 Participants with nonunion of the tibia or other long bone requiring secondary procedure to attain union
11
11
Forest plot of comparison: BMP versus bone graft substitutes, outcome: 1.7 Acute fracture: participants with hardware failure
1.1
1.1. Analysis
Comparison 1 BMP versus control (usually surgery alone) or bone graft, Outcome 1 Participants with acute tibial fracture attaining union without secondary procedure.
1.2
1.2. Analysis
Comparison 1 BMP versus control (usually surgery alone) or bone graft, Outcome 2 Participants with prior nonunion of the long bones attaining union.
1.3
1.3. Analysis
Comparison 1 BMP versus control (usually surgery alone) or bone graft, Outcome 3 Participants attaining union without secondary intervention after osteotomy for radial malunion.
1.4
1.4. Analysis
Comparison 1 BMP versus control (usually surgery alone) or bone graft, Outcome 4 Acute fracture: participants requiring secondary procedure to attain union.
1.5
1.5. Analysis
Comparison 1 BMP versus control (usually surgery alone) or bone graft, Outcome 5 Participants with nonunion of the tibia or other long bone requiring secondary procedure to attain union.
1.6
1.6. Analysis
Comparison 1 BMP versus control (usually surgery alone) or bone graft, Outcome 6 Post corrective osteotomy for radial malunion: participants requiring secondary procedure to attain union.
1.7
1.7. Analysis
Comparison 1 BMP versus control (usually surgery alone) or bone graft, Outcome 7 Acute fracture: participants with hardware failure.
1.8
1.8. Analysis
Comparison 1 BMP versus control (usually surgery alone) or bone graft, Outcome 8 Participants with nonunion of the tibia or other long bone: hardware failure.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Alt 2006b {published data only}
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US Study Group {unpublished data only}
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References to other published versions of this review

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