Authors' objectives:

"The objectives of this study were to assess the clinical effectiveness and cost-effectiveness of bone morphogenetic protein (BMP) for the treatment of spinal fusions and the healing of fractures compared with the current standards of care."

(from executive summary)

Authors' results and conclusions: Quantity and quality of included RCTs Eight randomised trials of BMP for tibial fractures, one for scaphoid non-union and 12 randomised trials of BMP for spinal fusion were included. These trials had several methodological weaknesses, including unreported randomisation and allocation methods, incomparable baseline characteristics between the groups, failure to perform intention-to-treat analysis or to use independent blinded assessors and failure to report reasons for drop-outs. Some secondary outcomes were not measured and/or reported. Because of insufficient sample size in most trials, patient baseline comparability between trial arms was not achieved and the statistical power to detect a moderate effect was low. Effectiveness of BMP for tibial fractures According to the data from three trials (494 patients in total), the use of BMP increased fracture union among patients with acute tibial fractures [pooled odds ratio (OR) 1.65, 95% confidence interval (CI) 1.12 to 2.45]. This pooled analysis was dominated by the data from a large trial (n = 450). Data from the largest trial (n = 450) also indicated that high-dose BMP (1.5 mg/ml) is more effective than a lower dose (0.75 mg/ml) for open tibial fractures. Four small trials (245 patients in total) found that the healing rate in the BMP group was not statistically significantly different from that in the autogenous bone grafting group for patients with tibial non-union fractures (pooled OR for union rate 0.82, 95% CI 0.25 to 2.64). The use of BMP reduced the number of secondary interventions in patients with acute tibial fractures compared with controls. Effectiveness of BMP for scaphoid non-union Only one small RCT (n = 18) was identified. Very limited evidence indicated that BMP in scaphoid non-union was safe and may help to accelerate non-union healing when used in conjunction with either autograft or allograft Effectiveness of BMP for spinal fusion Evidence from seven trials (n = 631 in total) showed that BMP-2 is more effective than autogenous bone graft for radiographic fusion in patients with single-level degenerative disc disease (pooled OR 3.87, 95% CI 1.74 to 8.59). Two small trials (n = 56 in total) compared BMP-7 and autograft for degenerative spondylolisthesis with spinal stenosis and found no statistically significant difference (pooled OR 0.87, 95% CI 0.15 to 5.08). No statistically significant difference was observed in one small trial (n = 20) that compared BMP-7 and autograftspondylolysis (pooled OR 0.38, 95% CI 0.05 to 2.77). The use of BMP was associated with an average of 25-minute reduction (95% CI 11 to 37 minutes) in operating time and a shorter hospital stay (0.75 days, 95% CI 0.31 to 1.19 days) compared with autograft. BMP may be associated with improvement in clinical outcomes such as Oswestry Disability Index score, SF-36 score and back and leg pain. The proportion of secondary interventions tended to be lower in the BMP group than that in the control group, but the difference was not statistically significant (pooled OR 0.62, 95% CI 0.28 to 1.39). Data from trials on time to return to work postoperatively were sometimes difficult to interpret because of unclear or inappropriate methods used for data analysis and results presentation.

Authors' recommendations: Additional BMP treatment plus conventional interventions is more effective than the conventional intervention alone for union of acute open tibial fractures. The cost-effectiveness of additional BMP may be improved if the price of BMP is reduced or BMP is mainly used in severe cases. The use of BMP may eliminate the need for autogenous bone grafting so that costs and complications related to harvesting autograft can be avoided. In non-unions, there is no evidence that BMP is more or less effective than bone graft; however, it is currently used when bone graft and other treatments have failed. The use of BMP-2 in spinal fusion surgery seems more effective than autogenous bone graft in terms of radiographic spinal fusion among patients with single-level degenerative disc disease. There is a lack of evidence about the effectiveness of BMP for other spinal disorders including spondylolisthesis and spinal stenosis. There was limited evidence showing that BMP is associated with greater improvement in clinical outcomes such as Oswestry Disability Index score, SF-36 score and back and leg pain. According to the results of economic evaluation, the use of BMP for spinal fusion is unlikely to be cost-effective.

Authors' methods: Review

Project Status: Completed

URL for project: http://www.hta.ac.uk/1481

Year Published: 2007

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England, United Kingdom

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk

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