Intervention to improve fracture healing in adults

Broken bones (fractures) that do not heal or unite quickly or completely can result in significant pain and loss of function. This may affect the person's ability to work and an associated reduction in their quality of life. There is also a considerable economic burden to society associated with delayed union (healing) or nonunion of fractures. The intervention tested in this review is bone morphogenetic protein (BMP). This is produced naturally by the body and it has been shown to play an important role in bone and cartilage formation. The review set out to find whether BMP applied at the fracture site can help to speed up and improve fracture healing.

The review included 11 trials. All were flawed which means that their results may be biased. Four trials involved people with acute fractures of the tibia (shin bone). Evidence from these trials showed that BMP may enhance healing of these fractures, and that people with these fractures when treated with BMP required fewer subsequent procedures. Six trials testing BMP for fractures that had not healed during first course of treatment (nonunions) showed BMP was neither better or worse at healing than bone grafts. One small trial found no difference between BMP and done grafts in people whose bone had been cut so in order to treat a healed but misaligned fracture. Trial participants who received BMP experienced similar adverse effects to those no receiving BMP (infection, hardware failure, heterotopic bone formation and immunogenic reactions). However, patients given BMP instead of bone autografts will have avoided problems associated with extraction of the bone from another site in their body.

The review also included four economic evaluations. Three of these found that the costs associated with using BMP, based on one large trial of acute open tibia fractures, were likely to be higher than standard care treatment without BMP. The difference in costs decreased with increased fracture severity.

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.

Read the full abstract...

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


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.