Abstract: 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. 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.

Plain-language summary: 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.