title: Bone morphogenetic protein (BMP) for fracture healing in adults.
abstract: BACKGROUND
  Delay in fracture healing is a complex clinical and economic issue for patients and health services.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  We searched The Cochrane Library (2008, Issue 4), MEDLINE, and other major health and health economics databases (to October 2008).
  
  
  METHODS
  Randomised controlled trials (RCTs) and full or partial economic evaluations of BMP for fracture healing in skeletally mature adults.
  
  
  METHODS
  All clinical and economic data were extracted by one author and checked by another.
  
  
  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.
  
  
  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.
authors.affiliation: School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, Norfolk, UK, NR4 7TJ.
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Garrison
authors.forename: Ian
authors.initials: I
authors.lastname: Shemilt
authors.forename: Simon
authors.initials: S
authors.lastname: Donell
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Ryder
authors.forename: Miranda
authors.initials: M
authors.lastname: Mugford
authors.forename: Ian
authors.initials: I
authors.lastname: Harvey
authors.forename: Fujian
authors.initials: F
authors.lastname: Song
authors.forename: Volker
authors.initials: V
authors.lastname: Alt
mesh_terms: D000328:Adult; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7 / Q000191:economics / Q000627:therapeutic use*; D019485:Bone Morphogenetic Proteins / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D050723:Fractures, Bone / Q000188:drug therapy* / Q000191:economics; D017759:Fractures, Malunited / Q000188:drug therapy / Q000191:economics; D005599:Fractures, Ununited / Q000188:drug therapy / Q000191:economics; D017048:Health Care Costs; D006801:Humans; D011885:Radius Fractures / Q000188:drug therapy / Q000191:economics; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000191:economics / Q000627:therapeutic use*; D013978:Tibial Fractures / Q000188:drug therapy / Q000191:economics; D016212:Transforming Growth Factor beta / Q000191:economics / Q000627:therapeutic use*
chemical_list: C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2