Background: The use of recombinant human bone morphogenetic
protein-2 (rhBMP-2) to improve the healing of open tibial shaft fractures has
been the focus of two prospective clinical studies. The objective of the
current study was to perform a subgroup analysis of the combined data from
Methods: Two prospective, randomized clinical studies were
conducted. A total of 510 patients with open tibial fractures were randomized
to receive the control treatment (intramedullary nail fixation and routine
soft-tissue management) or the control treatment and an absorbable collagen
sponge impregnated with one of two concentrations of rhBMP-2. The rhBMP-2
implant was placed over the fracture at the time of definitive wound closure.
For the purpose of this analysis, only the control treatment and the Food and
Drug Administration-approved concentration of rhBMP-2 (1.50 mg/mL) were
compared. Patients who anticipated receiving planned bone-grafting as part of
a staged treatment were excluded from enrollment.
Results: Fifty-nine trauma centers in twelve countries participated,
and patients were followed for twelve months postoperatively. Two subgroups
were analyzed: (1) the 131 patients with a Gustilo-Anderson type-IIIA or IIIB
open tibial fracture and (2) the 113 patients treated with reamed
intramedullary nailing. The first subgroup demonstrated significant
improvements in the rhBMP-2 group, with fewer bone-grafting procedures (p =
0.0005), fewer patients requiring invasive secondary interventions (p =
0.0065), and a lower rate of infection (p = 0.0234), compared with the control
group. The second subgroup analysis of fractures treated with reamed
intramedullary nailing demonstrated no significant difference between the
control and the rhBMP-2 groups.
Conclusions: The addition of rhBMP-2 to the treatment of type-III
open tibial fractures can significantly reduce the frequency of bone-grafting
procedures and other secondary interventions. This analysis establishes the
clinical efficacy of rhBMP-2 combined with an absorbable collagen sponge
implant for the treatment of these severe fractures.
Level of Evidence: Therapeutic Level I. See Instructions
to Authors for a complete description of levels of evidence.