Table 2.

Summary of selected clinical trials of recombinant human bone morphogenetic protein-2 use in the treatment of acute fractures and nonunions

Investigator and study design	Study groups	Outcome measures and follow-up (F/U)	Results
Aro et al. [38] (2011) Randomized, prospective, blinded study	Two hundred seventy-seven patients with open tibia fractures were randomly assigned to receive standard of care (SOC) (intramedullary nail and soft tissue management; n = 138) or SOC + rhBMP-2(1.5 mg/mL; n = 139).	Clinical and radiographic assessment of fracture healing, rates of secondary intervention F/U: 1 year	rhBMP-2 did not significantly accelerate fracture healing in open tibia fractures compared with the controls. The study was halted prior to completion because of a trend toward increasing infection in the rhBMP-2 group.
Jones et al. [37] (2006) Prospective, randomized, multicenter, controlled, and blinded study	Thirty diaphyseal tibia fractures with cortical defects were randomly assigned to two treatment groups: rhBMP-2 + allograft (n = 15) or autogenous ICBG (n = 15).	Clinical and radiographic assessment of fracture healing, functional outcome measure (SMFA)	No significant differences in the healing rates, number of secondary interventions, and functional outcome scores between the two groups
		F/U: 1 year
Swiontkowski et al. [85] (2006)	Open tibia fractures were randomly assigned to receive intramedullary nail and routine soft tissue management alone (n = 169) or in combination with rhBMP-2 (n = 169).	Clinical and radiographic assessment of fracture healing, number of secondary interventions and infection rates	rhBMP-2 decreased the frequency and invasiveness of secondary interventions and reduced the infection rates in grade III open tibia fractures.
Subgroup analysis of two prospective randomized studies	Two subgroups: open fracture (grade IIIA and IIIB; n = 131) and the reamed nailing group (n = 113)	F/U: 1 year
Govender et al. [36] (2002) Prospective, randomized, multicenter, controlled, single-blind study	Four hundred fifty patients with open tibia fractures were randomly assigned to receive SOC (intramedullary nail and soft tissue management) or SOC + rhBMP-2 (0.75 mg/mL) or SOC + rhBMP-2 (1.5 mg/mL).	Clinical and radiographic assessment of fracture healing, rates of secondary intervention F/U: 1 year	rhBMP-2 (1.5 mg/mL) use reduced the frequency and invasiveness of secondary interventions, reduced infection rate (grades IIIA and IIIB), and accelerated fracture and wound healing.

ICBG, iliac crest bone graft; rhBMP-2, human recombinant bone morphogenetic protein-2; SMFA, short musculoskeletal function assessment.