A Local Application of Recombinant Human Fibroblast Growth Factor 2 for Tibial Shaft Fractures: A Randomized, Placebo-Controlled Trial

Fibroblast growth factor 2 (FGF-2) is a potent mitogen for mesenchymal cells, and a local application of recombinant human FGF-2 (rhFGF-2) in a gelatin hydrogel has been reported to accelerate bone union in our animal studies and preparatory dose-escalation trial on patients with surgical osteotomy We have performed a randomized, double-blind, placebo-controlled trial in which patients with fresh tibial shaft fractures of transverse or short oblique type were randomly assigned to three groups receiving a single injection of the gelatin hydrogel containing either placebo or 0 8 mg (low-dosage group) or 24 mg (high-dosage group) of rhFGF-2 into the fracture gap at the end of an intramedullary nailing surgery Of 194 consecutive patients over 2 years, 85 met the eligibility criteria, and 70 (24 in the placebo group and 23 each in low- and high-dosage groups) completed the 24-week study The cumulative percentages of patients with radiographic bone union were higher in the rhFGF-2-treated groups (p = 031 and 009 in low- and high-dosage group, respectively) compared with the placebo group, although there was no significant difference between low- and high-dosage groups (p = 776) At 24 weeks, 4, 1, and 0 patients in the placebo, low-dosage, and high-dosage groups, respectively, continued to show delayed union No patient underwent a secondary intervention, and the time to full weight bearing without pain was not significantly different among the three groups (p = 567) There also was no significant difference in the profiles of adverse events among the groups In conclusion, a local application of the rhFGF-2 hydrogel accelerated healing of tibial shaft fractures with a safety profile (C) 2010 American Society for Bone and Mineral Research