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 2.4 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. © 2010 American Society for Bone and Mineral Research.