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.
Sensory and Motor System Medicine, University of Tokyo, Tokyo, Japan. kawaguchi-ort@h.u-tokyo.ac.jp.
Hiroshi
H
Kawaguchi
Hiroyuki
H
Oka
Seiya
S
Jingushi
Toshihiro
T
Izumi
Masao
M
Fukunaga
Katsumi
K
Sato
Takashi
T
Matsushita
Kozo
K
Nakamura
D000328:Adult; D000906:Antibodies / Q000097:blood; D048909:Diabetes Complications / Q000097:blood; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010919:Placebos; D011859:Radiography; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D013978:Tibial Fractures / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*
D000906:Antibodies; D010919:Placebos; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2