Acceleration of fracture healing in nonhuman primates by fibroblast growth factor-2.
One of the greatest needs in the clinical bone field is a bioactive agent to stimulate bone formation. We previously reported that fibroblast growth factor-2 (FGF-2) exhibited strong anabolic actions on bone formation in models of rodents and dogs. Aiming at a clinical application, this study was undertaken to clarify the effect of a single local application of recombinant human FGF-2 on fracture healing in nonhuman primates. After a fracture was created at the midshaft of the right ulna of animals and stabilized with an intramedullary nail, gelatin hydrogel alone (n = 10) or gelatin hydrogel containing 200 microg FGF-2 (n = 10) was injected into the fracture site. Although 4 of 10 animals treated with the vehicle alone remained in a nonunion state even after 10 weeks, bone union was complete at 6 weeks in all 10 animals treated with FGF-2. Significant differences in bone mineral content and density at the fracture site between the vehicle and FGF-2 groups were seen at 6 weeks and thereafter. FGF-2 also increased the mechanical property of the fracture site. We conclude that FGF-2 accelerates fracture healing and prevents nonunion in primates, and therefore propose that it is a potent bone anabolic agent for clinical use.
Kawaguchi
H
H
Department of Orthopedic Surgery, University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Bunkyo 113-8655, Tokyo. kawaguchi-ort@h.u-tokyo.ac.jp
Nakamura
K
K
Tabata
Y
Y
Ikada
Y
Y
Aoyama
I
I
Anzai
J
J
Nakamura
T
T
Hiyama
Y
Y
Tamura
M
M
D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D004195:Disease Models, Animal; D004285:Dogs; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D017102:Fracture Healing / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D012377:Rodentia; D014458:Ulna Fractures / Q000473:pathology / Q000503:physiopathology*
D000596:Amino Acids; D015415:Biomarkers; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; C036020:deoxypyridinoline; D003404:Creatinine; D000469:Alkaline Phosphatase