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Acceleration of Fracture Healing in Nonhuman Primates by Fibroblast Growth Factor-2

Department of Orthopedic Surgery, University of Tokyo Graduate School of Medicine (H.K., K.N.), Hongo 7-3-1, Bunkyo 113-8655, Tokyo; Institute for Frontier in Medical Science, Kyoto University (Y.T.), Kyoto; Faculty of Medical Engineering, Suzuka University of Medical Science (Y.I.), Mie; and Kaken Pharmaceutical Co., Ltd. (I.A., J.A., T.N., Y.H., M.T.), Minamikawara-machi, Kyoto, Japan

Address all correspondence and requests for reprints to: Hiroshi Kawaguchi, M.D., Ph.D., Department of Orthopedic Surgery, University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail: kawaguchi-ort{at}h.u-tokyo.ac.jp

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 µg 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.

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