Local application of recombinant human fibroblast growth factor-2 on bone repair: a dose-escalation prospective trial on patients with osteotomy.
Based on preclinical evidence in animal models, the present study examined the clinical efficacy and safety of recombinant human fibroblast growth factor-2 (rhFGF-2) to accelerate bone repair in a dose-escalation prospective trial. One of three dosages (200, 400 or 800 microg) of rhFGF-2 in a biodegradable gelatin hydrogel was injected during surgery into the osteotomy site of 59 knee osteoarthritis patients undergoing high tibial osteotomy, and 57 of them were monitored for 16 weeks. The rhFGF-2 dose dependently increased the percentage of patients with radiographic bone union, and decreased the average time needed for such union. The percentages of patients with an absence of pain and full-weight bearing were also greater in the higher dosage groups than in the low dosage group, especially in the clinically critical periods 6, 8, and 10 weeks. Neither blood chemistries nor clinical adverse events were associated with the rhFGF-2 dosages. We therefore conclude that the rhFGF-2 in gelatin hydrogel dose dependently accelerated radiographic bone union of a surgical osteotomy with a safety profile at least at the dosages used, suggesting the clinical efficacy of this agent for bone repair.
Kawaguchi
Hiroshi
H
Sensory & Motor System Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo, Tokyo 113-8655, Japan. kawaguchi-ort@h.u-tokyo.ac.jp
Jingushi
Seiya
S
Izumi
Toshihiro
T
Fukunaga
Masao
M
Matsushita
Takashi
T
Nakamura
Takashi
T
Mizuno
Kosaku
K
Nakamura
Toshitaka
T
Nakamura
Kozo
K
D000328:Adult; D000368:Aged; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000601:surgery; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D010027:Osteotomy / Q000379:methods*; D011446:Prospective Studies; D011859:Radiography; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D013977:Tibia / Q000000981:diagnostic imaging / Q000502:physiology
D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate