title: Treatment of experimental osteonecrosis of the hip in adult rabbits with a single local injection of recombinant human FGF-2 microspheres.
abstract: Basic fibroblast growth factor (FGF-2) exerts anabolic actions on bone formation. Here we investigated the potential effects of recombinant human FGF-2 (rhFGF-2) on the repair process of osteonecrosis of the femoral head (ONFH) and the development of secondary osteoarthritis (OA) in adult rabbits. ONFH was induced by intramuscular injection with methylprednisolone, and vascular occlusion of the capital femoral epiphysis by electrocoagulation, in adult Japanese white rabbits. Animals were randomized into two groups: treatment and control. The treatment group was given a single local injection into the femoral head of 100 μg rhFGF-2 in 100 μl gelatin hydrogel microspheres 8 weeks after the ONFH procedure, and the control group was given phosphate-buffered saline in 100 μl gelatin hydrogel microspheres. Morphological, histopathological, and radiologic analyses, including micro-computed tomography scans and magnetic resonance imaging, showed collapse of the femoral head and progression of articular cartilage degeneration in the control group at 16 weeks after the single local injection of rhFGF-2. In contrast, rhFGF-2 treatment resulted in new bone formation in the femoral head and prevented the femoral head from collapsing. In addition, the changes in OA, assessed by the modified Mankin score, was significantly lower in the treatment group. Our results indicate that a single local injection of rhFGF-2 microspheres promoted the repair of the osteonecrotic femoral head and inhibited femoral head collapse and OA progression. rhFGF-2 may be a promising strategy for the treatment of ONFH.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Kawahara-cho 54, Sakyo-ku, Kyoto, Japan. ykuromd@kuhp.kyoto-u.ac.jp
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawanabe
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D018450:Disease Progression; D004564:Electrocoagulation / Q000009:adverse effects; D005270:Femur Head / Q000187:drug effects* / Q000473:pathology; D005271:Femur Head Necrosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000633:toxicity; D020100:Hydrogels; D015552:Injections, Intralesional; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000633:toxicity; D008863:Microspheres; D015207:Osteoarthritis, Hip / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D010012:Osteogenesis / Q000187:drug effects; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000627:therapeutic use*; D012720:Severity of Illness Index
chemical_list: D050071:Bone Density Conservation Agents; D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D020100:Hydrogels; C100666:KCB-1 protein, recombinant; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D008775:Methylprednisolone