title: A pilot study of regenerative therapy using controlled release of recombinant human fibroblast growth factor for patients with pre-collapse osteonecrosis of the femoral head.
abstract: We evaluated the safety and clinical outcomes of a single local administration of gelatin hydrogel impregnated with recombinant human fibroblast growth factor (rhFGF)-2 for the treatment of the precollapse stage of osteonecrosis of the femoral head (ONFH).
  
  
  
  Patients with ONFH (precollapse stage ≤2) received a single local administration of 800 μg of rhFGF-2-impregnated gelatin hydrogel and were followed up for one year. The surgery was performed using a minimally invasive technique involving a 1-cm skin incision, and walking was allowed from day one postoperatively. The primary outcomes included occurrence of adverse events and complications. The secondary outcomes included changes in the Harris hip scores, visual analog scale for pain scores, University of California, Los Angeles (UCLA) activity scores, and radiological images.
  
  
  
  We included ten patients, of which five experienced 14 adverse events, including one complication from spinal anesthesia. However, patients completely recovered from all adverse events. The mean clinical scores significantly improved by one year postoperatively compared with the pre-operative scores (before vs. after: visual analog score for pain, 21.2 vs. 5.3 mm; UCLA activity score, 5.5 vs. 6.6; Harris hip score, 81.0 vs. 96.9 points). There was only one case of femoral head collapse; however, this occurred in a hip with extensive necrosis. Stage progression and collapse did not occur in the other nine cases. Computed tomography confirmed bone regeneration in the femoral heads.
  
  
  
  Clinical application of rhFGF-2-impregnated gelatin hydrogel for patients with precollapse ONFH was feasible and safe.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Kawahara-cho 54, Sakyo-ku, Kyoto, 606-8507, Japan. ykuromd@kuhp.kyoto-u.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kuroda
authors.affiliation: Clinical Research Center, Gifu University Hospital, Gifu, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Asada
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Kawahara-cho 54, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: So
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yonezawa
authors.affiliation: Rehabilitation Unit, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Nankaku
authors.affiliation: Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Research (iACT), Kyoto University Hospital, Kyoto, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Mukai
authors.affiliation: Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Research (iACT), Kyoto University Hospital, Kyoto, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Ito-Ihara
authors.affiliation: Department of Data Science, Institute for Advancement of Clinical and Translational Research (iACT), Kyoto University Hospital, Kyoto, Japan.
authors.forename: Harue
authors.initials: H
authors.lastname: Tada
authors.affiliation: Department of Data Science, Institute for Advancement of Clinical and Translational Research (iACT), Kyoto University Hospital, Kyoto, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Research (iACT), Kyoto University Hospital, Kyoto, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Murayama
authors.affiliation: Department of Data Science, Institute for Advancement of Clinical and Translational Research (iACT), Kyoto University Hospital, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Research (iACT), Kyoto University Hospital, Kyoto, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokode
authors.affiliation: Department of Experimental Therapeutics, Institute for Advancement of Clinical and Translational Research (iACT), Kyoto University Hospital, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Kawahara-cho 54, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Orthopaedic Surgery, Gifu University, Gifu, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
mesh_terms: D000328:Adult; D003692:Delayed-Action Preparations; D005260:Female; D005270:Femur Head / Q000601:surgery*; D005271:Femur Head Necrosis / Q000601:surgery*; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011859:Radiography; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism*; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D014057:Tomography, X-Ray Computed
chemical_list: D003692:Delayed-Action Preparations; C100666:KCB-1 protein, recombinant; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2
keywords: Clinical trial; FGF; Femoral head; Growth factor; Osteonecrosis; Regenerative therapy