title: Continuous local infusion of fibroblast growth factor-2 enhances consolidation of the bone segment lengthened by distraction osteogenesis in rabbit experiment.
abstract: Experimental tibial lengthening was achieved in 61 rabbits to examine the effect of continuous local infusion of recombinant human fibroblast growth factor-2 (rhFGF-2) on bone healing of the lengthened segment. The tibial diaphysis was separated by osteotomy and was subjected to slow progressive distraction (rate: 0.35 mm/12 h) using a monolateral external fixator. There were a lag phase for 1 week, a distraction phase for 2 weeks, and a consolidation phase for 5 weeks in this experiment. At various stages of distraction, rhFGF-2 was infused continuously for 2 weeks into the lengthened segment (rate: 14.28 microg/60 microl/day) using an osmotic pump implanted under the skin. Bone healing was significantly accelerated when rhFGF-2 was infused in the beginning of consolidation phase, but not in the distraction phase or in the lag phase. Infusion of normal saline (N/S) using the same osmotic pump had no effect. Dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT) studies demonstrated that rhFGF-2-treated tibia had increased bone mineral density (BMD), bone mineral content (BMC) and cortical bone thickness (CBT) when compared with N/S-treated tibia. Three-point bending test demonstrated that rhFGF-2-treated bone had significantly stronger mechanical properties than N/S-treated bone. Finally, distribution of the infused materials was checked by using Indian ink or radio-opaque. The dyes distributed widely but exclusively in the lengthened segment. Based on these results, we conclude that direct delivery of rhFGF-2 into the lengthened segment can shorten the consolidation phase of limb lengthening and the method is applicable to the clinical treatment.
authors.affiliation: Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
authors.forename: Aziz
authors.initials: A
authors.lastname: Abbaspour
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Takata
authors.forename: Koichi
authors.initials: K
authors.lastname: Sairyo
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Katoh
authors.forename: Kiminori
authors.initials: K
authors.lastname: Yukata
authors.forename: Natsuo
authors.initials: N
authors.lastname: Yasui
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D015552:Injections, Intralesional; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D019857:Osteogenesis, Distraction; D011817:Rabbits; D014057:Tomography, X-Ray Computed
chemical_list: D016222:Fibroblast Growth Factor 2