Continuous local infusion of fibroblast growth factor-2 enhances consolidation of the bone segment lengthened by distraction osteogenesis in rabbit experiment

被引:34
作者
Abbaspour, Aziz [1 ]
Takata, Shinjiro [1 ]
Sairyo, Koichi [1 ]
Katoh, Shinsuke [1 ]
Yukata, Kiminori [1 ]
Yasui, Natsuo [1 ]
机构
[1] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Orthoped, Tokushima 7708503, Japan
关键词
local injection; FGF-2; distraction osteogenesis; osmotic pump; limb lengthening;
D O I
10.1016/j.bone.2007.08.031
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
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 mu g/60 mu l/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. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:98 / 106
页数:9
相关论文
共 29 条
[1]
The Nicolas Andry Award - Modulation of distraction osteogenesis in the aged rat by fibroblast growth factor [J].
Aronson, J .
CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 2004, (425) :264-283
[2]
Proteinuria in a placebo-controlled study of basic fibroblast growth factor for intermittent claudication [J].
Cooper, LT ;
Hiatt, WR ;
Creager, MA ;
Regensteiner, JG ;
Casscells, W ;
Isner, JM ;
Cooke, JP ;
Hirsch, AT .
VASCULAR MEDICINE, 2001, 6 (04) :235-239
[3]
NEW BONE-FORMATION DURING LEG LENGTHENING - EVALUATED BY DUAL ENERGY X-RAY ABSORPTIOMETRY [J].
EYRES, KS ;
BELL, MJ ;
KANIS, JA .
JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME, 1993, 75 (01) :96-106
[4]
FISCHGRUND J, 1994, CLIN ORTHOP RELAT R, P31
[5]
THE TENSION STRESS EFFECT ON THE GENESIS AND GROWTH OF TISSUES .1. THE INFLUENCE OF STABILITY OF FIXATION AND SOFT-TISSUE PRESERVATION [J].
ILIZAROV, GA .
CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 1989, (238) :249-281
[6]
REGULATION OF PROLIFERATION AND OSTEOCHONDROGENIC DIFFERENTIATION OF PERIOSTEUM-DERIVED CELLS BY TRANSFORMING GROWTH-FACTOR-BETA AND BASIC FIBROBLAST GROWTH-FACTOR [J].
IWASAKI, M ;
NAKAHARA, H ;
NAKATA, K ;
NAKASE, T ;
KIMURA, T ;
ONO, K .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 1995, 77A (04) :543-554
[7]
IWASAKI M, 1994, J BONE MINER RES, V9, P1195
[8]
Acceleration of fracture healing in nonhuman primates by fibroblast growth factor-A [J].
Kawaguchi, H ;
Nakamura, K ;
Tabata, Y ;
Ikada, Y ;
Aoyama, I ;
Anzai, J ;
Nakamura, T ;
Hiyama, Y ;
Tamura, M .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (02) :875-880
[9]
BONE LENGTHENING IN RABBITS BY CALLUS DISTRACTION - THE ROLE OF PERIOSTEUM AND ENDOSTEUM [J].
KOJIMOTO, H ;
YASUI, N ;
GOTO, T ;
MATSUDA, S ;
SHIMOMURA, Y .
JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME, 1988, 70 (04) :543-549
[10]
Pharmacodynamics of basic fibroblast growth factor: route of administration determines myocardial and systemic distribution [J].
Lazarous, DF ;
Shou, M ;
Stiber, JA ;
Dadhania, DM ;
Thirumurti, V ;
Hodge, E ;
Unger, EF .
CARDIOVASCULAR RESEARCH, 1997, 36 (01) :78-85