Bone consolidation is enhanced by rhBMP-2 in a rabbit model of distraction osteogenesis

被引:114
作者
Li, G [1 ]
Bouxsein, ML
Luppen, C
Li, XJ
Wood, M
Seeherman, HJ
Wozney, JM
Simpson, H
机构
[1] Queens Univ Belfast, Musgrave Pk Hosp, Dept Traumat & Orthopaed Surg, Belfast BT9 7JB, Antrim, North Ireland
[2] Genet Inst Wyeth Ayerst Res, Musculoskeletal Sci, Cambridge, MA 02140 USA
[3] Univ Oxford, Nuffield Dept Orthopaed Surg, Oxford OX3 7LD, England
[4] Univ Edinburgh, Dept Orthopaed Surg, Princess Margaret Rose Orthopaed Hosp, Edinburgh EH10 7ED, Midlothian, Scotland
关键词
rhBMP-2; ACS; injection; distraction osteogenesis; pQCT; BMC; rabbit;
D O I
10.1016/S0736-0266(01)00166-8
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a differentiation factor which has been shown to induce bone formation and heal bony defects in a variety of animal models. A possible application of rhBMP-2 is to accelerate bone regeneration during distraction osteogenesis, which clinically is a long procedure, often involving significant complications. In this study we tested the ability of rhBMP-2 to accelerate the consolidation phase of distraction osteogenesis in a rabbit model of leg lengthening. Tibiae were lengthened 2 cm over a period of ten days, rhBMP-2 was administered at the end of the lengthening phase. Two modes of rhBMP-2 application were tested: surgical implantation of rhBMP-2/ACS (absorbable collagen sponge) into the regenerate (50 mul of 1.5 mg/ml rhBMP-2, total dose = 75 mug rhBMP-2), and percutaneous injection of rhBMP-2/buffer (0.1 ml of 0.75 mg/ml rhBMP-2, total dose = 75 mug rhBMP-2) into three sites within the regenerate. Also, there were three groups of control animals: (1) no surgical intervention, (2) surgical implantation of buffer/ACS and (3) percutaneous injection of buffer. Rabbits were sacrificed at 5, 14 and 28 days after the interventions. Radiographic evaluation indicated a significant increase in bony union of the distraction regenerate in the rhBMP-2 treated groups compared with the untreated groups at 5 and 14 days. At 28 days, formation of a cortex and reestablishment of the medullary canal was evident only in the rhBMP-2 treated groups. The bone mineral content (BMC) of the regenerate was significantly higher in the rhBMP-2 treated groups at 4 and 14 days. However, at 28 days, BMC of the regenerate was similar in all groups. The average volumetric density of the regenerate was significantly higher in the rhBMP-2 injection group at day 14. In summary, both injection of rhBMP-2/buffer and implantation of rhBMP-2/ACS enhanced the consolidation stage of distraction osteogenesis in this rabbit model. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:779 / 788
页数:10
相关论文
共 40 条
[21]   Distraction osteogenesis of the lower extremity with use of monolateral external fixation -: A study of two hundred and sixty-one femora and tibiae [J].
Noonan, KJ ;
Leyes, M ;
Forriol, F ;
Cañadell, J .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 1998, 80A (06) :793-806
[22]   INVITRO CHEMOTACTIC RESPONSE OF OSTEOBLAST-LIKE OSTEOSARCOMA CELLS TO A PARTIALLY PURIFIED PROTEIN EXTRACT OF DEMINERALIZED BONE-MATRIX [J].
PADLEY, RA ;
COBB, CM ;
KILLOY, WJ ;
NEWHOUSE, NL ;
BOYAN, BD .
JOURNAL OF PERIODONTOLOGY, 1991, 62 (01) :15-20
[23]   Longitudinal growth rate following slow physeal distraction - The proximal tibial growth plate studied in rabbits [J].
Pereira, BP ;
Cavanagh, SP ;
Pho, RWH .
ACTA ORTHOPAEDICA SCANDINAVICA, 1997, 68 (03) :262-268
[24]  
RICHARDS M, 1998, CLIN ORTHOP S, V355, pS191, DOI DOI 10.1097/00003086-199810001-00020
[25]  
Riedel GE, 1999, ORTHOPEDICS, V22, P663
[26]   Bone morphogenetic protein-2: Biology and applications [J].
Riley, EH ;
Lane, JM ;
Urist, MR ;
Lyons, KM ;
Lieberman, JR .
CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 1996, (324) :39-46
[27]   Bone morphogenetic proteins: From basic studies to clinical approaches [J].
Sakou, T .
BONE, 1998, 22 (06) :591-603
[28]   Mechanical tension-stress induces expression of bone morphogenetic protein (BMP)-2 and BMP-4, but not BMP-6, BMP-7, and GDF-5 mRNA, during distraction osteogenesis [J].
Sato, M ;
Ochi, T ;
Nakase, T ;
Hirota, S ;
Kitamura, Y ;
Nomura, S ;
Yasui, N .
JOURNAL OF BONE AND MINERAL RESEARCH, 1999, 14 (07) :1084-1095
[29]   Evaluation of recombinant human bone morphogenetic protein-2 as a bone-graft substitute in a canine segmental defect model [J].
Sciadini, MF ;
Johnson, KD .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2000, 18 (02) :289-302
[30]   THE RESPONSE OF MUSCLE TO LEG LENGTHENING [J].
SIMPSON, AHRW ;
WILLIAMS, PE ;
KYBERD, P ;
GOLDSPINK, G ;
KENWRIGHT, J .
JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME, 1995, 77B (04) :630-636