den Boer F C, Bramer J A M, Blokhuis T J, Van Soest E J, Jenner J M G T, Patka P, Bakker F C, Burger E H, Haarman H J T M
Department of Surgery, VU University Medical Centre, Amsterdam, The Netherlands.
Bone. 2002 Jul;31(1):158-64. doi: 10.1016/s8756-3282(02)00816-5.
Osteogenic protein-1 (OP-1), or bone morphogenetic protein-7, is an osteoinductive morphogen that is involved in embryonic skeletogenesis and in bone repair. In bone defect models without spontaneous healing, local administration of recombinant human OP-1 (rhOP-1) induces complete healing. To investigate the ability of rhOP-1 to accelerate normal physiologic fracture healing, an experimental study was performed. In 40 adult female goats a closed tibial fracture was made, stabilized with an external fixator, and treated as follows: (1) no injection; (2) injection of 1 mg rhOP-1 dissolved in aqueous buffer; (3) injection of collagen matrix; and (4) injection of 1 mg rhOP-1 bound to collagen matrix. The test substances were injected in the fracture gap under fluoroscopic control. At 2 and 4 weeks, fracture healing was evaluated with radiographs, three-dimensional computed tomography (CT), dual-energy X-ray absorptiometry, biomechanical tests, and histology. At 2 weeks, callus diameter, callus volume, and bone mineral content at the fracture site were significantly increased in both rhOP-1 groups compared with the no-injection group. As signs of accelerated callus maturation, bending and torsional stiffness were higher and bony bridging of the fracture gap was observed more often in the group with rhOP-1 dissolved in aqueous buffer than in uninjected fractures. Treatment with rhOP-1 plus collagen matrix did not result in improved biomechanical properties or bony bridging of the fracture gap at 2 weeks. At 4 weeks there were no differences between groups, except for a larger callus volume in the rhOP-1 plus collagen matrix group compared with the control groups. All fractures showed an advanced stage of healing at 4 weeks. In conclusion, the healing of a closed fracture in a goat model can be accelerated by a single local administration of rhOP-1. The use of a carrier material does not seem to be crucial in this application of rhOP-1.
成骨蛋白-1（OP-1），即骨形态发生蛋白-7，是一种骨诱导形态发生素，参与胚胎骨骼生成和骨修复过程。在无自发愈合的骨缺损模型中，局部应用重组人OP-1（rhOP-1）可诱导完全愈合。为研究rhOP-1加速正常生理性骨折愈合的能力，进行了一项实验研究。对40只成年雌性山羊造成闭合性胫骨骨折，用外固定器固定，并进行如下处理：（1）不注射；（2）注射溶解于水性缓冲液中的1mg rhOP-1；（3）注射胶原基质；（4）注射结合于胶原基质的1mg rhOP-1。在荧光镜控制下将受试物质注射到骨折间隙。在2周和4周时，通过X线片、三维计算机断层扫描（CT）、双能X线吸收法、生物力学测试和组织学评估骨折愈合情况。在2周时，与未注射组相比，两个rhOP-1组的骨痂直径、骨痂体积和骨折部位的骨矿物质含量均显著增加。作为骨痂成熟加速的迹象，与未注射骨折相比，溶解于水性缓冲液中的rhOP-1组的弯曲和扭转刚度更高，骨折间隙的骨桥形成更常见。在2周时，rhOP-1加胶原基质治疗并未改善生物力学性能或骨折间隙的骨桥形成。在4周时，除rhOP-1加胶原基质组的骨痂体积比对照组大外，各组之间无差异。所有骨折在4周时均显示愈合的高级阶段。总之，在山羊模型中，单次局部应用rhOP-1可加速闭合性骨折的愈合。在rhOP-1的这种应用中，载体材料的使用似乎并非关键因素。
