Baas Jorgen, Elmengaard Brian, Jensen Thomas B, Jakobsen Thomas, Andersen Niels T, Soballe Kjeld
Orthopaedic Research Laboratory, Aarhus University Hospital, Norrebrogade 44, Building 1a, 8000 Aarhus C, Denmark.
Biomaterials. 2008 Jul;29(19):2915-22. doi: 10.1016/j.biomaterials.2008.03.010. Epub 2008 Apr 14.
BMPs stimulate new bone formation, but may also accelerate bone resorption. We added rhBMP-2 and pamidronate to morselized bone allograft packed around uncemented HA-coated and non-coated porous Ti implants in sixteen dogs. Each dog received four implants where the allograft was added (1) nothing, (2) BMP, (3) BP, and (4) BMP+BP. After four weeks, the untreated control implants had better mechanical fixation than all other treatment groups. The rhBMP-2-treated group had abundant formation of new bone on and around the implant. However, almost all allografts were resorbed, rendering the implant mechanically unstable. In the pamidronate-treated group the allograft was preserved, but the implants were covered by fibrous tissue and there was almost no new bone formation. This was also the case for the combined BMP+BP group, although fibrous tissue was absent on these implants. The HA-coated implants had more than twice as good mechanical fixation and improved osseointegration compared to the corresponding Ti implants. RhBMP-2 raised the total metabolic turnover of bone within the allograft with a net negative result on implant fixation. Pamidronate virtually blocked bone metabolism, also when combined with rhBMP-2. The results warrant a conservative approach and emphasize the importance of identifying a therapeutic window for these substances prior to clinical use.
骨形态发生蛋白(BMPs)可刺激新骨形成,但也可能加速骨吸收。我们将重组人骨形态发生蛋白-2(rhBMP-2)和帕米膦酸盐添加到16只犬的非骨水泥型羟基磷灰石(HA)涂层和未涂层多孔钛植入物周围的碎骨同种异体移植物中。每只犬接受4个添加了同种异体移植物的植入物,分别为(1)不添加任何物质、(2)BMP、(3)BP和(4)BMP+BP。4周后,未治疗的对照植入物比所有其他治疗组具有更好的机械固定。rhBMP-2治疗组在植入物及其周围有大量新骨形成。然而,几乎所有的同种异体移植物都被吸收,导致植入物机械不稳定。在帕米膦酸盐治疗组中,同种异体移植物得以保留,但植入物被纤维组织覆盖,几乎没有新骨形成。BMP+BP联合治疗组也是如此,尽管这些植入物上没有纤维组织。与相应的钛植入物相比,HA涂层植入物的机械固定效果好两倍多,骨整合得到改善。rhBMP-2提高了同种异体移植物内骨的总代谢周转率,对植入物固定产生净负面结果。帕米膦酸盐实际上阻断了骨代谢,与rhBMP-2联合使用时也是如此。这些结果表明应采取保守方法,并强调在临床使用前确定这些物质治疗窗口的重要性。