Baas Jorgen, Vestermark Marianne, Jensen Thomas, Bechtold Joan, Soballe Kjeld, Jakobsen Thomas
Orthopaedic Research Laboratory, Aarhus University Hospital, 8000 Aarhus C, Denmark.
Minneapolis Medical Research Foundation, University of Minnesota, Minneapolis, MN 55415, USA.
Bone. 2017 Apr;97:76-82. doi: 10.1016/j.bone.2017.01.007. Epub 2017 Jan 7.
Bone allograft is used in total joint arthroplasties in order to enhance implant fixation. BMPs are known to stimulate new bone formation within allograft, but also known to accelerate graft resorption. Bisphosphonates are strong inhibitor of bone resorption. The aim of this study was to investigate whether the bisphosphonate zoledronate was able to counteract the accelerated graft resorption without interfering with the BMP induced bone formation. In the present study the two drugs alone and in combination were studied in our canine model of impaction bone grafting. We included 10 dogs in this study. Cancellous allograft bone grafts were soaked in either saline or zoledronate solution (0.005mg/mL) and then vehicle or BMP2 (0.15mg rhBMP2) was added. This produced four treatment groups: A) control, B) BMP2, C) zoledronate and D) BMP2+zoledronate. The allograft treated with A, B, C or D was impacted into a circumferential defect of 2.5mm around HA-coated porous Ti implants. Each dog received all four treatment groups with two implants in the distal part of each femur. The group with allograft soaked in zoledronate (C) showed better biomechanical fixation than all other groups (p<0.05). It had less allograft resorption compared to all other groups (p<0.005) without any statistically significant change in new bone formation. The addition of BMP2 to the allograft did not increase new bone formation significantly, but did accelerate allograft resorption. This was also the case where the allograft was treated with BMP2 and zoledronate in combination (D). This caused a decrease in mechanical implant fixation in both these groups compared to the control group, however only statistically significant for the BMP2 group compared to control. The study shows that topical zoledronate can be a valuable tool for augmenting bone grafts when administered optimally. The use of BMP2 in bone grafting procedures seems associated with a high risk of bone resorption and mechanical weakening.
骨移植常用于全关节置换术中，以增强植入物的固定。已知骨形态发生蛋白（BMPs）可刺激移植骨内新骨形成，但也会加速移植骨的吸收。双膦酸盐是骨吸收的强效抑制剂。本研究的目的是调查双膦酸盐唑来膦酸是否能够在不干扰BMP诱导的骨形成的情况下，抵消加速的移植骨吸收。在本研究中，单独使用和联合使用这两种药物在我们的犬类嵌压植骨模型中进行了研究。本研究纳入了10只犬。松质骨移植骨浸泡在生理盐水或唑来膦酸溶液（0.005mg/mL）中，然后添加赋形剂或BMP2（0.15mg重组人骨形态发生蛋白2）。这产生了四个治疗组：A）对照组，B）BMP2组，C）唑来膦酸组和D）BMP2 + 唑来膦酸组。用A、B、C或D处理的移植骨被嵌入HA涂层多孔钛植入物周围2.5mm 的环形缺损中。每只犬在每侧股骨远端接受所有四个治疗组，每组两个植入物。浸泡在唑来膦酸中的移植骨组（C）显示出比所有其他组更好的生物力学固定（p<0.05）。与所有其他组相比，其移植骨吸收更少（p<0.005），新骨形成没有任何统计学上的显著变化。将BMP2添加到移植骨中并没有显著增加新骨形成，但确实加速了移植骨吸收。移植骨联合使用BMP2和唑来膦酸处理（D）的情况也是如此。与对照组相比，这两组的机械植入物固定均下降，然而只有BMP2组与对照组相比具有统计学意义。该研究表明，局部使用唑来膦酸在最佳给药时可以成为增强骨移植的有价值工具。在骨移植手术中使用BMP2似乎与骨吸收和机械强度减弱的高风险相关。
