Arnoldi Joerg, Alves Antoine, Procter Philip
Stryker Osteosynthesis, Selzach, Switzerland.
BMC Musculoskelet Disord. 2014 Mar 23;15:97. doi: 10.1186/1471-2474-15-97.
In fracture treatment, adequate fixation of implants is crucial to long-term clinical performance. Bisphosphonates (BP), potent inhibitors of osteoclastic bone resorption, are known to increase peri-implant bone mass and accelerate primary fixation. However, adverse effects are associated with systemic use of BPs. Thus, Zoledronic acid (ZOL) a potent BP was loaded on bone screws and evaluated in a local delivery model. Whilst mid- to long-term effects are already reported, early cellular events occurring at the implant/bone interface are not well described. The present study investigated early tissue responses to ZOL locally delivered, by bone screw, into a compromised cancellous bone site.
ZOL was immobilized on fibrinogen coated titanium screws. Using a bilateral approach, ZOL loaded test and non-loaded control screws were implanted into femoral condyle bone defects, created by an overdrilling technique. Histological analyses of the local tissue effects such as new bone formation and osteointegration were performed at days 1, 5 and 10.
Histological evaluation of the five day ZOL group, demonstrated a higher osseous differentiation trend. At ten days an early influx of mesenchymal and osteoprogenitor cells was seen and a higher level of cellular proliferation and differentiation (p < 5%). In the ZOL group bone-to-screw contact and bone volume values within the defect tended to increase. Local drug release did not induce any adverse cellular effects.
This study indicates that local ZOL delivery into a compromised cancellous bone site actively supports peri-implant osteogenesis, positively affecting mesenchymal cells, at earlier time points than previously reported in the literature.
在骨折治疗中，植入物的充分固定对长期临床效果至关重要。双膦酸盐（BP）是破骨细胞骨吸收的有效抑制剂，已知可增加种植体周围骨量并加速初始固定。然而，全身使用BP会产生不良反应。因此，将强效BP唑来膦酸（ZOL）加载到骨螺钉上，并在局部递送模型中进行评估。虽然已经报道了中长期效果，但在植入物/骨界面发生的早期细胞事件尚未得到充分描述。本研究调查了通过骨螺钉局部递送ZOL后，在受损松质骨部位的早期组织反应。
将ZOL固定在纤维蛋白原包被的钛螺钉上。采用双侧方法，将加载ZOL的测试螺钉和未加载的对照螺钉植入通过钻孔技术创建的股骨髁骨缺损处。在第1、5和10天对局部组织效应进行组织学分析，如新骨形成和骨整合。
对五天ZOL组的组织学评估显示出更高的骨分化趋势。在第10天，可见间充质细胞和骨祖细胞早期流入，细胞增殖和分化水平更高（p<5%）。在ZOL组中，缺损内的骨与螺钉接触面积和骨体积值有增加趋势。局部药物释放未诱导任何不良细胞效应。
本研究表明，在受损松质骨部位局部递送ZOL可积极支持种植体周围骨生成，比文献中先前报道的时间点更早地对间充质细胞产生积极影响。
