Lillis Theodoros, Veis Alexander, Sakellaridis Nikolaos, Tsirlis Anastasios, Dailiana Zoe
Department of Orthopaedic Surgery, Faculty of Medicine, University of Thessaly, Biopolis, Larissa 41500, Greece.
Department of Dentoalveolar Surgery, Implantology and Oral Radiology, Faculty of Dentistry, Aristotle University of Thessaloniki, Panepistimioupoli, Thessaloniki 54124, Greece.
World J Orthop. 2019 Dec 18;10(12):434-445. doi: 10.5312/wjo.v10.i12.434.
Clopidogrel is a widely prescribed drug for prevention of myocardial infarction and stroke in patients at risk. It inhibits thrombus formation inhibition of the P2Y purinergic receptor on platelets, which is important in their activation by ADP. However, the P2Y receptor has also been found to be expressed in both osteoblasts and osteoclasts. Accumulated evidence suggests that purinergic receptors regulate important functions of bone turnover. Previous studies on the effect of clopidogrel on bone metabolism indicated potential harmful effects, but their results remain conflicting. Thus, clopidogrel treatment may affect bone healing, but it has not yet been studied.
To evaluate if continuous perioperative clopidogrel treatment has any negative effect on bone healing in the rabbit calvarial defect model.
Sixteen male white New Zealand rabbits were randomly assigned in two groups: One group received daily 3 mg/kg of clopidogrel per os and the other group received the vehicle alone for a week prior to the surgical procedures; the treatments were continued for another 6 wk postoperatively. The surgical procedures included generation of two circular calvarial defects 11 mm in diameter in every animal. After the 6-wk period of healing, postmortem radiographic and histomorphometric evaluation of the defects was performed.
Both the surgical procedures and the postoperative period were uneventful and well tolerated by all the animals, without any surgical wound dehiscence, signs of infection or other complication. New bone was formed either inwards from the defect margins or in the central portion of the defect as separated bony islets. While defect healing was still incomplete in both groups, the clopidogrel group had significantly improved radiographic healing scores. Moreover, the histomorphometric analysis showed that bone regeneration (%) was 28.07 ± 7.7 for the clopidogrel group and 19.47 ± 4.9 for the control group, showing a statistically significant difference between them ( = 0.018). Statistically significant difference was also found in the defect bridging (%), . 72.17 ± 21.2 for the clopidogrel group and 41.17 ± 8.5 for the control group, respectively ( = 0.004), whereas there was no statistical difference in bone tissue density between the groups.
Our results indicate that maintenance of perioperative clopidogrel treatment does not negatively affect bone healing but rather promotes it. Further research is needed in order to find useful applications of this finding.
氯吡格雷是一种广泛用于预防有风险患者心肌梗死和中风的药物。它通过抑制血小板上的P2Y嘌呤能受体来抑制血栓形成，而该受体在二磷酸腺苷（ADP）激活血小板过程中起重要作用。然而，人们还发现P2Y受体在成骨细胞和破骨细胞中均有表达。越来越多的证据表明，嘌呤能受体调节骨转换的重要功能。先前关于氯吡格雷对骨代谢影响的研究表明存在潜在有害作用，但其结果仍相互矛盾。因此，氯吡格雷治疗可能会影响骨愈合，但尚未进行相关研究。
评估围手术期持续使用氯吡格雷治疗对兔颅骨缺损模型的骨愈合是否有负面影响。
16只雄性新西兰白兔被随机分为两组：一组在手术前一周每天口服3mg/kg氯吡格雷，另一组仅给予赋形剂；术后继续治疗6周。手术操作包括在每只动物颅骨上制造两个直径11mm的圆形缺损。在愈合6周后，对缺损进行死后影像学和组织形态计量学评估。
所有动物的手术过程和术后期间均顺利且耐受性良好，无任何手术伤口裂开、感染迹象或其他并发症。新骨从缺损边缘向内生长，或在缺损中央部分以分离的骨岛形式形成。虽然两组的缺损愈合仍不完全，但氯吡格雷组的影像学愈合评分有显著改善。此外，组织形态计量学分析显示，氯吡格雷组的骨再生率（%）为28.07±7.7，对照组为19.47±4.9，两组间差异有统计学意义（P = 0.018）。在缺损桥接率（%）方面也发现有统计学意义的差异，氯吡格雷组为72.17±21.2，对照组为41.17±8.5（P = 0.004），而两组间骨组织密度无统计学差异。
我们的结果表明，围手术期持续使用氯吡格雷治疗对骨愈合没有负面影响，反而有促进作用。为了找到这一发现的有用应用，还需要进一步研究。
