Abstract：
OBJECTIVE: To evaluate the effect of continuous perioperative clopidogrel treatment on the osseointegration of titanium implants.
METHODS: A total of 32 New Zealand rabbits were randomly divided between two groups: a clopidogrel group (n = 16) and a control group (n = 16). For 1 week prior to the surgical placement of a titanium implant in their medial femoral condyle, rabbits in the clopidogrel group received 3 mg/kg of clopidogrel daily, and the control group received only the vehicle. This treatment was continued for another 6 weeks postoperatively. At 6 weeks, the rabbits were euthanized and postmortem histologic and histomorphometric evaluation of the implants was performed.
RESULTS: The surgical procedures and postoperative period were uneventful and well tolerated by all animals without any surgical wound dehiscence, signs of infection, or other complication. No implant failure was observed in any of the groups. Histomorphometric analysis showed that bone-to-implant contact (BIC) was 48.77% for the clopidogrel group and 34.65% for the control group, with statistically significant difference between them (P < .001). Moreover, clopidogrel group had significantly greater bone tissue density (40.52% vs 28.74%, respectively; P <.001) and mean trabecular thickness (284.7 μm vs 180.7 μm, respectively; P < .001) in proximity to the implant surface than the control group, while the mean trabecular number had no difference between groups (1.56 vs 1.60, respectively; P = .961).
CONCLUSIONS: The present study showed that continuous clopidogrel treatment does not negatively affect osseointegration, but rather promotes it in terms of BIC and bone density around the titanium implants. Further studies on the effect of the P2Y12 receptor and its antagonists on peri-implant bone homeostasis may provide useful information or applications for long-term success of dental implant therapy.
METHODS: A total of 32 New Zealand rabbits were randomly divided between two groups: a clopidogrel group (n = 16) and a control group (n = 16). For 1 week prior to the surgical placement of a titanium implant in their medial femoral condyle, rabbits in the clopidogrel group received 3 mg/kg of clopidogrel daily, and the control group received only the vehicle. This treatment was continued for another 6 weeks postoperatively. At 6 weeks, the rabbits were euthanized and postmortem histologic and histomorphometric evaluation of the implants was performed.
RESULTS: The surgical procedures and postoperative period were uneventful and well tolerated by all animals without any surgical wound dehiscence, signs of infection, or other complication. No implant failure was observed in any of the groups. Histomorphometric analysis showed that bone-to-implant contact (BIC) was 48.77% for the clopidogrel group and 34.65% for the control group, with statistically significant difference between them (P < .001). Moreover, clopidogrel group had significantly greater bone tissue density (40.52% vs 28.74%, respectively; P <.001) and mean trabecular thickness (284.7 μm vs 180.7 μm, respectively; P < .001) in proximity to the implant surface than the control group, while the mean trabecular number had no difference between groups (1.56 vs 1.60, respectively; P = .961).
CONCLUSIONS: The present study showed that continuous clopidogrel treatment does not negatively affect osseointegration, but rather promotes it in terms of BIC and bone density around the titanium implants. Further studies on the effect of the P2Y12 receptor and its antagonists on peri-implant bone homeostasis may provide useful information or applications for long-term success of dental implant therapy.
摘要：
目的：氯吡格雷是一种P2Y12嘌呤受体抑制剂，是一种常用的预防动脉粥样硬化事件的抗血小板药物。越来越多的证据表明，嘌呤能受体调节骨骼愈合和稳态的重要功能。本研究的目的是评估围手术期持续氯吡格雷治疗对钛植入物骨整合的影响。
方法：将32只新西兰大白兔随机分为两组：氯吡格雷组和对照组。氯吡格雷组的兔子每天接受3mg/kg的氯吡格雷，而对照组在其股骨内侧髁手术放置钛植入物之前接受了一周的赋形剂；术后再继续治疗六周。此时,对植入物进行死后组织学和组织形态学评估.
结果：所有动物的外科手术和术后时间都是平稳的，耐受性良好，没有任何手术伤口裂开，感染或其他并发症的迹象。在任何组中都没有观察到植入失败。组织形态学分析显示，氯吡格雷组BIC（％）为48.77％，对照组为34.65％，差异有统计学意义（P<0.001）。此外，氯吡格雷组的骨组织密度明显增高(40.52%vs28.74%,p<0.001）和平均小梁厚度（284.7μm对180.7μm，p<0.001)靠近植入物表面，而平均骨小梁数量在组间没有差异(1.56vs1.60,p=0.961)。
结论：本研究表明，持续氯吡格雷治疗不会对骨整合产生负面影响，而是在钛植入物周围的BIC和骨密度方面促进它。对P2Y12受体及其拮抗剂对种植体周围骨稳态的影响的进一步研究可能会为牙科种植治疗的长期成功提供有用的信息或应用。
方法：将32只新西兰大白兔随机分为两组：氯吡格雷组和对照组。氯吡格雷组的兔子每天接受3mg/kg的氯吡格雷，而对照组在其股骨内侧髁手术放置钛植入物之前接受了一周的赋形剂；术后再继续治疗六周。此时,对植入物进行死后组织学和组织形态学评估.
结果：所有动物的外科手术和术后时间都是平稳的，耐受性良好，没有任何手术伤口裂开，感染或其他并发症的迹象。在任何组中都没有观察到植入失败。组织形态学分析显示，氯吡格雷组BIC（％）为48.77％，对照组为34.65％，差异有统计学意义（P<0.001）。此外，氯吡格雷组的骨组织密度明显增高(40.52%vs28.74%,p<0.001）和平均小梁厚度（284.7μm对180.7μm，p<0.001)靠近植入物表面，而平均骨小梁数量在组间没有差异(1.56vs1.60,p=0.961)。
结论：本研究表明，持续氯吡格雷治疗不会对骨整合产生负面影响，而是在钛植入物周围的BIC和骨密度方面促进它。对P2Y12受体及其拮抗剂对种植体周围骨稳态的影响的进一步研究可能会为牙科种植治疗的长期成功提供有用的信息或应用。
