The effects of dual anti-platelet therapy on titanium implant osseointegration: an experimental study

Abstract

Aim: In this study, we aim to investigate the effect of dual anti-platelet agents on osseointegration by studying a sample of rats with titanium implants in their tibias. Material and Method: The titanium implants were placed surgically to the left tibias of a sample group of 50 rats. After implantation, the rats were randomly divided into five groups: acetylsalicylic acid (ASA) (n =10), treated with 20 mg/kg of ASA; ASA+ clopidogrel (CLPD) (n=10), treated with 20 mg/kg of ASA and 30 mg/kg of CLPD; ASA+ prasugrel (PRSG) (n=10), treated with 20 mg/kg of ASA and 15 mg/kg of PRSG; ASA+ ticagrelor (TCGR) (n=10), treated with 20 mg/kg of ASA and 300 mg/kg of TCGR; and a control group (CNT) (n =10) received no further treatment following implant surgery. The experimental period lasted four weeks, during which all medications were administered with oral gavage. Concluding the experimental period, the animals were euthanized, and researchers collected blood serums and the implants, along with some surrounding bones, from each rats. Results: Bone implant connection and bone filling ratios (%) were observed histologically and documented. The bone-implant connection and bone filling ratios of the rats do not show statistically significant differences between the groups examined (P>0.05). Conclusion: In this study, it was shown that there was no bone healing problem between the antiaggregant given groups and between these groups and the control group. Too many people have to take single or double antiaggregant due to many diseases. We think that it is an important study in terms of knowing that bone healing will not be negatively affected when dental implants or other bone prosthesis procedures are applied to these patients. The results of this study should be supported by further research.

Keywords

• Anti-platelet drugs
• bone healing
• bone-implant connection
• dental implant osseointegration
• dual antiplatelet theraphy.

References

1. Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J 2020; ; 41: 407-77.
2. Population Division. Department of Economic and Social Affairs. United Nations. Revision of World Population Prospects https: //esa.un.org/unpd/wpp/.
3. Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373: 1849–60.
4. Henderson JT, Whitlock EP, O’Connor E, Senger CA, Thompson JH, Rowland MG. Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2014; 160: 695–703.
5. Kumar A, Cannon CP. Acute coronary syndromes: diagnosis and management, part I. Mayo Clin Proc 2009; 84: 917-38.
6. Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual anti- platelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual anti-platelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2018; 39: 213-60.
7. Brandt JT, Payne CD, Wiviott SD, et al. A comparison of prasugrel and clopidogrel loading doses on platelet function: magnitude of platelet inhibition is related to active metabolite formation. Am Heart J 2007; 153: 66.e9–e16.
8. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopi- dogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001–15.

9. Storey RF. Pharmacology and clinical trials of reversibly-binding P2Y12 inhibitors. Thromb Haemost 2007; 105: S75–81.
10. Dehghani P, Lavoie A, Lavi S, et al. Effects of ticagrelor versus clopidogrel on platelet func- tion in fibrinolytic-treated STEMI patients undergoing early PCI. Am Heart J 2017; 192: 105–12.
11. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045–57.
12. Bozoglan A, Dundar S, Yildirim TT, et al. Effects of different levels of restraint stress on bone-implant contact. J Craniofac Surg 2019; 30: 1294–7.
13. Dundar S, Bozoglan A, Bulmus O, et al. Effects of restraint stress and high-fat diet on osseointegration of titanium implants: an experimental study. Braz Oral Res 2020; 34: e008.
14. Birnbaum Y, Tran D, Chen H, Nylander S, Sampaio LC, Ye Y. Ticagrelor improves remodeling, reduces apoptosis, inflammation and fibrosis and increases the number of progenitor stem cells after myocardial infarction in a rat model of ischemia reperfusion. Cell Physiol Biochem 2019; 53: 961-81.
15. Artas G, Gul M, Acikan I, et al. A comparison of different bone graft materials in peri-implant guided bone regeneration. Braz Oral Res 2018; 32: 59.
16. Collaborative overview of randomized trials of anti- platelet treatment, I: prevention of vascular death, MI and stroke by prolonged anti-platelet therapy in different categories of patients. Anti-platelet Trialists Collaboration. Br Med J 1994; 308: 235–46.
17. Vestergaard P, Steinberg TH, Schwarz P, Jørgensen NR. Use of the oral platelet inhibitors dipyridamole and acetylsalicylic acid is associated with increased risk of fracture. Int J Cardiol 2012; 160: 36–40
18. Hunter AM , Tyler PM , Charles CP, et al. Postoperative aspirin use and its effect on bone healing in the treatment of Ankle Fractures. Injury 2020; 51: 554-8.
19. Syberg S, Brandao-Burch A, Patel JJ, et al. Clopidogrel (Plavix), a P2Y12 receptor antagonist, inhibits bone cell function in vitro and decreases trabecular bone in vivo. J Bone Miner Res 2012; 27: 2373-86.
20. Su X, Floyd DH, Hughes A, et al. The ADP receptor P2RY12 regulates osteoclast function and pathologic bone remodeling. J Clin Invest 2012; 122: 3579-92.
21. Lillis T, Veis A, Sakellaridis N, Tsirlis A, Dailiana Z. Effect of clopidogrel in bone healing-experimental study in rabbits. World J Orthop 2019; 10: 434-45.
22. Mediero A, Wilder T, Reddy VS, et al. Ticagrelor regulates osteoblast and osteoclast function and promotes bone formation in vivo via an adenosine-dependent mechanism. FASEB J 2016; 30: 3887-900.
23. Wong ND. Epidemiological studies of CHD and the evolution of preventive cardiology. Nat Rev Cardiol 2014; 11: 276–89.