The antiplatelet drug clopidogrel promotes osseointegration. Histomorphometric study in rabbits

15989 ORAL COMMUNICATION BASIC RESEARCH

Background

Clopidogrel is a widely prescribed antithrombotic drug which inhibits plateletsí aggregation through blocking of P2Y12 purinergic receptor. Purinergic receptors, including P2Y12, are also expressed in bone cells and accumulated evidence suggests that they regulate important functions in bone. Several studies have demonstrated that clopidogrel treatment may negatively affect bone metabolism, but their results are controversial, while its effect in osseointegration has not been studied yet.

Aim/Hypothesis

The present study conducted in order to investigate if systemic clopidogrel treatment has any negative effect on osseointegration of titanium implants, representing the clinical scenario of osseointegration of dental implants in patients in chronic use of this drug for cardiovascular indications.

Material and Methods

Thirty-two white New Zealand rabbits were randomly assigned in two groups- a clopidogrel group and a control group. Rabbits of the clopidogrel group received 3 mg/kg day of clopidogrel orally, which has been previously demonstrated to cause similar level of platelet aggregation inhibition with that of usual daily dose in human; and rabbits of the control group received only vehicle. The administration of clopidogrel or vehicle respectively, started one week prior to the surgical procedures of implant placement and continued for six weeks postoperatively. A cylindrical crew titanium dental implant was placed into the left medial femur condyle of every rabbit. After the six weeks of healing, postmortem histomorphometric evaluation of the titanium implants was performed. Bone-implant contact ratios (BIC) were calculated and means between groups were compared by t-test, since data were distributed normally as indicated by Sapiro-Wilk test.

Results

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 BIC (%) was 52.8% for the clopidogrel group and 34.6% for the control group with statistically significant difference between them (P < 0.001). Interestingly, in clopidogrel group new bone formation was also found to be more extensive around the trabeculae proximal to the surface of the titanium implant, compared to control group.

Conclusion and clinical implications

Our present results indicate that clopidogrel treatment does not impair osseointegration of titanium implants. On the contrary, it seems that systemic clopidogrel administration promoted peri-implant contact osteogenesis. Further research is needed, in order to find useful applications, such as topical delivery systems of clopidogrel or other P2Y12 inhibitors, in order to improve osseointegration outcomes.