Warfarin which antagonizes vitamin K is clinically used as a anticoaagulant agent. However, the effect of warfarin on bone remodeling is still unclear.The present study was to investigate the effect of warfarin on the healing process of tooth extraction wounds. Sprague-Dawley male rats were injected with warfarin according to the maintenance protocol by Price as the experimental group. Rats without the injection were used as the control group. The upper first molars of rats were extracted in both groups. These rats were killed on days 1, 2, 4, 7, and 10 and on weeks 2, 3, 4, and 6 postoperatively. Serial histological sections were stained with hematoxylin and eosin for light microscopy. And the osseous healing process was observed on day 4 and on weeks 1, 2, 3, 4, and 6 after extraction by microradiography.The results obtained were as follows:1. Warfarin-treated rats demonstrated that the number of mesenchymal cells and new capillaries were less than that of the control in the early stage after extraction.2. New bone formation in the sockets of control rats initiated on day 4 after operation, however, new bone formation in experimental rats was delayed and the number of osteoblasts were less than that of the control. In both groups, the new bone occupied the middle 2/3 of the socket on week 1, lower 4/5 on day 10, and whole socket on week 2, respectively. No significant difference was found in the location of new bone between the control and experimental groups. However, the thickness and volume of new bone were statistically different between the groups.3. The control group showed that osteoclasts appeared in the socket wall and fundus on day 1. They increased and reached a maximum number on day 2, and disappeared after day 4. In contrast, the experimental group demonstrated that osteoclasts appeared within on day 2, and reached a maximum number on day 4 and dispersed on day 10.4. 6 weeks after extraction, there were almost no remarkable differences between the experimental group and the control group.These results prove that warfarin delayed the healing process of soft tissue and the new bone formation in the early stage of wound healing, suggesting that warfarin affected the proliferation and the metabolism of mesenchymal cells, osteoblasts and osteoclasts.
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