cortical thickness and porosity were similar among groups. Only rats treated with warfarin showed an alteration of bone volume and structure, suggesting increased bone fragility compared to dabigatran and control rats pattern. For the meaning of abbreviations see No differences in cortical thickness and porosity were found among groups, indirectly suggesting that neither warfarin nor dabigatran affected parathyroid activity. Discussion Warfarin, a vitamin K antagonist, reduces the risk of stroke in patients with atrial fibrillation but has some limitations, including an increased risk of bleeding and the need for close monitoring. Such limitations led to the development of new oral anticoagulants. Dabigatran is an oral direct thrombin inhibitor, whose administration to patients with atrial fibrillation was associated with rates of stroke and systemic embolism similar as warfarin, but with lower rates of major haemorrhage. Warfarin as a VKA interferes with vitamin K actions, including 7 / 15 Dabigatran vs. Warfarin Effects on Bone PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19747723 Fig 4. Significant histomorphometric results of cellular parameters in femur and vertebra analysis of rats. The main alteration of cellular parameters in warfarin treated rats was the increased osteoclast activity, although in femur a decreased osteoblast activity was also detected. ES/BS: Erosion Surface / Bone Surface; OS/BS: Osteoid Surface / Bone Surface. p< 0.01 vs control; #p<0.001 vs dabigatran; ##p< 0.005 vs dabigatran. doi:10.1371/journal.pone.0133847.g004 the carboxylation of vitamin K dependent proteins MGP and BGP causing critical adverse side effects on bone and vascular health. Dabigatran and other new oral anticoagulants do not affect vitamin K metabolism. Thus, besides reducing major haemorrhage, they might also attenuate serious adverse side effects induced by vitamin K deficiency, as vascular calcifications and bone fractures. This experimental study in rats shows that treatment with warfarin is associated with significant bone abnormalities, differently from dabigatran and placebo treatment, but is not associated with vascular calcification. Dabigatran preserves vertebral volume and structure. According to what DCC-2618 price observed in the femur, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19749456 analysis of vertebrae showed increased bone volume, trabecular thickness and number, with lesser trabecular separation in rats treated with dabigatran with respect to warfarin treated study animals. Bone of a representative normal control rat is also shown. No significant differences in microarchitecture were observed between study groups. Warfarin treated rats showed thinner trabeculae with increased separation in the marrow space, highlighting a potentially increased fragility, despite similar microarchitecture.Dabigatran vs. Warfarin Effects on Bone Fig 6. Significant histomorphometric results of structural and dynamic parameters in vertebrae of rats. Similar to the findings in femur, in warfarin treated rats we observed lower bone volume and trabecular thickness with increased trabecular separation compared to dabigatran treated and control rats. In addition, treatment with warfarin was associated with a significant increase of turnover parameters, i.e. BFR/BS and activation frequency. Microarchitecture, cortical thickness and porosity were similar among groups. In DBA/2 mice and in apolipoprotein Edeficient non-CKD mice, a recognized model of atherosclerosis, vascular calcifications developed in less than 4 weeks with the administration of supra-therapeutic
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