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dc.contributor.authorFusaro, Maria
dc.contributor.authorDalle Carbonare, Luca
dc.contributor.authorDusso Rosso, Adriana
dc.contributor.authorArcidiacono, Maria V.
dc.contributor.authorValenti, Maria Teresa
dc.contributor.authorAghi, Andrea
dc.contributor.authorPasho, Sabina
dc.contributor.authorGallieni, Maurizio
dc.description.abstractBackground: Warfarin, a widely used anticoagulant, is a vitamin K antagonist impairing the activity of vitamin K-dependent Bone Gla Protein (BGP or Osteocalcin) and Matrix Gla Protein (MGP). Because dabigatran, a new anticoagulant, has no effect on vitamin K metabolism, the aim of this study was to compare the impact of warfarin and dabigatran administration on bone structure and vascular calcification. Methods: Rats with normal renal function received for 6 weeks warfarin, dabigatran or placebo. Bone was evaluated immuno-histochemically and hystomorphometrically after double labelling with declomycin and calcein. Aorta and iliac arteries were examined histologically. Results: Histomorphometric analysis of femur and vertebrae showed significantly decreased bone volume and increased trabecular separation in rats treated with warfarin. Vertebra analysis showed that the trabecular number was higher in dabigatran treated rats. Osteoblast activity and resorption parameters were similar among groups, except for maximum erosion depth, which was higher in warfarin treated rats, suggesting a higher osteoclastic activity. Therefore, warfarin treatment was also associated with higher bone formation rate/bone surface and activation frequency. Warfarin treatment may cause an increased bone turnover characterized by increased remodelling cycles, with stronger osteoclast activity compared to the other groups. There were no differences among experimental groups in calcium deposition either in aortic or iliac arteries. Conclusions: These findings suggest for the first time that dabigatran has a better bone safety profile than warfarin, as warfarin treatment affects bone by reducing trabecular size and structure, increasing turnover and reducing mineralization. These differences could potentially result in a lower incidence of fractures in dabigatran treated patients.ca_ES
dc.description.sponsorshipThis study was supported by a grant form Boehringer-Ingelheim Pharma, Germany (manufacturer of Dabigatran). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.ca_ES
dc.publisherPublic Library of Scienceca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofPlos One, 2015, vol. 10, núm. 8, p. e0133847ca_ES
dc.rightscc-by (c) Fusaro et al., 2015ca_ES
dc.subject.otherAnticoagulants (Medicina)ca_ES
dc.subject.otherRates (Animals de laboratori)ca_ES
dc.titleDifferential Effects of Dabigatran and Warfarin on Bone Volume and Structure in Rats with Normal Renal Functionca_ES

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