Differential effects of dabigatran and warfarin on bone volume and structure in rats with normal renal function

PLoS ONE

Volumn 10, Issue 8, 2015, Pages

  Fusaro, Maria ^a   Carbonare, Luca Dalle ^b   Dusso, Adriana ^c   Arcidiacono, Maria Vittoria ^d   Valenti, Maria Teresa ^e   Aghi, Andrea ^e   Pasho, Sabina ^a   Gallieni, Maurizio ^b  

^a CNR   (Italy)

^b UNIVERSITY OF VERONA   (Italy)

^c UNIVERSITY OF LLEIDA   (Spain)

^d UNIVERSITY OF PADOVA   (Italy)

^e UNIVERSITY OF MILAN   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CALCEIN; DABIGATRAN; DEMECLOCYCLINE; MATRIX GLA PROTEIN; MATRIX PROTEIN; OSTEOCALCIN; UNCLASSIFIED DRUG; WARFARIN; ANTICOAGULANT AGENT; ANTITHROMBIN; MINERAL; VITAMIN K GROUP;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AORTA; ARTERY CALCIFICATION; ARTICLE; BONE EROSION; BONE EXAMINATION; BONE MASS; BONE STRUCTURE; BONE TURNOVER; CHEMICAL LABELING; CONTROLLED STUDY; DRUG EFFECT; DRUG SAFETY; FEMALE; FEMUR; ILIAC ARTERY; IMMUNOHISTOCHEMISTRY; INTERNATIONAL NORMALIZED RATIO; KIDNEY FUNCTION; MORPHOMETRICS; NONHUMAN; OSSIFICATION; OSTEOCLAST ACTIVITY; OSTEOLYSIS; OSTEOSCLEROSIS; PROTHROMBIN TIME; RAT; SURFACE PROPERTY; TRABECULAR BONE; ANIMAL; ANTAGONISTS AND INHIBITORS; BONE; BONE REMODELING; CALCINOSIS; CHEMICALLY INDUCED; DRUG EFFECTS; FRACTURES, SPONTANEOUS; KIDNEY; METABOLIC BONE DISEASE; METABOLISM; OSTEOBLAST; OSTEOCLAST; PATHOLOGY; PHYSIOLOGY; RANDOMIZATION; SPRAGUE DAWLEY RAT; ULTRASTRUCTURE; VASCULAR DISEASE;

ANIMALS; ANTICOAGULANTS; ANTITHROMBINS; AORTA; BONE AND BONES; BONE DISEASES, METABOLIC; BONE REMODELING; CALCINOSIS; DABIGATRAN; FEMALE; FRACTURES, SPONTANEOUS; ILIAC ARTERY; KIDNEY; MINERALS; OSTEOBLASTS; OSTEOCLASTS; RANDOM ALLOCATION; RATS; RATS, SPRAGUE-DAWLEY; VASCULAR DISEASES; VITAMIN K; WARFARIN;

EID: 84941965263     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0133847     Document Type: Article

References (46)

1. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133 (Suppl. 6): 160S-198S.
2. Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature. 1997; 386: 78-81.
3. Price PA, Faus SA, Williamson MK. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler Thromb Vasc Biol. 1998; 18: 1400-1407.
4. Azuma K, Shiba S, Hasegawa T, Ikeda K, Urano T, Horie-Inoue K, et al. Osteoblast-Specific γ-Glutamyl Carboxylase-Deficient Mice Display Enhanced Bone Formation with Aberrant Mineralization. J Bone Miner Res. 2015; 30: 1245-1254. doi: 10.1002/jbmr.2463
5. Weber P. Vitamin K and bone health. Nutrition. 2001; 17 (10): 880-887.
6. Lanham-New SA. Importance of calcium, vitamin D and vitamin K for osteoporosis prevention and treatment. Proc Nutr Soc. 2008; 67 (2): 163-176. doi: 10.1017/S0029665108007003
7. Torbergsen AC, Watne LO, Wyller TB, Frihagen F, Stromsoe K, Bohmer T, et al. Vitamin K1 and 25 (OH)D are independently and synergistically associated with a risk for hip fracture in an elderly population: A case control study. Clinical Nutrition. 2015; 34: 101-106. doi: 10.1016/j.clnu.2014.01.016
8. Menon RK, Gill DS, Thomas M, Kernoff PB, Dandona P. Impaired carboxylation of osteocalcin in warfarin-treated patients. J Clin Endocrinol Metab 1987; 64: 59-61.
9. Stangier J, Clemens A. Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost. 2009; 15 Suppl 1: 9S-16S. doi: 10. 1177/1076029609343004
10. Stangier J, Feuring M. Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran. Blood Coagul Fibrinolysis. 2012; 23: 138-143. doi: 10.1097/MBC. 0b013e32834f1b0c
11. Kimmel DB. Quantitative histologic changes in the proximal tibial growth cartilage of aged female rats. Cells Materials 1991; suppl 1: : 11-18.
12. Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Malluche H, et al. Standardized Nomenclature, Symbols, and Units for Bone Histomorphometry: A 2012 Update of the Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2013; 28::1-16. doi: 10. 1002/jbmr.1805
13. Dalle Carbonare L, Valenti MT, Bertoldo F, Zanatta M, Zenari S, Realdi G, et al. Bone microarchitecture evaluated by histomorphometry. Micron 2005; 36: 609-616.
14. Mellish RW, Ferguson-Pell MW, Cochran GV, Lindsay R, Dempster DW. A new manual method for assessing two-dimensional cancellous bone structure was employed: comparison between iliac crest and lumbar vertebra. J Bone Miner Res 1991; 6: 689-696.
15. Vesterby A, Gundersen HJG, Melsen F. Star volume of marrow space and trabeculae of the first lumbar vertebra: sampling efficiency and biological variation. Bone 1989; 10: 7-13.
16. Weinstein RS, Majumdar S. Fractal geometry and vertebral compression fractures. J Bone Miner Res 1994; 9: 1797-1802.
17. Fusaro M, Crepaldi G, Maggi S, D'Angelo A, Calo L, Miozzo D, et al. Bleeding, vertebral fractures and vascular calcifications in patients treated with warfarin: hope for lower risks with alternative therapies. Curr Vasc Pharmacol 2011; 9: 763-769.
18. Fusaro M, Noale M, Viola V, Galli F, Tripepi G, Vajente N, et al. Vitamin K, vertebral fractures, vascular calcifications, and mortality: VItamin K Italian (VIKI) dialysis study. J Bone Miner Res 2012; 27: 2271-2278. doi: 10.1002/jbmr.1677
19. Fusaro M, Tripepi G, Noale M, Plebani M, Zaninotto M, Piccoli A, et al. Prevalence of vertebral fractures, vascular calcifications, and mortality in warfarin treated hemodialysis patients. Curr Vasc Pharmacol 2015; 13: 248-258.
20. Danziger J. Vitamin K-dependent proteins, warfarin, and vascular calcification. Clin J Am Soc Nephrol 2008; 3: 1504-1510. doi: 10.2215/CJN.00770208
21. McCabe KM, Booth SL, Fu X, Shobeiri N, Pang JJ, Adams MA, et al. Dietary vitamin K and therapeutic warfarin alter the susceptibility to vascular calcification in experimental chronic kidney disease. Kidney Int 2013; 83: 835-844. doi: 10.1038/ki.2012.477
22. Kruger T, Oelenberg S, Kaesler N, Schurgers LJ, van de Sandt AM, Boor P, et al. Warfarin induces cardiovascular damage in mice. Arterioscler Thromb Vasc Biol. 2013; 33: 2618-24. doi: 10.1161/ATVBAHA.113.302244
23. Schurgers LJ, Joosen IA, Laufer EM, Chatrou ML, Herfs M, Winkens MH, et al. Vitamin K-Antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype. PLoS One 2012; 7: e43229. doi: 10.1371/journal.pone.0043229
24. Price PA, Kaneda Y. Vitamin K counteracts the effect of warfarin in liver but not in bone. Thrombosis 1987; 46: 121-131.
25. Ichikawa T, Horie-Inoue K, Ikeda K, Blumberg B, Inoue S. Steroid and xenobiotic receptor SXR mediates vitamin K2-Activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. J Biol Chem 2006; 281: 16927-16934.
26. Sugiyama T, Takaki T, Sakanaka K, Sadamaru H, Mori K, Kato Y, et al. Warfarin-induced impairment of cortical bone material quality and compensatory adaptation of cortical bone structure to mechanical stimuli. J Endocrinol 2007; 194: 213-222.
27. Thijssen HH, Drittij-Reijnders MJ, Fischer MA. Phylloquinone and menaquinone-4 distribution in rats: synthesis rather than uptake determines menaquinone-4 organ concentrations. J Nutr 1996; 126: 537-543.
28. Thijssen HH, Vervoort LM, Schurgers LJ, Shearer MJ. Menadione is a metabolite of oral vitamin K. Br J Nutr 2006; 95: 260-266.
29. Okano T, Shimomura Y, Yamane M, Suhara Y, Kamao M, Sugiura M, et al. Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice. J Biol Chem 2008; 283: 11270-11279.
30. Hirota Y, Tsugawa N, Nakagawa K, Suhara Y, Tanaka K, Uchino Y. Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating precursor of tissue menaquinone-4 (vitamin K2) in rats. J Biol Chem 2013; 288: 33071-33080. doi: 10.1074/jbc.M113. 477356
31. Nakagawa K, Hirota Y, Sawada N, Yuge N, Watanabe M, Uchino Y, et al. Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature 2010; 468: 117-121. doi: 10.1038/nature09464
32. Pettifor JM, Benson R. Congenital malformations associated with the administration of oral anticoagulants during pregnancy. J Pediatr 1975; 86: 459-462.
33. Philip WJ, Martin JC, Richardson JM, Reid DM, Webster J, Douglas AS. Decreased axial and peripheral bone density in patients taking long-term warfarin. Q J Med 1995; 88: 635-640.
34. Caraballo PJ, Heit JA, Atkinson EJ, Silverstein MD, O'Fallon WM, Castro MR, et al. Long-term use of oral anticoagulants and the risk of fracture. Arch Intern Med 1999; 59: 1750-1756.
35. Caraballo PJ, Gabriel SE, Castro MR, Atkinson EJ, Melton LJ. Changes in bone density after exposure to oral anticoagulants: a metanalysis. Osteop Int 1999; 9: 441-448.
36. Gage BF, Birman-Deych E, Radford MJ, Nilasena DS, Binder EF. Risk of osteoporotic fracture in elderly patients taking warfarin. Results from the National Registry of Atrial Fibrillation 2. Arch Intern Med 2006; 166: 241-246.
37. Eastell R. Does warfarin increase the risk of osteoporotic fracture? Nature Clin Pract Endocrinol Metab 2006; 2: 484-485.
38. Jamal SA, Browner WS, Bauer DC, Cummings SR. Warfarin use and risk for osteoporosis in elderly women. Ann Intern Med 1998; 128; 829-832.
39. Mamdani M, Upshur RE, Anderson G, Bartle BR, Laupacis A. Warfarin therapy and risk of hip fracture among elderly patients. Pharmacotherapy 2003; 23: 1-4.
40. Amizuka N, Li M, Hara K, Kobayashi M, de Freitas PH, Ubaidus S, et al. Warfarin administration disrupts the assembly of mineralized nodules in the osteoid. J Electron Microsc (Tokyo) 2009; 58: 55-65.
41. Haffa A, Krueger D, Bruner J, Engelke J, Gundberg C, Akhter M, et al. Diet-or warfarin-induced vitamin K insufficiency elevates circulating undercarboxylated osteocalcin without altering skeletal status in growing female rats. J Bone Miner Res 2000; 15: 872-878.
42. Lian JB, Tassinari M, Glowacki J. Resorption of implanted bone prepared from normal and warfarintreated rats. J Clin Invest 1984; 73: 1223-1226.
43. Serre CM, Price P, Delmas PD. Degradation of subcutaneous implants of bone particles from normal and warfarin treated rats. J. Bone Miner. Res. 1995; 10:1158-1167.
44. Ducy P, Desbois C, Boyce B, ero G, Story B, Dunstan C, et al. Increased bone formation in osteocalcindeficient mice. Nature. 1996; 382:448-52.
45. Binkley N, Krueger D, Engelke J, et al. Vitamin K deficiency from long-term warfarin anticoagulation does not alter skeletal status in male rhesus monkeys. J Bone Miner Res 2007; 22: 695-700.
46. Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, et al. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. 2008; 5: e196. doi: 10.1371/journal.pmed.0050196