Summary
The anticoagulant, dicumarol, inhibits the vitamin K cycle by blocking the conversion of the vitamin K epoxide. The effects of dicumarol on ossification have been tested by feeding it to rats in which a closed fracture of the metatarsals had been induced; the effects were studied up to 12 days postfracture. At 12 days, treatment with dicumarol caused a highly significant decrease in the amount of bone produced, without affecting the total size of the callus. Quantitative cytochemistry of unfixed, undemineralized sections showed that dicumarol also markedly affected the periosteal activities of glucose 6-phosphate dehydrogenase and of alkaline phosphatase in the first 2 mm from the fracture measured at 3 and 5 days postfracture when normally, new bone is first formed. In contrast, dicumarol had little effect on these activities in the fully formed callus.
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Hauschka PV, Lian JB, Gallop PM (1975) Direct identification of the calcium-binding amino acid, γ-carboxyglutamate, in mineralised tissue. Proc Natl Acad Sci 72:3925–3929
Price PA, Otsuka AS, Poser JW, Kristaponis J, Raman N (1976) Characterization of a γ-carboxyglutamic acid-containing protein from bone. Proc Natl Acad Sci 73:1447–1451
Hauschka PV, Lian JB, Gallop PM (1978) Vitamin K and mineralization. Trends in Biochemical Science 3:75–78
Olson RE, Houser RM, Searcey MT, Gardner EJ, Scheinbuks J, Subba Rao GN, Jones J, Hall AL (1978) Nature of the vitamin K-dependent CO2 fixation in microsomal membranes. Fed Proc 37:2610–2614
Stenflo J, Suttie JW (1977) Vitamin K-dependent formation of γ-carboxyglutamic acid. Ann Rev Biochem 46:157–172
Suttie JW, Larson AE, Canfield LM, Carlisle TL (1978) Relationship between vitamin K-dependent carboxylation and vitamin K epoxidation. Fed Proc 37:2605–2609
Dunham J, Shedden RG, Catterall A, Bitensky L, Chayen J (1977) Pentose-shunt oxidation in the periosteal cells in healing fractures. Calcif Tissue Res 23:77–81
Whitlon DS, Sadowski JA, Suttie JW (1978) Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry 17:1371–1377
Chayen J, Bitensky L, Butcher RG (1973) Practical histochemistry. John Wiley & Sons, London, New York
Johnstone JJA (1979) The routine sectioning of undecalcified bone for cytochemical studies. Histochem J 11:359–365
Chambers DJ, Braimbridge MV, Frost GTB, Nahir AM, Chayen J (1982) A quantitative cytochemical method for the measurement of β-hydroxyacyl CoA dehydrogenase activity in rat heart muscle. Histochemistry 75:67–76
Stinchfield FE, Sankaran B, Samilson R (1956) The effect of anticoagulant therapy on bone repair. J Bone Jt Surg 38A:270–282
Price PA, Williamson MK (1981) Effects of warfarin on bone. J Biol Chem 256:12754–12759
Krebs HA, Eggleston LV (1974) The regulation of the pentose phosphate cycle. Adv Enzyme Regul 12:421–434
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Dodds, R.A., Catterall, A., Bitensky, L. et al. Effects on fracture healing of an antagonist of the vitamin K cycle. Calcif Tissue Int 36, 233–238 (1984). https://doi.org/10.1007/BF02405322
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DOI: https://doi.org/10.1007/BF02405322