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The short-term effects of high doses of ethylene-1-hydroxy-1, 1-diphosphonate upon early dentin formation

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Abstract

The effects of high doses of ethylene-1-hydroxy-1,1-diphosphonate (EHDP) were investigated at the light microscopic and subcellular level. The administration of EHDP at a concentration of 7.5–10 mg P/kg body weight/day over a short period of time resulted in complete inhibition of crystal formation in predentin and pre-enamel. An increased predentin width was observed and within newly-formed predentin areas the formation ofcollagen fibrils was grossly disturbed. In addition, fine precipitates appeared in the ground substance. The presence of unusual thread-like elements within specific bodies in the cytoplasm of the odontoblastic processes may be indicative of an interference by EHDP in e.g. the synthesis of precollagen. The possibility of an inhibition by EHDP of the extracellular aggregation of collagen molecules is also discussed. EHDP further inhibited crystal formation within dentinal globules. Functioning ameloblasts were grossly affected in EHDP-treated rats, and it is suggested that this is related to an inhibition of crystal formation in pre-enamel.

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References

  • Anderson, H. C.: Calcium-accumulating vesicles in the intercellular matrix of bone. In: Hard tissue growth, repair and remineralization (Ciba Foundation Symposium 11), p. 213–246. Amsterdam: Associated Scientific Publishers 1973

    Google Scholar 

  • Bernard, G. W., Pease, D. C.: An electron microscopic study of initial intramembranous osteogenesis. Amer. J. Anat.125, 271–290 (1969)

    PubMed  Google Scholar 

  • Davis, N. R., Walker, T. E.: The role of carboxyl groups in collagen calcification. Biochem. Biophys. Res. Commun.48, 1656–1662 (1972)

    Article  PubMed  Google Scholar 

  • Doty, S. B., Jones, R., Finerman, G. A.: Diphosphonate influence on bone cell structure and lysosomal activity. J. Bone Jt. Surg. A54, 1128–1129 (1972)

    Google Scholar 

  • Fleisch, H., Russel, R. G. G., Bisaz, S., Bonjour, J.-P.: The effects of pyrophosphate and diphosphonates on calcium metabolism. In: Hard tissue growth, repair and remineralization (Ciba Foundation Symposium 11), p. 331–358. Amsterdam: Associated Scientific Publishers 1973

    Google Scholar 

  • Fleisch, H., Russel, R. G. G., Francis, M. D.: Diphosphonates inhibit hydroxyapatite dissolutionin vitro and bone resorption in tissue culture andin vivo. Science165, 1262–1264 (1969)

    PubMed  Google Scholar 

  • Forssmann, W. G., Siegrist, G., Orci, L., Girardier, L., Pictet, R., Rouiller, C.: Fixation par perfusion pour la microscopie electronique J. Microscopie6, 279–304 (1967)

    Google Scholar 

  • Francis, M. D.: The inhibition of calcium hydroxyapatite crystal growth by polyphosphonates and polyphosphates. Calcif. Tiss. Res.3, 151–162 (1969)

    Google Scholar 

  • Francis, M. D., Briner, W. W., Gray, J. A.: Chemical agents in the control of calcification processes in biological systems. In: Hard tissue growth, repair and remineralization (Ciba Foundation Symposium 11), p. 57–90. Amsterdam: Associated Scientific Publishers 1973

    Google Scholar 

  • Gasser, A. B., Morgan, D. B., Fleisch, H., Richelle, L. J.: The influence of two diphosphonates on calcium metabolism in the rat. Clin. Sci.42, 197–207 (1972)

    PubMed  Google Scholar 

  • Glimcher, M. J., Krane, S. M.: The organization and structure of bone, and the mechanism of calcification. In: Treatise on collagen (B. S. Gould, ed.), vol. 2, part B, p. 67–251. London and New York: Academic Press 1968

    Google Scholar 

  • Höhling, H. J., Boyde, A., Rosenstiel, A. P. von: Combined electronprobe and electron diffraction analysis of prestages and early stages of dentine formation in rat incisors. Calcif. Tiss. Res.2, (Suppl.), 5 (1968)

    Google Scholar 

  • Jowsey, J., Holley, K. E., Linman, J. W.: Effect of sodium etidronate in adult cats. J. Lab. clin. Med.76, 126–133 (1970)

    PubMed  Google Scholar 

  • Jung, A., Bisaz, S., Fleisch, H.: The binding of pyrophosphate and two diphosphonates by hydroxyapatite crystals. Calcif. Tiss. Res.11, 269–280 (1973)

    Google Scholar 

  • Kallenbach, E.: Electron microscopy of the differentiating rat incisor ameloblast. J. Ultrastruct. Res.35, 508–531 (1971)

    Article  PubMed  Google Scholar 

  • Katchburian, E., Holt, S. J.: Ultrastructural studies on lysosomes and acid phosphatase in odontoblasts. In: Dentine and pulp (Symons N. B. B., ed.), p. 43–57. Edinburgh and London: E. & S. Livingstone Ltd. 1968

    Google Scholar 

  • King, W. R., Francis, M. D., Michael, W. R.: Effect of disodium ethane-1-hydroxy-1,1-diphosphonate on bone formation. Clin. Orthop.78, 251–270 (1971)

    PubMed  Google Scholar 

  • Lapière, C. M., Lenaers, A., Kohn, L. D.: Procollagen peptidase: an enzyme excising the coordination peptides of procollagen. Proc. nat. Acad. Sci. (Wash.)68, 3054–3058 (1971)

    Google Scholar 

  • Larsson, Å.: Ultrastructural observations on early dentin formation with special reference to “dentinal globules” and alkaline phosphatase activity. Z. Anat. Entwickl.-Gesch.142, 103–115 (1973)

    Article  Google Scholar 

  • Larsson, Å.: The interaction between lead-pyrophosphate solutions and dentinal globules. Calc. Tiss. Res. (1974, in press)

  • Larsson, Å., Bloom, G. D.: Fine structure of developing odontoblasts and predentin in relation to the mineralization process. Z. Anat. Entwickl.-Gesch.139, 227–246 (1973)

    Article  Google Scholar 

  • Larsson, Å., Larsson, S.-E.: Ethane-1-hydroxy-1,1-diphosphonate (EHDP) inhibits crystal growth in predentin calcification. Virchows Arch. Abt. A360 315–325 (1973)

    Article  Google Scholar 

  • Luft, J. H.: Improvements in epoxy resin embedding methods. J. biophys. biochem. Cytol.9, 409–414 (1961)

    PubMed  Google Scholar 

  • Matsuzawa, T., Anderson, H. C.: Phosphatases of epiphyseal cartilage studied by electron microscopic cytochemical methods. J. Histochem. Cytochem.19, 801–808 (1971)

    PubMed  Google Scholar 

  • Quintarelli, G., Belocci, M., Geremia, R.: On phosphotungstic acid staining. IV. Selectivity of the staining reaction. J. Histochem. Cytochem.21, 155–160 (1973)

    PubMed  Google Scholar 

  • Reith, E. J.: The early stages of amelogenesis as observed in molar teeth of young rats. J. Ultrastruct. Res.17, 503–526 (1967)

    Article  PubMed  Google Scholar 

  • Reynolds, J. J., Murphy, H., Mühlbauer, R. C., Morgan, D. B., Fleisch, H.: Inhibition by diphosphonates of bone resorption in mice and comparison with grey-lethal osteopetrosis. Calcif. Tiss. Res.12, 59–71 (1973)

    Article  Google Scholar 

  • Robertson, W. G., Morgan, D. B., Fleisch, H., Francis, M. D.: The effects of diphosphonates on the exchangeable and non-exchangeable calcium and phosphate of hydroxyapatite. Biochim. biophys. Acta (Amst.)261, 517–525 (1972)

    Google Scholar 

  • Russell, R. G. G., Kislig, A.-M., Casey, P. A., Fleisch, H., Thornton, J., Schenk, R., Williams, D. A.: Effect of diphosphonates and calcitonin on the chemistry and quantitative histology of rat bone. Calcif. Tiss. Res.11, 179–195 (1973)

    Google Scholar 

  • Russell, R. G. G., Smith, R.: Diphosphonates. J. Bone Jt. Surg. B55, 66–86 (1973)

    Google Scholar 

  • Schenk, R., Merz, W. A., Mühlbauer, R., Russell, R. G. G., Gleisch, H.: Effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) and dichloromethylene diphosponate (Cl2MDP) on the calcification and resorption of cartilage and bone in the tibial epiphysis and metaphysis of rats. Calcif. Tiss. Res.11, 196–214 (1973)

    Google Scholar 

  • Slavkin, H. C., Tetreault, C., Nimni, M. N., Bavetta, L. A.: Autoradiographic and biochemical investigations of collagen biosynthesis and participation in the dentine extracellular organic matrix. Proc. Soc. exp. Biol. (N. Y.)126, 439–442 (1967)

    Google Scholar 

  • Strates, B. S., Firschein, H. E., Urist, M. R.: Alkaline phosphatase and failure of calcification under the influence of a diphosphonate. Biochim. biophys. Acta (Amst.)244, 121–124 (1971)

    Google Scholar 

  • Urist, M. R.: Recent advances in the physiology of calcification. J. Bone Jt Surg. A46, 889–900 (1964)

    Google Scholar 

  • Urry, D. W.: Neutral sites for calcium binding to elastin and collagen: a charge neutralization theory for calcification and its relationship to atherosclerosis. Proc. nat. Acad. Sci. (Wash.)68, 810–814 (1971)

    Google Scholar 

  • Veis, A., Perry, A.: The phosphoprotein of the dentin matrix. Biochemistry (Wash.)6, 2409–2416 (1967)

    Google Scholar 

  • Veis, A., Spector, A. R., Carmichael, D. J.: The organization and polymerization of bone and dentin collagens. Clin. Orthop.66, 188–211 (1969)

    PubMed  Google Scholar 

  • Veis, A., Spector, A. R., Zamoscianyk, H.: The isolation of an EDTA-soluble phosphoprotein from mineralizing bovine dentin. Biochim. biophys. Acta (Amst.)257, 404–413 (1971)

    Google Scholar 

  • Weinstock, M.: Collagen formation—observations on its intracellular packaging and transport. Z. Zellforsch.129, 455–470 (1972)

    Article  PubMed  Google Scholar 

  • Weinstock, A., King, P. C., Wuthier, R. E.: The ion-binding characteristics of reconstituted collagen. Biochem. J.102, 983–988 (1967)

    Google Scholar 

  • Weinstock, M., Leblond, C. P.: Radioautographic visualization of the deposition of a phosphoprotein at the mineralization front in the dentin of rat incisors. J. Cell Biol.56, 838–845 (1973)

    Article  PubMed  Google Scholar 

  • Wöltgens, J. H. M., Bonting, S. L.: Inorganic pyrophosphatase in mineralizing hamster molars. II. Effects of pH and bivalent cations. Calcif. Tiss. Res.13, 143–150 (1973)

    Article  Google Scholar 

  • Wöltgens, J. H. M., Bonting, S. L., Bijvoet, O. L. M.: Inorganic pyrophosphatase in mineralizing hamster molars. III. Influence of diphosphonates. Calcif. Tiss. Res.13, 151–157 (1973)

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Oral Surgery, University of Umeå, Umeå, Sweden

    Åke Larsson

  2. Departments of Histology and Anatomy, University of Umeå, Carl Gustavs väg 34, 214 21, Umeå, Sweden

    Åke Larsson

  3. Department of Oral Histopathology, Faculty of Dentistry, University of Lund, Carl Gustavs väg 34, 214 21, Malmö, Sweden

    Åke Larsson

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Larsson, Å. The short-term effects of high doses of ethylene-1-hydroxy-1, 1-diphosphonate upon early dentin formation. Calc. Tis Res. 16, 109–127 (1974). https://doi.org/10.1007/BF02008217

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  • DOI: https://doi.org/10.1007/BF02008217

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