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The Inhibitory Effect of Phosphonates on the Formation of Calcium Phosphate Crystals in vitro and on Aortic and Kidney Calcification in vivo
Author(s) -
Fleisch H. A.,
Russell R. G. G.,
Bisaz S.,
Mühlbauer R. C.,
Williams D. A.
Publication year - 1970
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1970.tb00591.x
Subject(s) - diphosphonates , chemistry , calcification , phosphate , pyrophosphate , in vivo , calcium , calcium pyrophosphate , in vitro , biochemistry , endocrinology , medicine , enzyme , organic chemistry , biology , bone resorption , microbiology and biotechnology
1. Various phosphonates, which are compounds containing C‐P bonds, have been studied to see whether they are able to inhibit, in a manner similar to that of pyrophosphate and the condensed phosphates, the crystallization of calcium phosphate in vitro and the pathological calcification of the aorta and the kidneys of rats given large amounts of vitamin D 3 . 2. Six of the ten compounds studied markedly increased the minimum product, [Ca] × [P], required to induce the precipitation of calcium phosphate in vitro under physiological conditions of pH, ionic strength and temperature. Inhibition was observed at concentrations as low as 10 ‐7 —10 6 M. 3. Most of the diphosphonates, particularly those possessing P‐C‐P bonds, showed some ability to inhibit the calcification of the aortas and kidneys of rats treated with large amounts of vitamin D 3 . The most effective inhibitors were methylene diphosphonate (MDP), ethane‐1‐hydroxy‐1: I‐diphosphonate (EHDP) and diehloromethylene diphosphonate (Cl 2 MDP). 4. The phosphonates that possess P‐C‐P bonds thus appear to have effects on the deposition of calcium phosphate in vitro and in vivo similar to those of inorganic pyrophosphate and the condensed phosphates, which possess P‐O‐P bonds. These phosphonates differ from the condensed phosphates in that they inhibit kidney calcification as well as aortic calcification and are active by mouth as well as parenterally. The wider spectrum of activity of the phosphonates in vivo may be due to the fact that they are more resistant to chemical and enzymic breakdown. 5. Phosphonates might be used therapeutically in man against diseases in which calcium salts deposit in soft tissues.