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Pyrophosphate and Diphosphonates in Calcium Metabolism and Their Possible Role in Renal Failure

R. Graham G. Russell, MA, PhD; Silvia Bisaz, PhD; Herbert Fleisch, MD
Arch Intern Med. 1969;124(5):571-577. doi:10.1001/archinte.1969.00300210053007.
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We have recently suggested that inorganic pyrophosphate may be a physiological inhibitor of calcification in soft tissues and a physiological regulator of calcium homeostasis through its effect on the formation and destruction of mineralized tissues.1-6 This communication is concerned with the possible role of pyrophosphate in the metastatic calcification and bone disease associated with renal failure.

Mineralization in General  Very little is known of the mechanisms responsible for the deposition of calcium salts at normal or abnormal sites within the body. In recent years some clarification has come from studies on the mechanism of precipitation in vitro. It is now established that the concentrations of calcium and phosphate in plasma, extracellular fluid, and even in fluid withdrawn from calcifying cartilage 7 are much lower than those required to form crystals in vitro.1,8 The formation of apatite crystals in vivo therefore requires some local promoting mechanism at the site

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