Pyrophosphate and diphosphonates in skeletal metabolism. Physiological, clinical and therapeutic aspects

Pyrophosphate and diphosphonates produce striking results on calcium metabolism in experimental animals and man. Compounds containing P-O-P- bonds (e.g. inorganic pyrophosphate [PP-ii1 or P-C-P bonds (diphosponates) inhibit both the formation and dissolution of calcium phosphate crystals in vitro. PP-i may have a physiological function in regulating calcification and bone turnover, and obnormalities in its metabolism may occur in some human diseases notably hypophosphatasia and pseudogout. Diphosphonates inhibit ectopic calcification, and slow down resorption and bone turnover in several experimental systems in vivo. They have helped in studies of various aspects of the regulation of calcium metabolism. The diphosphonate, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) has been shown in clinical studies to be effective against ectopic calcification particularly in myositis ossificans progressiva and in disorders of increased bone resorption such as Paget's diseases and some types of osteoporosis. -99mTechnetium complexes of EHDP, PP-i and other polyphosphates have also recently been used successfully as bone scanning agents.