Inorganic pyrophosphate in plasma in normal persons and in patients with hypophosphatasia, osteogenesis imperfecta, and other disorders of bone

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Abstract
An isotope dilution method, using 32P-labeled pyrophosphate, has been developed for the measurement of inorganic pyrophosphate (PP1) in human plasma. The specificity of the method was better than 90% as assessed by elution patterns during ion-exchange chromatography, by paper chromatography, and by incubation with inorganic pyrophosphatase. The 99% confidence limits for a single estimation of plasma PP1 was ±13%. There were no differences in plasma PP1 between men and women, but the values in young people (0-15 yr) were slightly higher than in older people. The mean concentration (±SE) of PP1 in the plasma of 73 men and women was 3.50 ±0.11 μmoles/liter (0.217 ±0.007 μg P/ml) and the normal range (99% limits) was 1.19-5.65 μmoles/liter (0.074-0.350 μg P/ml). It has been suggested that PP1 may be important in calcium metabolism because PP1 can prevent the precipitation of calcium phosphates in vitro and in vivo, and can slow the rates at which hydroxyapatite crystals grow and dissolve. Plasma PP1 was therefore measured in several disorders of bone. Normal values were found in osteogenesis imperfecta, osteopetrosis, “acute” osteoporosis, and primary hyperparathyroidism. Plasma PP1 was invariably raised in hypophosphatasia. The excess of PP1 in plasma might be the cause of the defective mineralization in hypophosphatasia and the function of alkaline phosphatase in bone may be to act as a pyrophosphatase at sites of calcium deposition.