pyrophosphate and Osteopetrosis

Topics: Calcitonin; Calcium; Calcium Radioisotopes; Consanguinity; Craniofacial Abnormalities; Diphosphates; Female; Hepatomegaly; Hospitalization; Humans; Hypocalcemia; Infant; Infant, Newborn; Intestinal Absorption; Male; Osteopetrosis; Parathyroid Hormone; Pedigree; Phosphorus; Seizures; Splenomegaly; Water-Electrolyte Balance

Topics: Bone and Bones; Calcification, Physiologic; Calcitonin; Calcium; Collagen; Cushing Syndrome; Diphosphates; Diphosphonates; Enzymes; Humans; Osteoblasts; Osteopetrosis; Parathyroid Hormone; Pyrophosphatases; Thyroidectomy; Vitamin D; Vitamins

An isotope dilution method, using (32)P-labeled pyrophosphate, has been developed for the measurement of inorganic pyrophosphate (PP(1)) 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 PP(1) was +/-13%. There were no differences in plasma PP(1) 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 PP(1) in the plasma of 73 men and women was 3.50 +/-0.11 mumoles/liter (0.217 +/-0.007 mug P/ml) and the normal range (99% limits) was 1.19-5.65 mumoles/liter (0.074-0.350 mug P/ml). It has been suggested that PP(1) may be important in calcium metabolism because PP(1) 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 PP(1) was therefore measured in several disorders of bone. Normal values were found in osteogenesis imperfecta, osteopetrosis, "acute" osteoporosis, and primary hyperparathyroidism. Plasma PP(1) was invariably raised in hypophosphatasia. The excess of PP(1) 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.

Topics: Adenine Nucleotides; Adenosine Triphosphate; Bone Diseases; Calcium; Chromatography, Ion Exchange; Chromatography, Paper; Dialysis; Diphosphates; Humans; Hypophosphatasia; Metabolism, Inborn Errors; Osteogenesis Imperfecta; Osteopetrosis; Phosphoric Monoester Hydrolases; Phosphorus Isotopes; Pyrophosphatases; Radioisotope Dilution Technique