pyrophosphate and Osteomalacia

Topics: Androgens; Bone Diseases; Diphosphates; Estrogens; Fluorides; Heparin; Humans; Hyperparathyroidism; Metabolic Diseases; Organophosphonates; Osteitis Deformans; Osteomalacia; Osteoporosis; Parathyroid Hormone; Phosphates; Plicamycin

Topics: Adrenal Cortex Hormones; Aged; Aging; Bone and Bones; Bone Diseases; Bone Resorption; Calcium; Diphosphates; Female; Humans; Hyperparathyroidism; Hypoparathyroidism; Menopause; Metabolic Diseases; Osteogenesis; Osteomalacia; Osteoporosis; Space Flight

Topics: Absorption; Acidosis, Renal Tubular; Alkalies; Aluminum; Biopsy; Bone Diseases; Calcium; Diphosphates; Humans; Hydroxides; Hyperparathyroidism; Hypocalcemia; Kidney Failure, Chronic; Kidney Glomerulus; Magnesium; Ossification, Heterotopic; Osteitis Fibrosa Cystica; Osteomalacia; Osteoporosis; Osteosclerosis; Parathyroid Glands; Phosphates; Radiography; Renal Dialysis; Vitamin D

Topics: Animals; Bone Diseases; Bone Resorption; Calcinosis; Calcium; Diphosphates; Homeostasis; Humans; Hydroxyapatites; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Organophosphonates; Osteogenesis; Osteomalacia; Rats; Renal Dialysis; Uremia

We present 2 human immunodeficiency virus-infected patients with tenofovir disoproxil fumarate-induced Fanconi syndrome, leading to osteomalacia. Intracellular tenofovir diphosphate levels were measured in 1 patient and were found to be very high, with plasma tenofovir levels just slightly elevated. Fibroblast growth factor-23, a phosphaturic hormone, was decreased in both patients and is therefore unlikely to have a pathophysiological role in this pathology. The different potential factors contributing to the development of tenofovir-related kidney proximal tubular dysfunction are discussed and the data presented may help to further elucidate its pathogenesis.

Topics: Adenine; Adult; Anti-HIV Agents; Diphosphates; Fanconi Syndrome; HIV Infections; Humans; Male; Middle Aged; Organophosphonates; Osteomalacia; Radionuclide Imaging; Tenofovir; Whole Body Imaging

Osteoblasts mineralize bone matrix by promoting hydroxyapatite crystal formation and growth in the interior of membrane-limited matrix vesicles (MVs) and by propagating the crystals onto the collagenous extracellular matrix. Two osteoblast proteins, tissue-nonspecific alkaline phosphatase (TNAP) and plasma cell membrane glycoprotein-1 (PC-1) are involved in this process. Mutations in the TNAP gene result in the inborn error of metabolism known as hypophosphatasia, characterized by poorly mineralized bones, spontaneous fractures, and elevated extracellular concentrations of inorganic pyrophosphate (PP(i)). PP(i) suppresses the formation and growth of hydroxyapatite crystals. PP(i) is produced by the nucleoside triphosphate pyrophosphohydrolase activity of a family of isozymes, with PC-1 being the only member present in MVs. Mice with spontaneous mutations in the PC-1 gene have hypermineralization abnormalities that include osteoarthritis and ossification of the posterior longitudinal ligament of the spine. Here, we show the respective correction of bone mineralization abnormalities in knockout mice null for both the TNAP (Akp2) and PC-1 (Enpp1) genes. Each allele of Akp2 and Enpp1 has a measurable influence on mineralization status in vivo. Ex vivo experiments using cultured double-knockout osteoblasts and their MVs demonstrate normalization of PP(i) content and mineral deposition. Our data provide evidence that TNAP and PC-1 are key regulators of the extracellular PP(i) concentrations required for controlled bone mineralization. Our results suggest that inhibiting PC-1 function may be a viable therapeutic strategy for hypophosphatasia. Conversely, interfering with TNAP activity may correct pathological hyperossification because of PP(i) insufficiency.

Topics: Alkaline Phosphatase; Animals; Calcification, Physiologic; Diphosphates; Female; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoblasts; Osteomalacia; Phosphoric Diester Hydrolases; Pyrophosphatases; Rickets; Tissue Distribution

Topics: Absorptiometry, Photon; Acidosis, Renal Tubular; Adolescent; Bone and Bones; Bone Diseases; Child; Child, Preschool; Diphosphates; Fanconi Syndrome; Humans; Kidney Diseases; Osteomalacia; Phosphorus Metabolism Disorders; Radionuclide Imaging; Renal Tubular Transport, Inborn Errors; Technetium

This communication describes a series of clinical and animal in vivo and in vitro investigations designed to elucidate the mechanism of 99mTc-Sn-phosphate complex concentration in metabolic bone disease. Rachitic and lathyritic animals were used as experimental models. Based on these studies it is concluded that 99mTc alters the pharmacology of the phosphate complexes, in particular pyrophosphate, which was the test agent most extensively employed, so that the usual affinity for mineral is for the greater part replaced by organic matrix binding. There is also evidence to suggest the immature collagen moiety of the organic matrix is the prime target of 99mTc-Sn-phosphate complex binding. Specifically, the aldehyde groups of the collagen molecule are suspected as being the major site of interaction.

Topics: Aminopropionitrile; Animals; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Diphosphates; Humans; Hydroxyproline; Hyperparathyroidism; In Vitro Techniques; Lathyrism; Organophosphorus Compounds; Osteitis Deformans; Osteomalacia; Radionuclide Imaging; Rats; Renal Dialysis; Rickets; Technetium

A study was undertaken to investigate the behavior of 99mTc-Sn-pyrophosphate complex in metabolic bone disease. Of clinical importance was the generalized increased periarticular bone accumulation of the radiopharmaceutical in osteomalacia and in combined osteomalacia and osteitis fibrosa as found in patients with chronic renal failure. The pattern in primary hyperparathyroidism was variable. There was no correlation between the initial rates of accumulation of the radiophosphate complex or its bone to soft-tissue uptake ratio at 5 hr when compared with the degree of osteomalacia and osteitis fibrosa. It is postulated that the 99mTc-Sn-pyrophosphate complex has greater affinity for immature collagen than the crystal surface.

Topics: Adenocarcinoma; Adult; Aged; Anorexia Nervosa; Bone Diseases; Diphosphates; Female; Humans; Hyperparathyroidism; Hyperparathyroidism, Secondary; Middle Aged; Osteitis Deformans; Osteitis Fibrosa Cystica; Osteomalacia; Parathyroid Neoplasms; Radionuclide Imaging; Renal Dialysis; Technetium

Topics: Arthritis; Bone Diseases; Bone Neoplasms; Diagnosis, Differential; Diphosphates; Hodgkin Disease; Humans; Multiple Myeloma; Neoplasm Metastasis; Osteitis Deformans; Osteoarthritis; Osteolysis; Osteomalacia; Osteoporosis; Radionuclide Imaging; Reflex Sympathetic Dystrophy; Rheumatic Diseases; Technetium; Tin

Topics: Adolescent; Adult; Aged; Bone Diseases; Child; Child, Preschool; Diphosphates; Female; Humans; Hydroxyproline; Hyperparathyroidism; Hyperthyroidism; Male; Middle Aged; Osteitis Deformans; Osteomalacia; Osteoporosis; Parathyroid Glands; Phosphorus Isotopes