Bone biopsies were performed and serum concentrations of vitamin D metabolites were measured in twenty-four patients with chronic renal failure. The concentrations of three metabolites--25-dihydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D (24,25-OH2D) and 1,25-dihydroxyvitamin D (1,25-OH2D)--were significantly lower in uraemic than in normal sera. There was a positive correlation between serum 24,25-OH2D and serum 25-OHD, whereas serum 1,25-OH2D values, which were independent of those of the other vitamin D metabolites, were negatively correlated with serum creatinine and serum inorganic phosphate. The two major skeletal lesions, osteomalacia and parathyroid osteopathy, while coexisting in many patients, varied independently in relation to their severity and were correlated with different vitamin D metabolites. The severity of osteomalacia was negatively correlated with the serum concentrations of 25-OHD and 24,25-OH2D while th severity of parathyroid osteopathy was negatively correlated with serum 1,25-OH2D values. To our knowledge these are the first systematic studies correlating skeletal histology with dihydroxylated vitamin D metabolites in renal failure in man.

Bone and Bones↗

PubMed1980

Biochemical properties of the 1 alpha, 25-dihydroxyvitamin D3 cytosol receptors from human and chicken intestinal mucosa.

Specific cytoplasmic receptors for 1 alpha,25-dihydroxyvitamin D3 are shown to be present in human intestinal cytosol which are very similar to the analogous 1 alpha,25-dihydroxyvitamin D3 receptors present in chick intestinal cytosol. Both receptors are 3.5S proteins which aggregate under low ionic strength conditions. They have molecular weights of approximately 60,000 and Stokes' molecular radii of 33 A. The equilibrium dissociation constants for the receptors were both 2 X 10(-10) M at 4 C. The association rate constant for the human receptor was found to be 2.5 X 10(7) M-1 min-1 at 0 C, while a value of 0.5 X 10(7) M-1 min-1 was obtained for the chick receptor. The dissociation rate constants at 4 C were 6.4 X 10(-4) min-1 (human) and 3.6 X 10(-5) min-1 (chick). In addition, it was found that both receptors possessed reduced cysteine residues near the 1 alpha,25-dihydroxyvitamin D3-binding site which were critical for receptor-binding activity. The similarities between the human and the chick receptors suggests that homologous mechanisms for 1 alpha,25-dihydroxyvitamin D3 interactions may be at work in both mammalian and avian intestinal systems.

Animals↗

PubMed1980

Testing for disorders of calcium metabolism.

Assays of serum immunoreactive parathyroid hormone are clinically useful in the differential diagnosis of hypercalcaemic states and in the assessment of the severity of parathyroid bone disease in uraemic patients. Serum immunoreactive calcitonin measurements are essential in the investigation of individuals who might be suffering from medullary carcinoma, and such measurements may be used in the detection of metastases. Serum 25-hydroxyvitamin D assays are useful in patients receiving pharmacological doses of vitamin D, to monitor patient compliance and to prevent the occurrence of vitamin D intoxication. Low values in patients with renal failure and in patients with malabsorption and highly suggestive of the presence of osteomalacia. The measurement of serum levels of dihydroxylated vitamin D metabolites is currently of doubtful clinical relevance, though such measurements may become useful in monitoring patients receiving these compounds therapeutically.

Calcitonin↗

PubMed1980

Parathyroid hormone effect on 1,25-dihydroxyvitamin D in hypoparathyroidism.

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Dihydroxycholecalciferols↗

PubMed1980

A simplified assay for dihydroxylated vitamin D metabolites in human serum: application to hyper- and hypovitaminosis D.

We describe a simplified assay for 24,25-and 1.25-dihydroxyvitamin D in human serum. It involves two preparative steps, and normal chick intestine is used in preparing cytosol-binding protein. Our results for 24,25-dihydroxyvitamin D include a reference interval of 2.9--16 nmol/L (1.2--6.7 microgram/L), a mean of 6.7 nmol/L (2.8 microgram/L), an intra-assay CV of 11%, and an interassay CV of 22%. For 1,25-dihydroxyvitamin D, these data were 29--168 pmol/L (12--70 ng/L), 86 pmol/L (36 ng/L), 12%, and 22%, respectively. In hypoparathyroid patients with vitamin D intoxication, mean concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum were significantly above normal; the 1,25-dihydroxyvitamin D concentrations were significantly below normal. Patients with malabsorption and/or post-gastrectomy states had significantly subnormal values for both 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum, and there was a significantly negative correlation between each of these biochemical values and the severity of osteomalacia. We also discuss cost effectiveness of assaying vitamin D metabolites in human serum.

Adult↗

PubMed1980

The measurement of calcium-regulating hormones in clinical medicine.

Assays of serum immunoreactive parathyroid hormone are clinically useful in the differential diagnosis of hypercalcaemic states and in the assessment of the severity of parathyroid bone disease in uraemic patients. Serum immunoreactive calcitonin measurements are essential in the investigation of individuals who might be suffering from medullary carcinoma and may be used in the detection of metastases. Serum 25-hydroxyvitamin D assays should be performed in patients receiving pharmacological doses of vitamin D to monitor patient compliance and to prevent the occurrence of vitamin D intoxication. Low values in patients with renal failure and in patients with malabsorption are highly suggestive of the presence of osteomalacia. The measurement of serum levels of dihydroxylated vitamin D metabolites is currently of doubtful relevance though such measurements may become useful in monitoring patients receiving these compounds therapeutically.

Calcitonin↗

PubMed1979

The relevance of 25-hydroxycalciferol measurements in the treatment of hypoparathyroidism.

In twenty-one patients with chronic hypoparathyroidism a close correlation was observed between the prescribed dose of ergocalciferol and mean serum 25-hydroxycalciferol levels. In the 75 serum specimens examined, a significant correlation was found between 25-hydroxycalciferol levels and calcium concentrations. The measurement of serum 25-hydroxycalciferol levels is of potential clinical value in the prediction of hyper- or hypocalcaemic episodes and in monitoring patient compliance.

Adolescent↗

PubMed1979

The management of primary hyperparathyroidism.

With the advent of serum parathyroid hormone assays the diagnosis of hyperparathyroidism has become relatively straightforward. Current unresolved problems comprise the selection of patients for surgery, the pre-operative localization of lesions and the medical management of patients who, for one reason or another, are unsuitable for surgery.

Adult↗

PubMed1979

The relevance of 25-hydroxycalciferol measurements in sera of patients with renal failure.

Iliac crest biopsies and serum specimens were obtained from 36 non-dialyzed uraemic patients. The mean serum 25-hydroxycalciferol concentration of the patients was lower than that of normal subjects and a significant correlation was found between 25-hydroxycalciferol values and the severity of osteomalacia. Parathyroid osteopathy was significantly correlated with serum immunoreactive parathyroid hormone but not with serum 25-hydroxycalciferol values. While normal serum 25-hydroxycalciferol concentrations in uraemic patients do not exclude the presence of osteomalacia, a low concentration is virtually diagnostic of this disorder.

Antigens↗

PubMed1979

Specific cytosol receptors for 1,25-dihydroxyvitamin D3 in human intestine.

Human intestine is shown to contain a specific, high affinity cytosol receptor or binding protein for 1,25-(OH)2-vitamin D3 [1,25 (OH)2D3]. This receptor is a protein which sediments at 3.5S on sucrose gradients containing 0.3 M KCL. The receptor binds 1,25 (OH)2D3 with a Kd of approximately 2 x 10(-10) M at 4 degrees C. Competition binding studies using structural analogs of 1,25 (OH)2D3 indicate that the relative specificity of the receptor is 1,25 (OH)2D3 greater than 1,24R,25(OH)3D3 greater than greater than 25OHD3 1 OHD3 greater than 24R,25(OH)2D3.

Adult↗

PubMed1979

The treatment of metabolic bone disease.

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Bone Diseases↗

PubMed1977

Some problems associated with assay of 25-hydroxycalciferol in human serum.

Methods available for the assay of 25-hydroxycalciferol in human serum are evaluated and compared to one another. Ethanol was chosen for use in the initial extraction procedure and rat-kidney cytosol as the binding protein, although good alternative methods are also available. We used silicic acid for chromatography and found this an essential step. Reproducibility was increased when, after "bound" and "free" material were separated, an aliquot of the supernate was pipetted into the counting vial instead of the entire supernatant fluid being decanted. Beta-lipo-protein added to the assay system was of no advantage; added bovine serum albumin interfered with the assay by giving rise to high blank values. With ethanol extraction, silicic acid chromatography, rat kidney cytosol and separation on dextran-coated charcoal, sera from normal subjects showed a mean 25-hydroxycalciferol concentration of 28.5 microng/liter (range, 13.1 to 43.9) during the fall season. Coefficients of variation for a control serum were 4.9% (intra-assay) and 10.9% (interassay).

Animals↗