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At least 343 records · Page 19Linked to original sources
PubMed1986

Renal ultrasound in metabolic bone disease.

Fifty-one patients aged 1 year to 56 years with metabolic bone disease underwent renal ultrasound. Medullary nephrocalcinosis was found in nine of 24 patients with X-linked hypophosphatemic rickets and is considered to be iatrogenic, related to vitamin D therapy. Another three in this group of 24 with both medullary and cortical increased renal echogenicity had suffered from repeated episodes of vitamin D intoxication and had secondary hyperparathyroidism. Nephrocalcinosis was less frequent in patients with treated vitamin D-dependent rickets or hypophosphatemic bone disease where generally smaller doses of vitamin D are given. Patients with pseudohypoparathyroidism, on small doses of vitamin D, had a normal renal ultrasound. In cystinosis and Fanconi's syndrome, the kidneys are small, echodense (both the cortex and medulla) with a tendency to cyst formation.

Adolescent↗
PubMed1983

Effects of phosphate and 1,25(OH)2D3 on in vitro bone collagen synthesis in the hypophosphatemic mouse.

Calvarial bones from hypophosphatemic (Hyp) mice and normal littermates were cultured in a chemically defined medium to determine: (a) the effect of medium phosphate (Pi) concentration (1, 2, and 3 mM) on collagen synthesis; (b) the effect of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] (10(-12)M-10(-7)M) on collagen synthesis; and (c) whether bone responsiveness to 1,25(OH)2D3 was affected by changes in medium Pi concentration. Bone collagen synthesis was evaluated by measuring [ 3H ]hydroxyproline formation. The distribution of labeled hydroxyproline between bone explant and culture medium (total and dialyzable fraction) was studied. These experiments confirm that 1,25(OH)2D3 inhibits specifically bone collagen synthesis in vitro. We did not detect any effect of medium Pi concentration on basal collagen synthesis but were able to demonstrate that lowering medium Pi concentration increased the 1,25(OH)2D3-induced inhibition of collagen synthesis. Bones from both genotypes responded to 1,25(OH)2D3, but modulation of this response by changes in Pi concentration was altered in Hyp bone as, in contrast to normal bone, its response to 1,25(OH)2D3 was unaffected when medium Pi concentration was decreased from 3 to 2 mM. These findings support the hypothesis of an altered response of bone to 1,25(OH)2D3 in the Hyp mouse.

Animals↗
PubMed1983

Normal milk composition in lactating X-linked hypophosphatemic mice despite continued hypophosphatemia.

Patients with X-linked hypophosphatemia and mice bearing the Hyp gene have reduced renal tubular reabsorption of phosphate and an osteomalacic bone disease. To test if altered phosphate transport also exists in the mammary glands, milk was analyzed from normal (n = 9) and heterozygous Hyp (n = 8) mice 14 days after giving birth. Inorganic phosphate, total phosphate, calcium, magnesium, sodium, and potassium were measured; percent cream, fat, water, and nonfat organic solids were measured; and protein was measured. No significant differences (NSD) were found except for greater sodium in Hyp milk. There was also NSD in litter weight. The lactating Hyp had a lower body weight and remained hypophosphatemic relative to lactating normals, but both groups had higher plasma phosphate than nonlactating controls of the same genotype. The data suggest that Hyp mice can accumulate a normal amount of phosphate in their milk despite the plasma phosphate being two-thirds of normal. These data, with other recent reports of different organ systems, suggest that the altered phosphate transport activity may be restricted to the kidney.

Animals↗
PubMed1984

Metabolites of vitamin D in normal and X-linked hypophosphatemic mice.

Hyp mice are a model for human X-linked hypophosphatemia (vitamin D-resistant rickets.) To determine whether an abnormality of vitamin D metabolism exists in this disease, the profiles of the metabolites of vitamin D were determined in normal and Hyp mouse plasma. Hyp and normal mice were fed a vitamin D-deficient diet and received 1,2 3H-vitamin D3 at 16 Ci/mmol by stomach tube at 5 ng/g body weight (0.21 microCi/g b.w.) on alternate days for 14 days. The dose of vitamin D given maintained near normal plasma 25-OH-vitamin D. Thus the mice were in a vitamin D-replete state with all metabolite pools labeled with 3H. Plasma was collected from 4 normal and 4 Hyp mice. The plasma was extracted, and the extracts were chromatographed separately for each mouse on an LH-20 column. Each major peak of radioactivity was rechromatographed using high performance liquid chromatography on a Zorbax-Sil column using solvent systems known to resolve several vitamin D metabolites. Twenty-one radio-active peaks were identified. The disintegrations per minute of 3H in each peak were quantified and converted to plasma concentration using the known specific activity of the administered vitamin D. The 25-OH-vitamin D accounted for 55% of the circulating radioactivity, and 24,25-(OH)2-vitamin D accounted for 22%. The plasma levels of 24,25-(OH)2-vitamin D were similar to levels previously reported by us using protein binding assays. No peaks of radioactivity were missing in the plasma extracts of the Hyp mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

The collagen crosslinking in the hypophosphatemic male mouse.

In order to evaluate the influence of bone mineralization on collagen metabolism, the bone collagen crosslinks were determined in femur diaphyses of mice with X-linked hypophosphatemia and of control littermates. No quantitative difference could be elicited between the two groups. It was also noted that in the mouse, cortical bone maturation is accompanied by a slight increase in the number of reducible crosslinks.

Animals↗
PubMed1981

Serum 1,25-dihydroxyvitamin D concentration in hypophosphatemic vitamin D-resistant rickets.

Fasting serum 1 alpha, 25-dihydroxyvitamin D [1,25-(OH)2D] levels were measured in 3 groups of hypophosphatemic vitamin D-resistant rickets (VDRR) patients; those untreated; those treated with vitamin D and phosphate; and those treated with 1,25-(OH)2D3 and phosphate. In the untreated patients, the mean 1,25-(OH)2D level was higher than in our age-matched control group. Except for one at 66 pg/ml, individual values were however within normal limits. Long term vitamin D2 therapy was accompanied by a slight but significant decrease in 1,25-(OH)2D concentrations; nonetheless the levels remained within the normal range. In the third group of patients, the concentration of 1,25-(OH)2D rose to supranormal levels when sampling was done 1-3 hours after administration of the hormone, decreasing rapidly to levels below that of normal subjects when the specimens were collected 12-24 hours later. Our data show that an alteration of the vitamin D activation pathway is unlikely to be part of the pathogenic mechanism underlying the VDRR condition.

Adolescent↗
PubMed1982

Serum 1,25-dihydroxyvitamin D levels in subjects with X-linked hypophosphatemic rickets and osteomalacia.

In order to determine whether a defect in vitamin D metabolism might play a role in the pathogenesis of X-linked hypophosphatemic rickets and osteomalacia (XLH), we compared the serum 1,25-dihydroxyvitamin D [1,25(OH)2D] level in 52 normal subjects and 37 patients with XLH. In untreated patients, adults were found to have values similar to age-matched controls, while youths had values similar to growth-rate-matched controls but significantly lower than the levels of age-matched controls who were growing at a normal rate. In contrast, treated XLH patients of all ages had serum levels significantly lower than both controls and untreated XLH patients. Further, the serum levels of 1,25(OH)2D in these treated patients had a significant inverse linear correlation with serum 25-(OH)D concentrations. We propose that subjects with XLH have serum 1,25(OH)2D levels within appropriate age- and growth-rate-matched normal ranges. However, in the presence of hypophosphatemia, we would have anticipated elevated levels of 1,25(OH)2D; viewed in this light the serum 1,25(OH)2D levels are inadequate, suggesting the presence of a relative deficiency of this active vitamin D metabolite.

Adolescent↗
PubMed1982

Bone response to phosphate and vitamin D metabolites in the hypophosphatemic male mouse.

The hypophosphatemic male mouse (Hyp/y), the proposed model for human vitamin D-resistant rickets (VDRR), is characterized by chronic hypophosphatemia, dwarfism, and rachitic and osteomalacic bone lesions. We have reported that treatment of Hyp/y mice with phosphate salts (Pi) heals rickets but does not correct the defective endosteal bone mineralization. In an attempt to cure osteomalacia, mutant male animals were treated with Pi combined with 25-hydroxyvitamin D3 (25OHD3, 1 microgram/kg/day), 24,25-dihydroxyvitamin D3 [24,25(OH)2D3, 0.5 microgram/kg/day], or 1,25-dihydroxyvitamin D3 [1,25(OH)2D3, 0.05--0.25 microgram/kg/day] infused constantly for 3 weeks. The biochemical and skeletal effects of treatment were assessed by analytical methods and bone histomorphometry. The results show that only 1,25(OH)2D3 produced a dose-dependent elevation of serum calcium and phosphorus, and greatly improved bone mineralization at doses high enough to increase serum calcium and phosphorus concentrations within or above the normal range. Better improvement of bone mineralization was obtained when Pi was combined to 1,25(OH)2D3. In conjunction with the correction of hypocalcemia, Pi + 1,25(OH)2D3 suppressed the stimulation of bone turnover induced by Pi supplementation. The results show that, as in VDRR children, 1,25(OH)2D3 produces beneficial effects on bone lesions in Hyp/y mice, mainly through enhancement of mineral availability. However, the persistence of osteomalacia despite correction of serum mineral concentrations suggests that there is a specific bone cell resistance to mineral and/or hormonal influences in Hyp/y mice.

24,25-Dihydroxyvitamin D 3↗
PubMed1985

Abnormal parathyroid function in the X-linked hypophosphatemic mouse.

Employing a cytochemical bioassay, we compared parathyroid function in normal and X-linked hypophosphatemic (Hyp) mice. Under basal conditions Hyp mice manifested hypocalcemia and, in accord, had a plasma bioactive parathyroid hormone concentration (3.04 +/- 0.14 pg/ml) significantly greater than that of normals (2.16 +/- 0.14 pg/ml). We confirmed the validity of the bioassay by demonstrating that the plasma collected from both mouse models diluted parallel to the assay standard curve. Moreover, after parathyroidectomy, normal and Hyp mice had plasma bioactive parathyroid hormone levels approximately 90% less than those obtained under basal conditions and indistinguishable from one another. In further studies we observed that dietary calcium and/or vitamin D deprivation in both animal models resulted in a comparable decline of the plasma calcium concentration. However, the concordant increase of the circulating bioactive parathyroid hormone level was greater in the normal mice. Thus, the bioactive parathyroid hormone concentration obtained in response to a low calcium challenge in normals was significantly greater than that in Hyp mice. In contrast, in response to dietary calcium loading, the plasma bioactive parathyroid hormone levels did not decrease significantly from basal values in either animal model. These data illustrate that the bioactive parathyroid hormone concentration in both normal and Hyp mice is inversely correlated with the plasma calcium. However, while the Hyp mice maintain an elevated plasma parathyroid hormone concentration under basal conditions (in response to a decreased plasma calcium), the parathyroid activity of the mutants after a more severe hypocalcemic challenge is attenuated, resulting in a significantly different model of linear correlation. Thus, these data indicate that Hyp mice manifested abnormal regulation of parathyroid function.

Animals↗
PubMed1985

Response of tissue phosphate content to acute dietary phosphate deprivation in the X-linked hypophosphatemic mouse.

In order to evaluate a possible role for tissue phosphate or phosphorylated compounds in mediating the increase in plasma 1,25(OH)2D3 levels during dietary phosphate deprivation, renal cortical phosphate content has been measured in both normal and X-linked hypophosphatemic mice on a normal diet and also after acute dietary phosphate deprivation. We find that the metabolism of inorganic phosphate and phosphorylated organic compounds in the renal cortex of Hyp mice is not altered in response to their very low levels of serum phosphate. Skeletal muscle does not lose inorganic phosphate and/or phosphorylated metabolites to compensate for drastic loses of serum phosphate during acute dietary deprivation in either normal or Hyp mice. Furthermore, the chronic low level of serum phosphate and altered hormonal regulation in Hyp mice do not produce alterations in mineral composition of the bone with the possible exception that the stoichiometry of the apatite might be slightly different.

Animals↗
PubMed1986

Reduced absorption of 45calcium from isolated duodenal segments in vivo in juvenile but not adult X-linked hypophosphatemic mice.

In juvenile X-linked hypophosphatemic (Hyp) mice, whole body calcium balances are significantly lower than in genetically normal mice. This is associated with low duodenal vitamin D-dependent calcium-binding protein and a failure of skeletal mineralization. To seek more specific evidence of an intestinal defect in these mice, absorption of 45Ca was measured in isolated duodenal segments in vivo in mice from 2-13 weeks of age. The duodenum was isolated by sutures and 45Ca was injected into the lumen in 150 mM NaCl and 2 mM CaCl2 at pH = 7.2. Absorption was measured by the amount of isotope remaining in the lumen and by the plasma isotope level. Hemizygous Hyp male and heterozygous Hyp female mice absorbed significantly less 45Ca at 4 and 7 weeks of age than genetically normal mice while Hyp mice at 2, 10, and 13 weeks of age were not significantly affected. At 4 and 7 weeks of age, the Hyp mice also had significantly reduced plasma radioactivity midway through the collection period as well as at the end of the period. To explore a possible mechanism for this malabsorption, 1,25(OH)2-vitamin D receptors were measured in cytosol prepared from 4-week-old normal and Hyp duodenum. There were non-significant differences between the normal and Hyp mice in both binding affinity, Kd, and the number of receptors, nmax. In conclusion, juvenile Hyp mice at 4 and 7 weeks of ages malabsorbed calcium from their duodenum. Hyp mice younger than this period were not affected nor were adult Hyp mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMedDate not supplied

McCune Albright syndrome and hypophosphatemic rickets.

A 4 year-old girl had coxa vara, tibial bowing and hyperpigmented macules. The x-ray showed polyostotic fibrous dysplasia and evidence of rickets. Biochemical investigations confirmed hyperphosphaturic hypophosphatemic rickets. The literature has been reviewed.

Child, Preschool↗
PubMedDate not supplied

Nutritional and metabolic rickets.

Nutritional rickets is caused by vitamin D deficiency due to lack of exposure to sunlight. Neonatal rickets occurs only in infants born to mothers with very severe osteomalacia. Calcium deficiency alone does not cause mineralisation defects. It only causes osteoporosis and secondary hyperparathyroidism with raised plasma, 1,25 (OH)2D and osteocalcin. Low 25-OHD, increased IPTH, increased alkaline phosphatase in plasma and decreased calcium and increased hydroxyproline in urine are diagnostic of rickets. Low or undetectable plasma levels of 25-OHD, in presence of high plasma 1,25(OH)2D and IPTH are often observed during treatment with vitamin D. Even the marginal intakes of fluoride (> 2.5 mg/day) cause rickets in calcium deficient children. Indian children often need high dose of vitamin D due to severely depleted D stores, high IPTH and severe bone disease (radiologic and histomorphometric) for treatment.

Calcium, Dietary↗
PubMedDate not supplied

Brown tumour as a complication of secondary hyperparathyroidism in severe long-lasting vitamin D deficiency rickets.

UNLABELLED: Brown tumour is a localised form of fibrous-cystic osteitis associated with primary or secondary hyperparathyroidism. Despite the fact that secondary hyperparathyroidism occurs in vitamin D deficiency rickets, no cases of rickets with brown tumour have so far been described. We present a 2.9-year-old girl who had brown tumour of the mandible due to severe vitamin D deficiency rickets. Treatment with vitamin D3 corrected the hyperparathyroidism rapidly which was followed by gradual regression in tumour size. CONCLUSION: Brown tumour can develop in severe, long-standing vitamin D deficiency rickets and responds to vitamin D treatment.

Child, Preschool↗