Contrasting effects of intravenous and oral etidronate on vitamin D metabolism in man

1988 ◽  
Vol 74 (1) ◽  
pp. 101-106 ◽  
Author(s):  
P. J. Lawson-Matthew ◽  
D. F. Guilland-Cumming ◽  
A. J. P. Yates ◽  
R. G. G. Russell ◽  
J. A. Kanis
Keyword(s):  
Vitamin D ◽  
Urinary Excretion ◽  
Progressive Increase ◽  
Urinary Calcium ◽  
Calcium Excretion ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D3 ◽  
Renal Tubular Reabsorption ◽  
Early Effects ◽  
Renal Tubular

1. We have studied the early effects of intravenously and orally administered etidronate on vitamin D metabolism and indirect indices of calcium and skeletal metabolism in 17 patients with Paget's disease of bone. 2. Administration of etidronate by mouth (700–1400 mg daily for 1 month) or its intravenous infusion (300 mg daily for 5 days) decreased bone resorption as judged by urinary excretion of hydroxyproline and significantly increased renal tubular reabsorption of phosphate. No significant change in serum activity of alkaline phosphatase was noted with either regimen. 3. When etidronate was given by mouth there was a progressive decrease in fasting urinary calcium excretion and a rise in serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. In contrast, intravenous etidronate decreased serum values of l,25-(OH)2D3 and was associated with a progressive increase in fasting calcium excretion, suggesting a decrease in the net influx of calcium from the extracellular compartment to bone. Significant inverse correlations were noted between the change induced in 1,25-(OH)2D3 values at 2 weeks and the changes in serum calcium, phosphate and fasting urinary excretion of calcium. 4. These observations suggest that the different effects of intravenous and oral etidronate on l,25-(OH)2D3 values are a consequence of different doses of etidronate used and the different effects of these regimens on the accretion of calcium into bone.

Effect of alcohol ingestion on bone and mineral metabolism in rats

1980 ◽  
Vol 238 (6) ◽  
pp. E507-E510 ◽  
Author(s):  
D. T. Baran ◽  
S. L. Teitelbaum ◽  
M. A. Bergfeld ◽  
G. Parker ◽  
E. M. Cruvant ◽  
...  
Keyword(s):  
Mineral Metabolism ◽  
Serum Levels ◽  
Urinary Calcium ◽  
Alcohol Ingestion ◽  
Ethanol Administration ◽  
Calcium Excretion ◽  
Hydroxyvitamin D ◽  
Renal Tubular Reabsorption ◽  
Renal Tubular ◽  
Circulating Levels

Chronic ethanol administration to growing rats for 56 days resulted in circulating levels of 140 mg/dl, approximating concentrations that characterize alcoholic intoxication in man. This degree of alcohol ingestion, although without gross or histological effect on the liver or testicles, was attended by decreased trabecular bone volume despite a normal rate of skeletal mineralization as measured by time-spaced tetracycline labeling. Concomitant serum levels of calcium, phosphate, magnesium, creatinine, glutamic oxalacetic transaminase, alkaline phosphatase, testosterone, and 25-hydroxyvitamin D were normal. Although alcohol treatment was associated with a significant decrease in urinary calcium excretion, it had no effect on phosphate excretion nor on its renal tubular reabsorption. The data reveal that circulating levels of alcohol that do not result in hepatic or testicular injury are toxic for bone.

Familial hypocalciuric hypercalcaemia: observations on vitamin D metabolism and parathyroid function

1983 ◽  
Vol 104 (2) ◽  
pp. 210-215 ◽  
Author(s):  
M. Davies ◽  
P. H. Adams ◽  
J. L. Berry ◽  
G. A. Lumb ◽  
P. S. Klimiuk ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Concentration ◽  
Primary Hyperparathyroidism ◽  
Calcium Excretion ◽  
Renal Tubules ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Renal Tubular

Abstract. Serum vitamin D metabolites, the renal tubular maximum reabsorptive rate for phosphate (TMP/GFR) nephrogenic cyclic AMP (NcAMPI, and CaE (urinary calcium excretion per litre of glomerular filtrate) were measured in 14 adults with familial hypocalciuric hypercalcaemia (FHH). The findings were compared with analyses in 14 patients with surgically proven primary hyperparathyroidism matched for serum calcium, creatinine clearance and vitamin D status (assessed by serum concentrations of 25 hydroxyvitamin D). Vitamin D metabolites were also measured in 16 normocalcaemic relatives of patients with FHH. The serum concentration of 24, 25 dihydroxycholecalciferol was appropriate for the prevailing 25 hydroxyvitamin D and no difference was found between groups. The serum concentration of 1, 25 dihydroxycholecalciferol was significantly greater in primary hyperparathyroidism (P < 0.0005) compared with patients with FHH and their normocalcaemic relatives. TMP/GFR was reduced in both primary hyperparathyroidism (0.53 ± 0.12 mmol/l GF, mean ± sem) and FHH (0.86 ±0.14 mmol/l GF). Patients with primary hyperparathyroidism showed an increase in NcAMP output in the urine (38.5 ± 16 mmol/l GF) which was significantly greater (P < 0.0001) than the normal NcAMP (13.5 ± 9.2 nmol/l GF) found in FHH. CaE was low in FHH indicating increased renal tubular reabsorption of calcium. It is concluded that there is no abnormality of vitamin D metabolism in FHH comparable with the changes observed in primary hyperparathyroidism. It is suggested that the biochemical abnormalities in FHH cannot be explained solely upon an increased sensitivity of the renal tubules to the effects of endogenous parathyroid hormone.

Studies on vitamin D metabolism: Catabolism of 1α, 25-dihydroxyvitamin D3 and 1α-hydroxyvitamin D3 to a metabolite inactive on bone mineral mobilization

Steroids ◽  
1980 ◽  
Vol 36 (1) ◽  
pp. 27-39 ◽  
Author(s):  
Ohnuma Norio ◽  
Kiyoki Mamoru ◽  
Bannai Kiyoshi ◽  
Naruchi Tatsuyuki ◽  
Hashimoto Yoshinobu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Mineral ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D3

scholarly journals The effect of disodium ethane-1-hydroxy-1,1-diphosphonate on the metabolism of calcitriol in chicks

1987 ◽  
Vol 243 (1) ◽  
pp. 75-78 ◽  
Author(s):  
C Lidor ◽  
M S Meyer ◽  
R H Wasserman ◽  
S Edelstein
Keyword(s):  
Vitamin D ◽  
Urinary Excretion ◽  
Intestinal Absorption ◽  
Binding Protein ◽  
Sole Source ◽  
Treated Group ◽  
Response To Treatment ◽  
Vitamin D Metabolism ◽  
Calbindin D28k ◽  
25 Hydroxycholecalciferol

Decreased intestinal absorption of Ca2+ occurs in response to treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP). The effect is due to decreased 1-hydroxylation of calcidiol (25-hydroxycholecalciferol) in the kidney. In an attempt to establish whether impairment of vitamin D metabolism at steps beyond kidney hydroxylation occurs due to treatment with EHDP, chicks were depleted of vitamin D and were treated with calcitriol (1,25-dihydroxycholecalciferol) as their sole source of the vitamin. The chicks were then divided into two groups, one being treated with EHDP while the second group served as control. Intestinal absorption of Ca2+ in the EHDP-treated group was found to be impaired, along with decreases in concentrations of calbindin D28K (the 28,000-Mr vitamin D-dependent Ca2+-binding protein). When the chicks were dosed with [3H]calcitriol, significantly lower concentrations of the sterol were detected in the duodena of EHDP-treated birds. Measurement of levels of receptors for calcitriol in duodena showed no difference between groups, but levels of calcitriol in sera were considerably lower in the EHDP-treated group along with the elevated biliary and urinary excretion of glucuronidated conjugates. It is therefore concluded that treatment with EHDP results in increased catabolism of calcitriol in addition to the known suppression of the renal production of the hormone.

scholarly journals Transgenic Mice Overexpressing Human Fibroblast Growth Factor 23 (R176Q) Delineate a Putative Role for Parathyroid Hormone in Renal Phosphate Wasting Disorders

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5269-5279 ◽  
Author(s):  
Xiuying Bai ◽  
Dengshun Miao ◽  
Jiarong Li ◽  
David Goltzman ◽  
Andrew C. Karaplis
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Fibroblast Growth Factor ◽  
Calcium Homeostasis ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D3 ◽  
Circulating Levels

Abstract Fibroblast growth factor 23 (FGF23) is a recently characterized protein likely involved in the regulation of serum phosphate homeostasis. Increased circulating levels of FGF23 have been reported in patients with renal phosphate-wasting disorders, but it is unclear whether FGF23 is the direct mediator responsible for the decreased phosphate transport at the proximal renal tubules and the altered vitamin D metabolism associated with these states. To examine this question, we generated transgenic mice expressing and secreting from the liver human FGF23 (R176Q), a mutant form that fails to be degraded by furin proteases. At 1 and 2 months of age, mice carrying the transgene recapitulated the biochemical (decreased urinary phosphate reabsorption, hypophosphatemia, low serum 1,25-dihydroxyvitamin D3) and skeletal (rickets and osteomalacia) alterations associated with these disorders. Unexpectantly, marked changes in parameters of calcium homeostasis were also observed, consistent with secondary hyperparathyroidism. Moreover, in the kidney the anticipated alterations in the expression of hydroxylases associated with vitamin D metabolism were not observed despite the profound hypophosphatemia and increased circulating levels of PTH, both major physiological stimuli for 1,25-dihydroxyvitamin D3 production. Our findings strongly support the novel concept that high circulating levels of FGF23 are associated with profound disturbances in the regulation of phosphate and vitamin D metabolism as well as calcium homeostasis and that elevated PTH levels likely also contribute to the renal phosphate wasting associated with these disorders.

scholarly journals Genetic variants of calcium and vitamin D metabolism in kidney stone disease

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sarah A. Howles ◽  
Akira Wiberg ◽  
Michelle Goldsworthy ◽  
Asha L. Bayliss ◽  
Anna K. Gluck ◽  
...  
Keyword(s):  
Vitamin D ◽  
Kidney Stone ◽  
Association Studies ◽  
Vitamin D Supplementation ◽  
Stone Disease ◽  
Calcium Excretion ◽  
Genome Wide Association Studies ◽  
Vitamin D Metabolism ◽  
Kidney Stone Disease

AbstractKidney stone disease (nephrolithiasis) is a major clinical and economic health burden with a heritability of ~45–60%. We present genome-wide association studies in British and Japanese populations and a trans-ethnic meta-analysis that include 12,123 cases and 417,378 controls, and identify 20 nephrolithiasis-associated loci, seven of which are previously unreported. A CYP24A1 locus is predicted to affect vitamin D metabolism and five loci, DGKD, DGKH, WDR72, GPIC1, and BCR, are predicted to influence calcium-sensing receptor (CaSR) signaling. In a validation cohort of only nephrolithiasis patients, the CYP24A1-associated locus correlates with serum calcium concentration and a number of nephrolithiasis episodes while the DGKD-associated locus correlates with urinary calcium excretion. In vitro, DGKD knockdown impairs CaSR-signal transduction, an effect rectified with the calcimimetic cinacalcet. Our findings indicate that studies of genotype-guided precision-medicine approaches, including withholding vitamin D supplementation and targeting vitamin D activation or CaSR-signaling pathways in patients with recurrent kidney stones, are warranted.

Calcium and vitamin D metabolism in acromegaly

1981 ◽  
Vol 96 (4) ◽  
pp. 444-450 ◽  
Author(s):  
Bjarne Lund ◽  
Peter Claes Eskildsen ◽  
Birger Lund ◽  
Anthony W. Norman ◽  
Ole Helmer Sørensen
Keyword(s):  
Growth Hormone ◽  
Serum Concentration ◽  
Urinary Excretion ◽  
Direct Action ◽  
Elevated Serum ◽  
Serum Levels ◽  
Calcium Excretion ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D ◽  
Free Cortisol

Abstract. Acromegalic subjects were found to have elevated serum levels of both 1,25-dihydroxyvitamin D (1,25-(OH)2D), (67 ± 22 (sd) pg/ml) and 24,25-dihydroxyvitamin D (24,25-(OH)2D), (6.9 ± 1.5 (sd) ng/ml). The serum concentration of 1,25-(OH)2D correlated positively (P < 0.02, R = 0.56) to the 24 h urinary excretion of growth hormone, but not to the serum levels of parathyroid hormone, prolactin, thyroid hormones or the urinary excretion of free cortisol. Fourteen patients were treated with bromocriptine at doses from 15–45 mg/day for a period of about 6 months. This was accompanied by a significant decrease in the urinary excretion of growth hormone and calcium and in the serum concentrations of 1,25-(OH)2D and 24,25-(OH)2D. A relationship was demonstrated between the decrease in urinary calcium excretion and the decrease in serum 1,25-(OH)2D (P < 0.02, R = 0.64). It is concluded that the serum concentration of 1,25-(OH)2D is elevated in acromegaly, perhaps as a consequence of a direct action of growth hormone on the renal lα-hydroxylase activity.

scholarly journals Vitamin D Repletion in Patients with Primary Hyperparathyroidism and Coexistent Vitamin D Insufficiency

2005 ◽  
Vol 90 (4) ◽  
pp. 2122-2126 ◽  
Author(s):  
Andrew Grey ◽  
Jenny Lucas ◽  
Anne Horne ◽  
Greg Gamble ◽  
James S. Davidson ◽  
...  
Keyword(s):  
Vitamin D ◽  
Primary Hyperparathyroidism ◽  
Serum Calcium ◽  
Serum Alkaline Phosphatase ◽  
Vitamin D Insufficiency ◽  
Urinary Calcium ◽  
Urinary Calcium Excretion ◽  
Total Serum ◽  
Calcium Excretion ◽  
Intact Pth

Abstract Vitamin D insufficiency is common in patients with primary hyperparathyroidism (PHPT) and may be associated with more severe and progressive disease. Uncertainty exists, however, as to whether repletion of vitamin D should be undertaken in patients with PHPT. Here we report the effects of vitamin D repletion on biochemical outcomes over 1 yr in a group of 21 patients with mild PHPT [serum calcium &lt;12 mg/dl (3 mmol/liter)] and coexistent vitamin D insufficiency [serum 25 hydroxyvitamin D [25(OH)D] &lt;20 μg/liter (50 nmol/liter)]. In response to vitamin D repletion to a serum 25(OH)D level greater than 20 μg/liter (50 nmol/liter), mean levels of serum calcium and phosphate did not change, and serum calcium did not exceed 12 mg/dl (3 mmol/liter) in any patient. Levels of intact PTH fell by 24% at 6 months (P &lt; 0.01) and 26% at 12 months (P &lt; 0.01). There was an inverse relationship between the change in serum 25(OH)D and that in intact PTH (r = −0.43, P = 0.056). At 12 months, total serum alkaline phosphatase was significantly lower, and urine N-telopeptides tended to be lower than baseline values (P = 0.02 and 0.13, respectively). In two patients, 24-h urinary calcium excretion rose to exceed 400 mg/d, but the group mean 24-h urinary calcium excretion did not change. These preliminary data suggest that vitamin D repletion in patients with PHPT does not exacerbate hypercalcemia and may decrease levels of PTH and bone turnover. Some patients with PHPT may experience an increase in urinary calcium excretion after vitamin D repletion.

Thyroparathyroidectomy exaggerates calciuric action of ammonium chloride in rats

1984 ◽  
Vol 246 (1) ◽  
pp. F54-F58 ◽  
Author(s):  
A. Goulding ◽  
D. R. Campbell
Keyword(s):  
Bone Resorption ◽  
Ammonium Chloride ◽  
Chronic Administration ◽  
Urinary Calcium ◽  
Urinary Hydroxyproline ◽  
Renal Tubular Reabsorption ◽  
Renal Tubular ◽  
Hydroxyproline Excretion ◽  
Calcium Loss ◽  
Intact Rats

The effects of chronic ammonium chloride (NH4Cl) administration on urinary calcium, urinary hydroxyproline, and calcium and phosphate balances were studied in intact and thyroparathyroidectomized (TPTX) rats. NH4Cl (2 g/100 g diet) was administered for 16 days to growing rats consuming a low calcium (0.1% Ca) diet. NH4Cl increased urinary calcium and hydroxyproline. NH4Cl caused greater urinary calcium loss in TPTX than in intact rats, but hydroxyproline excretion in these groups was similar. Compensatory increases in net alimentary absorption of calcium and phosphate occurred in intact but not in TPTX rats. Urinary cAMP was depressed by thyroparathyroidectomy but was unaffected by NH4Cl. It is concluded that NH4Cl depresses renal tubular reabsorption of calcium and increases bone resorption in the presence and absence of the thyroid and parathyroid glands. However, our results suggest that parathyroid hormone plays an important calcium-sparing role, while calcitonin may act to limit the rate of bone resorption, in intact rats during chronic administration of NH4Cl.

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