Action of 1,25-dihydroxyvitamin D3 and a diphosphonate on calcium metabolism in rats

1975 ◽  
Vol 229 (2) ◽  
pp. 402-408 ◽  
Author(s):  
JP Bonjour ◽  
U Trechsel ◽  
H Fleisch ◽  
R Schenk ◽  
HF DeLuca ◽  
...  
Keyword(s):  
Calcium Metabolism ◽  
Calcium Absorption ◽  
Bone Mineralization ◽  
Concomitant Administration ◽  
Urinary Calcium ◽  
Intestinal Calcium Absorption ◽  
Bone Morphology ◽  
Dihydroxyvitamin D3 ◽  
Calcium Retention ◽  
Endogenous Production

The effect of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) on Ca balance, 45Ca kinetics, and bone morphology has been studied in control rats and rats given disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), 10 mg P/kg sc per day. This large dose of EHDP is known to inhibit bone mineralization and intestinal calcium absorption and to depress the endogenous production of 1,25-(OH)2D3. In conctrol rats, 1,25-(OH)2D3 increased intestinal calcium absorption. However, in contrast to the enhanced calcium absorption that results from an augmentation of dietary calcium, the 1,25(OH)2D3-induced augmentation of calcium absorption does not lead to a rise in calcium retention, the intestinal effect being matched by an increased excretion of urinary calcium. The EHDP-induced decrease of intestinal calcium absorption could be completely prevented by the concomitant administration of 1,25-(OH)2D3 but not the inhibition of bone mineralization. Therefore, in contrast to the impairment of calcium absorption, that of bone mineralization brought about by large doses of EHDP cannot be merely attributed to a decreased production of 1,25-(OH)2D3.

Increased clearance of 1,25(OH)2D3 and tissue-specific responsiveness to 1,25(OH)2D3 in diabetic rats

1993 ◽  
Vol 265 (2) ◽  
pp. E215-E223 ◽  
Author(s):  
J. Verhaeghe ◽  
A. M. Suiker ◽  
R. Van Bree ◽  
E. Van Herck ◽  
I. Jans ◽  
...  
Keyword(s):  
Calcium Absorption ◽  
Bone Mineralization ◽  
Diabetic Rats ◽  
Urinary Calcium ◽  
Metabolic Clearance ◽  
Dihydroxyvitamin D3 ◽  
Virtual Absence ◽  
Relative Production ◽  
Relative Production Rate

The kinetics of 1,25-dihydroxyvitamin D3 [1,25(OH)2-D3] and the in vivo response to 1,25(OH)2D3 (7.5, 15, and 30 ng/100 g body wt), infused or injected subcutaneously for 12-14 days, were studied in male spontaneously diabetic and control BB rats. In control rats, increasing doses of 1,25(OH)2D3 produced parallel increases in plasma 1,25(OH)2D3 and calcium, urinary calcium, duodenal CaBP9K, and renal CaBP28K. 1,25-(OH)2D3 at 30 ng/100 g markedly raised plasma osteocalcin and osteoblast/osteoid surfaces in the tibial metaphysis, but inhibited bone mineralization rate. In diabetic rats, plasma 1,25-(OH)2D3 concentrations were decreased, and the rise of plasma 1,25(OH)2D3 during 1,25(OH)2D3 infusion was blunted, but the free 1,25(OH)2D3 index remained normal or above normal. Diabetic rats had an increased metabolic clearance rate of 1,25-(OH)2D3 (0.38 +/- 0.015 vs. 0.24 +/- 0.007 ml.min-1.kg-1), with no further increase in 1,25(OH)2D3-infused diabetic rats; their relative production rate of 1,25(OH)2D3 was unchanged. The responses of plasma and urinary calcium, duodenal CaBP9K, and renal CaBP28K to infused 1,25(OH)2D3 were normal, as was duodenal calcium absorption in 1,25(OH)2D3-injected diabetic rats. However, the virtual absence of osteoblasts/osteoid in trabecular bone was unaltered in diabetic rats infused with 30 ng/100 g 1,25(OH)2D3, with only minimal increase of their low plasma osteocalcin levels. 1,25(OH)2D3 treatment therefore cannot be expected to reverse diabetic osteopenia.

Preclinical screening of the applicability of strontium as a marker for intestinal calcium absorption

1997 ◽  
Vol 272 (3) ◽  
pp. E422-E428 ◽  
Author(s):  
A. J. Sips ◽  
R. Barto ◽  
J. C. Netelenbos ◽  
W. J. van der Vijgh
Keyword(s):  
Body Weight ◽  
Calcium Absorption ◽  
Intestinal Calcium Absorption ◽  
Dose Finding ◽  
Male Rats ◽  
Controlled Study ◽  
Dihydroxyvitamin D3 ◽  
Before And After ◽  
Stable Strontium ◽  
Preclinical Screening

The applicability of stable strontium as a marker for measuring intestinal calcium absorption is mainly dependent on the validity of the assumption that calcium and strontium are absorbed with a constant ratio. Up to now, it is not clear whether this ratio is affected by intervention therapy. Therefore, preclinical screening of this ratio before and after treatment is indispensable for a clinical calcium absorption test based on the use of stable strontium as a marker. We studied the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D(3)], a potent enhancer of active intestinal calcium absorption, on the pharmacokinetics of both calcium-45 and strontium in adult male rats, in a short-term dose-finding study [0-50 ng 1,25(OH)2D(3)/100 g body weight] and also in a placebo-controlled study in which 12.5 ng 1,25(OH)2D(3)/100 g body weight were applied to assess the long-term pharmacokinetics. The mean bioavailability (true absorption) was 33% for calcium and 19% for strontium (ratio 1.7:1), whereas, after 1,25(OH)2D(3) pretreatment, it was 73 and 43% (ratio 1.7:1), respectively. These findings demonstrate that intestinal strontium absorption has, like intestinal calcium absorption, an active component. Moreover, they underscore the applicability of stable strontium as a tool for investigating calcium absorption under various conditions.

scholarly journals Evidence for Involvement of 17β-Estradiol in Intestinal Calcium Absorption Independent of 1,25-Dihydroxyvitamin D3 Level in the Rat

1999 ◽  
Vol 14 (1) ◽  
pp. 57-64 ◽  
Author(s):  
E. M. Colin ◽  
G. J. C. M. Van Den Bemd ◽  
M. Van Aken ◽  
S. Christakos ◽  
H. R. De Jonge ◽  
...  
Keyword(s):  
Calcium Absorption ◽  
Intestinal Calcium Absorption ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
17Β Estradiol

The Measurement of Intestinal Calcium Absorption by External Radioisotope Counting: Application to Study of Nephrolithiasis

1970 ◽  
Vol 39 (1) ◽  
pp. 95-106 ◽  
Author(s):  
M. R. Wills ◽  
E. Zisman ◽  
J. Wortsman ◽  
R. G. Evens ◽  
C. Y. C. Pak ◽  
...  
Keyword(s):  
Calcium Absorption ◽  
Scintillation Counter ◽  
Renal Stones ◽  
Normal Subjects ◽  
Total Radioactivity ◽  
Urinary Calcium ◽  
Intestinal Calcium Absorption ◽  
Absolute Amount ◽  
Calcium Load ◽  
Fractional Calcium Absorption

1. Gastro-intestinal absorption of calcium was studied in man by the measurement of forearm radioactivity in a large-volume liquid scintillation counter following separate oral and intravenous doses of 47CaCl2. From the ratio of the percentages of total radioactivity appearing in the forearm following these separate determinations the fractional absorption of calcium was estimated. 2. Changes of forearm radioactivity with time following the administration of this isotope were studied; evidence is presented that the radioactivity in the forearm at 4 h after administration of the isotope gives a valid assessment of fractional calcium absorption. 3. Fractional calcium absorption determined by this technique correlated well with the net calcium absorption as determined from stool radioactivity after oral administration of isotope. 4. In normal subjects it was shown that fractional calcium absorption measured by this technique varies inversely with the stable calcium load and that the absolute amount of calcium absorbed from given loads increases with the size of the load in the range 20–1000 mg calcium. 5. Gastro-intestinal calcium absorption was measured at various oral calcium loads in a group of fifteen patients with recurrent calcium-containing renal stones. All the patients were normocalcaemic; some had hypercalciuria. In the patients with hypercalciuria, calcium absorption, fractional and absolute, was significantly increased at all calcium loads as compared to that of patients with normal urinary calcium. 6. It is concluded that hyperabsorption of calcium from the gastro-intestinal tract plays a crucial role in the aetiology of hypercalciuria, probably by causing an increase in the renal filtered calcium load.

Relation between bone mineralization, Ca absorption, and plasma Ca in phosphonate-treated rats.

1977 ◽  
Vol 232 (3) ◽  
pp. E298
Author(s):  
U Trechsel ◽  
R Schenk ◽  
J P Bonjour ◽  
R G Russell ◽  
H Fleisch
Keyword(s):  
Calcium Absorption ◽  
Bone Mineralization ◽  
Close Correlation ◽  
Plasma Calcium ◽  
Intestinal Calcium Absorption ◽  
Phosphate Salts ◽  
Dose Response Study ◽  
Skeletal Mineralization

Disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) is known to inhibit the crystallization of calcium phosphate salts in vitro. Large doses of EHDP administered in vivo inhibit skeletal mineralization, decrease intestinal calcium absorption, and produce hypercalcemia. In the present study, EHDP or one of 13 other phosphonates were given to rats at 10 mg P/kg-day sc for 7 days in order to better define the nature of the relationship between bone mineralization, intestinal absorption, and plasma calcium in the regulation of calcium homeostasis. Each of the phosphonates which inhibited skeletal mineralization in vivo also inhibited crystallization in vitro, but the converse was not true. A very close correlation was found between inhibition of skeletal mineralization, decreased intestinal calcium absorption, and slight hypercalcemia. A dose-response study with two compounds also revealed the same close correlation. It is argued that the impairment of intestinal calcium absorption in phosphonate-treated rats may represent a secondary homeostatic response to the primary effect of the drugs on bone mineralization. This response may be mediated by an elevation of a fraction of plasma calcium.

Calcium metabolism in dairy sheep

1984 ◽  
Vol 102 (3) ◽  
pp. 601-608 ◽  
Author(s):  
S. Economides
Keyword(s):  
Calcium Intake ◽  
Calcium Metabolism ◽  
Dry Matter ◽  
Calcium Absorption ◽  
Urinary Calcium ◽  
Calcium Balance ◽  
Dairy Sheep ◽  
Deficient Diet ◽  
Pregnant Sheep ◽  
Calcium Loss

SummaryCalcium metabolism in dairy sheep was studied using radioisotope and balance techniques. The rate of calcium absorption increased, but the efficiency of calcium absorption decreased, with increasing calcium intake in dry sheep. Endogenous faecal and urinary calcium losses, and the rate of calcium absorption, decreased, but the efficiency of calcium absorption increased in pregnant sheep given a calcium-deficient diet. The rate and the efficiency of calcium absorption and the calcium balance of lactating ewes were not influenced by the prepartum level of calcium intake, when calcium intake in early lactation was high. Endogenous faecal calcium loss was related to dry-matter intake, and total faecal calcium loss was related to calcium intake.

Mechanism of chronic hypercalciuria with furosemide: increased calcium absorption

1986 ◽  
Vol 251 (1) ◽  
pp. F17-F24 ◽  
Author(s):  
D. A. Bushinsky ◽  
M. J. Favus ◽  
C. B. Langman ◽  
F. L. Coe
Keyword(s):  
Calcium Absorption ◽  
Chronic Administration ◽  
Urinary Calcium ◽  
Intestinal Calcium Absorption ◽  
Calcium Excretion ◽  
Calcium Balance ◽  
Urine Calcium ◽  
Calcium Diet ◽  
Filtered Load ◽  
Urine Calcium Excretion

Furosemide produces chronic hypercalciuria. The source of the additional urinary calcium is not known but must be either bone mineral or calcium absorbed by the intestine. Without bone calcium dissolution or increased absorption the filtered load of calcium would fall and urinary calcium excretion would return to pretreatment levels. To determine whether furosemide alters intestinal calcium absorption, we fed furosemide (75 mg . kg body-1 wt . day-1) to 11 rats eating 15 g/day of a 0.60% calcium diet. Compared with 11 control rats, furosemide increased urine calcium (15.6 +/- 0.8 mg/5 days vs. 4.1 +/- 0.3, P less than 0.001). Fecal calcium excretion fell (194 +/- 7 mg/5 days vs. 223 +/- 12, P less than 0.05), indicating an increase in intestinal calcium absorption sufficient to sustain the hypercalciuria. The increase in absorption occurred without an increase in the level of serum 1,25-dihydroxycholecalciferol (180 +/- 20 pg/ml vs. 220 +/- 16, furosemide vs. control, respectively, P = NS). To determine whether the intestinal effect of furosemide persists after the initial sodium diuresis abates, we analyzed only the last 3 days of balance. Again, rats fed furosemide had increased urine excretion and intestinal absorption of calcium, so that net calcium balance was not different from that of controls. Twelve additional rats were fed a 0.02% calcium diet to which 35 mg . kg body wt-1 . day-1 of furosemide was added. Compared with eleven controls, urine calcium increased and fecal calcium excretion again fell, but balance was not different. Chronic administration of furosemide increases intestinal calcium absorption enough to permit urine calcium excretion to remain elevated without the necessity for bone dissolution.

Sign in / Sign up

Export Citation Format

Share Document