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

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.

1993 ◽  
Vol 85 (2) ◽  
pp. 223-228 ◽  
Author(s):  
Jean-Luc Riond

1. The influence of the time of the day of the administration of synthetic human parathyroid hormone fragment-(1-34) [hPTH-(1-34)] on its anabolic effect in bone was investigated in 23 60-day-old female Wistar rats. Rats were randomly assigned to the groups vehicle control morning, hPTH-(1-34)-treated morning, vehicle control afternoon and hPTH-(1-34)-treated afternoon, and once daily received a subcutaneous injection of 8 μg of hPTH-(1-34)/100 g body weight for 11 days. The increase in net intestinal calcium absorption and the increase in calcium balance were not influenced by the time of day of hPTH-(1-34) treatment. Four days after cessation of treatment, the net intestinal calcium absorption and calcium balance in hPTH-(1-34)-treated rats were not different from those of the control rats. 2. Modulation of the anabolic effect by variation of the hPTH-(1-34) dosage regimen was investigated in 43 60-day-old female Wistar rats. Rats were randomly assigned to the groups vehicle control, environmental control, 8 μg of hPTH-(1-34)/100 g body weight every 3 days for 24 days, 8 μg of hPTH-(1-34)/100g body weight every 2 days for 16 days, 8 μg of hPTH-(1-34)/100 g body weight every day for 8 days, 4 μg of hPTH-(1-34)/100 g body weight twice a day for 8 days and 2.7 μg of hPTH-(1-34)/100 g body weight three times a day for 8 days. In all cases, the total dose of hPTH-(1-34) received was 64 μg/100g body weight. Net intestinal calcium absorption and calcium balance increased significantly in the groups that received hPTH-(1-34) once a day, twice a day and three times a day. In relation with increased frequency of dosing, a significant linear trend existed for the increase in net intestinal calcium absorption and calcium balance. The hPTH-(1-34)-induced increase in total tibia calcium, total vertebrae calcium, tibia dry weight and vertebrae dry weight also tended to be more pronounced with more frequent dosing, although the trend was not significant. 3. Thus, smaller intervals between doses of hPTH-(1-34) enhance the anabolic response in bone despite the smaller doses. This effect may be secondary to 1,25-dihydroxyvitamin D3-induced increased intestinal calcium absorption, decreased 1,25-dihydroxyvitamin D3-induced bone resorption, up-regularion of osteoblast receptors for parathyroid hormone, or a combination of these three factors.


1975 ◽  
Vol 229 (2) ◽  
pp. 402-408 ◽  
Author(s):  
JP Bonjour ◽  
U Trechsel ◽  
H Fleisch ◽  
R Schenk ◽  
HF DeLuca ◽  
...  

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.


1984 ◽  
Vol 247 (5) ◽  
pp. F746-F752 ◽  
Author(s):  
D. A. Bushinsky ◽  
M. J. Favus ◽  
F. L. Coe

Chlorthalidone, like other benzothiadiazides, lowers urine calcium excretion chronically. If intestinal calcium absorption did not fall or bone accretion did not increase, serum calcium and the filtered load of calcium would increase and urine calcium would return to pretreatment levels. To determine whether overall intestinal calcium absorption fell, we fed chlorthalidone (5 mg X kg body wt-1 X 24 h-1) to 10 adult male rats eating 15 g/day of a 0.6% calcium diet. Compared with 10 control rats, chlorthalidone reduced urine calcium [2.1 +/- 0.1 (SE) vs. 5.8 +/- 0.5 mg/6 days; P less than 0.001]. Fecal calcium rose (307 +/- 9 vs. 257 +/- 12; P less than 0.005) because percent intestinal calcium absorption fell (41 +/- 2 vs. 52 +/- 2; P less than 0.002). Twenty other rats given the same diet were injected subcutaneously with 1,25(OH)2D3 (50 ng/day). In these rats, chlorthalidone reduced urine calcium (23 +/- 3 vs. 59 +/- 3; P less than 0.001) and percent intestinal calcium absorption (60 +/- 1 vs. 66 +/- 1; P less than 0.01). With or without 1,25(OH)2D3, chronic administration of chlorthalidone reduces intestinal calcium absorption, and this reduction seems to be the mechanism that permits urine calcium excretion to remain low.


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 ◽  
...  

2011 ◽  
Vol 105 (10) ◽  
pp. 1553-1562 ◽  
Author(s):  
Craig A. Melville ◽  
Susan Boyle ◽  
Susan Miller ◽  
Susan Macmillan ◽  
Victoria Penpraze ◽  
...  

Adults with intellectual disabilities experience high rates of obesity. Despite this higher risk, there is little evidence on the effectiveness of weight-loss interventions for adults with intellectual disabilities and obesity. The present study examined the effectiveness of the TAKE 5 multi-component weight-loss intervention. Adults with obesity were invited using specialist intellectual disability services to participate in the study. Obesity was defined as a BMI of 30 kg/m2 or greater. TAKE 5 included a daily energy-deficit diet of 2510 kJ (600 kcal), achieved via a personalised dietary prescription. Participants' body weight, BMI, waist circumference and levels of physical activity and sedentary behaviour were measured before and after the intervention. A total of fifty-four individuals consented to participate, of which forty-seven (87 %) completed the intervention in the study period. There was a significant decrease in body weight (mean difference − 4·47 (95 % CI − 5·91, − 3·03) kg; P < 0·0001), BMI ( − 1·82 (95 % CI − 2·36, − 1·29) kg/m2; P < 0·0001), waist circumference ( − 6·29 (95 % CI − 7·85, − 4·73) cm; P < 0·0001) and daily sedentary behaviour of participants ( − 41·40 (95 % CI − 62·45, − 20·35) min; P = 0·00 034). Of the participants who completed the intervention, seventeen (36·2 %) lost 5 % or more of their initial body weight. Findings from the study suggest that TAKE 5 is an effective weight-loss intervention for adults with intellectual disabilities and obesity. The effectiveness of TAKE 5 should be examined further in a controlled study.


2000 ◽  
Vol 30 (12) ◽  
pp. 1036-1043 ◽  
Author(s):  
A. Zittermann ◽  
M. Heer ◽  
A. Caillot-Augusso ◽  
P. Rettberg ◽  
K. Scheld ◽  
...  

1995 ◽  
Vol 89 (1) ◽  
pp. 107-107 ◽  
Author(s):  
A. J. A. M. Sips ◽  
J. C. Netelenbos ◽  
R. Barto ◽  
W. J. F. Van Der Vijgh

1984 ◽  
Vol 103 (3) ◽  
pp. 295-300 ◽  
Author(s):  
S. D. H. Chan ◽  
D. K. H. Chiu ◽  
D. Atkins

ABSTRACT The distribution of 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3) receptors in isolated jejunal villous and crypt cells was investigated in normal and adrenalectomized male rats, and also in animals treated with the synthetic glucocorticoid, dexamethasone, and/or the glucocorticoid antagonist, 11-deoxycortisol. Adrenalectomy caused an increase in 1,25-(OH)2D3 receptors whilst dexamethasone treatment led to a reduction in receptor number. 11-Deoxycortisol was able to reverse the 'down-regulation' effect caused by glucocorticoids. In all cases, the changes in receptor numbers were more pronounced in crypt cells. The data suggest that, in the small intestine, glucocorticoids may control the synthesis of 1,25-(OH)2D3 receptors via the mediation of a glucocorticoid receptor, and that the adrenal hormones mainly express their effect in crypt cells. It is proposed that this phenomenon may, in part, explain the reduction in calcium absorption which occurs in man after chronic glucocorticoid treatment. J. Endocr. (1984) 103, 295–300


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