Vitamin D Metabolism in Osteogenesis Imperfecta During Calcitonin Therapy

PEDIATRICS ◽  
1984 ◽  
Vol 73 (4) ◽  
pp. 538-542
Author(s):  
Yoshikazu Nishi ◽  
Sumio Hyodo ◽  
Kazunori Yoshimitsu ◽  
Kunihiko Sawano ◽  
Kanji Yamaoka ◽  
...  

The effect of calcitonin on plasma concentrations of 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] was studied in six patients with osteogenesis imperfecta. The mean pretreatment value of plasma 1,25-(OH)2D was significantly higher than the mean value of age-matched control subjects (P < .05). High or normal plasma levels of 1,25-(OH)2D before calcitonin therapy were decreased after 1 month of therapy and remained normal thereafter in all six patients. Plasma 25-hydroxyvitamin D concentrations, which were normal before calcitonin injection, remained normal during calcitonin administration. These results indicate that there may be acute and chronic effects of calcitonin on vitamin D metabolism.

2000 ◽  
Vol 164 (3) ◽  
pp. 339-348 ◽  
Author(s):  
N Akeno ◽  
A Matsunuma ◽  
T Maeda ◽  
T Kawane ◽  
N Horiuchi

We investigated the effects of dexamethasone on vitamin D-1alpha-hydroxylase and -24-hydroxylase expression and on vitamin D receptor (VDR) content in the kidneys of mice fed either a normal (NCD) diet or a calcium- and vitamin D-deficient (LCD) diet for 2 weeks. For the last 5 days mice received either vehicle or dexamethasone (2 mg/kg per day s.c.). Dexamethasone significantly increased plasma calcium concentrations without changing plasma concentrations of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) in both NCD and LCD groups. Northern blot and enzyme activity analyses in NCD mice revealed that dexamethasone increased renal VDR mRNA expression modestly and greatly increased 24-hydroxylase mRNA abundance and enzyme activity, but did not affect 1alpha-hydroxylase mRNA abundance and enzyme activity. In mice fed an LCD diet, dexamethasone increased renal VDR mRNA expression 1.5-fold, decreased 1alpha-hydroxylase mRNA abundance (52%) and activity (34%), and markedly increased 24-hydroxylase mRNA abundance (16-fold) and enzyme activity (9-fold). Dexamethasone treatment did not alter functional VDR number (B(max) 125-141 fmol/mg protein) or ligand affinity (K(d) 0.13-0.10 nM) in LCD mice. Subcutaneous injections of 1,25(OH)(2)D(3) (0.24 nmol/kg per day for 5 days) into NCD mice strongly increased renal 24-hydroxylase mRNA abundance and enzyme activity, while there was no effect of dexamethasone on renal 24-hydroxylase expression in these mice. This may be due to overwhelming induction of 24-hydroxylase by 1,25(OH)(2)D(3). These findings suggest that glucocorticoid-induced osteoporosis is caused by direct action of the steroids on bone, and the regulatory effect of glucocorticoids on renal 25-hydroxyvitamin D(3) metabolism may be less implicated in the initiation and progression of the disease.


2007 ◽  
Vol 13 (5) ◽  
pp. 670-672 ◽  
Author(s):  
M.S. Barnes ◽  
M.P. Bonham ◽  
P.J. Robson ◽  
J.J. Strain ◽  
A.S. Lowe-Strong ◽  
...  

Populations with insufficient ultraviolet exposure and who consume diets low in vitamin D have low vitamin D status (plasma 25-hydroxyvitamin D (25(OH)D) concentrations) and a reported higher incidence of multiple sclerosis (MS). The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is an effective anti-inflammatory molecule. No research to date has assessed 1,25(OH)2D3 concentrations in individuals with MS. In this study, plasma concentrations of 25(OH)D, 1,25(OH)2D 3 and parathyroid hormone (PTH) were measured in 29 individuals with MS and 22 age- and sex-matched control volunteers. There were no significant differences in plasma PTH, 25(OH)D and 1,25(OH)2D3 concentrations between individuals with MS and control volunteers. Women with MS had significantly higher 25(OH)D and 1,25(OH)2D3 concentrations than men with MS (79.1 ±45.4 versus 50.2±15.3 nmol/L, P=0.019 and 103.8± 36.8 versus 70.4±28.7 pmol/L, P=0.019, respectively). There was a significant positive correlation between 25(OH)D and 1,25(OH)2D 3 concentrations in all subjects (r=0.564, P=0.000), but secondary analysis revealed that the correlation was driven by women with MS (r=0.677, P= 0.001). Significant sex differences in vitamin D metabolism were observed and were most marked in individuals with MS, suggesting that vitamin D requirements may differ between the sexes, as well as by underlying disease state. Multiple Sclerosis 2007; 13: 670-672. http://msj.sagepub.com


1988 ◽  
Vol 254 (2) ◽  
pp. E150-E154
Author(s):  
T. O. Carpenter ◽  
M. L. Pendrak ◽  
C. S. Anast

Wilson's disease results in excess tissue accumulation of copper and is often complicated by skeletal and mineral abnormalities. We investigated vitamin D metabolism in rats fed a copper-laden diet rendering hepatic copper content comparable with that found in Wilson's disease. Injection of 25-hydroxyvitamin D3 [25(OH)D3] resulted in reduced 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in copper-intoxicated rats. In vitro 25(OH)D-1 alpha-hydroxylase activity was impaired in renal mitochondria from copper-intoxicated animals. Activity was also inhibited in mitochondria from controls when copper was added to incubation media. Impaired conversion of 25(OH)D to 1,25(OH)2D occurs in copper intoxication and suggests that altered vitamin D metabolism is a potential factor in the development of bone and mineral abnormalities in Wilson's disease.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Youssra Dakroury ◽  
Alexandra E. Butler ◽  
Soha R. Dargham ◽  
Aishah Latif ◽  
Amal Robay ◽  
...  

Objective. Genetic studies have identified four Qatari genotypes: Q1 Arab, Bedouin; Q2 Asian/Persian; Q3 African; and a fourth admixed group not fitting into the previous 3 groups. This study was undertaken to determine if there was an increased risk of deficiency of vitamin D and its metabolites associated with differing genotypes, perhaps due to genetic differences in skin pigmentation. Methods. 398 Qatari subjects (220 type 2 diabetes and 178 controls) had their genotype determined by Affymetrix 500 k SNP arrays. Total values of 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25(OH)D), 24,25-dihydroxyvitamin D (24,25(OH)2D), and 25-hydroxy-3epi-vitamin D (3epi-25(OH)D) concentrations were measured by the LC-MS/MS analysis. Results. The distribution was as follows: 164 (41.2%) genotyped Q1, 149 (37.4%) genotyped Q2, 31 (7.8%) genotyped Q3, and 54 (13.6%) genotyped “admixed.” Median levels of 25(OH)D and 3epi-25(OH)D did not differ across Q1, Q2, Q3, and “admixed” genotypes, respectively. 1,25(OH)2D levels were lower (p<0.04) between Q2 and the admixed groups, and 24,25(OH)2D levels were lower (p<0.05) between Q1 and the admixed groups. Vitamin D metabolite levels were lower in females for 25(OH)D, 1,25(OH)2D (p<0.001), and 24,25(OH)2D (p<0.006), but 3epi-25(OH)D did not differ (p<0.26). Diabetes prevalence was not different between genotypes. Total 1,25(OH)2D (p<0.001), total 24,25(OH)2D (p<0.001), and total 3epi-25(OH)D (p<0.005) were all significantly lower in diabetes patients compared to controls whilst the total 25(OH)D was higher in diabetes than controls (p<0.001). Conclusion. Whilst 25(OH)D levels did not differ between genotype groups, 1,25(OH)2D and 24,25(OH)2D were lower in the admixed group, suggesting that there are genetic differences in vitamin D metabolism that may be of importance in a population that may allow a more targeted approach to vitamin D replacement. This may be of specific importance in vitamin D replacement strategies with the Q2 genotype requiring less, and the other genotypes requiring more to increase 1,25(OH)2D. Whilst overall the group was vitamin D deficient, total 25(OH)D was higher in diabetes, but 1,25(OH)2D, 24,25(OH)2D, and 3epi-25(OH)D were lower in diabetes that did not affect the relationship to genotype.


2004 ◽  
Vol 17 (2) ◽  
pp. 241-248 ◽  
Author(s):  
James C. Fleet ◽  
Jie Hong ◽  
Zhentao Zhang

AbstractAlthough the biological requirement for vitamin D can be met by epidermal exposure to UV light, there are a number of conditions where this production does not occur or is not sufficient to meet biological needs. When this happens, vitamin D must be consumed and is a nutrient. However, two distinct observations have caused researchers to rethink certain dogma in vitamin D biology. First, it appears that in addition to the hormonally active form of 1,25 dihydroxyvitamin D (1,25(OH)2D), circulating levels of 25 hydroxyvitamin D have a critical importance for optimal human health. This and other data suggest that extra-renal production of 1,25(OH)2D contributes to Ca homeostasis and cancer prevention. Second, in addition to its role in the transcriptional activation of genes through the vitamin D receptor there is now compelling evidence that 1,25(OH)2D has a second molecular mode of action; the rapid activation of second-messenger and kinase pathways. The purpose of this second mode of action is only now being explored. The present review will discuss how these two areas are reshaping our understanding of vitamin D metabolism and action.


1987 ◽  
Vol 115 (3) ◽  
pp. 345-352 ◽  
Author(s):  
Reinhard Kaune ◽  
Johein Harmeyer

Abstract. Vitamin D metabolism was studied in the 'Hannover Pig', a strain which suffers from pseudo vitamin D-deficiency rickets, type I. Animals of this strain are known to be devoid of renal 25-hydroxyvitamin D3-1α-hydroxylase and -24-hydroxylase activities. Pigs with florid rickets and hypocalcaemia were treated with single im injections of 0.25 to 1.25 mg of vitamin D3, doses that have been shown in previous studies to be effective in producing transient healing of rachitic symptoms. The levels of vitamin D3 and its most relevant physiological metabolites in plasma were estimated at intervals before and after this vitamin D3 treatment. Vitamin D3 rose from 14.8 ± 8.1 to 364 ± 190 nmol/l (mean ± sd) 2 to 3 days post injectionem, 25-hydroxyvitamin D3 from 131.0 ± 46.2 to 1068 ± 160 nmol/l within 7 days post injectionem. The 1α,25-dihydroxyvitamin D3 concentration in plasma was elevated from 73.9 ± 25.0 to 281 ± 168 pmol/l 2 to 3 days post injectionem and declined continually from that time. 24R,25-dihydroxyvitamin D3 and 25S,26-dihydroxyvitamin D3 levels after treatment showed different responses in different animals being either elevated or unchanged. Clinical healing of the pigs with these doses of vitamin D3 was attributed to the transient rise of 1α,25-dihydroxyvitamin D3 in plasma. It was assumed that 1α,25-dihydroxyvitamin D3 synthesis takes place under these circumstances in extrarenal tissues.


1982 ◽  
Vol 204 (1) ◽  
pp. 185-189 ◽  
Author(s):  
R L Horst ◽  
J L Napoli ◽  
E T Littledike

Vitamin D-deficient pigs, rats and chicks were repleted with four daily oral doses of crystalline ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) containing equal concentrations of each. At 24 h after the last dose, the plasma of each species was analysed for vitamin D and 25-hydroxyvitamin D by standard methods. The mean (+/- S.D.) ratios of plasma cholecalciferol to ergocalciferol concentration were 1.5 +/- 0.1 (pig). 1.7 +/- 0.1 (rat) and 6.3 +/- 1.2 (chick). The mean ratios of plasma 25-hydroxycholecalciferol to 25-hydroxyergocalciferol concentration were 4.0 +/- 0.1 (pig), 0.4 +/- 0.02 (rat) and 10.7 +/- 3.4 (chick). The mean plasma cholecalciferol/ergocalciferol ratios for the 24,25-dihydroxy-, 25,26-dihydroxy- and 1,25-dihydroxy-derivatives in the pig were 2.6 +/- 0.6, 5.8 +/- 1.3 and 5.8 +/- 0.8 respectively. This is the first evidence that mammals other than the New World monkey, like birds, discriminate between ergocalciferol and cholecalciferol. These data, therefore, suggest that species discrimination between the different forms of vitamin D is probably a general phenomenon in mammals. Moreover, this is the first indication of a species (rat) that discriminates against a cholecalciferol metabolite in favour of an ergocalciferol metabolite. Species discrimination against particular forms of vitamin D may be important to the choice of experimental animal models for studying the regulation of vitamin D metabolism and may also be an important consideration in dietary vitamin supplementation.


1994 ◽  
Vol 143 (2) ◽  
pp. 367-374 ◽  
Author(s):  
T Pitcher ◽  
I N Sergeev ◽  
R Buffenstein

Abstract Vitamin D may be endogenously synthezised in the skin in the presence of sunlight or, alternatively, acquired from dietary sources. Cryptomys damarensis appear to have a naturally impoverished vitamin D status with low plasma concentrations of both 25-hydroxyvitamin D (25(OH)D; <5 ng/ml) and 1,25-dihydroxyvitamin D (1,25(OH)2D; <20 pg/ml). We attribute this to their underground habitat and herbivorous habits. We questioned whether these subterranean mammals could utilize sunlight-mediated pathways and therefore compared vitamin D metabolism and function when animals were (a) housed naturally (control), (b) given an oral vitamin D3 (D3) supplement (1 IU/g dry matter food eaten per day) and (c) exposed to 10 h of sunlight. Control animals exhibited a highly efficient apparent fractional absorption of both calcium (Ca) and inorganic phosphorus (Pi) (>90%), passive mode of intestinal mineral uptake, yet tightly regulated serum ionized calcium (Ca2+). The ratio of 25(OH)D-1α-hydroxylase (1-OHase) to 25(OH)D-24R-hydroxylase (24-OHase) activity in the kidney, corresponded with a state of vitamin D deficiency. Cryptomys damarensis responded to both oral D3 supplementation and sun exposure by an increase in plasma concentration of 1,25(OH)2D with a commensurate decline (P<0·05) in 1-OHase activity, and a resulting decrease (P<0·05) in the ratio of 1-OHase:24-OHase activity. Despite these changes, the intestinal mode of Ca uptake and plasma total Ca, Ca2+ and Pi remained unchanged with either treatment. Responses to sunlight were less pronounced than that of oral D3 supplementation. These data confirm that naturally vitamin D-deficient mole-rats can convert vitamin D to the active hormone 1,25(OH)2D, and indicate that mole-rats function optimally at the low concentrations of vitamin D metabolites found naturally. Furthermore, these animals exhibit a highly efficient vitamin D-independent mode of intestinal Ca absorption. Journal of Endocrinology (1994) 143, 367–374


1983 ◽  
Vol 104 (1) ◽  
pp. 96-102 ◽  
Author(s):  
Hitoshi Ishida ◽  
Yutaka Seino ◽  
Kinsuke Tsuda ◽  
Jiro Takemura ◽  
Sigeo Nishi ◽  
...  

Abstract. In order to investigate vitamin D metabolism in insulin-deficient diabetic rats, plasma vitamin D metabolites were measured at various periods after induction of diabetes by iv administration of 60 mg/kg streptozotocin (STZ). After STZ injection, plasma insulin was significantly decreased and plasma urea nitrogen increased with the duration of diabetes, while plasma creatinine remained unchanged. Plasma calcium, 25-hydroxyvitamin D (25(OH)D), and 24,25-dihydroxyvitamin D (24,25(OH)2D) progressively decreased. On the other hand, plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) did not change at any period, but the ratio of 1,25(OH)2D to 25(OH)D became high in proportion to the severity of hypocalcaemia. Since significantly lower 25(OH)D and 24,25(OH)2D levels were observed at the later stage of diabetes, it is suggested that the altered vitamin D metabolism in diabetes is secondary to the disturbances in metabolic homeostasis derived form the insulin deficiency.


2005 ◽  
Vol 93 (3) ◽  
pp. 299-307 ◽  
Author(s):  
Tsui-Shan Chau ◽  
Wan-Ping Lai ◽  
Pik-Yuen Cheung ◽  
Murray J. Favus ◽  
Man-Sau Wong

The responses of renal vitamin D metabolism to its major stimuli alter with age. Previous studies showed that the increase in circulating 1,25-dihydroxyvitamin D (1,25(OH)2D3) as well as renal 25-hydroxyvitamin D3 1-α hydroxylase (1-OHase) activity in response to dietary Ca or P restriction reduced with age in rats. We hypothesized that the mechanism involved in increasing circulating 1,25(OH)2D3 in response to mineral deficiency alters with age. In the present study, we tested the hypothesis by studying the expression of genes involved in renal vitamin D metabolism (renal 1-OHase, 25-hydroxyvitamin D 24-hydroxylase (24-OHase) and vitamin D receptor (VDR)) in young (1-month-old) and adult (6-month-old) rats in response to low-phosphate diet (LPD). As expected, serum 1,25(OH)2D3 increased in both young and adult rats upon LPD treatment and the increase was much higher in younger rats. In young rats, LPD treatment decreased renal 24-OHase (days 1–7, P<0·01) and increased renal 1-OHase mRNA expression (days 1–5, P<0·01). LPD treatment failed to increase renal 1-OHase but did suppress 24-OHase mRNA expression (P<0·01) within 7 d of LPD treatment in adult rats. Renal expression of VDR mRNA decreased with age (P<0·001) and was suppressed by LPD treatment in both age groups (P<0·05) Feeding of adult rats with 10 d of LPD increased 1-OHase (P<0·05) and suppressed 24-OHase (P<0·001) as well as VDR (P<0·05) mRNA expression. These results indicate that the increase in serum 1,25(OH)2D3 level in adult rats during short-term LPD treatment is likely to be mediated by a decrease in metabolic clearance via the down-regulation of both renal 24-OHase and VDR expression. The induction of renal 1-OHase mRNA expression in adult rats requires longer duration of LPD treatment than in younger rats.


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