scholarly journals Characteristics of Serum Ratios of 1,25-Dihydroxyvitamin D to 25-Hydroxyvitamin D for Assessment of Bone Metabolism

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A272-A273
Author(s):  
Koichiro Yamamoto ◽  
Manami Fujita ◽  
Hiroyuki Honda ◽  
Yoshihisa Hanayama ◽  
Kazuki Tokumasu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Metabolism ◽  
Active Form ◽  
The Body ◽  
Ultraviolet B ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Gender Specific

Abstract Vitamin D is obtained in the body by food intake or by production from 7-dehydrocholesterol by exposure of the skin to ultraviolet B radiation. It is first metabolized in the liver to 25-hydroxyvitamin D (25D), which is a major circulating metabolite. In the kidney, 25D is subsequently metabolized to the hormonally active form, 1,25-dihydroxyvitamin D (1,25D), via 1α-hydroxylase encoded by the CYP27B1 gene. 1,25D has a cellular effect through the vitamin D receptor, which leads to calcium absorption in the gut, bone metabolism, and parathyroid function. A recent study showed that a low vitamin D status is common worldwide and is associated with various diseases including kidney, heart, and liver failure, secondary hyperparathyroidism, osteomalacia, inflammatory bowel disease, granuloma-forming disorders (sarcoidosis and tuberculosis), and cancer. Vitamin D deficiency also increases the risks of falls, fractures, bone loss, sarcopenia, leading to worse outcomes of illness severity, morbidity, and mortality. The 1,25D/25D ratio is considered to be a useful tool for diagnosis of ocular sarcoidosis; however, its clinical utility and relevance to pathophysiology of evaluation of the ratio 1,25D/25D which indicates vitamin D activation have remained unknown. To clarify the clinical usefulness of markers for vitamin D activation, 87 patients in whom serum 25D and 1,25D level was measured were retrospectively reviewed in the present study. Data for 79 patients (33 males and 46 females) were analyzed after exclusion of 8 patients taking vitamin D. The median serum 1,25D/25D ratio was significantly lower in males than in females: 4.1 (IQR: 2.3–5.8) x 10−3 versus 6.8 (3.0–9.8) x 10−3. However, individual levels of 25D and 1,25D were not different in males and females. The major categories of main disorders were endocrine (30.6 %), inflammatory (18.5 %), and bone-related (16.7 %) disorders. The ratios of serum 1,25D/25D had significant negative correlations with femoral dual energy X-ray absorptiometry % young adult mean (DEXA %YAM) (R=-0.35) and lumbar DEXA %YAM (R=-0.32). Significant correlations were found between 1,25D/25D ratio and serum levels of inorganic phosphate (R=-0.34), intact parathyroid hormone (R=0.64) and alkaline phosphatase (R=0.46) in all patients. Of interest, the 1,25D/25D ratio had gender-specific characteristics: the ratio had a significant correlation with age in males (R=0.49), while it had a significant correlation with body mass index (BMI) in females (R=0.34). Collectively, the results revealed that the ratio of serum 1,25D/25D as a marker for activation of vitamin D had relevance to clinical parameters, especially bone turnover, with gender-specific features. It is suggested that the existence of a gender-specific difference of aging males and obese females regarding the activation of vitamin D that is functionally linked to bone metabolism.

scholarly journals Vitamin D Regulation, Metabolism, AndFunction

2020 ◽  
Author(s):  
MARINA GERGES
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Uv Light ◽  
The Body ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
A Cell ◽  
25 Hydroxyvitamin D ◽  
Made In

Interest in vitamin D has dramatically increased over the past several decades. From the beginning, vitamin D was incorrectly named a vitamin when later it was discovered to be a member of the steroid hormone family. Over time, the vitamin D receptor was discovered along with its major circulating form, 25-hydroxyvitamin D, and its the hormonal ligand, 1,25-dihydroxyvitamin D. Classically, vitamin D was known to be important for enhancing intestinal absorption of calcium; however, interest grew in vitamin D when it was determined that vitamin D may be utilized by other tissues of the body. Vitamin D3 is made in the skin from 7-dehydrocholesterol under the influence of UV light. Vitamin D2 (ergocalciferol) is derived from the plant sterol ergosterol. Vitamin D is metabolized first to 25 hydroxyvitamin D (25OHD), then to the hormonal form 1,25- dihydroxyvitamin D (1,25(OH)2D). CYP2R1 is the most important 25-hydroxylase; CYP27B1 is the key 1-hydroxylase. Both 25OHD and 1,25(OH)2D are catabolized by CYP24A1. 1,25(OH)2D is the ligand for the vitamin D receptor (VDR), a transcription factor, binding to sites in the DNA called vitamin D response elements (VDREs). There are thousands of these binding sites regulating hundreds of genes in a cell-specific fashion. VDR-regulated transcription is dependent on modulators, the profile of which is also cell-specific. Analogs of 1,25(OH)2D are being developed to target specific diseases with minimal side effects.(Bikle , 2014)

scholarly journals Deficient Mineralization of Intramembranous Bone in Vitamin D-24-Hydroxylase-Ablated Mice Is Due to Elevated 1,25-Dihydroxyvitamin D and Not to the Absence of 24,25-Dihydroxyvitamin D*

Endocrinology ◽  
2000 ◽  
Vol 141 (7) ◽  
pp. 2658-2666 ◽  
Author(s):  
René St-Arnaud ◽  
Alice Arabian ◽  
Rose Travers ◽  
Frank Barletta ◽  
Mihali Raval-Pandya ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Receptor Gene ◽  
Active Form ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Physiological Importance ◽  
1,25 Dihydroxyvitamin D ◽  
Intramembranous Bone ◽  
25 Hydroxyvitamin D

The 25-hydroxyvitamin D-24-hydroxylase enzyme (24-OHase) is responsible for the catabolic breakdown of 1,25-dihydroxyvitamin D[ 1,25(OH)2D], the active form of vitamin D. The 24-OHase enzyme can also act on the 25-hydroxyvitamin D substrate to generate 24,25-dihydroxyvitamin D, a metabolite whose physiological importance remains unclear. We report that mice with a targeted inactivating mutation of the 24-OHase gene had impaired 1,25(OH)2D catabolism. Surprisingly, complete absence of 24-OHase activity during development leads to impaired intramembranous bone mineralization. This phenotype was rescued by crossing the 24-OHase mutant mice to mice harboring a targeted mutation in the vitamin D receptor gene, confirming that the elevated 1,25(OH)2D levels, acting through the vitamin D receptor, were responsible for the observed accumulation of osteoid. Our results confirm the physiological importance of the 24-OHase enzyme for maintaining vitamin D homeostasis, and they reveal that 24,25-dihydroxyvitamin D is a dispensable metabolite during bone development.

scholarly journals Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment

2016 ◽  
Vol 37 (5) ◽  
pp. 521-547 ◽  
Author(s):  
Peter J. Tebben ◽  
Ravinder J. Singh ◽  
Rajiv Kumar
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Active Form ◽  
Elevated Serum ◽  
Diagnosis And Treatment ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Stone Formers ◽  
25 Hydroxyvitamin D

AbstractHypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.

Responses of serum calcium and phosphorus in the frog Rana tigrina to injection of various vitamin D analogs

1987 ◽  
Vol 65 (8) ◽  
pp. 2111-2112 ◽  
Author(s):  
Ajai K. Srivastav ◽  
L. Rani ◽  
K. Swarup
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Vitamin D Analogs ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Rana Tigrina ◽  
Calcium Deposits ◽  
25 Hydroxyvitamin D ◽  
Calcium And Phosphorus

Intraperitoneal injections of either vitamin D3 (4 IU/100 g body wt.), 25 hydroxyvitamin D3 (100 ng/100 g body wt.), or 1,25 dihydroxyvitamin D3 (100 ng/100 g body wt.) for 15 days induced hypercalcemia, hyperphosphatemia, and depletion of calcium deposits in the paravertebral lime sacs in an anuran, Rana tigrina.

Cyclosporin a and Vitamin D Metabolism: Studies in Patients with Psoriasis and in Rats

1994 ◽  
Vol 86 (5) ◽  
pp. 627-632 ◽  
Author(s):  
A. J. Shaw ◽  
M. E. Hayes ◽  
M. Davies ◽  
B. D. Edwards ◽  
F. W. Ballardie ◽  
...  
Keyword(s):  
Vitamin D ◽  
Synovial Fluid ◽  
Cyclosporin A ◽  
Severity Index ◽  
Hydroxylase Activity ◽  
Local Synthesis ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

1. Cyclosporin A, an immunosuppressive drug used to treat psoriasis, stimulates renal synthesis of 1,25-dihydroxyvitamin D in rats. 1,25-Dihydroxy vitamin D can also reduce the activity of psoriasis, and in the present study we have examined the possibility that cyclosporin A mediates some of its actions in psoriasis by renal or extra-renal production of 1,25-dihydroxyvitamin D. 2. Treatment of 12 psoriatic patients with cyclosporin A (5 mg day−1 kg−1) for 3 months significantly improved the psoriasis activity and severity index and reduced glomerular filtration rate, but serum 1,25-dihydroxyvitamin D levels were not changed. However, 1–3 months after stopping cyclosporin A treatment, an increase in the psoriasis activity and severity index score was accompanied by a small, but significant, increase in serum 1,25-dihydroxyvitamin D concentration. Plasma 1,25-dihydroxyvitamin D levels in rats gavaged with cyclosporin A (15 mg day−1 kg−1 for 2 weeks) were significantly increased compared with controls, but a lower dose of cyclosporin A (2.4 mg day−1 kg−1) had no effect. Renal 25-hydroxyvitamin D-24-hydroxylase activity in rat kidney homogenates was not different between control and cyclosporin A-treated rats. Renal 25-hydroxyvitamin D-1α-hydroxylase activity was not detectable in these homogenates. Extra-renal production of 1,25-dihydroxyvitamin D by activated macrophages isolated from the synovial fluid of patients with inflammatory arthritis was reduced after incubation with cyclosporin A (0.1–10 μmol/l) for 30 h or 5 days. 3. It is unlikely that alteration of circulating 1,25-dihydroxyvitamin D concentration is one of the modes of action of cyclosporin A in psoriasis. Since cyclosporin A inhibits 1,25-dihydroxyvitamin D production by activated synovial fluid macrophages, it is unlikely that cyclosporin A mediates some of its therapeutic actions by local synthesis of 1,25-dihydroxyvitamin D within the psoriatic lesion.

Vitamin D and Calcitonin Treatment in Patients with Femoral Neck Fracture: A Prospective Controlled Clinical Study

1989 ◽  
Vol 17 (3) ◽  
pp. 226-242 ◽  
Author(s):  
E. Harju ◽  
R. Punnonen ◽  
R. Tuimala ◽  
J. Salmi ◽  
I. Paronen
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Serum Levels ◽  
Serum Calcitonin ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Age Related ◽  
Neck Fracture ◽  
25 Hydroxyvitamin D

The effects on general and bone metabolism of femoral neck fracture patients of 0.25 μg α-calcoid given orally twice daily ( n=9) and 25 μg calcitonin given subcutaneously 30 times ( n=10) in 10 weeks were studied against a control ( n=ll). Bone histology and histomorphometry showed non-age related osteoporosis in 30% and osteomalacia in 22% of the patients studied. Impaired serum vitamin D status was found in 47 – 88% of patients, secondary hyperparathyroidism and increased serum parathyroid hormone in 59% and decreased serum calcitonin levels in 69%. On histology, normal findings and non-age related osteoporosis on histology were associated with low serum levels of 25-hydroxyvitamin D3,1,25- and 24,25-dihydroxy vitamin D3. Very high serum levels of 1,25-dihydroxyvitamin D3 and low levels of 25-hydroxyvitamin D3 occurred in fracture patients with osteomalacia. Calcitonin improved calcium balance, reduced osteoporosis and increased the serum 1,25- and 24,25-dihydroxyvitamin D3 levels but had no effect on osteomalacia. Vitamin D reduced osteomalacia, slightly increased the serum 1,25-dihydroxyvitamin D3 concentration and decreased serum levels of parathyroid hormone. Both treatments gave a similar slight decrease in serum calcitonin concentrations. A mechanism of action for the treatments is suggested.

1α-Hydroxyvitamin D3 Treatment of Three Patients With 1,25-Dihydroxyvitamin D-Receptor-Defect Rickets and Alopecia

PEDIATRICS ◽  
1987 ◽  
Vol 80 (1) ◽  
pp. 97-101
Author(s):  
E. Takeda ◽  
Y. Kuroda ◽  
T. Saijo ◽  
E. Naito ◽  
H. Kobashi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Lactate ◽  
Type Ii ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

Three patients with clinically different severities of vitamin D-dependent rickets, type II, with alopecia, which is 1,25-dihydroxyvitamin D-receptor-defect rickets and is particularly resistant to treatment with calciferol analogues, were treated with large doses of lα-hydroxyvitamin D3 (1α-(OH)D3) and 2 g of calcium lactate. Except for the alopecia, all of the abnormalities of patients 1 and 2 were reversed by treatment with 3 µg/kg/d of 1α-(OH)D3, and those of patient 3, who had the severest manifestations, were reversed by treatment with 6 µg/kg/d. The serum 24,25-dihydroxyvitamin D concentrations of the three patients were low before treatment and those of patients 1 and 2 increased during treatment. These findings suggest that in patients 1 and 2, 25-hydroxyvitamin D-24-hydroxylase was stimulated via a 1,25-dihydroxyvitamin D-receptor-mediated system by treatment with 1α-(OH)D3.

Simultaneous determination of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D in plasma or serum.

1981 ◽  
Vol 27 (10) ◽  
pp. 1757-1760 ◽  
Author(s):  
M J Jongen ◽  
W J van der Vijgh ◽  
H J Willems ◽  
J C Netelenbos ◽  
P Lips
Keyword(s):  
Vitamin D ◽  
Vitamin D Metabolites ◽  
Binding Assays ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Extraction And Purification ◽  
Chromatographic Procedure ◽  
25 Hydroxyvitamin D ◽  
Liquid Chromatographic

Abstract We describe a simultaneous assay for the principal vitamin D metabolites: 25-hydroxyvitamin D, 24-25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D. Special attention has been paid to simplification of the extensive extraction and purification procedures used in previously described simultaneous assays. All three metabolites were isolated with a single extraction step, followed by only one gradient liquid-chromatographic procedure. For final quantitation we used competitive protein binding assays, involving readily available binding proteins and commercially purchased tritiated vitamin D metabolites. Concentrations in the plasma of healthy subjects (mean age, 27 years), sampled during December were 51 (SD 17) nmol/L, 4.1 (SD 1.3) nmol/L, and 124 (SD 26) pmol/L for 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D, respectively. Intra- and interassay CVs for the three metabolites were 4.4 and 3.9%, 6.7 and 8.0%, and 7.0 and 4.8%, respectively.

Determinants of the serum concentration of 1,25-dihydroxyvitamin D in primary hyperparathyroidism

1989 ◽  
Vol 76 (1) ◽  
pp. 81-86 ◽  
Author(s):  
B. C. Lalor ◽  
E. B. Mawer ◽  
M. Davies ◽  
G. A. Lumb ◽  
L. Hunt ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Concentration ◽  
Primary Hyperparathyroidism ◽  
Serum Concentrations ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Relevant Variables ◽  
Biological Determinants ◽  
25 Hydroxyvitamin D

1. The serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 44 patients with primary hyperparathyroidism. 2. In 14 patients the serum concentration of 1,25-dihydroxyvitamin D was greater than normal (142–337 pmol/l). One patient had a subnormal concentration of 1,25-dihydroxyvitamin D (36 pmol/l) but no other evidence of vitamin D deficiency. 3. The possible biological determinants of the serum concentration of 1,25-dihydroxyvitamin D were sought by multivariate analysis of relevant variables. The serum concentration of 1,25-dihydroxyvitamin D was found to be significantly and positively correlated with the serum concentrations of 25-hydroxyvitamin D (P < 0.001) and parathyroid hormone (P < 0.003), and with the glomerular filtration rate (P < 0.03), and negatively correlated with the serum concentrations of calcium (P < 0.02) and phosphate (P = 0.055) (multiple R = 0.638,P < 0.002). 4. In primary hyperparathyroidism the major determinant of serum 1,25-dihydroxyvitamin D is the availability of precursor 25-hydroxyvitamin D. 5. The finding that serum 1,25-dihydroxyvitamin D is commonly normal in patients with primary hyperparathyroidism despite an adequate state of vitamin D nutrition, can be explained in terms of the constraining influences of hypercalcaemia and variable degrees of renal dysfunction on the biosynthesis of 1,25-dihydroxyvitamin D.

scholarly journals Reshaping the way we view vitamin D signalling and the role of vitamin D in health

2004 ◽  
Vol 17 (2) ◽  
pp. 241-248 ◽  
Author(s):  
James C. Fleet ◽  
Jie Hong ◽  
Zhentao Zhang
Keyword(s):  
Vitamin D ◽  
Transcriptional Activation ◽  
Mode Of Action ◽  
Uv Light ◽  
Active Form ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Molecular Mode

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.

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