Active Vitamin D (1,25-Dihydroxyvitamin D) and Bone Health in Middle-Aged and Elderly Men: The European Male Aging Study (EMAS)

Abstract. The parathyroid gland possesses receptors for 1,25-dihydroxyvitamin D3, the active metabolite of the vitamin D system, and in vitro experiments have shown that 1,25-dihydroxyvitamin D3 can inhibit the secretion of PTH. In this study 31 subjects who had displayed persistent mild hypercalcemia for 14 years and presumably had mild primary hyperparathyroidism (HPT) were challenged with 1.0 μg alphacalcidol (1α-(OH)-vitamin D3) over 6 months in a double-blind, placebo-controlled study. Before initiation of therapy, the hyperparathyroid subjects showed lower serum levels of 1,25-dihydroxyvitamin D in relation to PTH or calcium when compared with age- and sex-matched controls. Treatment induced a slight rise in serum calcium (0.05 mmol/l), but no significant decrease of the PTH levels. Eighteen of the subjects thereafter entered an open study with a higher dose of alphacalcidol (2.0 μg) over 1 year. Although this high dose induced a marked rise in serum calcium (0.17 mmol/l), there was only a transient reduction of the PTH levels. Thus, during long-term condition there was an escape from the suppressive action of the elevated calcium concentrations and no evidence of a specific inhibition of PTH secretion by a small oral dose of active vitamin D.

Download Full-text

Impact of Chrysin on Vitamin D and Bone Health - Preclinical Studies

10.1101/2020.11.19.390757 ◽

2020 ◽

Author(s):

Siva Swapna Kasarla ◽

Sujatha Dodoala ◽

Sunitha Sampathi ◽

Narendra Kumar Talluri

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Bone Health ◽

Low Dose ◽

Active Vitamin ◽

Deficient Diet ◽

Bone Parameters ◽

Active Vitamin D ◽

Vitamin D Levels ◽

The Impact

AbstractVitamin D deficiency is an endemic problem existing worldwide. Although several strategies were established to enhance vitamin D3 levels, studies specifically focussing inhibition of vitamin D metabolism which may prolong the availability of active vitamin D in pathological conditions are less explored. Studies also suggest that higher doses of vitamin D3 fail to achieve optimum vitamin D levels. In this context, we focussed on the enzyme CYP3A4 which promotes inactivation of active vitamin D. The current study was aimed to decipher the impact of chrysin, a proven CYP3A4 inhibitor as an intervention and its effects in combination with low dose vitamin D3 (40 IU) and bone health in vitamin D deficiency condition. The in-vivo activity of chrysin was evaluated on female Wistar albino rats fed with a vitamin D deficient diet to attain vitamin D deficiency for 28 days. Chrysin was given alone and in combination with calcium carbonate (CaCO3) and/or vitamin D3. All the therapeutic interventions were assessed for serum 25-OH-D3 by LC-MS, biochemical, urinary, and bone parameters. Animals treated with chrysin alone and in combination with low dose vitamin D3 and/or CaCO3 showed an eminent rise in serum 25-OH-D3 levels along with increased serum biochemical parameters. On contrary, a significant decrease in the urinary parameters followed by beneficial effects on bone parameters was noticed in contrast with the vitamin D deficient diet group. Our findings revealed that although chrysin alone showed a notable effect on 25-OH-D3 and osseous tissue, comparatively it showed intensified therapeutic effect in combination with vitamin D3 and CaCO3 which can be employed as a cost-effective option to improve bone health.Graphical Abstract

Download Full-text

Long-term vitamin D deficiency promotes renal fibrosis and functional impairment in middle-aged male mice

British Journal Of Nutrition ◽

10.1017/s0007114520003232 ◽

2020 ◽

pp. 1-10

Author(s):

Zhi-Hui Zhang ◽

Biao Luo ◽

Shen Xu ◽

Zhi-Cheng Zhang ◽

Wei-Yang Xing ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Functional Impairment ◽

Renal Fibrosis ◽

Male Mice ◽

Middle Aged ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Middle Aged Male

Abstract Renal fibrosis is common especially in the elderly population. Recently, we found that vitamin D deficiency caused prostatic hyperplasia. This study aimed to investigate whether vitamin D deficiency promotes renal fibrosis and functional impairment. All mice except controls were fed with vitamin D-deficient (VDD) diets, beginning from their early life. The absolute and relative kidney weights on postnatal week 20 were decreased in VDD diet-fed male pups but not in female pups. A mild pathological damage was observed in VDD diet-fed male pups but not in females. Further analysis showed that VDD-induced pathological damage was aggravated, accompanied by renal dysfunction in 40-week-old male pups. An obvious collagen deposition was observed in VDD diet-fed 40-week-old male pups. Moreover, renal α-smooth muscle actin (α-SMA), a marker of epithelial–mesenchymal transition (EMT), and Tgf-β mRNA were up-regulated. The in vitro experiment showed that 1,25-dihydroxyvitamin D3 alleviated transforming growth factor-β1 (TGF-β1)-mediated down-regulation of E-cadherin and inhibited TGF-β1-evoked up-regulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25-dihydroxyvitamin D3 suppressed TGF-β1-evoked Smad2/3 phosphorylation in HK-2 cells. These results provide experimental evidence that long-term vitamin D deficiency promotes renal fibrosis and functional impairment, at least partially, through aggravating TGF-β/Smad2/3-mediated EMT in middle-aged male mice.

Download Full-text

Pharmacotherapy in chronic kidney disease hyperphosphatemia – effects on vascular calcification and bone health

Macedonian Pharmaceutical Bulletin ◽

10.33320/maced.pharm.bull.2017.63.01.001 ◽

2017 ◽

Vol 63 (01) ◽

pp. 3-24

Author(s):

Dimce Dzingarski ◽

Kristina Mladenovska

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Kidney Disease ◽

Bone Health ◽

Mineral Metabolism ◽

Phosphate Binders ◽

Active Vitamin ◽

Bone Disorders ◽

Active Vitamin D ◽

Active Vitamin D Sterols

Hyperphosphatemia (HP) in patients with chronic kidney disease (CKD) leads to complications such as renal osteodistrophy, cardiovascular calcification and hemodynamic abnormalities, all of them having a serious impact on the survival rate and quality of life. Also, HP is a key pathogenic factor in the development of secondary hyperparathyroidism (SHPT) in CKD. Having in regard the significance of controlling serum phosphorus levels (Pi), in this paper, the needs and obstacles to successful pharmacological management of HP in CKD are presented, with an overview of major classes of phosphate binders (PBs) and other drugs affecting Pi level, such as active vitamin D sterols and calcimimetics (CMs). In addition, their effects on progression of cardiovascular calcification and bone health are elaborated. In this regard, a PubMed search was carried out to capture all abstracts and articles relevant to the topic of CKD, HP and mineral metabolism, bone disorders and vascular/valvular calcification (VC), published from January 2007 to August 2017. The search was limited to English language, with the search terms including drug name AND hyperphosphatemia or cardiovascular calcification or bone disorder. Comparative studies, clinical studies/trials and meta-analyses related to different classes/representatives of PBs, vitamin D analogues and CMs were reviewed and research data related to their efficacy and safety compared. Keywords: chronic kidney disease, hyperphosphatemia, phosphate binders, active vitamin D sterols, calcimimetics, bone disorders, cardiovascular calcification

Download Full-text

Age-dependent variations in serum 1,25-dihydroxyvitamin D in childhood

Acta Endocrinologica ◽

10.1530/acta.0.0940426 ◽

1980 ◽

Vol 94 (3) ◽

pp. 426-429 ◽

Cited By ~ 34

Author(s):

Bjarne Lund ◽

Niels Clausen ◽

Birger Lund ◽

Else Andersen ◽

Ole H. Sørensen

Keyword(s):

Vitamin D ◽

Growth Velocity ◽

Growth And Development ◽

Biologically Active ◽

Active Vitamin ◽

Physiological Factor ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Age Dependent ◽

Regulation Of Growth

Abstract. Circulating 1,25-dihydroxyvitamin D (1,25-(OH)2D) was measured in 87 children aged 3 months to 15 years, and in 11 adolescents 16–19 years of age. A positive correlation to growth velocity was observed, indicating that the biologically active vitamin D metabolite is an important physiological factor in the regulation of growth and development of the skeleton.

Download Full-text

Relationship between 1,25-Dihydroxyvitamin D and Body Composition in Middle-Aged Sedentary Adults: The FIT-AGEING Study

Nutrients ◽

10.3390/nu11112567 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2567 ◽

Cited By ~ 1

Author(s):

Alejandro De-la-O ◽

Lucas Jurado-Fasoli ◽

Manuel J. Castillo ◽

Luis Gracia-Marco ◽

Ángel Gutierrez ◽

...

Keyword(s):

Vitamin D ◽

Body Composition ◽

Body Mass ◽

Fat Body ◽

Middle Aged ◽

Mineral Density ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Wide Range ◽

Fat Body Mass

Vitamin D deficiency is a worldwide health problem that, in addition to its well-known negative effects on musculoskeletal health, has been related to a wide range of acute and chronic age-related diseases. However, little is known about the association of body composition with the active, hormonal form of vitamin D, 1,25-dihydroxyvitamin D plasma levels (1,25(OH)2D). Therefore, the aim of this study was to investigate the association of 1,25(OH)2D with body composition including lean and fat body mass as well as bone mineral density (BMD) in middle-aged sedentary adults. A total of 73 (39 women) middle-aged sedentary adults (53.7 ± 5.1 years old) participated in the current study. We measured weight and height, and we used dual energy X-ray absorptiometry to measure lean body mass, fat body mass and BMD. Body mass index (BMI), lean mass index (LMI), and fat mass index (FMI) were calculated. 1,25(OH)2D was measured using a DiaSorin Liaison® immunochemiluminometric analyzer. The results showed a negative association of 1,25(OH)2D with BMI, LMI and BMD (β = −0.274, R2 = 0.075, p = 0.019; β = −0.268, R2 = 0.072, p = 0.022; and β = −0.325, R2 = 0.105, p = 0.005, respectively), which persisted after controlling for age and sex. No significant differences in 1,25(OH)2D across body weight status were observed after controlling for the same covariates. In summary, our results suggest that 1,25(OH)2D could be negatively associated with BMI, LMI and BMD whereas no association was found with FMI in middle-aged sedentary adults.

Download Full-text

A Vitamin D3 Steroid Hormone in the Calcinogenic Grass Trisetum flavescens

Zeitschrift für Naturforschung C ◽

10.1515/znc-1987-0417 ◽

1987 ◽

Vol 42 (4) ◽

pp. 430-434 ◽

Cited By ~ 3

Author(s):

W. A. Rambeck ◽

H. Weiser ◽

H. Zucker

Keyword(s):

Vitamin D ◽

Soft Tissue ◽

Steroid Hormone ◽

Vitamin D Metabolites ◽

Soft Tissue Calcification ◽

Active Vitamin ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Synthetic Vitamin ◽

Physiological Regulator

Abstract The grass Trisetum flavescens (golden oat grass, Goldhafer) causes soft tissue calcification in cattle and in sheep. The calcinogenic principle of the plant is the active vitamin D steroid hormone 1,25-Dihydroxyvitamin D3, the major physiological regulator of calcium homeostasis in higher animals. From comparison with synthetic vitamin D metabolites in different bioassays, it is concluded that T. flavescens contains the 25-glucoside of 1,25(OH)2D3. This compound, or rather the 1,25(OH)2D3 liberated by ruminal fluid, is the calcinogenic factor of the grass.

Download Full-text