Effects of vitamin D replacement therapy on serum FGF23 concentrations in vitamin D-deficient women in short term

ObjectiveFibroblast growth factor 23 (FGF23), a phosphatonin, inhibits renal phosphate reabsorption and suppresses 1-α hydroxylase activity. Calcitriol stimulates FGF23 synthesis in bone. We aimed to determine the effect of vitamin D replacement therapy on serum FGF23 concentrations in vitamin D-deficient women and to compare the FGF23 concentrations of vitamin D-deficient patients with healthy subjects and patients with genetically determined hypophosphatemic rachitis.Design and methodsThe study group was composed of vitamin D-deficient females (n=18, mean age 29.1±9.9 years), vitamin D-sufficient healthy females (control group;n=19, mean age 28.5±5.2 years), and patients with genetically determined hypophosphatemic rachitis (n=13, mean age 26.5±15.1 years). The groups were compared for serum FGF23, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), calcium, phosphate, bone turnover markers, intact parathyroid hormone (PTH), and urinary excretion of calcium and phosphate. The vitamin D-deficient group was re-evaluated after a standard treatment regimen.ResultsSerum FGF23 concentrations were significantly lower in vitamin D-deficient patients than in vitamin D-sufficient women and hypophosphatemic rachitis group. Serum FGF23 and phosphate concentrations further decreased significantly during replacement of vitamin D (P<0.05). A significant negative correlation was evident between FGF23 and PTH before vitamin D replacement in the patients (r=−0.469,P<0.05).ConclusionDecreased FGF23 concentrations, which further decline during vitamin D replacement therapy, may have favorable action on bone mineralization by counterregulatory effect on phosphate homeostasis. Lower 1,25(OH)2D concentrations at baseline and hypophosphatemia during treatment may have dominating effects on FGF23 concentrations in vitamin D deficiency, leading to decreased FGF23 concentrations at baseline and during replacement therapy.

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The role of vitamin D replacement therapy in serum FGF23 concentration in children with myelomeningocele compared with healthy children – a preliminary study

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2018-0509 ◽

2019 ◽

Vol 32 (11) ◽

pp. 1259-1264

Author(s):

Joanna Bagińska ◽

Alicja Liszewska ◽

Agata Korzeniecka-Kozerska

Keyword(s):

Vitamin D ◽

Replacement Therapy ◽

Vitamin D3 ◽

Fibroblast Growth Factor 23 ◽

Control Group ◽

Healthy Children ◽

Vitamin D Metabolism ◽

Pathologic Fractures ◽

Vitamin D Levels ◽

Fgf23 Concentration

Abstract Background Fibroblast growth factor 23 (FGF23) is a recently discovered bone-derived regulator of vitamin D metabolism and phosphate homeostasis. It inhibits phosphate reabsorption and calcitriol production by the kidney. Myelomeningocele (MMC) remains the most severe form of neural tube defects involving serious locomotor disability, osteoporosis and pathologic fractures. We aimed to investigate the influence of vitamin D replacement therapy on serum FGF23 concentration in children with MMC and compare the results with healthy participants. Methods This prospective analysis was conducted on 16 children with MMC and 20 healthy children. Serum FGF23 levels were measured; for the studied group, before and after vitamin D replacement therapy with cholecalciferol (vitamin D3). The children’s medical charts were analyzed to determine age, sex, anthropometric measurements, calcium and phosphate, cholecalciferol and renal function parameters. Results There were significant differences in vitamin D and FGF23 serum concentrations between the studied groups. The median vitamin D levels in the MMC group increased during replacement therapy (7 vs. 18.5 ng/mL, p = 0.29) in comparison to the median of 25.5 ng/mL in the control group. In MMC children we found a significant decrease in median serum FGF23 after vitamin D replacement therapy (from 42.1 to 0 RU/mL, p < 0.001). FGF23 correlated positively with albumin, serum and urine phosphate levels and negatively with alkaline phosphatase. Conclusions 1. Serum concentration of FGF-23 is increased in MMC children in comparison to a healthy control group. 2. Vitamin D replacement therapy decreases FGF23 concentrations in MMC children, although further studies are still warranted to gain detailed insight on the FGF23 in the MMC population. 3. Children with MMC present vitamin D deficiency. Nutrition supplemented with low doses of cholecalciferol (vitamin D3) (intakes reaching recommended daily allowances) was insufficient to correct 25(OH)-D level in that population of patients.

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Metabolism of vitamin D in patients with primary biliary cirrhosis and alcoholic liver disease

Clinical Science ◽

10.1042/cs0690561 ◽

1985 ◽

Vol 69 (5) ◽

pp. 561-570 ◽

Cited By ~ 42

Author(s):

E. Barbara Mawer ◽

H. J. Klass ◽

T. W. Warnes ◽

Jacqueline L. Berry

Keyword(s):

Vitamin D ◽

Liver Disease ◽

Primary Biliary Cirrhosis ◽

Alcoholic Liver Disease ◽

Vitamin D3 ◽

Control Group ◽

Biliary Cirrhosis ◽

Vitamin D2 ◽

Dihydroxyvitamin D3 ◽

Poor Renal Function

1. The metabolism of isotopically labelled vitamin D2 and D3 has been investigated in eight patients with primary biliary cirrhosis and in five controls. The concentration of labelled vitamin D2 was lower than that of vitamin D3 in serum of patients with primary biliary cirrhosis on days 1 and 2 after intravenous injection (P < 0.005 and P < 0.05, respectively) but no difference was seen in controls. 2. Similar amounts of labelled 25-hydroxyvitamin D2 and D3 were seen in serum of the control group; the same pattern was observed in the primary biliary cirrhosis group, and no significant differences were observed between the two groups. 3. In both control and primary biliary cirrhosis groups, the serum concentration of labelled 24,25-dihydroxyvitamin D2 exceeded that of 24,25-dihydroxyvitamin D3 (significant for controls on day 2, P < 0.02) but concentrations in the two groups were not different. 4. Concentrations of labelled 25,26-dihydroxyvitamin D3 were significantly higher than those of 25,26-dihydroxyvitamin D2 in the primary biliary cirrhosis group at all times and in the control group on days 2 and 3. Both 25,26-dihydroxyvitamin D2 and D3 were higher in the serum of patients with primary biliary cirrhosis than in controls (significant on day 1, P < 0.05). 5. Urinary excretion over days 0–3 of radioactivity from both vitamins D2 and D3 was significantly higher in the primary biliary cirrhosis group than in controls: 12.03 vs 1.80% for vitamin D2 and 8.98 vs 1.76% for vitamin D3(P < 0.005). Vitamin D2-derived urinary radioactivity in primary biliary cirrhosis correlated strongly with serum bilirubin (P = 0.005). 6. The metabolism of labelled vitamin D3 was studied in seven patients with alcoholic liver disease, three of whom showed low serum concentrations of labelled 25-hydroxyvitamin D3 suggesting impaired hepatic synthesis. The 25-hydroxylation response was quantified as the relative index of 25-hydroxylation and was significantly related to two other indices of liver function. It is concluded that impaired 25-hydroxylation of vitamin D may occur in alcoholic liver disease and results from hepatocellular dysfunction. 7. Less than the predicted amounts of 1,25-dihydroxyvitamin D3 were produced in four of the seven patients with alcoholic liver disease; this defect may be attributable in part to decreased precursor 25-hydroxyvitamin D and to poor renal function.

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The Effect of Vitamin D and Its Metabolites on Fracture Repair in Chicks

Clinical Science ◽

10.1042/cs0650429 ◽

1983 ◽

Vol 65 (4) ◽

pp. 429-436 ◽

Cited By ~ 23

Author(s):

S. Dekel ◽

R. Salama ◽

S. Edelstein

Keyword(s):

Vitamin D ◽

Bone Formation ◽

Vitamin D3 ◽

Fracture Repair ◽

Control Group ◽

Clinical Implications ◽

Torsional Stress ◽

Active Vitamin ◽

Dihydroxyvitamin D3 ◽

24,25 Dihydroxyvitamin D3

1. One-day-old chicks were depleted of vitamin D. At 3 weeks their right tibiae, and those of a control group given vitamin D3, were fractured and pinned. After fracture the controls were kept on vitamin D3. Another group was left vitamin D-deficient. The remaining depleted chicks, divided into four groups, were given vitamin D3, 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or a combination of 24,25(OH)2D3 and 1,25(OH)2D3. 2. The callus obtained after 9 and 14 days was subjected to torsional stress. The callus of chicks given vitamin D continuously showed the greatest resistance, whereas that of vitamin D-deficient chicks showed the smallest resistance. Repletion with either vitamin D3 or its metabolites increased the strength of the callus. Repletion with the combination of 24,25(OH)2D3 and 1,25(OH)2D3 produced the most marked results, in that the callus was even stronger than that of chicks replete with vitamin D3. 3. It is concluded that 24,25(OH)2D3 is essential for bone formation in addition to the known active vitamin D metabolite 1,25(OH)2D3, and the possible clinical implications of these findings are discussed.

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P0299EVALUATION OF THE CORRELATION BETWEEN VITAMIN D LEVELS AND THROMBOCYTE MARKERS IN PATIENTS WITH DİALYSİS, CHRONIC RENAL DISEASE AND RENAL TRANSPLANTATION PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0299 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

KÖNÜL AHMEDOVA ◽

Garip SAHIN ◽

Cengiz Bal ◽

Rüya Mutluay

Keyword(s):

Vitamin D ◽

Renal Transplantation ◽

Renal Disease ◽

Negative Correlation ◽

Chronic Renal Disease ◽

Significant Negative Correlation ◽

Vitamin D Supplementation ◽

Control Group ◽

Before And After ◽

Grade 3

Abstract Background and Aims 25(OH)D3 levels are known to be lower in patients with chronic renal disease (CRD). Vitamin D supplementation has been shown to have beneficial effects on mortality in these patients. In our study, we have evaluated the pleiotropic effect of vitamin D on thrombocyte markers, which is known very little by most. Method The main thrombocyte function markers (MPV, PDW and PCT) were obtained in patients which underwent dialysis, renal transplantation and patients with grade 3-4 CRD before and after vitamin D supplementation. 40 healthy individuals were chosen as control group and 24 patients underwent renal transplantation, 25 patients underwent dialysis for at least 3 months, 32 patients were diagnosed as Grade 3-4 CRD. All of the patients above had 25(OH)D3 levels <20ng/mL (<50nmol/L). Thrombocyte markers were evaluated before and after vitamin D supplementation (which was given 50.000 IU orally once a week for 8 weeks). Results Statistically no significant difference were found between MPV values in- and across- group comparison before and after vitamin D supplementation. After the correlation analyses were reviewed, statistically significant negative correlation was found (r=-0,422 p<0.05) between ΔMPV and ΔVitamin D in renal transplantation group. Also statistically significant positive correlation was found between ΔPDW and ΔVitamin D. In the control group with healty participants, a statistically significant negative correlation was found (r=-0,493 p<0.05) between ΔVitamin D and ΔThrombocyte count. In the dialysis group a statistically significant negative correlation was found (r=-0,422 p<0.05) between ΔVitamin D and ΔMPV. Conclusion A significant correlation was found particularly between Vitamin D and MPV in dialysis and renal transplantation patients. In order to prevent cardiovascular events due to thrombosis caused by Vitamin D deficiency which increases MPV, it has been thought that Vitamin D supplementation and antiaggregant therapy might be beneficial.

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Transgenic Mice Overexpressing Human Fibroblast Growth Factor 23 (R176Q) Delineate a Putative Role for Parathyroid Hormone in Renal Phosphate Wasting Disorders

Endocrinology ◽

10.1210/en.2004-0233 ◽

2004 ◽

Vol 145 (11) ◽

pp. 5269-5279 ◽

Cited By ~ 241

Author(s):

Xiuying Bai ◽

Dengshun Miao ◽

Jiarong Li ◽

David Goltzman ◽

Andrew C. Karaplis

Keyword(s):

Vitamin D ◽

Growth Factor ◽

Transgenic Mice ◽

Fibroblast Growth Factor ◽

Calcium Homeostasis ◽

Fibroblast Growth Factor 23 ◽

Fibroblast Growth ◽

Vitamin D Metabolism ◽

Dihydroxyvitamin D3 ◽

Circulating Levels

Abstract Fibroblast growth factor 23 (FGF23) is a recently characterized protein likely involved in the regulation of serum phosphate homeostasis. Increased circulating levels of FGF23 have been reported in patients with renal phosphate-wasting disorders, but it is unclear whether FGF23 is the direct mediator responsible for the decreased phosphate transport at the proximal renal tubules and the altered vitamin D metabolism associated with these states. To examine this question, we generated transgenic mice expressing and secreting from the liver human FGF23 (R176Q), a mutant form that fails to be degraded by furin proteases. At 1 and 2 months of age, mice carrying the transgene recapitulated the biochemical (decreased urinary phosphate reabsorption, hypophosphatemia, low serum 1,25-dihydroxyvitamin D3) and skeletal (rickets and osteomalacia) alterations associated with these disorders. Unexpectantly, marked changes in parameters of calcium homeostasis were also observed, consistent with secondary hyperparathyroidism. Moreover, in the kidney the anticipated alterations in the expression of hydroxylases associated with vitamin D metabolism were not observed despite the profound hypophosphatemia and increased circulating levels of PTH, both major physiological stimuli for 1,25-dihydroxyvitamin D3 production. Our findings strongly support the novel concept that high circulating levels of FGF23 are associated with profound disturbances in the regulation of phosphate and vitamin D metabolism as well as calcium homeostasis and that elevated PTH levels likely also contribute to the renal phosphate wasting associated with these disorders.

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Is the Vitamin D Receptor Found in Muscle?

Endocrinology ◽

10.1210/en.2010-1109 ◽

2010 ◽

Vol 152 (2) ◽

pp. 354-363 ◽

Cited By ~ 165

Author(s):

Yongji Wang ◽

Hector F. DeLuca

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Bone Mineralization ◽

Active Form ◽

Dihydroxyvitamin D3 ◽

Neuromuscular Activity ◽

Immunohistochemical Assay ◽

Underlying Mechanisms ◽

Positive Results ◽

Phosphorus Levels

Abstract The active form of vitamin D, 1α,25-dihydroxyvitamin D3, is critical for the regulation of serum calcium and phosphorus levels that in turn support bone mineralization and neuromuscular activity. It is well known that vitamin D deficiency causes rachitic/osteomalacic myopathy and cardiac disorder and the provision of vitamin D can reverse the symptoms. However, the underlying mechanisms remain unclear. The question of whether the vitamin D receptor is found in muscle has been debated but not settled. We recently studied all available antibodies against the vitamin D receptor and found that most antibodies used detect proteins other than the vitamin D receptor, and therefore, the utility of these antibodies may generate the false-positive results. Using antibodies that do not detect proteins in tissues from vitamin D receptor null mice, we have developed a specific and sensitive immunohistochemical assay. The results from this investigation show that the vitamin D receptor is undetectable in skeletal, cardiac, and smooth muscle, suggesting that the function of vitamin D on muscle is either of an indirect nature or does not involve the known receptor.

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Increased circulating levels of FGF23: an adaptive response in primary hyperparathyroidism?

Acta Endocrinologica ◽

10.1530/eje-11-0523 ◽

2012 ◽

Vol 166 (1) ◽

pp. 55-60 ◽

Cited By ~ 15

Author(s):

Janneke E Witteveen ◽

Antoon H van Lierop ◽

Socrates E Papapoulos ◽

Neveen A T Hamdy

Keyword(s):

Primary Hyperparathyroidism ◽

Fibroblast Growth Factor 23 ◽

Negative Relationship ◽

Significant Negative Correlation ◽

Fgf23 Concentration ◽

Biochemical Evaluation ◽

Turnover Markers ◽

The Relationship ◽

Circulating Levels

IntroductionFibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) are major players in the bone–parathyroid–kidney axis controlling phosphate homeostasis. In patients with primary hyperparathyroidism (PHPT), data on the relationship between PTH and FGF23 are scarce and not always concordant.ObjectiveThe aim of our study was to evaluate the relationship between PTH and FGF23 in patients with PHPT and in euparathyroid patients cured after successful parathyroidectomy (PTx).Patients and methodsTwenty-one patients with PHPT and 24 patients in long-term cure after successful PTx (EuPTH) were studied. All patients underwent biochemical evaluation of renal function, parathyroid status, vitamin D status, bone turnover markers, and serum intact FGF23 levels.ResultsMean serum FGF23 concentration was significantly higher in PHPT than in EuPTH patients (50.8±6.1 vs 33.1±2.6 pg/ml,P=0.01). FGF23 levels significantly correlated with PTH levels (r=0.361,P=0.02), also after correction for 1,25(OH)2D levels (r=0.419,P=0.01). FGF23 levels showed a significant negative correlation with 1,25(OH)2D, which was more pronounced in PHPT than in EuPTH patients (r=−0.674,P=0.001, vsr=−0.509,P=0.01).ConclusionOur findings suggest that in PHPT, FGF23 levels are increased independent of 1,25(OH)2D levels. The more pronounced negative relationship between FGF23 and 1,25(OH)2D in the presence of high circulating PTH levels suggests that the increase in FGF23 levels may be an adaptive mechanism to counteract the PTH-induced increase in 1,25(OH)2D levels, although not completely overriding it.

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Vitamin D measurement and effect on outcome in a cohort of patients with heart failure

Endocrine Connections ◽

10.1530/ec-18-0207 ◽

2018 ◽

Vol 7 (9) ◽

pp. 957-964 ◽

Cited By ~ 6

Author(s):

Federica Saponaro ◽

Alessandro Saba ◽

Sabina Frascarelli ◽

Concetta Prontera ◽

Aldo Clerico ◽

...

Keyword(s):

Heart Failure ◽

Vitamin D ◽

Outcome Data ◽

Control Group ◽

Risk Of Death ◽

Kaplan Meier ◽

Related Risk ◽

Patients With Heart Failure ◽

Design And Methods ◽

Good Agreement

Objectives The aims of this paper were to evaluate the levels of Vitamin D (VitD) in patients with heart failure (HF), compared to a control group, to assess the effects of VitD on HF outcome and to compare VitD measurement between LIAISON immunoassay and HPLC-MS-MS methods in this population. Design and Methods We collected clinical, biochemical and outcome data from 247 patients with HF and in a subgroup of 151 patients, we measured VitD both with LIAISON and HPLC-MS-MS. Results HF patients had statistically lower 25OHD levels (45.2 ± 23.7 nmol/L vs 58.2 ± 24.0 nmol/L, P < 0.001) and a statistically higher prevalence of VitD insufficiency (61.1% vs 39.5%, P < 0.001) and deficiency (24.7% vs 6.6%, P < 0.001), compared to healthy controls. There was a significant inverse relationship between baseline 25OHD and risk of HF-related death, with a HR of 0.59 (95% CI 0.37–0.92, P = 0.02), confirmed in a multivariate adjusted analysis. Kaplan–Meier survival analyses showed that VitD insufficiency was associated with reduced survival in HF patients (log rank P = 0.017). There was a good agreement between LIAISON and HPLC-MS-MS (Cohen’s kappa coefficient 0.70), but the prevalence of VitD insufficiency was significantly higher with the former compared to the latter method (58.3%, n = 88 vs 55.6%, n = 84, P < 0.001). LIAISON underestimated the 25OHD levels and showed a mean relative bias of −0.739% with 95% of limits of agreement (−9.00 to +7.52%), when compared to HPLC-MS-MS. Conclusions 25OHD levels adequately measured by HPLC-MS-MS showed to be low in HF population and to be correlated with HF-related risk of death.

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Metagenomic analysis of the gut microbiome composition associated with vitamin D supplementation in Taiwanese infants

Scientific Reports ◽

10.1038/s41598-021-82584-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wei-Te Lei ◽

Kai-Yao Huang ◽

Jhih-Hua Jhong ◽

Chia-Hung Chen ◽

Shun-Long Weng

Keyword(s):

Vitamin D ◽

Gut Microbiota ◽

Gut Microbiome ◽

Infant Health ◽

Bone Mineralization ◽

Vitamin D Supplementation ◽

Metagenomic Analysis ◽

Control Group ◽

Microbiome Composition ◽

Breastfed Infants

AbstractEarly childhood is a critical stage for the foundation and development of the gut microbiome, large amounts of essential nutrients are required such as vitamin D. Vitamin D plays an important role in regulating calcium homeostasis, and deficiency can impair bone mineralization. In addition, most people know that breastfeeding is advocated to be the best thing for a newborn; however, exclusively breastfeeding infants are not easily able to absorb an adequate amount of vitamin D from breast milk. Understanding the effects of vitamin D supplementation on gut microbiome can improve the knowledge of infant health and development. A total of 62 fecal sample from healthy infants were collected in Taiwan. Of the 62 infants, 31 were exclusively breastfed infants and 31 were mixed- or formula-fed infants. For each feeding type, one subgroup of infants received 400 IU of vitamin D per day, and the remaining infants received a placebo. In total, there are 15 breastfed and 20 formula-fed infants with additional vitamin D supplementation, and 16 breastfed and 11 formula-fed infants belong to control group, respectively. We performed a comparative metagenomic analysis to investigate the distribution and diversity of infant gut microbiota among different types of feeding regimes with and without vitamin D supplementation. Our results reveal that the characteristics of infant gut microbiota not only depend on the feeding types but also on nutrients intake, and demonstrated that the vitamin D plays an important role in modulating the infant gut microbiota, especially increase the proportion of probiotics in breast-fed infants.

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Plasma Ca influences vitamin D metabolite levels as rats develop vitamin D deficiency

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1991.260.3.e447 ◽

1991 ◽

Vol 260 (3) ◽

pp. E447-E452 ◽

Cited By ~ 2

Author(s):

U. Kollenkirchen ◽

M. R. Walters ◽

J. Fox

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Bone Mineralization ◽

Complete Characterization ◽

Vitamin D Metabolites ◽

Dihydroxyvitamin D3 ◽

Dietary Regimen ◽

Group A ◽

Group B ◽

Group D

The hypocalcemia that accompanies vitamin D deficiency is a major obstacle to proper interpretation of the role(s) of vitamin D metabolites in Ca-sensitive tissues. This paper describes the development and complete characterization of a dietary regimen with which normocalcemia was maintained in rats throughout the development of vitamin D deficiency. Normal weanling rats were fed diets containing 0.8% Ca, 0.5% P, and vitamin D3 (group A), or vitamin D-deficient diets containing 0.8% Ca and 0.5% P (group B); 2.0% Ca and 1.25% P (group C); or 2.0% Ca, 1.25% P, and 20% lactose (group D) for 19 wk. Group D rats were normocalcemic and normophosphatemic with normal parathyroid hormone (PTH) levels throughout the study. In contrast, from 4-19 diet wk, groups B and C were hypocalcemic with elevated PTH. Initially, plasma 25-hydroxyvitamin D3 [25(OH)D3] levels decreased most rapidly, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels decreased least rapidly in group B rats, such that plasma 25(OH)D3 levels were reduced to 200-300 pg/ml before a decrease in 1,25(OH)2D3 levels was observed. However, vitamin D metabolite levels were similar in groups B, C, and D from 4-19 wk. Duodenal active Ca transport mirrored changes in plasma 1,25(OH)2D3 levels and was abolished after 10 wk. The results also suggested that vitamin D may not be necessary for normal bone mineralization since tibia mineral content and plasma alkaline phosphatase levels were similar in normocalcemic groups A and D throughout the study.

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