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Aim: To provide reference data of biochemical markers of bone turnover and vitamin D metabolites for children and young adults. Methods: Blood samples were taken from 176 healthy Dutch children and young adults (age range 7.6–25.3 years) to assess serum calcium, alkaline phosphatase, inorganic phosphate, osteocalcin, collagen type I cross-linked N-telopeptide, N-terminal propeptide of type I procollagen , 25-hydroxyvitamin D[sub 3] , and 1,25-dihydroxyvitamin D[sub 3] levels. Cross-linked telopeptide of type I collagen and carboxy-terminal propeptide of type I procollagen were assessed in 286 subjects (age range 1.4–25.3 years). Results: Calcium and vitamin D levels were independent of age. The peak concentrations for collagen type I cross-linked N-telopeptide, cross-linked telopeptide of type I collagen, carboxy-terminal propeptide of type I procollagen, N-terminal propeptide of type I procollagen, alkaline phosphatase, and osteocalcin were found during puberty, in girls approximately 2.5 years earlier than in boys. Strong correlations were found between the markers of bone turnover, while no correlation was found between the markers of bone turnover and bone mineral density measured by dual-energy X-ray absorptiometry. Conclusions: Single measurements of bone markers cannot predict bone density. Reference data according to gender, age, and Tanner stage are given which allow calculating standard deviation scores adjusted for age and gender.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The brain's supply with vitamin D is poorly understood. Therefore, the present study aimed to determine 25-hydroxy vitamin D3 (25(OH)D) and 24,25-dihydroxy vitamin D (24,25(OH)2D3) in serum and cerebrospinal fluid (CSF) from individuals with intact and disturbed brain-CSF-barrier (BCB) function. In 292 pairs of serum and CSF samples the vitamin D metabolites were measured with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). CSF/serum ratios (QALB, Q25(OH)D, Q24,25(OH)2D3) were calculated. Median (IQR) serum concentrations of 25(OH)D and 24,25(OH)2D3 were 63.8 (43.4–83.9) nmol/L and 4.2 (2.2–6.2) nmol/L. The CSF concentrations of both metabolites accounted for 3.7 and 3.3% of the respective serum concentrations. Serum 25(OH)D correlated inversely with Q25(OH)D and Q24,25(OH)2D3 implying a more efficient transport of both metabolites across the BCB when the serum concentration of 25(OH)D is low. In patients with BCB dysfunction, the CSF concentrations and the CSF/serum ratios of both vitamin D metabolites were higher than in individuals with intact BCB. The CSF concentrations of 25(OH)D and 24,25(OH)2D3 depend on BCB function and the respective serum concentrations of both metabolites. Higher vitamin D metabolite concentrations in CSF of patients with impaired BCB function may be due to passive diffusion across the BCB. [ABSTRACT FROM AUTHOR]

Neonatal dried blood spots (DBS) provide a remarkable resource for biobanks. These microsamples can provide information related to the genetic correlates of disease and can be used to quantify a range of analytes, such as proteins and small molecules. However, after routine neonatal screening, the amount of DBS sample available is limited. To optimize the use of these samples, there is a need for sensitive assays which are integrated across different analytic platforms. For example, after DNA extraction, protein extracts are available for additional analyses. We describe a sensitive and robust LC-MS/MS method for 25-hydroxyvitamin D 2 and 25-hydroxyvitamin D 3 optimized for leftover protein extracts from DBS, which has excellent recovery, precision, and accuracy.

The active metabolites of vitamin D3 (D3) and lumisterol (L3) exert a variety of antiaging and photoprotective effects on the skin. These are achieved through immunomodulation and include anti-inflammatory actions, regulation of keratinocytes proliferation, and differentiation programs to build the epidermal barrier necessary for maintaining skin homeostasis. In addition, they induce antioxidative responses, inhibit DNA damage and induce DNA repair mechanisms to attenuate premature skin aging and cancerogenesis. The mechanism of action would involve interaction with multiple nuclear receptors including VDR, AhR, LXR, reverse agonism on RORα and -γ, and nongenomic actions through 1,25D3-MARRS receptor and interaction with the nongenomic binding site of the VDR. Therefore, active forms of vitamin D3 including its canonical (1,25(OH)2D3) and noncanonical (CYP11A1-intitated) D3 derivatives as well as L3 derivatives are promising agents for the prevention, attenuation, or treatment of premature skin aging. They could be administrated orally and/or topically. Other forms of parenteral application of vitamin D3 precursor should be considered to avoid its predominant metabolism to 25(OH)D3 that is not recognized by CYP11A1 enzyme. The efficacy of topically applied vitamin D3 and L3 derivatives needs further clinical evaluation in future trials. [ABSTRACT FROM AUTHOR]

(1) Background: Vitamin D, a well-established regulator of calcium and phosphate metabolism, also has immune-modulatory functions. An uncontrolled immune response and cytokine storm are tightly linked to fatal courses of COVID-19. The present retrospective study aimed to inves-tigate vitamin D status markers and vitamin D degradation products in a mixed cohort of 148 hospitalized COVID-19 patients with various clinical courses of COVID-19. (2) Methods: The serum concentrations of 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, and 25,26(OH)2D3 were determined by a validated liquid-chromatography tandem mass-spectrometry method in leftover serum samples from 148 COVID-19 patients that were admitted to the University Hospital of the Medical Uni-versity of Graz between April and November 2020. Anthropometric and clinical data, as well as outcomes were obtained from the laboratory and hospital information systems. (3) Results: From the 148 patients, 34 (23%) died within 30 days after admission. The frequency of fatal outcomes did not differ between males and females. Non-survivors were significantly older than survivors, had higher peak concentrations of IL-6 and CRP, and required mechanical ventilation more frequently. The serum concentrations of all vitamin D metabolites and the vitamin D metabolite ratio (VMR) did not differ significantly between survivors and non-survivors. Additionally, the need for res-piratory support was unrelated to the serum concentrations of 25(OH)D vitamin D and the two vitamin D catabolites, as well as the VMR. (4) Conclusion: The present results do not support a relevant role of vitamin D for the course and outcome of COVID-19. [ABSTRACT FROM AUTHOR]

The effects of i.v. 1,25-dihydroxycholecalciferol (DHCC) on blood pressure and insulin sensitivity were studied in 7 patients on maintenance hemodialysis and compared with 7 healthy controls. Three days after discontinuing oral 1,25-DHCC, the dialysis patients were evaluated by glucose clamp studies to quantitate insulin sensitivity, with (+D) and without (−D) a prior single dose of i.v. 1,25-DHCC at 2μg/m. Blood pressure was measured just before the glucose studies. During −D studies, the patients were hypertensive (mean arterial blood pressure 108±2 mmHg, controls 84±4 mmHg, P<0.02) and insulin resistant (insulin sensitivity index 7.5±0.4 mg/kg·min per μU per ml, controls 14.2±0.7, P<0.01) i.v. 1,25-DHCC significantly reduced the mean arterial blood pressure (96±3 mmHg, P<0.05) and increased insulin sensivity (10.9±0.5 mg/kg·min per μU per ml, P<0.02) in the dialysis patients. I. V. 1,25-DHCC did not change blood pressure and insulin sensitivity in the control subjects. During −D studies, serum concentrations of 1,25-DHCC were significantly lower in patients than controls ( P<0.02). Serum 1,25-DHCC during the +D studies increased to supraphysiological levels in both patients and controls. Serum concentrations of intact parathyroid hormone, total and ionized calcium, magnesium, potassium, urea nitrogen and creatinine were not different between the +D and −D studies in either the dialysis patients or the controls. These results suggest that pharmacological doses of 1,25-DHCC may have therapeutic value in the treatment of hypertension and insulin resistance in dialysis patients. [ABSTRACT FROM AUTHOR]

Plasma concentrations of the vitamin D metabolites 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D and 25,26-dihydroxyvitamin D were determined in 12 solely breast-fed infants 4 days and 6 weeks after birth. They were not exposed to sunlight, but the mothers received an average of 600 IU vitamin D2 per day during the study period. The mothers' 25-hydroxyvitamin D levels did not change significantly (medians 42 and 58 nmol/l), but the median level dropped from 26 to 15 nmol/l in the infants (P less than 0.001). There was a close correlation between maternal and infant levels at 4 days (r = 0.95). The babies with the highest initial levels showed the most marked decrease by 6 weeks. The median concentrations of 24,25-dihydroxyvitamin D and 25,26-dihydroxyvitamin D decreased similarly from 1.7 to 0.8 and 0.63 to 0.35 nmol/l respectively, (P less than 0.001). The 1,25-dihydroxyvitamin D levels were within normal limits as were plasma calcium, phosphorus, and alkaline phosphatase. The data suggest that fetal stores of vitamin D may be rapidly depleted, and that breast milk may be inadequate as the only source of vitamin D, even for breast-fed infants of vitamin D-supplemented mothers. [ABSTRACT FROM AUTHOR]

Calcium metabolism and plasma concentrations of vitamin D metabolites were investigated in 27 children on long-term anticonvulsant therapy. Serum calcium was in the low normal range, phosphorus was normal, parathyroid hormone concentrations and alkaline phosphatase were elevated. Plasma 25-hydroxyvitamin D (25-OH D) and 24,25-dihydroxyvitamin D (24,25-(OH)D) were decreased, but 1,25-dihydroxyvitamin D (1,25-(OH)D) was normal when compared with a synchronous control group. The serum concentrations of all anticonvulsant drugs given were measured. The decreases in 25-OH D and 24,25-(OH)D did not depend on the blood level of a single drug, or any combination of drugs given, or on the duration of therapy. The 25-OH D levels were negatively correlated with the number of different drugs used, which may reflect the severity of the neurologic disorder, and therefore with non-specific factors such as exposure to sunlight, nutrition, or physical activity. Our data do not support the hypothesis that anticonvulsant drugs act on vitamin D metabolism. [ABSTRACT FROM AUTHOR]

Samples of CSF and plasma were obtained simultaneously from 46 adult patients who had no endocrine disorders and were undergoing routine diagnostic lumbar puncture because of suspected or proved prolapse of a disc. Concentrations of 25-OHD, 24,25(OH)D and 1,25(OH)D were measured. The samples were purified by column chromatography and fractionated by HPLC. In the appropriate fractions the vitamin D metabolites were measured by PBA, and cytoreceptor assay. The results were as follows (median, range in brackets): 25-OHD in CSF 8.3 ng/ml (2.0-24.8), in plasma 14.5 ng/ml (7.0-36.0). 24,25(OH)D in CSF 1.8 ng/ml (0.3-4.6) and 2.5 ng/ml (0.4-4.7) in plasma. 1.25(OH) D in CSF 25.0 pg/ml (2.2-39.0) and 31.0 pg/ml (10.1-55.0) in plasma. The correlations between plasma and CSF concentrations were as follows: 25-OHD r=0.479 ( P<0.001); 24,25(OH)D r=0.815 ( P<0.001) and for 1.25(OH)D r=0.497 ( P<0.001). Our findings showed vitamin D metabolites to be present in human CSF. [ABSTRACT FROM AUTHOR]

Cell cultures derived from young rat epiphyseal cartilage were grown for approximately 2 wk in BGJ medium supplemented with 10% fetal bovine serum to reach confluence. These cells were identified as chondrocytes as checked by morphology, the presence of alkaline phosphatase, and a positive type II collagen antibody reaction. The cells also responded to different hormonal treatment. Parathyroid hormone (PTH) increased cyclic AMP production by 50% within 15 min of treatment, whereas prostaglandin E (PGE) caused an increase of 160%. Calcitonin (CT) did not affect cAMP production in these cells. DNA synthesis 24 h after hormonal treatment was increased by PTH (2.5-fold) and PGE (2-fold), but not by CT. Among the vitamin D metabolites, 24,25(OH)D increased significantly the [H]thymidine incorporation into DNA, whereas 1,25(OH)D effect was minimal. These results provide evidence for the use of these cell cultures as a model for cartilage in vitro when studying biological and hormonal responsiveness. [ABSTRACT FROM AUTHOR]

Serum concentrations of 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D [24,25(OH)D], and 1α,25-dihydroxyvitamin D [1α,25(OH)D] were measured in ten cadmium (Cd)-exposed subjects and five non exposed subjects. The Cd-exposed subjects were divided into two groups according to serum 1α,25(OH)D levels. No significant differences for 25(OH)D were found between the Cd-exposed group with low or normal serum 1α,25(OH)D and the non exposed group. The concentrations of 24,25(OH)D were the lowest in the Cd-exposed group with low serum 1α,25(OH)D, highest in the non exposed group, and significantly lower in the Cd-exposed group with normal serum 1α,25(OH)D than in the non exposed group. Renal function was much worse in the Cd-exposed group with low serum 1α,25(OH)D than in the group with normal serum 1α,25(OH)D. These findings indicate that Cd initially disturbs hydroxylation from 25(OH)D to 24,25(OH)D and then disturbs hydroxylation from 25(OH)D to 1α,25(OH)D. The decrease of serum 24,25(OH)D and 1α,25(OH)D in Cd-exposed subjects is not due to a decrease of the serum 25(OH)D level. [ABSTRACT FROM AUTHOR]

Caffeine has been cited as a risk factor for osteoporosis in humans. In rats, caffeine increases calcium absorption and excretion and raises parathyroid hormone (iPTH) levels. This study investigated the effect of chronic caffeine administration on bone histomorphometry and serum markers of bone mineral metabolism. Twenty-seven male Sprague Dawley rats weighing approximately 300 g were divided into three groups: Group A (n=8) served as controls, Group B (n=9) received 2.5 mg/100 g caffeine in their drinking water, and Group C (n=10) received 10 mg/100 g body weight caffeine in their drinking water. Animals were bled serially for the 8 week study period: Ionized calcium was measured from tail vein blood and serum iPTH and osteocalcin (BGP) from orbital sinus blood. All three groups received two doses of tetracycline for bone histomorphometry which was performed on a right tibial section from each animal. Ionized calcium was not different among the three groups at any time point. No alteration in serum iPTH levels was demonstrated except for day 56 when the high-dose group (C) showed a raised level (mean=59.1, SE=±8.9 pg/ml ( P<0.05). By week 8 Group C showed a failure to gain weight compared with Group A. Group C mean weight=384.0±6.6 g, Group A 427.4±10.8 g ( P<0.005). Serum BGP was significantly increased in Group C compared with control ( P<0.001). No differences in bone histomorphometry were observed among the three groups. We conclude that although chronic caffeine administration in the rat may slightly increase bone turnover as evidenced by the BGP increase, bone histomorphometry was not altered. This makes the role of caffeine by itself doubtful as an etiological factor for osteoporosis. [ABSTRACT FROM AUTHOR]

The biochemical parameters of bone mineral metabolism in patients with nonhypercalcemic malignancy have not been extensively investigated. Therefore, a group of 29 such patients with different types of malignancy was studied. Ten patients received corticosteroids. In the entire group, serum ionized calcium (Ca2+), bone gla protein (BGP), 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D (1,25(OH)2D) were all lower than in age-matched controls, and carboxy-terminal parathyroid hormone (CPTH) was higher. Although both corticosteroid- and noncorticosteroid-treated patients had decreased BGP values, the corticosteroid-treated patients had lower BGP levels than those not on steroids (4.24 +/- 0.70 SE vs. 11.50 +/- 2.20 ng/ml; P less than 0.005). Patients on corticosteroids had lower 1,25(OH)2D values than controls (18.81 +/- 2.71 vs. 27.83 +/- 1.17 pg/ml; P less than 0.01), whereas those not on corticosteroids had normal 1,25(OH)2D values. These results suggest that patients with nonhypercalcemic malignancy have nutritional vitamin-D deficiency and secondary hyperparathyroidism with perhaps corticosteroid-induced suppression of serum 1,25(OH)2D and BGP. The decreased levels of serum BGP in the nonsteroid-treated patients suggest, in addition, a defect in osteoblast function. [ABSTRACT FROM AUTHOR]

Bone gla protein, the vitamin K-dependent protein synthesized by osteoblasts and measured in blood by radioimmunoassay, has been used as an index of the rate of bone turnover. The relationship of bone gla protein with other markers of bone mineral metabolism was determined in 31 untreated postmenopausal women with the osteoporotic syndrome. In addition to serum osteocalcin (BGP) we measured parathyroid hormone (PTH) (carboxyl and mid-molecule fragments), 25(OH)D, alkaline phosphatase, estradiol (E2), estrone (E1), dietary calcium intake, 24 hour urinary calcium excretion, and bone mineral density by CT scan of the lumbar vertebrae. Significant osteopenia was present on CT in untreated postmenopausal osteoporotic women (bone density in 18 out of 31 was below the critical value of 60 mg/cm3). Serum BGP correlated positively with CT scan (r + 0.647, P less than 0.001). CT and age were negatively correlated (r - 0.661, P less than 0.001) while CT and E2 showed a positive correlation (r + 0.554, P less than 0.01). Unexpectedly, BGP and age revealed a significant negative correlation (r - 0.421, P less than 0.05). These findings suggest a state of low bone turnover in this group with untreated postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

The relative roles of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2D) and 24,25-dihydroxyvitamin D (24,25-(OH)2D) in bone mineralization are largely unknown. Young vitamin D depleted rats were fed increasing amounts of vitamin D and grouped radiologically in accordance with the rat line test. They ranged from severely rachitic to normal. Radiology was correlated with serum levels of 25-OHD, 1,25-(OH)2D, 24,25-(OH)2D, ionized calcium, magnesium, and phosphate, with bone histology, and with the total mineral content of the animals. Serum 1,25-(OH)2D rose in a linear fashion to supranormal values during bone healing and correlated with the radiological degree of rickets. Serum 25-OHD was below detection limit in the most rachitic and low in the radiologically normal rats, whereas 24,25-(OH)2D was low in all groups. These two metabolites showed no correlation with the radiologic, histologic or biochemical parameters. In rachitic rats, 1,25-(OH)2D appears to play a major role in bone healing and possibly exerts a direct effect on bone cells. It cannot be ruled out, however, that the effect is mediated through a rise in serum levels of calcium and phosphorus, although signs of bone healing were seen in the presence of a subnormal calcium X phosphorus product. Initiation of mineralization can take place with unmeasurable 25-OHD, and 24,25-(OH)2D seems to be without importance. [ABSTRACT FROM AUTHOR]

25-hydroxycholecalciferol (25OHD) and 1,25-dihydroxycholecalciferol (1,25(OH)D) at physiological concentrations exerted direct effects on Ca fluxes in cultured vitamin D-deficient chick soleus muscle and myoblasts. Isotopic desaturation curves of soleus muscle prelabeled withCa indicated that the action of 25OHD is localized in a slow-exchangeable Ca pool where it stimulates net Ca uptake. On the other hand, the predominant effects of 1,25(OH)D consist in an increase of the rate constant of Ca efflux of this pool and in an increase of net Ca uptake in a fast-exchangeable pool. 24,25-dihydroxycholecalciferal proved to be inactive on both Ca uptake and efflux. In addition, 1,25(OH)D significantly increasedCa labeling of cultured chick myoblasts. These effects were accompanied by changes in the growth and differentiation of the cultures. The results suggest a direct involvement in vivo of 25OHD and 1,25(OH)D on muscle cellular calcium. [ABSTRACT FROM AUTHOR]

The effect of the vitamin D metabolites 1,25 dihydroxyvitamin D (100 pg/ml) and 25-hydroxyvitamin D (30 ng/ml) on hepatic production ofH-25 hydroxyvitamin D was investigated using rachitic liver perfusions and homogenates. 1,25 dihydroxyvitamin D inhibited hepaticH-25 hydroxyvitamin D production in the liver perfusion (3.6 ± 0.4 vs 2.0 ± 0.5 pmol/liver, P<0.05) and in liver homogenates (11.9 ± 0.6 vs 10.1 ± 0.4 pmol/g liver protein/3 h, P<0.02). Inhibition was time and dose dependent. 25-hydroxyvitamin D inhibited production in liver homogenates (11.9 ± 0.6 vs 9.2 ± 0.1 pmol/g liver protein/3 h, P<0.05) but not in the intact liver (3.6 ± 0.4 vs 3.4 ± 0.5 pmol/liver). The data indicate that 1,25 dihydroxyvitamin D is able to feedback regulate the production of its precursor, 25-hydroxyvitamin D. Although 25-hydroxyvitamin D also inhibits its own production in liver homogenates, it failed to alter total production in the intact liver, suggesting that this metabolite may require immediate access to the vitamin D 25-hydroxylase, located on the microsomes and mitochondria, to induce inhibition. [ABSTRACT FROM AUTHOR]

The effects of selected vitamin D metabolites and analogs on bone collagen synthesis in vitro were examined in organ cultures of neonatal mouse calvarial bone. The incorporation of [H]proline into the collagenase-digestible fraction of newly synthesized protein was progressively inhibited by 1α,25-dihydroxyvitamin D (1α,25-(OH)D) (10 M to 10 M) in 24-h cultures, and incorporation into noncollagen protein was also blunted at the higher doses employed. The synthetic analog 1α-hydroxyvitamin D (1α-OHD) was almost 300-fold less potent an inhibitor of collagen synthesis than was 1α,25(OH)D, and the natural metabolites 25-hydroxyvitamin D (25OHD) and 24R,25-dihydroxyvitamin D (24R,25(OH)D), 1000-fold less potent, although the dose-response curve for each of these compounds was not parallel with that for 1α,25(OH)D. The 24S,25(OH)D enantiomer was four-fold less potent than 24R,25-(OH)D or 25OHD, and vitamin D showed less than 2% the activity of 25OHD. The responses were unaffected by the substitution of 0.4% bovine albumin for 5% horse serum in the medium, and no stimulation of collagen synthesis was observed in response to 25-hydroxylated metabolites between 2×10 and 2×10 M or in cultures treated for up to 96 h with 24R,25(OH)D (2×10M). The overall results emphasize the similarity of the structural requirements for the inhibition of matrix synthesis and the stimulation of resorption by active vitamin D metabolites in bone. In addition, these studies support the importance of the 1-hydroxyl function to the biologic activity of vitamin D in the skeleton. [ABSTRACT FROM AUTHOR]

The hypophosphatemic male mouse (Hyp/y), the proposed model for human vitamin D-resistant rickets (VDRR), is characterized by chronic hypophosphatemia, dwarfism, and rachitic and osteomalacic bone lesions. We have reported that treatment of Hyp/y mice with phosphate salts (Pi) heals rickets but does not correct the defective endosteal bone mineralization. In an attempt to cure osteomalacia, mutant male animals were treated with Pi combined with 25-hydroxyvitamin D (25OHD, 1 µg/kg/day), 24,25-dihydroxyvitamin D [24,25(OH)D, 0.5 µg/kg/day], or 1,25-dihydroxyvitamin D [1,25(OH)D, 0.05-0.25 µg/kg/day] infused constantly for 3 weeks. The biochemical and skeletal effects of treatment were assessed by analytical methods and bone histomorphometry. The results show that only 1,25(OH)D produced a dose-dependent elevation of serum calcium and phosphorus, and greatly improved bone mineralization at doses high enough to increase serum calcium and phosphorus concentrations within or above the normal range. Better improvement of bone mineralization was obtained when Pi was combined to 1,25(OH)D. In conjunction with the correction of hypocalcemia, Pi+1,25(OH)D suppressed the stimulation of bone turnover induced by Pi supplementation. The results show that, as in VDRR children, 1,25(OH)D produces beneficial effects on bone lesions in Hyp/y mice, mainly through enhancement of mineral availability. However, the persistence of osteomalacia despite correction of serum mineral concentrations suggests that there is a specific bone cell resistance to mineral and/or hormonal influences in Hyp/y mice. [ABSTRACT FROM AUTHOR]

Adult male rats were fed a diet containing 0.15% calcium, 0.3% phosphorus, and either 100, 50, or 20 mg of prednisolone per kg of diet. All these levels of prednisolone led to osteopenia, decreased intestinal absorption of calcium, slightly lower serum calcium and phosphorus, and a decreased level of serum 1,25-dihydroxyvitamin D. Exogenous parenteral 1,25-dihydroxyvitamin D corrected steroid-induced changes in serum calcium and phosphorus, but could not completely correct the low intestinal calcium transport; nor did it prevent the development of osteopenia. The prednisolone-induced osteopenia seems at least in part to be caused by impaired intestinal calcium transport. The impaired calcium transport may be the result of low levels of 1,25-dihydroxyvitamin D and a direct effect of presnisolone on the intestine. [ABSTRACT FROM AUTHOR]

The present study was undertaken to test the in vitro action of aluminum on bone phosphatase activities and the possible interaction of this metal with parathyroid hormone (bPTH) or vitamin D dihydroxymetabolites [1,25- and 24,25(OH)D). Three-day-old rat calvaria were incubated for 24 h with one of the following: bPTH at 5×10M, 1,25-or 24,25(OH)D at 2.5×10M, Al at concentrations ranging from 3×10M to 6×10M, or their corresponding solvents. Al effects were also investigated when the medium phosphate or calcium concentrations were modified. In some experiments, Al was added simultaneously with bPTH or one of the vitamin D metabolites at the beginning of the 24 h incubation. At the end of all incubations, acid and alkaline phosphatase activities were measured in bone cytoplasmic extract. The results show that: (a) When compared to the value found in half calvaria incubated in a control medium, the bone acid and alkaline phosphatase content is significantly higher in paired halves incubated with Al (3×10M to 1.5×10M) as well as with bPTH, 1,25-, or 24,25(OH)D and sharply decreased with higher Al concentrations (6×10M). (b) The Al effect on phosphatase activities is modified in a free phosphate or a free calcium medium. (c) The presence of Al at 1.5×10M or 6×10M significantly decreases the bPTH or 1,25(OH)D-induced stimulation of bone phosphatase activities. (d) A similar interaction could not be found between Al and 24,25-(OH)D. [ABSTRACT FROM AUTHOR]

Weanling rats were given a vitamin D-deficient diet containing 1.4% calcium and 1.0% phosphorus. After 4 weeks these deficient animals were injected for 7 days with selected doses of one of the following vitamin D metabolites: 25(OH)D, 1,25(OH)D, 24,25(OH)D, 25,26(OH)D or the ethanol vehicle. A vitamin D-replete group was placed on the same diet but injected with 50 IU of vitamin D once a week for the entire 5-week period. By the use of a modified Ussing chamber [1], the measurements of calcium fluxes into and from the rat calvaria were possible. These data enabled the apparent mineral solubilities to be derived. After 5 weeks on this diet the vitamin D-deficient rats had low levels of serum calcium (1.41 mM) and decreased mineral solubility when compared to the vitamin D-replete group. The apparent solubility of the bone mineral increased toward the vitamin D-replete level in calvaria from vitamin D metabolite-treated rats. However, these changes did not directly reflect the alterations in the level of serum calcium. At any given dose level, 1,25(OH)D was the most effective metabolite in increasing serum calcium. In fact, the high dose (250 pmoles/day) was hypercalcemic. Next in effectiveness was 25(OH)D. These two metabolites were equally effective in increasing mineral solubility. At a 10 times higher dose, the 24,25(OH)D metabolite was able to normalize serum calcium and improve but not normalize mineral solubility. At the high dose (260 pmoles/day), the 25,26(OH)D metabolite caused no effect on mineral solubility and minimal increases in serum calcium. [ABSTRACT FROM AUTHOR]

We compared the effects of four vitamin D metabolites, 1α,25 dihydroxy vitamin D (1α,25(OH)D), 1α hydroxy vitamin D (1αOH D), 25 hydroxy vitamin D (25 OH D), and 24R,25 dihydroxy vitamin D (24R,25(OH)D) on resorption and collagen synthesis in fetal rat bone maintained in organ culture. Resorption was quantitated by measuring the release of previously incorporatedCa from long bone shafts of 19-day fetal rats, and collagen synthesis was assessed by measuring the incorporation ofH-proline into collagenase digestible protein (CDP) in calvaria from 21-day fetal rats. All four compounds stimulated bone resorption and inhibited collagen synthesis, but 1α,25(OH)D was approximately 1000 times more potent in both organ culture systems. Although the differences were small among the other three compounds, the order of potency was 1αOH D>25 OH D≧24R,25(OH)D. These results suggest that the receptor for 1α25(OH)D in both bone resorbing and bone forming cells has similar affinities for several vitamin D metabolites. [ABSTRACT FROM AUTHOR]

Results from in vitro works suggest that 1,25- and 24,25-dihydroxyvitamin D (1,25-(OH)D and 24,25-(OH)D) act on bone via different mechanisms. The present investigation was performed to study the effect of these two metabolites and of their precursor 25-hyxdroxyvitamin D (25-(OH)D) on bone cAMP content in vitro. Rats' paired half calvaria were incubated under sterile conditions with one vitamin D derivative (10 to 10 M) or with ethanol (0.005 ml for 15 min to 24 h in 1 ml medium containing 0, 0.2, 1, 2, or 3 mM calcium. In some experiments: (a) cycloheximide (10M) was added simultaneously with the vitamin D metabolites; (b) 1-84 bPTH (5 × 10 M) was added for 5 or 15 min at the end of the 24 h incubation. Calvaria were immersed in 1 ml TCA 5% 4°C and homogenized. The cAMP was extracted with diethylether and measured by a competitive protein binding assay. Results bring further evidence for a particular effect of low doses of 24,25-(OH)D (10 to 10M) and of 25-(OH)D (10 to 10M) on bone, different from that of 1,25-(OH)D: cAMP content was higher in 24,25-(OH)D- or 25-(OH)D-treated and lower in 1,25-(OH)D-treated calvaria than in ethanol-treated ones with 1 mM calcium. The 1,25-(OH)D effect persisted in calcium-free medium whereas 25-(OH)D and 24,25-(OH)D effects could not be observed with 0 mM nor with 3 mM calcium. The required duration of the preincubation (over 1 h) as well as the inhibitory action of cycloheximide may suggest an involvement of protein synthesis in the vitamin D metabolites effects. Neither 1,25-(OH)D nor 24,25-(OH)D affected the PTH-induced increase in bone cAMP content. [ABSTRACT FROM AUTHOR]

The in vitro effects of vitamin D metabolites, parathyroid extract (PTE), purified parathyroid hormone (bPTH), vitamin A, and heparin on acid and alkaline phosphatases in rat or mouse calvaria in culture were investigated. Results show that: (a) when compared to values found in half calvaria incubated for 24 h in control medium, the bone acid and alkaline phosphatase content is significantly higher in paired halves incubated with PTE (1 USP/ml), bPTH (4×10M), heparin (5 USP/ml), vitamin A (23 USP/ml), 25-(OH)D (2.5×10 to 2.5×10M), 24,25-(OH)D, and 1,25(OH)D (2.5×10 to 2.5×10M); (b) the presence of 24,25-(OH)D at low concentrations in the incubation medium decreases significantly the PTE, bPTH, vitamin A, or heparin induced stimulation of the phosphatase activities. This interaction is also observed when measuring β glucuronidase and glucose-6-phosphatase activities andCa release from previously labeled mouse calvaria; (c) a similar activity could not be found with 1,25-(OH)D suggesting that 24,25-(OH)D may have a specific role in bone metabolism. [ABSTRACT FROM AUTHOR]

The effects of a partially purified aqueous extract of Solanum malacoxylon (SM) leaves and of an SM extract incubated with ruminal fluid (RF) prior to administration on intestinal phosphate and calcium absorption in rachitic rats were compared with 1α, 25-dihydroxy-vitamin D[1α,25-(OH)-D] using a duodenal loop in situ method. The time course responses elicited by both extracts were qualitatively similar to that of 1α, 25-(OH)-D. However, a single dose of SMRF was significantly more effective in stimulatingP absorption than an equivalent dose of SM. Part of this difference can be accounted for by incomplete saturation of the phosphate transport system with the level of SM employed. Treatment with rumen potentiated the effects of SM onCa absorption to a lesser extent. Extraction of SMRF with nonpolar organic solvents and purification of the lipid extract by chromatography on Silica Gel G thin-layer plates and on Sephadex LH-20 columns yield two fractions which promote intestinalP absorption. The bioactive fraction eluting first from the Sephadex LH-20 column migrates similarly as 1α,25-(OH)-D. The greater effectiveness of SMRF extracts on intestinal phosphate and calcium absorption may be tentatively attributed to the release of 1α,25-(OH)-D from the corresponding glycoside, shown previously to be present in SM, and to steroid modification during incubation with rumen. [ABSTRACT FROM AUTHOR]

While the independent roles of vitamin D and sex hormones in skeletal health are well established, the associations of vitamin D and its metabolites to sex hormones and their indices are less investigated. In this observational study, clinical information of 189 Saudi postmenopausal women aged ≥50 years old [N = 80 with normal bone mineral density (BMD), aged 53.3 ± 7.7 years with body mass index (BMI)= 34.1kg/m2 ± 5.8, and N = 109 with low BMD (T-score −1.0 to −2.5), aged 57.0 ± 8.2 years, BMI = 32.4kg/m2 ± 6.2] was extracted from an existing capital-wide osteoporosis registry in Riyadh, Saudi Arabia. Data included were BMD scores, serum total 25(OH)D, sex hormones, and bone turnover markers which were measured using commercially available assays. Age- and BMI-adjusted comparisons revealed significantly higher parathyroid hormone (PTH) levels as well as significantly lower testosterone and bioavailable testosterone in the low BMD group than the normal BMD group (p-values 0.04, 0.02, and 0.03, respectively). Stepwise linear regression showed that circulating testosterone levels accounted for 9.7% and 8.9% of the variances perceived in bioavailable 25(OH)D and free 25(OH)D, respectively (p < 0.01), independent of other sex hormones, sex hormone indices, and bone turnover markers. Our study suggests that androgens are significantly associated with non-conventional vitamin D metabolites and these associations may have clinical relevance in assessing risk for low BMD and osteoporosis in Arab postmenopausal women. [ABSTRACT FROM AUTHOR]

Abstract: Human marrow stromal cells (hMSCs) are targets of 1α,25-dihydroxyvitamin D [1α,25(OH)2D3] action to promote their differentiation to osteoblasts, but they also participate in vitamin D metabolism by converting 25-dihydroxyvitamin D3 [25(OH)D3] to 1α,25(OH)2D3 by 1α-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is associated with impaired renal biosynthesis of 1α,25(OH)2D, low bone mass, and increased fracture risk. We tested whether CKD influences hMSCs’ responses to vitamin D3 metabolites. The hMSCs were obtained from tissues discarded during arthroplasty for hip osteoarthrosis, including a subject who had been undergoing hemodialysis for 2+ years. There was a significant positive correlation between in vitro stimulation of osteoblastogenesis (alkaline phosphatase activity) by 1α,25(OH)2D3 and subjects’ estimated glomerular filtration rate (eGFR, r =0.47, p =0.015, n =26, 56–83 years of age). Osteoblastogenesis was stimulated in hMSCs from both the hemodialysis and control subjects by 1α,25(OH)2D3 (10μM), 25(OH)D3 (100μM), or D3 (1000μM). Thus, vitamin D metabolism may play an autocrine/paracrine role in osteoblast differentiation of hMSCs. These findings suggest that in CKD patients 25(OH)D-sufficiency may play an important role in skeletal health; osteoblastic bone formation in CKD patients may not be optimal unless there is sufficient serum 25(OH)D substrate for the MSCs to synthesize and respond to local 1α,25(OH)2D. This article is part of a Special Issue entitled ‘Vitamin D Workshop’. [Copyright &y& Elsevier]

Abstract: As a Supra-Regional Assay Service (SAS) laboratory, we receive samples from all over the UK. Of these some are sent frozen and others by post or courier. We have examined transport and storage conditions to see whether they affect the measurement of Vitamin D metabolites and potentially contribute to the variation in measurement of 25-hydroxyvitamin D (25OHD) seen in the DEQAS scheme. We have also examined the samples received during 2005. We found that different transport and storage conditions did not contribute significantly to the normal variation seen in measuring Vitamin D metabolites (CV% (±S.E.) for stored versus assay controls: 5.1±0.06% versus 4.5±0.04% for 25OHD and 10.8±1.0% versus 12.3±1.0% for 1,25D). A review of the service showed a 240% increase in samples received over the last 5 years. Despite an increased awareness of the need to measure Vitamin D status, in this cross-section of patient samples 92% of Asian and 86% of white patients were found to be Vitamin D-insufficient (<30ng/ml) and 27% of Asian and 14% of white patients were profoundly deficient (<5ng/ml) and at risk of bone disease. [Copyright &y& Elsevier]

To analyze if the prometastatic activity of calcitriol (active vitamin D3 metabolite), which was previously observed in a 4T1 breast cancer model, is also found in other breast cancers, and to assess the impact of various schemes of vitamin D supply, we used 4T1 and E0771 mouse metastatic and 67NR nonmetastatic cells in this study. BALB/c and C57BL/6 healthy and tumor-bearing mice were exposed to a control (1000 IU), low- (100 IU), and high- (5000 IU) vitamin D3 diets. Additionally, from day 7 of tumor transplantation, the 1000 and 100 IU groups were gavaged with calcitriol (+cal). After 8 weeks of feeding, plasma levels of 25(OH)D3, 24,25(OH)2D3, and 3-epi-25(OH)D3 were significantly lower in calcitriol-treated and vitamin D-deficient groups than in the control, whereas the levels of all metabolites were increased in the 5000 IU group. The ratio of 25(OH)D3:24,25(OH)2D3 was increased in both calcitriol-treated groups, whereas the ratio of 25(OH)D3:3-epi-25(OH)D3 was increased only in the 100 IU group but decreased in the 5000 IU group. In contrast to E0771, 4T1 lung metastasis was accelerated in all vitamin D-supplemented mice, as well as in the deficient group with an increased inflammatory response. 67NR tumor growth was transiently inhibited in the 1000 IU+cal group, but single metastases were observed in the 5000 and 100 IU groups. Based on the results, we conclude that various schemes of vitamin D supply and vitamin D deficiency led to similar metabolite profiles irrespective of the mice strain and tumor burden. However, depending on the type of breast cancer, different effects on tumor growth and metastasis were noticed. [ABSTRACT FROM AUTHOR]

• EOP showed decreased 1α,25-(OH) 2 -D plasma levels and placental nuclear vitamin D receptor (VDR) protein levels. • LOP showed decreased 25-OH-D levels, placental 25-hydroxylase CYP2R1, and transporter cubulin expression. • Preeclampsia endogenous dysregulation was a significant determinant of 1α,25-(OH) 2 -D levels in early-onset pregnancies. • Maternal BMI was a significant determinant of 25-OH-D levels in late-onset pregnancies. Vitamin D deficiency has been associated with preeclampsia, however, vitamin D supplementation studies have shown equivocal data on amelioration of this disease. We hypothesize that women with preeclampsia have an altered endogenous vitamin D homeostasis that counteracts the beneficial effects of vitamin D supplementation. Our study population consisted of 66 maternal/neonate dyads: 16 early-onset (<34 weeks) preeclampsia (EOP), 16 early-onset controls (EOC), 17 late-onset (≥34 weeks) preeclampsia (LOP), and 17 late-onset controls (LOC). Plasma levels of 25-OH-D and the bioactive metabolite 1α,25-(OH) 2 -D were studied by ELISA. Placental expression of vitamin D transporters (cubulin and megalin), metabolic genes (CYP2R1, CYP27B1, CYP24A1), and vitamin D binding protein (GC), were studied by real-time PCR, and the nuclear and cytosolic levels of the vitamin D receptor (VDR) protein were analyzed by immunoblotting. Maternal admission, maternal postpartum, and umbilical cord blood levels of 1α,25-(OH) 2 -D and placental nuclear vitamin D receptor protein levels, were significantly lower in EOP compared to EOC. In contrast LOP was characterized by lower 25-OH-D levels in maternal postpartum and cord blood, and decreased placental cubulin expression compared to LOC. Both EOP and LOP showed decreased placental expression of CYP2R1 and GC compared to controls. Multivariable linear regression analysis demonstrated that preeclampsia was a significant predictor of decreased 1α,25-(OH) 2 -D levels in early-onset subjects, while maternal BMI, but not preeclampsia, was the main predictor of decreased 25-OH-D in late-onset subjects. The highest positive correlation between the two vitamin D metabolites was observed in LOC umbilical cord blood. Finally, paired analysis of maternal metabolites before and after delivery indicated that women without preeclampsia had better maintenance of vitamin D levels. We conclude that EOP is characterized by decreased bioactivation of vitamin D and VDR in association with fetal growth restriction (FGR). In contrast, LOP is characterized by decreased 25-OH-D levels in association with decreased placental CYP2R1 and cubulin expression; and uncoupling of the 25-OH-D with the 1α,25-(OH) 2 -D metabolite. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency in pregnant women and their offspring may result in unfavorable health outcomes for both mother and infant. A 25hydroxyvitamin D (25(OH)D) level of at least 75 nmol/L is recommended by the Endocrine Society. Validated, automated sample preparation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were used to determine the vitamin D metabolites status in mother-infant pairs. Detection of 3-Epi25(OH)D3 prevented overestimation of 25(OH)D3 and misclassification of vitamin D status. Sixty-three percent of maternal 25(OH)D plasma levels were less than the recommended level of 25(OH)D at 3 months. Additionally, breastmilk levels of 25(OH)D decreased from 60.1 nmol/L to 50.0 nmol/L between six weeks and three months (p < 0.01). Furthermore, there was a positive correlation between mother and infant plasma levels (p < 0.01, r = 0.56) at 3 months. Accordingly, 31% of the infants were categorized as vitamin D deficient (25(OH)D < 50 nmol/L) compared to 25% if 3-Epi25(OH)D3 was not distinguished from 25(OH)D3. This study highlights the importance of accurate quantification of 25(OH)D. Monitoring vitamin D metabolites in infant, maternal plasma, and breastmilk may be needed to ensure adequate levels in both mother and infant in the first 6 months of infant life. [ABSTRACT FROM AUTHOR]

• Novel formal synthesis of 11α,25-dihydroxyvitamin D 3. First formal synthesis of 11α,25-dihydroxyvitamin D 2. • Application of a SmI 2 mediated epoxide ring opening to introduce an 11α-hydroxy group at the CD ring moiety. Vitamin D deficiency might cause a wide variety of human disorders. As a prerequisite for appropriate diagnosis and therapy, medicinally relevant vitamin D metabolites have to be assayed most accurately and with high specificity. It has been demonstrated, that vitamin D conjugates, linked via a hydroxyl group at C11, might be promising for the development of highly specific antibodies to be employed in competitive protein binding assays. The connective synthesis of 3-TBDMS-11α,25-dihydroxyvitamin D 3 and D 2 ethers in 500 mg scale, starting from vitamin D 2 , is described. For installation of a hydroxyl group at C11 a sequence of Pd(OAc) 2 mediated oxidation of an enone, epoxidation and subsequent epoxide ring opening was applied to obtain a suitable CD-ring precursor, that was connected with an A-ring diphenylphosphine oxide by Wittig-Horner reaction. Finally, an appropriate side chain was installed, respectively. [ABSTRACT FROM AUTHOR]

• Population prevalence of gestational hypercalcemia was 1.7 % in the third trimester. • Hyperparathyroidism and vitamin D toxicity were excluded as main causes. • No cases with profiles suggestive of mutations in the CYP24A1 gene were found. • Hypercalcemic women had a relatively high serum 1,25(OH) 2 D concentration despite an appropriately suppressed PTH. Gestational hypercalcemia is associated with an increased risk of maternal, fetal and neonatal morbidity and mortality. Hypercalcemia may develop during pregnancy in individuals who were previously asymptomatic. The increased sensitivity during pregnancy may be related to physiological, gestational alterations in vitamin D and calcium metabolism and may be influenced by gene variants. The prevalence is unknown. We investigated the prevalence of hypercalcemia in trimester 3 (T3) in a population representative prospective cohort study (n = 1832) in South-West Sweden. Women with serum albumin (Alb) adjusted calcium (Ca Alb) ≥ 2.65 mmol/L in T3 (n = 30) were matched to normo-calcemic controls, and markers of calcium and vitamin D metabolism were investigated in trimester 1 (T1) and T3. Serum concentrations of Ca, phosphate (P), Magnesium (Mg), Alb and creatinine (Cr), parathyroid hormone (PTH; T3 only), vitamin D metabolites (total 25(OH)D, 1,25(OH) 2 D, 24,25(OH) 2 D, and free 25(OH)D) were analysed in T1 and T3. Ca Alb (Payne; inter-laboratory difference: UEA = 0.15 + 0.9*UGOT; UEA 2.54 = UGOT 2.65) and estimated glomerular filtration rate (eGFR; modified 4-variable MDRD) and vitamin D metabolites ratios (VMR) were calculated. Normally and non-normally distributed data were presented as mean (SD) or median (95 %CI). Group differences in relationships between vitamin D metabolites and with PTH were investigated with multiple regression analyses. Hypercalcemia in T3 was found in 1.7 % of women. PTH concentrations suggestive of primary hyperparathyroidism was found in 1 woman and none had 25(OH)D or 24,25(OH) 2 D concentrations in the toxicity range or suggestive of mutations in the CYP24A1 gene. Ca Alb was significantly higher in hypercalcemic cases compared to controls in T1 (2.44 (2.30–2.80) vs 2.37 (2.25–2.49) mmol/L) and T3 (2.63 (2.52–2.78) vs 2.46 (2.31–2.58) mmol/L). Serum P was higher among cases than controls in T3 (1.12 (0.16) vs 1.07 (0.18) mmol/L) but not in T1 (1.12 (0.18) and 1.12 (0.16) mmol/L). PTH in T3 was lower in cases (1.6 (1.6–2.8) vs 2.3 (2.1–2.8) pmol/L) but 1,25(OH) 2 D concentrations were similar. There were no significant group differences in serum 25(OH)D, free 25(OH)D, 24,25(OH) 2 D, Mg, Alb, Cr and eGFR. Regression analyses did not show significant differences between cases and controls in relationships between vitamin D metabolites and with PTH, except for the free 25(OH)D-PTH relationship and a higher free:total 25(OH)D ratio in cases at T1. In conclusion, most common causes of hypercalcemia were excluded in the majority of women. Hypercalcemic women had a relatively high serum 1,25(OH) 2 D concentration despite an appropriately suppressed PTH, suggestive of abnormal gestational adaptions. [ABSTRACT FROM AUTHOR]

Vitamin D-binding protein (VDBP), the main carrier of vitamin D, has recently been implicated in reproductive health and pregnancy outcomes including endometriosis, polycystic ovary syndrome (PCOS), pre-eclampsia, and gestational diabetes mellitus (GDM). Improved methods for measuring VDBP and an increased understanding of its role in biological processes have led to a number of newly published studies exploring VDBP in the context of pregnancy. Here, we synthesize the available evidence regarding the role of VDBP in reproductive health and pregnancy, and we highlight areas requiring further study. Overall, low levels of maternal serum VDBP concentrations have been associated with infertility, endometriosis, PCOS and spontaneous miscarriage, as well as adverse pregnancy outcomes including GDM, pre-eclampsia, preterm birth and fetal growth restriction. However, increased VDBP concentration in cervicovaginal fluid has been linked to unexplained recurrent pregnancy loss and premature rupture of membranes. Some genetic variants of VDBP have also been associated with these adverse outcomes. Further studies using more accurate VDBP assays and accounting for ethnic variation and potential confounders are needed to clarify whether VDBP is associated with reproductive health and pregnancy outcomes, and the mechanisms underlying these relationships. [ABSTRACT FROM AUTHOR]

Evidence gained from recent studies has generated increasing interest in the role of vitamin D in extraskeletal functions such as inflammation and immunoregulation. Although vitamin D deficiency has been implicated in the pathophysiology of inflammatory diseases including inflammatory bowel disease (IBD), evidence as to whether vitamin D supplementation may cure or prevent chronic disease is inconsistent. Since 25OH-vitamin D (25OHD) has been suggested to be an acute-phase protein, its utility as a vitamin D status marker is therefore questionable. In this study, possible interactions of vitamin D and inflammation were studied in 188 patients with IBD, with high-sensitivity C-reactive protein (hsCRP) levels ≥ 5 mg/dL and/or fecal calprotectin ≥ 250 µg/g defined as biochemical evidence of inflammatory activity. Levels of 25OHD and vitamin D-binding protein (VDBP) were determined by ELISA, and 1,25-dihydroxyvitamin D (1,25OHD) and dihydroxycholecalciferol (24,25OHD) by LC-MS/MS. Free and bioavailable vitamin D levels were calculated with the validated formula of Bikle. Serum 1,25OH2D and vitamin D binding protein (VDBP) levels were shown to differ between the inflammatory and noninflammatory groups: patients with inflammatory disease activity had significantly higher serum concentrations of 1,25OH2D (35.0 (16.4–67.3) vs. 18.5 (1.2–51.0) pg/mL, p < 0.001) and VDBP (351.2 (252.2–530.6) vs. 330.8 (183.5–560.3) mg/dL, p < 0.05) than patients without active inflammation. Serum 24,25OH2D levels were negatively correlated with erythrocyte sedimentation rate (ESR) (−0.155, p = 0.049) while concentrations of serum 1,25OH2D correlated positively with hsCRP (0.157, p = 0.036). Correlations with serum VDBP levels were found for ESR (0.150, p = 0.049), transferrin (0.160, p = 0.037) and hsCRP (0.261, p < 0.001). Levels of serum free and bioavailable 25OHD showed a negative correlation with ESR (−0.165, p = 0.031, −0.205, p < 0.001, respectively) and hsCRP (−0.164, p = 0.032, −0.208, p < 0.001 respectively), and a moderate negative correlation with fecal calprotectin (−0.377, p = 0.028, −0.409, p < 0.016, respectively). Serum total 25OHD concentration was the only vitamin D parameter found to have no specific correlation with any of the inflammatory markers. According to these results, the traditional parameter, total 25OHD, still appears to be the best marker of vitamin D status in patients with inflammatory bowel disease regardless of the presence of inflammation. [ABSTRACT FROM AUTHOR]

Background: Vitamin D is a well-established regulator of calcium and phosphate metabolism that has neurotrophic and neuroprotective properties. Deficiency of vitamin D has been proposed to promote cognitive dysfunction and brain atrophy. However, existing studies provide inconsistent results. Here we aimed to investigate the association between vitamin D metabolites, cognitive function and brain atrophy in a cohort of well-characterized community-dwelling elderly individuals with normal neurological status and without history of stroke and dementia., Methods: 25(OH)D 3 , 25(OH)D 2 and 24,25(OH) 2 D 3 were measured by liquid-chromatography tandem mass-spectrometry in serum samples from 390 community-dwelling elderly individuals. All participants underwent thorough neuropsychiatric tests capturing memory, executive function and visuopractical skills. In 139 of these individuals, MRI of the brain was performed in order to capture neurodegenerative and vascular changes., Results: Total 25(OH)D (ß=0.003, 0.037), 24,25(OH) 2 D 3 (ß=0.0456, p=0.010) and vitamin D metabolite ratio (VMR) (ß=0.0467, p=0.012) were significantly related to memory function. Adjustment for multiple testing weakened these relationships, but trends (p≤0.10) remained. 24,25(OH) 2 D 3 and VMR showed similar trends also for visuopractical skills and global cognitive function. No significant relationships existed between vitamin D metabolites and MRI derived indices of neurodegeneration and vascular changes. Sub-group analyses of individuals with low concentrations of 25(OH)D and 24,25(OH) 2 D 3 showed significantly worse memory function compared to individuals with normal or high concentrations., Conclusions: Vitamin D deficient individuals appear to have a modest reduction of memory function without structural brain atrophy. Future studies should explore if vitamin D supplementation can improve cognitive function.