Serum Total 25-hydroxyvitamin Research Articles

Vitamin D deficiency, parathyroid hormone levels, and bone disease among patients with end‐stage liver disease and normal serum creatinine awaiting liver transplantation

Vitamin D deficiency is common among patients with end-stage liver disease (ESLD). The primary aim of our study was to assess the prevalence of vitamin D deficiency, secondary hyperparathyroidism, and bone disease in patients with ESLD awaiting LT. We retrospectively studied 190 patients at our center. Serum total 25-hydroxyvitamin D (25-OH D), parathyroid hormone (PTH), calcium, and bone mineral analysis (BMA) were recorded. Standard World Health Organization (WHO) criteria were used to diagnose osteopenia/osteoporosis. Only patients with normal serum creatinine were analyzed. Thirty-two of 190 patients were excluded from the final analysis (missing serum total 25-OH D levels in three patients and elevated serum creatinine, 29 patients). 105 of 158 (66.4%) evaluable patients had 25-OH D levels <25 ng/mL. Patients included in the analysis (n = 158) were divided according to serum total 25-OH D levels: 0-10 ng/mL (n = 23), 11-20 ng/mL (n = 64), and >20 ng/mL (n = 71). There were no significant differences in mean serum PTH and corrected calcium levels among the three subgroups. Only three patients had elevated serum PTH. Patients with total 25-OH D ≤ 10 ng/mL had higher model for end-stage liver disease (MELD) scores vs. those with 25-OH D > 20 ng/mL (13.3 ± 3, range 8-21, vs. 11.9 ± 3.4, range 6-29, p = 0.004). Irrespective of vitamin D status, bone disease was present in 64.6% of patients. Low vitamin D levels and bone disease are common among patients with ESLD awaiting LT. Despite a high prevalence of low serum total 25-OH D, our cohort maintained normal corrected calcium levels and did not develop secondary hyperparathyroidism. We propose that free serum 25-OH D and vitamin D-binding protein may be necessary to accurately establish the diagnosis of vitamin D deficiency in the setting of ESLD. Additional studies are needed to further define mechanisms of bone disease in patients with ESLD.

The influence of vitamin D and receptor status in colorectal cancer.

435 Background: Since vitamin D is a modifiable factor, we have proposed to evaluate vitamin D levels and cognate receptor expression in patients presenting with colorectal cancer (CRC). Previously, we retrospectively assessed vitamin D receptor (VDR) level in 98 CRC tumor tissues and noted a variation of expression with tumor stage (GI ASCO 2009 abs # 371). Methods: We prospectively evaluated 38 cases of CRCs newly diagnosed during 3 consecutive summers and assessed demographics, pathological characteristics and long-term clinical outcomes. Skin color was determined by the Fitzpatrick photo typing scale. At the time of enrollment, vitamin D levels were assessed, and a twenty point lifestyle assessment questionnaire was administered. Descriptive statistics were performed. Tumor and corresponding normal tissues are being evaluated to identify the patterns of VDR expression and expression of the Wnt/B-catenin inhibitors-Dickkopft 1(DKK-1) and Dickkoft-4 (DKK-4), which have been implicated in development of CRCs. Results: 38 patients diagnosed with CRC 24 were men and 14 were women with median age at diagnosis was 59 yrs (range, 28-78 yrs). Median follow up after diagnosis was 2.1 yrs (range, 0.06, 3.68 yrs). Histological grades of adenocarcinomas were well differentiated as well (13%), moderately differentiated (66%), and poorly differentiated (7%), and mucinous types (11%). Patients were staged as I (8%), II (39%), III (34%), or IV (19%). 81% of patients were treated with chemotherapy in an adjuvant or neo-adjuvant setting. The median serum total 25-hydroxy vitamin D level was 23 ng/ml (range, 6-87 ng/ml). There was no substantial difference in median vitamin D levels between lower and higher stages (25 vs 21). Lower stages of CRC were associated with lighter skin types (Fitzpatrick scale types I and II) and advanced stages with darker skin types (IV-VI); this could be a reflection of variable VDR expression. Conclusions: We are analyzing VDR expression as a covariate to compare to vitamin D levels, skin color, and stage. Results will be reported at the time of presentation. These studies were supported by a pilot project grant by the UAB Comprehensive Cancer center.

Serum free and bio-available 25-hydroxyvitamin D correlate better with bone density than serum total 25-hydroxyvitamin D

In the circulation 25-hydroxyvitamin D (25(OH)D) is bound to vitamin D-binding protein (DBP) and albumin. Only a small fraction is in the unbound, free form. According to the ‘free-hormone-hypothesis’ only the free form is biologically active. Genetic differences in DBP may affect the binding to 25(OH)D and thereby the amount of free 25(OH)D. In the present study sera were obtained from 265 postmenopausal women with low bone mass density (BMD). Serum 25(OH)D, DBP and albumin were measured and the free and bio-available (free + albumin-bound) 25(OH)D calculated. Based on genotyping of the polymorphisms rs7041 and rs4588, the six common DBP phenotypes were identified and the free and bio-available 25(OH)D calculated according to the corresponding binding coefficients. Relations between measures of 25(OH)D and PTH and BMD were evaluated with linear regression adjusted for age and BMI. The calculated amount of free and bio-available 25(OH)D was 0.03% and 13.1%, respectively, of the measured total serum 25(OH)D. Adjusting for DBP phenotype affected the calculated free and bio-available 25(OH)D levels up to 37.5%. All measures of 25(OH)D correlated significantly with PTH, whereas a significant association with BMD was only seen for the free and bio-available 25(OH)D measures. Adjusting for the DBP phenotypes improved the associations. These relations were almost exclusively seen in subjects not using vitamin D and/or calcium supplements. In conclusion, the free and bio-available forms of 25(OH)D may be a more informative measure of vitamin D status than total 25(OH)D. Adjustment for DBP phenotype may improve this further.

Letter to the editor

Letter to the editor

Prospective Association of 25-Hydroxyvitamin D3 and D2 with Childhood Lung Function, Asthma, Wheezing, and Flexural Dermatitis

Higher serum total 25-hydroxyvitamin D (25(OH)D) concentrations have been associated with better lung function and lower risk of allergic disease. 25(OH)D3 constitutes the majority of total 25(OH)D and has been suggested to be more potent than 25(OH)D2. We studied the prospective associations of 25(OH)D2 and 25(OH)D3 with asthma, wheezing, flexural dermatitis, and lung function in children who participated in the Avon Longitudinal Study of Parents and Children-a population-based contemporary birth cohort of children born in 1991-1992 from South West England. Serum 25(OH)D2 and 25(OH)D3 concentrations, measured at a mean age of 9.8 years, were related to incident cases of wheezing (study sample: n = 3,323, 141 cases; 4%), asthma (n = 3,323, 464 cases; 14%), and flexural dermatitis (n = 3,748, 300 cases; 8%), as well as lung function (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], and mid-forced expiratory flow assessed at a mean age of 15.5 years: n = 2,259). 25(OH)D2 was inversely associated with flexural dermatitis (adjusted odds ratio per doubling of exposure = 0.83 [95% confidence interval = 0.72-0.94]) and wheezing (0.83 [0.68-1.00]), and 25(OH)D3 was positively associated with flexural dermatitis (1.09 [1.00-1.18]) and wheezing (1.14 [1.03-1.28]). 25(OH)D2 was weakly positively associated with FEV1, and FVC. 25(OH)D3 was not associated with lung function. These results suggest that higher 25(OH)D3 concentrations are associated with increased risk of wheezing and flexural dermatitis. Despite being one of the few prospective studies and being able to adjust for confounders, these findings need replication. Our results do not provide strong evidence that lower concentrations of vitamin D are detrimental to respiratory and allergic health in children.

Prospective Association of 25-Hydroxyvitamin D3 and D2 with Childhood Lung Function, Asthma, Wheezing, and Flexural Dermatitis

Higher serum total 25-hydroxyvitamin D (25(OH)D) concentrations have been associated with better lung function and lower risk of allergic disease. 25(OH)D3 constitutes the majority of total 25(OH)D and has been suggested to be more potent than 25(OH)D2. We studied the prospective associations of 25(OH)D2 and 25(OH)D3 with asthma, wheezing, flexural dermatitis, and lung function in children who participated in the Avon Longitudinal Study of Parents and Children-a population-based contemporary birth cohort of children born in 1991-1992 from South West England.Serum 25(OH)D2 and 25(OH)D3 concentrations, measured at a mean age of 9.8 years, were related to incident cases of wheezing (study sample: n = 3,323, 141 cases; 4%), asthma (n = 3,323, 464 cases; 14%), and flexural dermatitis (n = 3,748, 300 cases; 8%), as well as lung function (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], and mid-forced expiratory flow assessed at a mean age of 15.5 years: n = 2,259).25(OH)D2 was inversely associated with flexural dermatitis (adjusted odds ratio per doubling of exposure = 0.83 [95% confidence interval = 0.72-0.94]) and wheezing (0.83 [0.68-1.00]), and 25(OH)D3 was positively associated with flexural dermatitis (1.09 [1.00-1.18]) and wheezing (1.14 [1.03-1.28]). 25(OH)D2 was weakly positively associated with FEV1, and FVC. 25(OH)D3 was not associated with lung function.These results suggest that higher 25(OH)D3 concentrations are associated with increased risk of wheezing and flexural dermatitis. Despite being one of the few prospective studies and being able to adjust for confounders, these findings need replication. Our results do not provide strong evidence that lower concentrations of vitamin D are detrimental to respiratory and allergic health in children.

Vitamin D and depression in geriatric primary care patients.

Purpose:Vitamin D deficiency is common in the elderly. Vitamin D deficiency may affect the mood of people who are deficient. We investigated vitamin D status in older primary care patients and explored associations with depression.Patients and methods:A cross-sectional study was conducted and association analyses were performed. Primary care patients at a single academic medical center who were ≥60 years with serum total 25-hydroxyvitamin D (25[OH]D) levels were included in the analysis. The primary outcome was a diagnosis of depression. Frailty scores and medical comorbidity burden scores were collected as predictors.Results:There were 1618 patients with a mean age of 73.8 years (±8.48). The majority (81%) had optimal (≥25 ng/mL) 25(OH)D range, but 17% met mild-moderate (10–24 ng/mL) and 3% met severe (<10 ng/mL) deficiencies. Those with severe deficiency were older (P < 0.001), more frail (P < 0.001), had higher medical comorbidity burden (P < 0.001), and more frequent depression (P = 0.013). The 694 (43%) with depression had a lower 25(OH)D than the nondepressed group (32.7 vs 35.0, P = 0.002). 25(OH)D was negatively correlated with age (r = −0.070, P = 0.005), frailty (r = −0.113, P < 0.001), and medical comorbidity burden (r = −0.101, P < 0.001). A 25(OH)D level was correlated with depression (odds ratio = 0.990 and 95% confidence interval [CI] = 0.983–0.998, P = 0.012). Those with severe vitamin D deficiency were twice as likely to have depression (odds ratio = 2.093 with 95% CI 1.092–4.011, P = 0.026).Conclusion:Vitamin D deficiency was present in a fifth of this older primary care population. Lower vitamin D levels were associated with depression. Those with severe deficiency were older and more likely had depression.

Ergocalciferol from Mushrooms or Supplements Consumed with a Standard Meal Increases 25-Hydroxyergocalciferol but Decreases 25-Hydroxycholecalciferol in the Serum of Healthy Adults1–3

Few foods contain ergocalciferol or cholecalciferol. Treatment of mushrooms with UV light increases ergocalciferol content and could provide a dietary source of vitamin D. We evaluated the impact of consuming UV-treated white button mushrooms (Agaricus bisporus) on the vitamin D status of healthy adults. Thirty-eight volunteers were randomized to 4 treatments consumed with a standard meal for 6 wk: the control (C) group received untreated mushrooms providing 0.85 μg/d ergocalciferol (n = 10); groups M1 and M2 received UV-treated mushrooms providing 8.8 (n = 10) and 17.1 μg/d (n = 9), respectively; and the supplement (S) group received purified ergocalciferol plus untreated mushrooms, providing a total of 28.2 μg/d (n = 9). Serum total 25-hydroxyvitamin D [25(OH)D] and 25-hydroxyergocalciferol [25(OH)D2] were 83 ± 38 and 2.4 ± 2.0 nmol/L, respectively, at baseline (mean ± SD). At wk 6, 25(OH)D2 had increased and was higher in all treatment groups than in the C group, whereas 25-hydroxycholecalciferol [25(OH)D3] had decreased and was lower in the M2 and S groups than in the C group. Increases in 25(OH)D2 for groups C, M1, M2, and S were 1.2 ± 5.2, 13.8 ± 7.3, 12.7 ± 3.7, and 32.8 ± 3.3 nmol/L and decreases in 25(OH)D3 were -3.9 ± 16.3, -10.4 ± 6.4, -20.6 ± 14.6, and -29.5 ± 15.9 nmol/L, respectively. Concentrations did not change in group C. In summary, ergocalciferol was absorbed and metabolized to 25(OH)D2 but did not affect vitamin D status, because 25(OH)D3 decreased proportionally.

Treatment with 50000 IU Vitamin D2 Every Other Week and Effect on Serum 25-Hydroxyvitamin D2, 25-Hydroxyvitamin D3, and Total 25-Hydroxyvitamin D in Aclinical Setting

To examine the effect of 50,000 IU-vitamin D₂ supplementation in a clinical setting on serum total 25-hydroxyvitamin D (25[OH]D), 25-hydroxyvitamin D₂ (25[OH]D₂), and 25-hydroxyvitamin D3 (25[OH]D₃). This retrospective cohort study was performed in an urban tertiary referral hospital in Boston, Massachusetts. Patients who had been prescribed 50,000 IU vitamin D₂ repletion and maintenance programs were identified through a search of our electronic medical record. Baseline and follow-up total serum 25(OH)D, 25(OH)D₂, and 25(OH)D₃ levels were compared. We examined the medical records of 48 patients who had been prescribed 50,000 IU vitamin D₂ in our clinic. Mean ± standard deviation baseline total 25(OH)D was 31.0 ± 10.6 ng/mL and rose to 48.3 ± 13.4 ng/mL after treatment (P<.001). 25(OH)D₂ increased from 4.2 ± 4.3 ng/mL to 34.6 ± 12.3 ng/mL after treatment (P<.001), for an average of 158 days (range, 35-735 days). Serum 25(OH)D₃ decreased from 26.8 ± 10.8 ng/mL to 13.7 ± 7.9 ng/mL (P<.001). Fifty thousand IU vitamin D₂ repletion and maintenance therapy substantially increases total 25(OH)D and 25(OH)D₂ despite a decrease in serum 25(OH)D₃. This treatment program is an appropriate and effective strategy to treat and prevent vitamin D deficiency.

Clinical relevance of serum total 25-hydroxyvitamin D as measured by immunoassay and turboflow LC-MS/MS

Clinical relevance of serum total 25-hydroxyvitamin D as measured by immunoassay and turboflow LC-MS/MS

Low Vitamin D Status Among Obese Adolescents: Prevalence and Response to Treatment

To explore the prevalence of low vitamin D status among obese adolescents and to examine the effect of current management of low vitamin D status in these patients. A retrospective chart review of obese adolescents who had been screened for vitamin D status by serum total 25-hydroxyvitamin D (25(OH)D) level. Vitamin D deficiency was defined as 25(OH)D level of <20 ng/mL, vitamin D insufficiency as 25(OH)D level of 20-30 ng/mL, and vitamin D sufficiency as 25(OH)D level of >30 ng/mL. Adolescents with vitamin D deficiency were treated with 50,000 IU of vitamin D once a week for 6-8 weeks, whereas adolescents with vitamin D insufficiency were treated with 800 IU of vitamin D daily for 3 months. Repeat 25(OH)D was obtained after treatment. The prevalence rate of low vitamin D status among 68 obese adolescents (53% females, 47% males, age: 17 ± 1 years, body mass index: 38 ± 1 kg/m(2), Hispanic: 45%, African American: 40%, Caucasian: 15%) was 100% in females and 91% in males. Mean (±SE) 25(OH)D level was significantly higher in summer (20 ± 8 ng/mL) than in spring (14 ± 4 ng/mL, p < .02), and significantly lower in winter (15 ± 7 ng/mL) than in fall (25 ± 15 ng/mL, p < .05). Although there was a significant (p < .00001) increase in mean 25(OH)D after the initial course of treatment with vitamin D, 25(OH)D levels normalized in only 28% of the participants. Repeat courses with the same dosage in the other 72% did not significantly change their low vitamin D status. Increased surveillance and possibly higher vitamin D doses are warranted for obese adolescents whose total 25(OH)D levels do not normalize after the initial course of treatment.

An evaluation of automated methods for measurement of serum 25-hydroxyvitamin D

Objectives To compare two new automated assays with the well-established reference method, DiaSorin radioimmunoassay (RIA), for quantitation of serum total 25-hydroxyvitamin D [25(OH)D]. Methods 25(OH)D from human sera ( n = 158) was measured using DiaSorin RIA and two automated platforms, DiaSorin “LIAISON 25 OH Vitamin D TOTAL”, and Roche Modular “Vitamin D3 (25-OH)”. Methods were compared by regression and Bland–Altman analyses. Results DiaSorin LIAISON demonstrated a stronger correlation ( r = 0.918) and better agreement (bias = − 0.88 nmol/L) with DiaSorin RIA than the Roche Modular assay ( r = 0.871, bias = − 2.55 nmol/L). Precision ranges (CV%) for the RIA, LIAISON, and Roche Modular assays, respectively, were: within run (6.8–12.9%, 2.8–8.1%, and 1.9–5.5%), and total precision (7.4–14.5%, 7.3–17.5%, and 7.6–14.5%). Conclusion DiaSorin LIAISON displayed the best correlation and agreement with DiaSorin RIA. The DiaSorin LIAISON 25 OH Vitamin D TOTAL assay is an accurate and precise automated tool for serum total 25(OH)D determination.

Altered levels of biochemical indices of bone turnover and bone‐related vitamins in patients with Crohn's disease and ulcerative colitis

The pathogenesis of inflammatory bowel disease-associated osteopenia may be related to pathological rates of bone turnover; however, the literature shows mixed results. To compare bone biomarkers in inflammatory bowel disease patients (Crohn's disease: n = 68, and ulcerative colitis: n = 32, separately) with age- and sex-matched healthy controls. Patients and controls were recruited from Cork University Hospital and Cork City area, respectively. Relative to that in their respective controls, Crohn's disease (n = 47) and ulcerative colitis (n = 26) patients (i.e. excluding supplement users) had significantly (P < 0.05-0.001) higher serum undercarboxylated osteocalcin (by 27% and 63%, respectively) and bone-specific alkaline phosphatase (by 15% and 21%, respectively) and urinary Type I collagen cross-linked N-telopeptides concentrations (by 87% and 112%, respectively). Relative to that in their respective controls, Crohn's disease and ulcerative colitis patients had significantly (P < 0.01) lower serum total osteocalcin (by 20% and 42%, respectively) and 25-hydroxyvitamin D (by 37% and 42%, respectively), while serum parathyroid hormone levels were similar. In the combined patient group (n = 100), undercarboxylated osteocalcin was positively associated with bone markers. Both Crohn's disease and ulcerative colitis patients have altered bone turnover relative to that in healthy controls.

Hipovitaminose D em adultos: entendendo melhor a apresentação de uma velha doença

Vitamin D is synthesized in skin through a reaction mediated by sunlight, and it is metabolized to 25-hydroxyvitamin D, in liver, and in 1,25-dihydroxyvitamin D, in kidney. This last reaction has a tight feedback mechanism. 1,25-dihydroxyvitamin D is the active hormone, and its actions are mediated mainly by nuclear receptors. Its major functions are in calcium metabolism and bone mass maintenance. Hypovitaminosis D, as a disease in adult people, manifests itself with hypocalcemia and secondary hyperparathyroidism with subsequent loss of trabecular bone, thinning of cortical bone, and, eventually, a higher risk of fractures. Hypovitaminosis D is a very common condition in Europe, Africa, North America and some South American countries, such as Chile and Argentina. Measurement of serum total 25-hydroxyvitamin D concentration is the gold standard to diagnose vitamin D deficiency. Serum concentrations below 50 nmol/L are associated with an increase in parathyroid hormone concentration, and bone loss. Risk factors for vitamin D deficiency, like poor sunlight exposition, aging skin and factors that interfere with normal vitamin D metabolism, are well established. Oral vitamin D supplementation, an easy and inexpensive treatment, is needed to treat this illness.

528 BONE MINERALIZATION IN BREAST-FED PREMATURE INFANTS

Based on the calcium (Ca) and phosphate (P) requirements of premature infants, human milk (HM) may not provide for optimal bone mineralization. To determine the adequacy of HM in nursing premature infants we studied 11 breast-fed and 9 SimilacR (SIM) fed infants during the first 16 weeks of life. There were no differences between both groups in gestational age (33.7±0.5 (M±SE) for HM vs. 32.2±0.8 wks for SIM) or birth weight (1.98±.14 vs. 1.77±.16 kg). At 4-8 wks and 12-16 wks of age, bone mineral content (BMC) was measured by direct photon absorptiometry of the left wrist and blood drawn for serum total Ca, P, alkaline phosphatase (AP) and 25-hydroxyvitamin D (25-OH D) levels. At 4-8 wks, there were no differences between the HM or SIM groups in BMC (X, 65 vs. 58 mg/cm), P (X, 7.3 vs. 8.3 mg/dl), AP (X, 163 vs. 156 IU/L; normal children 47-112 IU/L), 25-OH D (X, 16 vs. 20 ng/m1; adult normal 10-40 ng/m1) or weight (X, 2.60 vs. 2.84 kg). The HM group had a higher serum Ca level than SIM (10.75±.08 vs. 9.99±.21 mg/d1, p<.01). Again, at 12-16 wks, there were no differences in BMC (x, 104 for HM vs. 88 mg/cm for SIM), Ca (X, 10.75 vs. 10.66 mg/d1), AP (x, 134 vs. 144 IU/L) or 25-OH D (X, 16 vs. 20 ng/ml) or weight (X, 4.26 kg for HM vs. 4.83 kg for SIM, p< .20). Our preliminary data suggest that human milk provides sufficient nutrients for bone mineralization in premature infants.