Canadian recommendations for vitamin D intake for persons affected by multiple sclerosis.

In 2016, the Multiple Sclerosis (MS) Society of Canada convened a panel of expert scientists, clinicians and patient advocate to review the evidence for an association between vitamin D status and MS prevention and/or disease modification. The goal was to develop clear and accurate recommendations on optimal vitamin D intake and status for people affected by MS for use in clinical practice and public health policy. The final consensus report was based on a review and grading of existing published papers combined with expert opinions of panel members. The report led to recommendations published in November of 2018 on the website of the MS Society of Canada, one in a format for use by health professionals and another in a question and answer format that was targeted to persons affected by MS and the general public. For people at risk of developing MS, the vitamin D recommendations are similar to those for the general public following the Dietary Reference Intakes (DRI) for Canada and the United States. Adults should achieve and maintain a normal vitamin D status with monitoring by physicians (serum 25-hydroxyvitamin D (25(OH)D) = 50-125 nmol/L, requiring 600-4000 IU vitamin D/d intake). For pregnant women, newborn infants, and all youth at risk of MS, vitamin D intakes should also follow DRI recommendations but additionally their serum 25-(OH)D should be monitored. For persons living with MS, existing evidence did not allow prediction of a vitamin D intake that might modify MS disease course. For this group the recommendations included: (1) serum 25-(OH)D should be maintained in the range of 50-125 nmol/L (600-4000 IU/d intake).; and (2) vitamin D should not be used as a standalone treatment for MS. For children and adolescents, serum 25OHD status was recommended to be measured upon diagnosis of a first clinical demyelinating event, and monitored every 6 months to achieve a target of 75 nmol/L Since people living with MS are at increased risk of osteoporosis, falls, and bone fractures, it was recommended to achieve a minimum serum 25OHD concentration that is protective for bone health in the general population. The revision of the MS Society recommendations on vitamin D awaits future clinical trial evidence.

Safety and Tolerability of Targeted Medical Nutrition for Cachexia in Non-Small-Cell Lung Cancer: A Randomized, Double-Blind, Controlled Pilot Trial.

Background: This pilot, double-blind, comparator-controlled trial evaluated the safety and tolerability of an oral targeted medical nutrition (TMN) supplement for the management of cachexia in patients with non-small-cell lung cancer (NSCLC).Methods: Patients receiving first-line chemotherapy for NSCLC with weight loss or low BMI were randomized 1:1 to receive juice-based TMN (∼200 kcal; 10 g whey protein; ≥2.0 g eicosapentaenoic acid/docosahexaenoic acid in fish oil; and 10 µg 25-hydroxy-vitamin D3) or a milk-based isocaloric comparator twice daily for 12 weeks (ClinicalTrials.gov: NCT02515032). Primary endpoints included number/type of adverse events and changes in vital signs/laboratory parameters. Secondary endpoints included measures of clinical relevance. Survival was an exploratory endpoint.Results: The TMN group (n = 26; mean 64.4 years) experienced fewer adverse events (64 vs. 87) than the comparator group (n = 29; mean 66.0 years), including fewer cases of neutropenia (0 vs. 4). Compliance was slightly lower in the TMN (58.5%) vs. comparator group (73.6%). There were no statistically significant between-group differences in efficacy endpoints. Fewer (4 vs. 10) patients who received TMN than comparator had died by 1-year post baseline.Conclusions: TMN was well tolerated. Trends for improved clinical outcomes with TMN identified in this study warrant further investigation.

Evaluating extended-release calcifediol as a treatment option for chronic kidney disease-mineral and bone disorder (CKD-MBD).

Introduction: Extended-release calcifediol (ERC) is an orally administered prohormone of active vitamin D (1,25-dihydroxyvitamin D [1,25D]) designed to safely and sufficiently increase serum total 25-hydroxyvitamin D (25D) to reduce elevated parathyroid hormone (PTH) in patients with non-dialysis-chronic kidney disease (ND-CKD). ERC is currently approved in the United States and Canada.Areas covered: Herein, key clinical data relating to the pharmacokinetics, pharmacodynamics, efficacy and safety of ERC are reviewed.Expert opinion: Currently available treatment options for secondary hyperparathyroidism (SHPT) in ND-CKD have limitations: the effectiveness of nutritional vitamin D supplements for reduction of PTH levels is unproven and active (1α-hydroxylated) vitamin D analogues elevate serum calcium, which increases the risk of hypercalcemia and vascular calcification. Clinical studies show that ERC is an effective, well tolerated treatment for SHPT in ND-CKD. ERC gradually raises serum 25D levels, resulting in physiologically regulated increases in serum 1,25D and sustained reductions in PTH, while avoiding clinically meaningful increases in serum phosphorus, calcium and fibroblast growth factor 23. ERC offers a new, effective and well tolerated treatment option for the early management of SHPT in patients with ND-CKD.

Questioning the Safety of Calcidiol in Hemodialysis Patients.

BACKGROUND: Epidemiological studies have suggested a survival benefit for hemodialysis patients on paricalcitol or calcitriol, but nutritional vitamin D supplementation of patients already on vitamin D receptor (VDR) activators is controversial. METHODS: This observational retrospective cohort study was conducted with prospectively collected data from all consecutive patients with chronic kidney disease (CKD) who underwent hemodialysis under routine clinical practice conditions for two years. RESULTS: Of the 129 patients, 89 were treated with calcidiol, paricalcitol, and/or calcitriol. The patients with any vitamin D formulation had higher serum concentrations of 25-hydroxy vitamin D and fibroblast growth factor-23 and tended to have higher mortality rates (42% vs. 25%, p = 0.07). On subgroup analysis, any calcidiol treatment or calcidiol combined with paricalcitol associated with significantly higher mortality rates than no treatment (47% and 62.5%, p = 0.043 and 0.008, respectively). The association between calcidiol/paricalcitol treatment and elevated mortality remained significant after adjusting for age, sex, diabetes, C-reactive protein, and hemodialysis vintage. Any calcidiol and calcidiol/paricalcitol treatment exhibited a dose-response relationship with mortality (p for trend: 0.002 and 0.005, respectively). CONCLUSIONS: These data draw attention to the hitherto unexplored safety of calcidiol supplementation in patients on hemodialysis, especially in those already on vitamin D. Until clinical trials demonstrate the safety and efficacy of this approach, caution should be exercised when prescribing these patients ≥0.5 calcidiol mg/month.

Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens.

RATIONALE: Calcidiol can be employed to correct vitamin D deficiency. MAIN RESULTS: Calcidiol administered at daily and weekly regimens over a period of 3 months was able to successfully raise 25-hydroxyvitamin D levels without altering other markers related to bone and mineral metabolism. SIGNIFICANCE: Calcidiol supplementation is effective and safe. INTRODUCTION: The correction of vitamin D status is necessary to maintain an optimal mineral and skeletal homeostasis. Despite cholecalciferol (vitamin D3) is the most commonly used drug for vitamin D supplementation, the more hydrophilic compound calcidiol (25-hydroxyvitamin D3) can be employed at daily, weekly, and monthly regimens to reach in the short term the target levels of serum 25-hydroxyvitamin D [25(OH)D]. In the administration of different doses of calcidiol pharmacokinetic study (ADDI-D study), the efficacy and safety of daily and weekly dosages of calcidiol were tested. METHODS: A total of 87 Caucasian, community-dwelling, postmenopausal women, aged 55 years or older, with vitamin D inadequacy (serum 25(OH)D levels <30 ng/ml, with mean 25(OH)D below 20 ng/ml, namely 16.5 ± 7.5 ng/ml) were randomized to receive three different dosages of calcidiol: 20 µg/day, 40 µg/day, and 125 µg/week for 3 months. The attained level of serum 25(OH)D was selected as primary endpoint to assess efficacy, while other parameters of mineral metabolism, (serum calcium, parathyroid hormone, phosphate, FGF23, urinary calcium, and markers of bone turnover) were assessed as secondary endpoints to establish safety. RESULTS: In all the three groups, serum 25(OH)D values significantly and promptly rose and plateaued above the 30 ng/ml threshold remaining within safety interval after 14 days of treatment, with similar efficacy for the similar daily and weekly dose regimens. The different dosages were also equally effective in controlling secondary hyperparathyroidism. No significant changes in calcium and phosphate metabolism and in bone turnover markers were observed for any of the treatments, confirming the safety of this compound. CONCLUSIONS: The results of this study demonstrate the short- and mid-term efficacy and safety on core parameters of mineral metabolism of different daily or weekly dosages of calcidiol when used to treat vitamin D inadequacy or deficiency in postmenopausal women. Further studies are needed to assess falls as primary outcome of calcidiol supplementation.

Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKD.

BACKGROUND AND OBJECTIVES: Vitamin D is implicated in vascular health in CKD. This study compared placebo, calcifediol, and calcitriol treatment with changes in vascular stiffness, BP, proteinuria, mineral metabolism parameters, C-reactive protein, and fibroblast growth factor 23 in patients with stable CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a double-blind, randomized controlled trial in out-patient CKD clinics in Vancouver, Canada, from February of 2011 to August of 2014, enrolling 119 patients with an eGFR of 15-45 ml/min per 1.73 m2. Change in pulse wave velocity (PWV) was measured after 6 months of treatment with a fixed dose of oral calcifediol (5000 IU 25-hydroxyvitamin D3), calcitriol (0.5 µg 1,25-dihydroxyvitamin D3), or placebo, thrice weekly. RESULTS: Eighty-seven participants were evaluated. Mean age was 66 years, 71% were men, 40% were diabetic, and mean baseline PWV was 11.5 m/s (SD=3.9 m/s). After 6 months, the PWV decreased in the calcifediol group (mean change, -1.1; 95% confidence interval [95% CI], -2.2 to 0.1 m/s), remained unchanged in the calcitriol group (mean change, 0.2; 95% CI, -0.9 to 1.4 m/s), and increased in the placebo group (mean change, 1.1; 95% CI, -0.1 to 2.2 m/s). The overall P value for between-arm changes was 0.03. Absolute PWV change was significantly different between groups (P=0.04): the combined vitamin D treatment group saw decreased PWV (mean change, -0.4; 95% CI, -1.2 to 0.4 m/s) whereas the placebo group saw increased PWV (mean change, +1.1; 95% CI, -0.1 to 2.2 m/s). The treatment group demonstrated significantly decreased serum parathyroid hormone (mean difference, -0.5; 95% CI, -0.7 to -0.3 ln[pg/ml]; P<0.001) and increased calcium (mean difference, 0.4; 95% CI, -0.1 to 0.7 mg/dl; P=0.02). In observational analysis, participants in the highest 25-hydroxyvitamin D tertile at trial end had significant decreases in PWV (mean change, -1.0; 95% CI, -2.0 to 0.0 m/s) compared with the middle and lowest tertiles (P<0.01). Side effects were minor and rare. CONCLUSIONS: Six months of supplemental vitamin D analogs at fixed doses may achieve a reduction of PWV in patients with advanced CKD. Because the treatment effect was attenuated when baseline PWV was included as a covariate, these findings should be replicated in larger populations and further studied.

Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease.

BACKGROUND/AIMS: Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23. METHODS: Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites. A total of 429 subjects, balanced between studies, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency were randomized 2:1 to receive oral ER calcifediol (30 or 60 µg) or placebo once daily at bedtime for 26 weeks. Most subjects (354 or 83%) completed dosing, and 298 (69%) entered a subsequent open-label extension study wherein ER calcifediol was administered without interruption for another 26 weeks. RESULTS: ER calcifediol normalized serum total 25-hydroxyvitamin D concentrations (>30 ng/ml) in >95% of per-protocol subjects and reduced plasma intact parathyroid hormone (iPTH) by at least 10% in 72%. The proportion of subjects receiving ER calcifediol who achieved iPTH reductions of ≥30% increased progressively with treatment duration, reaching 22, 40 and 50% at 12, 26 and 52 weeks, respectively. iPTH lowering with ER calcifediol was independent of CKD stage and significantly greater than with placebo. ER calcifediol had inconsequential impact on serum calcium, phosphorus, FGF23 and adverse events. CONCLUSION: Oral ER calcifediol is safe and effective in treating SHPT and vitamin D insufficiency in CKD.

Tolerance evaluation of overdosed dietary levels of 25-hydroxyvitamin D3 in growing piglets.

Forty-eight, cross-bred (GL × LW × P) piglets were used in a 42-day tolerance trial to assess the effects of feeding diets supplemented with vitamin D or increasing levels of 25-hydroxyvitamin D3 (25-OH-D3 ). Six-week-old piglets (24 castrate males, 24 females) were used. Two replicate groups of 6 piglets were randomized by weight and allocated to four dietary treatments. The control group (T1) was supplemented with 50 µg vitamin D3 /kg feed. The experimental groups received 25-OH-D3 at the recommended dose (T2: 50 µg/kg = 1x), at 250 µg/kg (T3: 5x) or at 500 µg/kg (T4: 10x) respectively. Feed intake and daily weight gain were measured weekly, and the animals were examined by a veterinarian daily. After 42 days, body mass, blood, urine, bone and tissue samples were analysed and a pathology examination conducted. Dietary treatments had no significant effect on final body mass or daily weight gain. The 25-OH-D3 plasma concentration in T1 was 17 ± 3 ng/ml (mean ± SD) while the respective values of the experimental groups were significantly increased in T2, T3 and T4. Tissue concentrations of 25-OH-D3 were higher in liver and muscle for T3 and T4 and in skin for T4 than in T1. However, neither gross pathology nor histology, nor blood and urine characteristics, nor bone parameters were affected by dietary treatments. Weight of organs as well as dry matter, ash and calcium content of kidneys remained unaffected by dietary 25-OH-D3 intake. Furthermore, no changes were observed for general indicators of health. The results of this study demonstrated that feeding piglets with 25-OH-D3 at 5 or 10 times the recommended level had no adverse effects on any of the biological parameters measured. It was concluded that 25-OH-D3 can be regarded as a supplement with a very high safety margin when used at the recommended level.

Comparison of two different vitamin D supplementation regimens with oral calcifediol in kidney transplant patients.

INTRODUCTION: Vitamin D deficiency is prevalent in kidney transplant recipients (KTR) and recommendations on how to replenish vitamin D deposits are scarce. AIM: To evaluate, in KTR, the safety and efficacy of calcifediol in two different vitamin D supplementation regimens, in order to assess the most suitable dose. PATIENTS AND METHODS: Prospective observational study with two calcifediol supplementation regimens randomly prescribed by clinicians in liquid form, at 266 mcg doses, monthly or biweekly. We analyzed 168 KTR with a functioning allograft for more than 6 months. Patients receiving other vitamin D forms, calcimimetics or bisphosphonates were excluded. Before calcifediol initiation (pre-treatment levels) and after at least 3 months of treatment (post-treatment levels), we measured serum levels of 25-OH vitamin D (25(OH)D), parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium (sCa), phosphate (sPO4) and creatinine (sCreat). RESULTS: In the monthly group (n = 72), 25(OH)D levels increased from 14 ng/ml [interquartile range, IQR 9-22] at baseline to 31 [20-38] (p = 0.000), PTH decreased from 124 pg/ml [87-172] to 114 [78-163] (p = 0.006), while sCa and sPO4 remained stable. In the biweekly group (n = 96), 25(OH)D increased from 14 ng/ml [9-20] at baseline to 39 [28-52] (p = 0), PTH decreased from 141 pg/ml [95-221] to 112 [90-180] (p = 0.000), sCa remained stable and sPO4 increased from 3.3 ± 0.6 mg/dl to 3.5 ± 0.6 (p = 0.003). Renal function remained stable in both groups. CONCLUSION: Vitamin D reposition with oral calcifediol, in a biweekly or monthly regimen, is safe and effective in improving 25(OH)D blood levels and in decreasing PTH in kidney transplant recipients.

Vitamin D and Calcium Attenuate Bone Loss With Antiretroviral Therapy Initiation: A Randomized Trial.

BACKGROUND: Antiretroviral therapy initiation for HIV-1 infection is associated with 2% to 6% loss of bone mineral density (BMD). OBJECTIVE: To evaluate the effect of vitamin D3 plus calcium supplementation on bone loss associated with antiretroviral therapy initiation. DESIGN: 48-week prospective, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT01403051). SETTING: 39 AIDS Clinical Trials Group units. PATIENTS: Adults with antiretroviral therapy-naive HIV. MEASUREMENTS: BMD by dual-energy x-ray absorptiometry, 25-hydroxyvitamin D levels, and other laboratory assessments. RESULTS: 165 eligible patients were randomly assigned (79 received vitamin D3 plus calcium and 86 received placebo). The study groups were well-balanced at baseline: 90% were men, 33% were non-Hispanic black, and the median CD4 count was 0.341 × 109 cells/L. At 48 weeks, the percentage of decline in total hip BMD was smaller in the vitamin D3 plus calcium group than in the placebo group: Medians were -1.36% (interquartile range [IQR], -3.43% to 0.50%) and -3.22% (IQR, -5.56% to -0.88%), respectively (P = 0.004). Similar results were seen at the lumbar spine. At 48 weeks, 90% of patients achieved HIV-1 RNA levels less than 50 copies/mL. Levels of 25-hydroxyvitamin D3 increased with vitamin D3 plus calcium but not with placebo: Median change was 61.2 nmol/L (IQR, 36.4 to 94.3) versus 1.7 nmol/L (IQR, -13.2 to 10.7) (P < 0.001). Overall, 103 patients (62%) reported 1 or more adverse event, with similar distribution between groups; no cases of hypercalcemia and 1 case of nephrolithiasis were reported in the placebo group. LIMITATION: No international sites were included, and follow-up was only 48 weeks. CONCLUSION: Vitamin D3 plus calcium supplementation mitigates the BMD loss seen with initiation of efavirenz/emtricitabine/tenofovir disoproxil fumarate.

Encefalopatía metabólica secundaria a intoxicación por vitamina D / Metabolic encephalopathy secondary to vitamin d intoxication

La asociación entre la deficiencia de vitamina D y un mayor riesgo de diversas enfermedades, entre ellas cardiovasculares y autoinmunes, ha aumentado en los últimos años el uso de suplementos para la normalización de los valores plasmáticos de esta vitamina. Desde entonces se ha descrito un mayor número de casos de intoxicación iatrogénica por vitamina D. Presentamos una enferma de 81 años con encefalopatía metabólica e insuficiencia renal secundarias a una intoxicación por vitamina D. Los suplementos orales con calcio y vitamina D se le prescribieron después de sufrir una fractura vertebral osteoporótica. La enferma mejoró clínica y analíticamente tras hidratación y diuréticos. Es importante destacar la hipercalcemia como causa de encefalopatía metabólica y considerar la intoxicación por vitamina D como etiología poco frecuente pero posible de hipercalcemia e insuficiencia renal reversibles (AU)

The association between vitamin D deficiency and increased risk of, among others, cardiovascular and autoimmune diseases has lead in the last years to an enhanced interest in the usage of supplements to achieve the normalization of plasmatic values at 25(OH) D. Apparently this search for normalization is resulting in an higher incidence on vitamin D intoxication. We present the case of an 81 years old woman with metabolic encephalopathy and renal failure secondary to iatrogenic vitamin D intoxication. Calcium and vitamin D oral supplements were prescribed after an osteoporotic vertebral fracture. The patient improved clinically as well as analytically after receiving treatment with diuretics and hydration. We emphasize the importance of discarding hypercalcemia as a cause of metabolic encephalopathy; moreover we highly recommend keeping vitamin D intoxication in mind as an uncommon although always possible etiology of reversible hypercalcemia and renal failure (AU)

Active vitamin D and accelerated progression of aortic stiffness in hemodialysis patients: a longitudinal observational study.

BACKGROUND: We hypothesized that high-dose active vitamin D therapy in the form of alphacalcidol (α-calcidol), used to treat secondary hyperparathyroidism in chronic kidney disease, could lead to vascular calcification and accelerated progression of aortic stiffness. METHODS: We conducted an observational study in 85 patients on chronic hemodialysis, among which 70 were taking a weekly dose of α-calcidol of <2 µg and 15 were taking a weekly dose of ≥2 µg (pharmacological dose). Parathyroid hormone, 25-hydroxyvitamin D, fibroblast growth factor 23, and α-klotho were determined. Aortic stiffness was assessed by determination of carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. A multivariable regression model was used to evaluate the impact of pharmacological dose of α-calcidol on the progression of aortic stiffness. RESULTS: At baseline, clinical, biological, and hemodynamic parameters were similar. At follow-up, cf-PWV increased more in patients with pharmacological dose of α-calcidol (0.583±2.291 m/s vs. 1.948±1.475 m/s; P = 0.04). After adjustment for changes in mean blood pressure and duration of follow-up, pharmacological dose of α-calcidol was associated with a higher rate of progression of cf-PWV (0.969 m/s; 95% confidence interval = 0.111-1.827; P = 0.03), and this association persisted after further adjustments for parameters of mineral metabolism. CONCLUSIONS: In this study, pharmacological dose of α-calcidol was associated with accelerated progression of aortic stiffness. This study suggest that the vascular safety of active vitamin D posology may need to be specifically addressed in the treatment of chronic kidney disease-related bone mineral disorder.

[Metabolic encephalopathy secondary to vitamin D intoxication]. / Encefalopatía metabólica secundaria a intoxicación por vitamina D.

The association between vitamin D deficiency and increased risk of, among others, cardiovascular and autoimmune diseases has lead in the last years to an enhanced interest in the usage of supplements to achieve the normalization of plasmatic values at 25(OH) D. Apparently this search for normalization is resulting in an higher incidence on vitamin D intoxication. We present the case of an 81 years old woman with metabolic encephalopathy and renal failure secondary to iatrogenic vitamin D intoxication. Calcium and vitamin D oral supplements were prescribed after an osteoporotic vertebral fracture. The patient improved clinically as well as analytically after receiving treatment with diuretics and hydration. We emphasize the importance of discarding hypercalcemia as a cause of metabolic encephalopathy; moreover we highly recommend keeping vitamin D intoxication in mind as an uncommon although always possible etiology of reversible hypercalcemia and renal failure.

La asociación entre la deficiencia de vitamina D y un mayor riesgo de diversas enfermedades, entre ellas cardiovasculares y autoinmunes, ha aumentado en los últimos años el uso de suplementos para la normalización de los valores plasmáticos de esta vitamina. Desde entonces se ha descrito un mayor número de casos de intoxicación iatrogénica por vitamina D. Presentamos una enferma de 81 años con encefalopatía metabólica e insuficiencia renal secundarias a una intoxicación por vitamina D. Los suplementos orales con calcio y vitamina D se le prescribieron después de sufrir una fractura vertebral osteoporótica. La enferma mejoró clínica y analíticamente tras hidratación y diuréticos. Es importante destacar la hipercalcemia como causa de encefalopatía metabólica y considerar la intoxicación por vitamina D como etiología poco frecuente pero posible de hipercalcemia e insuficiencia renal reversibles.

On-line haemodiafiltration improves response to calcifediol treatment.

INTRODUCTION: 25-hydroxy vitamin D (25-OH-vit D) levels in the blood are associated with multiple pathologies. "Normal" values have been defined based on cardiovascular risk, and under this framework, patients with chronic kidney disease often have a deficit. 25-OH-vit D replacement in patients on haemodialysis (HD), in which dosage has not yet been clearly established, is becoming a constant in our daily practice. OBJECTIVE: To assess whether dialysis technique influences the baseline concentration of 25-OH-vitamin D and the response to supplements. METHOD: Prospective observational study of two cohorts of patients, those patients treated with calcifediol and those untreated (controls). Blood levels of Ca, P, PTH, and 25-OH-vit D were measured in 59 prevalent patients on HD (35 male; mean age: 65.2 (15.7) years) in November 2010. Thirty-six patients with 25-OH-vit D<10 ng/ml were treated with weekly calcifediol (Hidroferol®, 1 ampoule: 266 µg) since January 2011, which was administered after HD by a nurse. They received 6 doses, and blood levels were measured again in March 2011. We compared the response based on the technique of HD (online haemodiafiltration [OL-HDF] vs HD). RESULTS: Mean baseline values (n=59): 25-OH-vit D: 9.8 (7.0)ng/ml, Ca: 9.3 (0.5)mg/dl, P: 4.5 (1.4)mg/dl, and iPTH: 299 (224)pg/ml. There were no differences by age, sex, or dialysis technique (HD vs OL-HDF). Treated patients (n=36): 25-OH-vit D levels rose from 6.2 (3.4)ng/ml to 51 (22.9)ng/ml (P<.0001), without significant changes in Ca. Serum phosphate increased an average of 0.6 (1.4)mg/dl, from 4.4 mg/dl to 5mg/dl, (P=.015). PTH decreased an average of 85 (208)pg/ml (P=.023). In these patients, the indication for phosphate binders increased by an average dose equivalent of 0.47 (0.82)mg/dl (P<.001). The 13 patients under treatment with OL-HDF reached 25-OH-vit D levels significantly higher than the 23 treated on HD: 63 (21)ng/ml vs 43 (21)ng/ml (P=.011). Dual treatment with native and active Vit D was associated with significantly increased levels of P (P=.043). Untreated patients (n=23): 25-OH-vit D levels decreased from 15.3 (7.5)ng/ml in November to 11.1 (6.8)ng/ml in March (P<.01), without significant changes in P or PTH and without differences according to age. 25-OH-vit D levels declined in patients on HD (15) but not in patients on OL-HDF. CONCLUSION: The patients on haemodialysis have low or very low baseline values for 25-OH-vit D. The response to treatment with calcifediol is good, with the most marked improvement occurring in patients on OL-HDF. Furthermore, 25-OH-vit D levels decreased in untreated patients, which was probably correlated with the lower sun exposure in winter. Some patients experienced an increase in phosphataemia despite increasing the dosage of phosphate binders, mainly in those receiving treatment with active vitamin D.

Safety of 25-hydroxyvitamin D3 as a source of vitamin D3 in layer poultry feed.

A target animal safety study investigated the effects of providing 25-hydroxyvitamin D3 (25-OH-D3) in laying hen feed at levels ranging from 0.5 to 10 times the level commonly used for vitamin D3 supplementation in the poultry industry. Following a 28-day preconditioning period, 5 groups of laying hens were fed commercial diets containing 68.9 micrograms of vitamin D3/kg feed (control) or 41.25 (0.5x), 82.5 (1x), 412.5 (5x), or 825 (10x) micrograms of 25-OH-D3/kg feed. The study compared the effects of the control level of vitamin D3 and the various test levels of 25-OH-D3 on health, performance, hematology, and 25-OH-D3 tissue concentrations in laying hens from 0 to 112 d of treatment and on health, performance, gross pathology and histopathology from 113 to 224 d of treatment. Gross pathologic and histopathologic examination of selected tissues after 224 d revealed no lesions attributable to vitamin D toxicity at any level of test material. Concentrations of 25-OH-D3 in edible tissues at 112 d were similar for birds in the control and 1x groups. On the basis of all variables monitored, including body weight gain and feed conversion, the 10x level of 25-OH-D3 produced clear toxicity (but no mortality), the 5x level caused limited threshold toxicity, and the 1x level induced no toxicity. These results indicate that 25-OH-D3 is safe for use in laying hen feed as a source of vitamin D3 at 82.5 micrograms/kg feed (1x), with a margin of safety of approximately 5x between the proposed 1x level and the 5x level (412.5 micrograms/kg feed) that constitutes threshold toxicity in layers.

Bone loss after cardiac transplantation: effects of calcium, calcidiol and monofluorophosphate.

Of 203 patients who underwent cardiac transplantation and were given long-term treatment with cyclosporine and 0.3 mg/kg per day prednisone, 123 were studied prospectively for at least 6 months and 46 for up to 2 years to evaluate the effects on lumbar bone mineral density (BMD) and calcium metabolism of a combined therapy with calcium, calcidiol and disodium monofluorophosphate (MFP). The population was arbitrarily assigned to one of two groups. Group I consisted of patients who had a lumbar spine BMD Z score above -1.5 SD as compared with an age- and sex-matched population and no vertebral fractures. They received daily 1 g elemental calcium and 25 micrograms (1000 IU) calcidiol. Group II consisted of patients who received daily the same doses of calcium and calcidiol combined with 200 mg MFP, and was divided into two subgroups: (a) osteopenic subjects who had a lumbar spine BMD Z score below -1.5 SD without vertebral fractures and (b) osteoporotic subjects with vertebral fractures. If serum creatinine was higher than 140 mumol/l the daily dose of MFP was tapered to 100 mg. Fifty-four and 27 patients from group I and 38 and 19 patients from group II were followed respectively for 12 and 24 months. In both groups serum parathyroid hormone levels were significantly reduced from the twelfth month in parallel with a significant increase in serum 25-OHD levels. No decline in lumbar BMD occurred in non-osteopenic and non-osteoporotic patients (group 1) who received the calcium and calcidiol supplement. In group II, where MFP was added, a significant and linear increase in lumbar BMD was observed.(ABSTRACT TRUNCATED AT 250 WORDS)