Dataset Information

Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial.

ABSTRACT: Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean ± standard deviation change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in patients treated with calcifediol and cholecalciferol, respectively). No relevant treatment-related safety issues were reported in any of the groups studied. These results thus confirm that calcifediol is effective, faster, and more potent than cholecalciferol in raising serum 25(OH)D levels and is a valuable option for the treatment of vitamin D deficiency. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

SUBMITTER: Perez-Castrillon JL

PROVIDER: S-EPMC8597097 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial.

Pérez-Castrillón José Luis JL Dueñas-Laita Antonio A Brandi Maria Luisa ML Jódar Esteban E Del Pino-Montes Javier J Quesada-Gómez José Manuel JM Cereto Castro Fernando F Gómez-Alonso Carlos C Gallego López Laura L Olmos Martínez José Manuel JM Alhambra Expósito María Rosa MR Galarraga Bernat B González-Macías Jesús J Bouillon Roger R Hernández-Herrero Gonzalo G Fernández-Hernando Nieves N Arranz-Gutiérrez Paula P Chinchilla Sandra P SP

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20210624 10

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D- ...[more]

PMID: 34101900

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Project description:ImportanceExperts debate optimal 25-hydroxyvitamin D (25[OH]D) levels for musculoskeletal health.ObjectiveTo compare the effects of placebo, low-dose cholecalciferol, and high-dose cholecalciferol on 1-year changes in total fractional calcium absorption, bone mineral density, Timed Up and Go and five sit-to-stand tests, and muscle mass in postmenopausal women with vitamin D insufficiency.Design, setting, and participantsThis randomized, double-blind, placebo-controlled clinical trial was conducted at a single center in Madison, Wisconsin, from May 1, 2010, through July 31, 2013, and the final visit was completed on August 8, 2014. A total of 230 postmenopausal women 75 years or younger with baseline 25(OH)D levels of 14 through 27 ng/mL and no osteoporosis were studied.InterventionsThree arms included daily white and twice monthly yellow placebo (n=76), daily 800 IU vitamin D3 and twice monthly yellow placebo (n=75), and daily white placebo and twice monthly 50,000 IU vitamin D3 (n=79). The high-dose vitamin D regimen achieved and maintained 25(OH)D levels≥30 ng/mL.Main outcomes and measuresOutcome measures were 1-year change in total fractional calcium absorption using 2 stable isotopes, bone mineral density and muscle mass using dual energy x-ray absorptiometry, Timed Up and Go and five sit-to-stand tests, functional status (Health Assessment Questionnaire), and physical activity (Physical Activity Scale for the Elderly), with Benjamini-Hochberg correction of P values to control for the false discovery rate.ResultsAfter baseline absorption was controlled for, calcium absorption increased 1% (10 mg/d) in the high-dose arm but decreased 2% in the low-dose arm (P = .005 vs high-dose arm) and 1.3% in the placebo arm (P = .03 vs high-dose arm). We found no between-arm changes in spine, mean total-hip, mean femoral neck, or total-body bone mineral density, trabecular bone score, muscle mass, and Timed Up and Go or five sit-to-stand test scores. Likewise, we found no between-arm differences for numbers of falls, number of fallers, physical activity, or functional status.Conclusions and relevanceHigh-dose cholecalciferol therapy increased calcium absorption, but the effect was small and did not translate into beneficial effects on bone mineral density, muscle function, muscle mass, or falls. We found no data to support experts' recommendations to maintain serum 25(OH)D levels of 30 ng/mL or higher in postmenopausal women. Instead, we found that low- and high-dose cholecalciferol were equivalent to placebo in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels less than 30 ng/mL.Trial registrationclinicaltrials.gov Identifier: NCT00933244.

Project description:BackgroundVitamin K has been widely promoted as a supplement for decreasing bone loss in postmenopausal women, but the long-term benefits and potential harms are unknown. This study was conducted to determine whether daily high-dose vitamin K1 supplementation safely reduces bone loss, bone turnover, and fractures.Methods and findingsThis single-center study was designed as a 2-y randomized, placebo-controlled, double-blind trial, extended for earlier participants for up to an additional 2 y because of interest in long-term safety and fractures. A total of 440 postmenopausal women with osteopenia were randomized to either 5 mg of vitamin K1 or placebo daily. Primary outcomes were changes in BMD at the lumbar spine and total hip at 2 y. Secondary outcomes included changes in BMD at other sites and other time points, bone turnover markers, height, fractures, adverse effects, and health-related quality of life. This study has a power of 90% to detect 3% differences in BMD between the two groups. The women in this study were vitamin D replete, with a mean serum 25-hydroxyvitamin D level of 77 nmol/l at baseline. Over 2 y, BMD decreased by -1.28% and -1.22% (p = 0.84) (difference of -0.06%; 95% confidence interval [CI] -0.67% to 0.54%) at the lumbar spine and -0.69% and -0.88% (p = 0.51) (difference of 0.19%; 95% CI -0.37% to 0.75%) at the total hip in the vitamin K and placebo groups, respectively. There were no significant differences in changes in BMD at any site between the two groups over the 2- to 4-y period. Daily vitamin K1 supplementation increased serum vitamin K1 levels by 10-fold, and decreased the percentage of undercarboxylated osteocalcin and total osteocalcin levels (bone formation marker). However, C-telopeptide levels (bone resorption marker) were not significantly different between the two groups. Fewer women in the vitamin K group had clinical fractures (nine versus 20, p = 0.04) and fewer had cancers (three versus 12, p = 0.02). Vitamin K supplements were well-tolerated over the 4-y period. There were no significant differences in adverse effects or health-related quality of life between the two groups. The study was not powered to examine fractures or cancers, and their numbers were small.ConclusionsDaily 5 mg of vitamin K1 supplementation for 2 to 4 y does not protect against age-related decline in BMD, but may protect against fractures and cancers in postmenopausal women with osteopenia. More studies are needed to further examine the effect of vitamin K on fractures and cancers.Trial registrationClinicalTrials.gov (#NCT00150969) and Current Controlled Trials (#ISRCTN61708241).

Project description:OBJECTIVES:To compare changes in vitamin D status and cathelicidin (LL-37) levels in septic ICU patients treated with placebo versus cholecalciferol. DESIGN:Randomized, placebo-controlled, trial. SETTING:Medical and surgical ICUs of a single teaching hospital in Boston, MA. PATIENTS:Thirty adult ICU patients. INTERVENTIONS:Placebo (n = 10) versus 200,000 IU cholecalciferol (n = 10) versus 400,000 IU cholecalciferol (n = 10), within 24 hours of new-onset severe sepsis or septic shock. MEASUREMENTS AND MAIN RESULTS:Blood samples were obtained at baseline (day 1) and on days 3, 5, and 7, to assess total 25-hydroxyvitamin D, as well as vitamin D-binding protein and albumin to calculate bioavailable 25-hydroxyvitamin D. Plasma LL-37 and high-sensitivity C-reactive protein levels were also measured. At baseline, median (interquartile range) plasma 25-hydroxyvitamin D was 17?ng/mL (13-22?ng/mL) and peaked by day 5 in both intervention groups. Groups were compared using Kruskal-Wallis tests. Relative to baseline, on day 5, median change in biomarkers for placebo, 200,000 IU cholecalciferol, and 400,000 IU cholecalciferol groups, respectively, were as follows: 1) total 25-hydroxyvitamin D, 3% (-3% to 8%), 49% (30-82%), and 69% (55-106%) (p < 0.001); 2) bioavailable 25-hydroxyvitamin D, 4% (-8% to 7%), 45% (40-70%), and 96% (58-136%) (p < 0.01); and 3) LL-37: -17% (-9% to -23%), 4% (-10% to 14%), and 30% (23-48%) (p = 0.04). Change in high-sensitivity C-reactive protein levels did not differ between groups. A positive correlation was observed between bioavailable 25-hydroxyvitamin D and LL-37 (Spearman ? = 0.44; p = 0.03) but not for total 25-hydroxyvitamin D and LL-37. CONCLUSIONS:High-dose cholecalciferol supplementation rapidly and safely improves 25-hydroxyvitamin D and bioavailable 25-hydroxyvitamin D levels in patients with severe sepsis or septic shock. Changes in bioavailable 25-hydroxyvitamin D are associated with concomitant increases in circulating LL-37 levels. Larger trials are needed to verify these findings and to assess whether optimizing vitamin D status improves sepsis-related clinical outcomes.

Project description:Few detailed data are available on the wide range of determinants of vitamin D status among postmenopausal women, and it is also unclear whether there may be undiscovered determinants. The objective of this study was to comprehensively evaluate determinants of serum 25-hydroxyvitamin D [25(OH)D] concentrations in a large cohort of postmenopausal women. Data from a subset of the Women's Health Initiative Observational Study were analyzed (50-79 y; n = 3345). Information on diet, lifestyle behaviors, secondhand smoke, use of dietary supplements and medication, chronic diseases, and anthropometry was collected at baseline (1993-1998) and on sun exposure at year 4 follow-up. Linear regression was performed to estimate regression coefficients (?). Significant determinants were total vitamin D intake (food plus supplements per 100 IU/d, ? = 2.08), years of supplemental vitamin D use (? = 0.15), total fat intake (grams per day, ? = -0.03), smoking status (? = -2.64, current vs. never), regional solar irradiance (? = 6.26, 475-500 vs. 300-325 Langleys), daylight time spent outdoors in summer (? = 5.15, >2 h vs. <30 min/d), recreational physical activity (metabolic equivalent task per hour per week, ? = 0.13), waist circumference (centimeters, ? = -0.26), and race/ethnicity (? = -11.94, black vs. white). Total vitamin D intake (partial R(2) = 0.09) explained the most variance in serum 25(OH)D concentrations (total R(2) = 0.29). The association between total vitamin D intake and serum 25(OH)D concentrations was stronger among participants who spent less rather than more daylight time outdoors in summer (P-interaction = 0.026). History and medications for hypertension, hyperlipidemia, and type 2 diabetes and secondhand smoke exposure were not associated with serum 25(OH)D. In conclusion, dietary factors and sun exposure remain important determinants of vitamin D status in postmenopausal women. Vitamin D intake should be emphasized for those with limited sun exposure.

Dataset Information

Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial.

Publications

Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial.

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