IMPORTANCE Experts debate optimal 25-hydroxyvitamin D (25[OH]D) levels for musculoskeletal health.OBJECTIVE To 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.INTERVENTIONS Three arms included daily white and twice monthly yellow placebo (n=76), daily 800 IU vitamin D 3 and twice monthly yellow placebo (n=75), and daily white placebo and twice monthly 50,000 IU vitamin D 3 (n=79). The high-dose vitamin D regimen achieved and maintained 25(OH)D levels Ն30 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.RESULTS After 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 RELEVANCE High-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 REGISTRATION clinicaltrials.gov Identifier: NCT00933244

Objective Our objective was to determine whether a questionnaire can identify subjects with vitamin D insufficiency (VDI). Design Subjects completed the vitamin D and sun (VIDSUN) questionnaire and we measured their serum 25(OH)D levels. We assessed the sensitivity and specificity of the questionnaire to identify VDI (25(OH)D level <50 nmol/L). Setting Clinical Research Unit, University of Wisconsin-Madison Subjects Postmenopausal women Results We recruited 609 postmenopausal women with a mean ± SD age of 61 ± 6 years, of whom 113 (19%) had VDI. Subjects with VDI were more likely to be Black (17% vs. 2%, p<0.001), heavier (BMI 33±7 kg/m2 vs. 29±7 kg/m2, p<0.001) and less likely to tan in the past year (49% vs. 72%, p<0.001), use sunscreen (57% vs. 72%, p<0.001) or report sun exposure in the last three months. They consumed less vitamin D from supplements (86±210 vs. 188±344 IU/day, p=0.003). In logistic regression models, Black race, BMI, suntan within one year, sun exposure in the past three months, sunscreen use and supplemental vitamin D intake were the most useful questions to identify VDI. From these six items, a composite score ≤2.25 demonstrated ≥89% sensitivity but ≤35% specificity for VDI. Conclusion The VIDSUN questionnaire provides an initial tool to identify postmenopausal women at high or low risk of VDI. Existing studies suggest that inclusion of physical activity and triglyceride levels might improve the performance of the VIDSUN questionnaire.

Studies suggest a link between magnesium status and osteoporosis. One barrier to more conclusive research on the potential relation is measuring intestinal magnesium absorption (MgA), which requires the use of stable isotopes and a ≥6-d stool or 3-d urine collection. We evaluated alternative methods of measuring MgA. We administered 2 stable magnesium isotopes to 15 postmenopausal women (cohort 1) aged 62 ± 8 y with a dietary magnesium intake of 345 ± 72 mg/d. Participants fasted from 1200 h to 0700 h and then consumed breakfast with ∼23 mg of oral ²⁶Mg and ∼11 mg of i.v. ²⁵Mg. We measured magnesium isotope concentrations in 72-h urine, spot urine (36, 48, 60, and 72 h), and spot serum (1, 3, and 5 h) samples collected after isotope dosing. We calculated MgA using the dose-corrected fraction of isotope concentrations from the 72-h urine collection. We validated new methods in 10 postmenopausal women (cohort 2) aged 59 ± 5 y with a dietary magnesium intake of 325 ± 122 mg/d. In cohort 1, MgA based on the 72-h urine collection was 0.28 ± 0.08. The 72-h MgA correlated most highly with 0-24 h urine MgA value alone (ρ = 0.95, P < 0.001) or the mean of the 0-24 h urine and the 3-h (ρ = 0.93, P < 0.001) or 5-h (ρ = 0.96, P < 0.001) serum MgA values. In cohort 2, Bland-Altman bias was lowest (-0.003, P = 0.82) using means of the 0-24 h urine and 3-h serum MgA values. We conclude that means of 0-24 h urine and 3-h serum MgA provide a reasonable estimate of 72-h MgA. However, if researchers seek to identify small changes in MgA, we recommend a 3-d urine or extended stool collection.

Extraintestinal pathogenic E. coli (ExPEC) are the major cause of most varieties of extra‐intestinal infection, including urinary tract infection, septicemia, and neonatal meningitis. Persistence of ExPEC in the gut increases the risk of subsequent extraintestinal infection. The mechanisms of persistence and effects of dietary Atype proanthocyanidins (PAC) on the mechanisms are poorly understood. Using a strain of ExPEC expressing both P‐ and type‐1 fimbriae, we studied the ability of ExPEC to invade gut epithelial cells and resist killing by macrophages. We also determined the effects of PAC on these mechanisms. ExPEC attached to and invaded enterocytes by hijacking the host cytoskeletal system, and survived within intracellular vacuoles without causing overt pathology. The ExPEC also resisted post phagocytic killing by macrophages. Exposure of ExPEC to PAC significantly inhibited invasion in a PAC dose dependent manner; higher molecular weight PAC were more effective in inhibiting invasion. Scanning electron microscopy revealed that PAC exposure disrupted surface structures on ExPEC. PAC also induced agglutination of ExPEC and increased killing by macrophages. This study provides novel mechanisms by which ExPEC may persist in the gut and suggests potential use of PAC in preventing gut colonization by ExPEC. Research was funded by Wisconsin Cranberry Board and Cranberry Institute.