Faculty Bibliography

CONTEXT: African Americans have a lower total serum 25-hydroxyvitamin D [25(OH)D] but superior bone health. This has been referred to as a paradox. A recent publication found that free serum 25(OH)D is the same in black and white individuals. However, the study was criticized because an indirect method was used to measure free 25(OH)D. A direct method has recently been developed. OBJECTIVE: We hypothesized that although total serum 25(OH)D is lower in African Americans, free serum 25(OH)D measured directly would not differ between races. DESIGN: White and black healthy postmenopausal women were matched for age and body mass index. Serum total 25(OH)D, PTH, 1,25-dihydroxyvitamin D, vitamin D binding protein (VDBP), and bone density were measured. Measurement of free 25(OH)D was carried out using an ELISA. SETTING: The study was conducted at an ambulatory research unit in a teaching hospital. OUTCOME: A cross-racial comparison of serum free 25(OH)D was performed. RESULTS: A propensity match resulted in the selection of a total of 164 women. Total 25(OH)D was lower in black women (19.5 +/- 4.7 vs 26.9 +/- 6.4 ng/mL), but a direct measurement of free 25(OH)D revealed almost identical values (5.25 +/- 1.2 vs 5.25 +/- 1.3 ng/mL) between races. VDBP was significantly lower in blacks when using a monoclonal-based ELISA but higher with a polyclonal-based ELISA. Serum PTH, 1,25-dihydroxyvitamin D, and bone density were higher in African Americans. CONCLUSIONS: Free serum 25(OH)D is the same across races despite the lower total serum 25(OH)D in black women. Results comparing VDBP between races using a monoclonal vs a polyclonal assay were discordant.

AIM: The objective of this study was to develop a reference range for urine calcium excretion (both 24-hour and fasting) for African American women compared to White women. In addition, the variables that determine urine calcium excretion were identified. MATERIAL: Data were analyzed for baseline studies of healthy postmenopausal volunteers who participated in seven separate studies conducted at one site. METHODS: Some studies included fasting urine Ca/Cr and others 24-hour urine calcium excretion. 24-hour urine calcium was considered with and without correction for urinary creatinine excretion. Calcium was measured initially by atomic absorption spectrophotometry and more recently by an automated method (ADVIA 2400 Chemistry System). RESULTS: Participants were considered healthy based on history and physical and routine laboratory studies. Those screened who had a history of nephrolithiasis were excluded. A reference range for 24-hour urine calcium and fasting urine calcium/ creatinine was developed. Reference intervals of 11 - 197 mg/24-hour urine calcium excretion and of 0.007 - 0.222 of fasting Ca/Cr were found for African American women compared to 21 - 221 mg/24 hours and 0.019 - 0.264 in White women, respectively. Urine creatinine excretion was higher in African Americans consistent with their higher muscle mass. CONCLUSION: Urine calcium excretion is lower in postmenopausal African American than White women. The reference range developed should be considered in the diagnosis of hypocalciuric states and may also be useful in the diagnosis of hypercalciuria.

UNLABELLED: Trabecular bone score (TBS) is a newly developed parameter that can be derived from DXA scans of the spine and may reflect bone quality. This study provides TBS values in healthy postmenopausal women of African descent. INTRODUCTION: African American women have a lower risk for osteoporotic fractures as a result of higher bone density and better bone quality. We examined TBS in postmenopausal African American women since there are no previous reports in this population. METHODS: This was a study of healthy African American volunteers using baseline values prior to their participation in two vitamin D intervention studies conducted at an ambulatory research center of an academic health center. RESULTS: The study population consisted of 518 healthy postmenopausal African American women with a mean age of 66 years and a BMI of 30.1. Mean TBS (L1 to L4) was 1.300(.100 SD). Significant negative correlations were found between TBS and age and BMI. None of the biochemical variables were significantly correlated with TBS whereas the various bone density sites were correlated with TBS. CONCLUSION: TBS values for African American women are higher than those reported in the literature for white women and are inversely related to age and BMI.

OBJECTIVE: The prevalence of vitamin D inadequacy is high in obese individuals. Determining the response of serum 25-hydroxyvitamin D (25[OH]D) to vitamin D3 supplementation in obese and nonobese individuals may lead to concurrent recommendations for optimal vitamin D intake in these populations. The objective of this study was to determine the dose response of vitamin D3 in subjects with a body mass index >/=35 kg/m2. METHODS: Randomized, double-blind, placebo-controlled study. This study is an extension of our previous study of vitamin D dosing in healthy adults. After an assessment of baseline 25(OH)D levels, participants were randomized to a vitamin D supplementation arm (100 mug daily if baseline 25[OH]D was <50 nmol/L, or 50 mug daily if baseline 25[OH]D was >/=50 nmol/L) or placebo arm. Subjects with baseline 25(OH)D level >/=80 nmol/L were excluded from the study. Two months following randomization, a repeat 25(OH)D measurement was done. RESULTS: Final analysis included 25 subjects (14 placebo, 11 active). At 2 months, serum 25(OH)D concentration increased to a mean of 75 nmol/L in the active group. Mean slope (i.e., vitamin D3 response), defined as 25(OH) D change/baseline dose, was 0.398 nmol/L/mug/day. CONCLUSION: The dose response of vitamin D3 (slope) in obese subjects was significantly lower (P<.03) at 0.398 nmol/L/mug/day compared to the slope in the previous study of healthy subjects (0.66 nmol/L/mug/day). These results suggest that obese individuals may require 40% higher vitamin D intake than nonobese individuals to attain the same serum 25(OH)D concentration.

BACKGROUND: The maximal calcium absorption in response to vitamin D has been proposed as a biomarker for vitamin D sufficiency. OBJECTIVE: The objective was to determine whether there is a threshold beyond which increasing doses of vitamin D, or concentrations of serum 25-hydroxyvitamin D [25(OH)D], no longer increase calcium absorption. DESIGN: This was a placebo-controlled, dose-response, randomized, double-blind study of the effect of vitamin D on calcium absorption in healthy postmenopausal women. Seventy-six healthy postmenopausal women were randomly assigned to placebo or 800 IU (20 mug), 2000 IU (50 mug), or 4000 IU (100 mug) vitamin D(3) for 8 wk. The technique of dual isotopes of stable calcium was used with a calcium carrier to measure calcium absorption at baseline and after 8 wk. RESULTS: Seventy-one women with a mean +/- SD age of 58.8 +/- 4.9 y completed the study. The mean calcium intake was 1142 +/- 509 mg/d and serum 25(OH)D was 63 +/- 14 nmol/L at baseline. A statistically significant linear trend of an increase in calcium absorption adjusted for age and body mass index with increasing vitamin D(3) dose or serum 25(OH)D concentration was observed. A 6.7% absolute increase in calcium absorption was found in the highest vitamin D(3) group (100 mug). No evidence of nonlinearity was observed in the dose-response curve. CONCLUSIONS: No evidence of a threshold of calcium absorption was found with a serum 25(OH)D range from 40 to 130 nmol/L. Calcium absorption in this range is not a useful biomarker to determine nutritional recommendations for vitamin D.

CONTEXT: Bone health is influenced by the intake of both calcium and vitamin D. OBJECTIVE: Our objective was to evaluate the influence of calcium and vitamin D supplementation on PTH and bone turnover. SETTING, PATIENTS, AND DESIGN: At an ambulatory research center, 159 postmenopausal healthy white women participated in this double-blind, placebo-controlled parallel, longitudinal factorial study that was 6 months in duration. INTERVENTIONS: Subjects were randomly allocated to 4 groups: 1) double placebo, 2) calcium (1200 mg daily) plus placebo, 3) vitamin D3 (100 mug) plus placebo, and 4) vitamin D3 and calcium. Serum and urine were collected fasting and 2 hours after a calcium load at baseline and at 3 and 6 months. MAIN OUTCOME MEASURES: Serum PTH, cross-linked C-telopeptide (CTX), and procollagen type I N-terminal propeptide (P1NP) were measured. RESULTS: Before study medication, a calcium load resulted in a decline in PTH and CTX and an increase in urinary calcium excretion. Serum CTX and P1NP declined over time with calcium supplementation but did not change with increased vitamin D intake. There was a decline in PTH in the vitamin D groups in the fasting state compared with placebo. Suppression of PTH was greater after a calcium load in the vitamin D groups. A calcium load decreased PTH and CTX and raised urinary calcium. CONCLUSIONS: Fasting PTH declines with vitamin D supplementation. PTH declines after calcium intake. Supplementation of the diet with 1200 mg calcium/d reduces bone turnover markers, whereas supplementation with up to100 mug vitamin D3/d does not.

BACKGROUND: Adequate calcium and vitamin D are needed to maintain calcium balance. OBJECTIVE: Our objective was to examine the influence of calcium intake and vitamin D exposure separately and their interaction on biomarkers of calcium sufficiency. DESIGN: Healthy men and women, age 20-80 yr, were randomly allocated to four groups: 1) double placebo, 2) calcium (1200 mg daily) plus placebo, 3) vitamin D(3) (100 microg) plus placebo, and 4) vitamin D(3) and calcium. Fasting serum and urine as well as serum and urine 2 h after a calcium load (600 mg of calcium carbonate) were obtained at baseline and 3 months. RESULTS: Ninety-nine participants were randomized; 78 completed the study. Baseline demographics, protein intake and laboratory studies did not differ among the four groups. Study medication compliance was 90%. Fasting bone turnover markers declined after 3 months only in the two groups given calcium supplements and increased in the vitamin D(3) plus placebo calcium group. The calcium load resulted in a decrease in PTH and in bone turnover markers that did not differ among groups. Urinary calcium excretion increased in the combined group. Mean serum 25-hydroxyvitamin D increased from a baseline of 67 (18 sd) nmol/liter to 111 (30 sd) nmol/liter after vitamin D supplementation. CONCLUSION: Increased habitual calcium intake lowered markers of bone turnover. Acute ingestion of a calcium load lowered PTH and bone turnover markers. Additional intake of 100 microg/d vitamin D(3) did not lower PTH or markers of bone turnover.

Background. The role of vitamin D in the body's ability to fight influenza and URI's may be dependent on regulation of specific cytokines that participate in the host inflammatory response. The aim of this study was to test the hypothesis that vitamin D can influence intracellular signaling to regulate the production of cytokines. Subjects and Methods. This study was a 3-month prospective placebo-controlled trial of vitamin D3 supplementation in ambulatory adults [Li-Ng et al., 2009]. 162 volunteers were randomized to receive either 50 mug/d (2000 IU) of vitamin D3 or matching placebo. 25(OH)D and the levels of 10 different cytokines (IL-2, 4, 5, 6, 8, 10, 13, GM-CSF, IFN-gamma, TNF-alpha) were measured in the serum of participants at baseline and the final visit. There were 6 drop-outs from the active vitamin D group and 8 from the placebo group. Results. In the active vitamin D group, we found a significant median percent decline in levels of GM-CSF (-62.9%, P < .0001), IFN-gamma (-38.9%, P < .0001), IL-4 (-50.8%, P = .001), IL-8 (-48.4%, P < .0001), and IL-10 (-70.4%, P < .0001). In the placebo group, there were significant declines for GM-CSF (-53.2%, P = .0007) and IFN-gamma (-34.4%, P = .0011). For each cytokine, there was no significant difference in the rate of decline between the two groups. 25(OH)D levels increased in the active vitamin D group from a mean of 64.3 +/- 25.4 nmol/L to 88.5 +/- 23.2 nmol/L. Conclusions. The present study did not show that vitamin D3 supplementation changed circulating cytokine levels among healthy adults.