Faculty Bibliography

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 vitamin D-endocrine system is thought to play a role in physiologic processes that range from mineral metabolism to immune function. Serum 25-hydroxyvitamin D [25(OH)D] is the accepted biomarker for vitamin D status. Skin color is a key determinant of circulating 25(OH)D concentrations, and genes responsible for melanin content have been shown to be under strong evolutionary selection in populations living in temperate zones. Little is known about the effect of latitude on mean concentrations of 25(OH)D in dark-skinned populations. OBJECTIVE: The objective was to describe the distribution of 25(OH)D and its subcomponents in 5 population samples of African origin from the United States, Jamaica, Ghana, South Africa, and the Seychelles. DESIGN: Participants were drawn from the Modeling of the Epidemiologic Transition Study, a cross-sectional observational study in 2500 adults, ages 25-45 y, enrolled between January 2010 and December 2011. Five hundred participants, approximately 50% of whom were female, were enrolled in each of 5 study sites: Chicago, IL (latitude: 41 degrees N); Kingston, Jamaica (17 degrees N); Kumasi, Ghana (6 degrees N); Victoria, Seychelles (4 degrees S); and Cape Town, South Africa (34 degrees S). All participants had an ancestry primarily of African origin; participants from the Seychelles trace their history to East Africa. RESULTS: A negative correlation between 25(OH)D and distance from the equator was observed across population samples. The frequency distribution of 25(OH)D in Ghana was almost perfectly normal (Gaussian), with progressively lower means and increasing skewness observed at higher latitudes. CONCLUSIONS: It is widely assumed that lighter skin color in populations outside the tropics resulted from positive selection, driven in part by the relation between sun exposure, skin melanin content, and 25(OH)D production. Our findings show that robust compensatory mechanisms exist that create tolerance for wide variation in circulating concentrations of 25(OH)D across populations, suggesting a more complex evolutionary relation between skin color and the vitamin D pathway.

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.

OBJECTIVES: African Americans (AA) have substantially lower levels of circulating 25-hydroxyvitamin D (25(OH)D) than whites. We compared population-based samples of 25(OH)D in women of African descent from Nigeria and metropolitan Chicago. METHODS: One hundred women of Yoruba ethnicity from southwest Nigeria and 94 African American women from metropolitan Chicago were recruited and compared using a standardized survey protocol and the same laboratory assay for 25(OH)D. RESULTS: Mean 25(OH)D levels were 64 nmol/l among the Nigerians and 29 nmol/l among the AA. Only 10% of the values were shared in common between the groups, and 76% of the Nigerians were above the currently defined threshold for adequate circulating 25(OH)D compared to 5% of the AA. Modest associations were seen between 25(OH)D and measures of obesity, although adjustment for these traits did not materially affect the group differences. CONCLUSION: These data support the presumption that skin color is an adaptive trait which has evolved in part to regulate 25(OH)D. It remains undetermined, however, whether lower values observed in AA have negative health consequences.