Predictors of serum 25-hydroxyvitamin D concentrations among postmenopausal women: the Women's Health Initiative Calcium plus Vitamin D clinical trial

Abstract

Background: It is unclear how well surrogate markers for vitamin D exposure (eg, oral intake of vitamin D and estimates of sunlight exposure), with and without consideration of other potential predictors of 25-hydroxyvitamin D [25(OH)D] concentrations, similarly rank individuals with respect to 25(OH)D blood concentrations.

Objective: The objective was to determine how much variation in serum 25(OH)D concentrations (nmol/L) could be explained by a predictive model with the use of different vitamin D surrogate markers (latitude of residence, mean annual regional solar irradiance estimates, and oral sources) and other individual characteristics that might influence vitamin D status.

Design: A random sample of 3055 postmenopausal women (aged 50-70 y) participating in 3 nested case-control studies of the Women's Health Initiative Calcium plus Vitamin D Clinical Trial was used. Serum 25(OH)D values, assessed at year 1 (1995-2000), and potential predictors of 25(OH)D concentrations, assessed at year 1 or Women's Health Initiative baseline (1993-1998), were used.

Results: More than half of the women (57.1%) had deficient (<50 nmol/L) concentrations of 25(OH)D. Distributions of 25(OH)D concentrations by level of latitude of residence, mean annual regional solar irradiance, and intake of vitamin D varied considerably. The predictive model for 25(OH)D explained 21% of the variation in 25(OH)D concentrations. After adjustment for month of blood draw, breast cancer status, colorectal cancer status, fracture status, participation in the hormone therapy trial, and randomization to the dietary modification trial, the predictive model included total vitamin D intake from foods and supplements, waist circumference, recreational physical activity, race-ethnicity, regional solar irradiance, and age.

Conclusions: Surrogate markers for 25(OH)D concentrations, although somewhat correlated, do not adequately reflect serum vitamin D measures. These markers and predictive models of blood 25(OH)D concentrations should not be given as much weight in epidemiologic studies of cancer risk.

FIGURE 1

Serum 25-hydroxyvitamin D [25(OH)D] concentrations, adjusted for month of blood draw, in participants of the nested case-control studies of the Women's Health Initiative Calcium plus Vitamin D Clinical Trial (n = 3055). The box plots for each month cover the interquartile range, the horizontal line represents the median, and the whiskers extend to the most extreme point that is ≤1.5 times the interquartile range.

FIGURE 2

Distribution of serum 25-hydroxyvitamin D [25(OH)D] concentrations, adjusted for month of blood draw, at year 1 of the Women's Health Initiative nested case-control studies of the Calcium plus Vitamin D Clinical Trial by Watt quintile of clinic center (A) and quintile of energy-adjusted total vitamin D intake (B). n = 3055. Panel B contains a sample of 2865 women, because 190 women were missing data on total vitamin D intake. The lines connect the mean serum 25(OH)D concentrations by Watt quintiles (quintile 1 = 48.3, quintile 2 = 49.0, quintile 3 = 48.5, quintile 4 = 50.2, quintile 5 = 51.3) in panel A and by total vitamin D quintiles (quintile 1 = 40.8, quintile 2 = 45.8, quintile 3 = 50.1, quintile 4 = 53.5, quintile 5 = 58.2) in panel B. To control for month of blood draw, serum 25(OH)D concentrations were regressed on month of blood draw to compute residuals, which were added back to the mean serum 25(OH)D concentration in the sample.

FIGURE 3

Percentage of participants categorized as severely vitamin D deficient, moderately deficient, insufficient, and sufficient based on a model used to predict serum 25-hydroxyvitamin D [25(OH)D] concentrations by actual 25(OH)D concentration. Analyses were conducted in a validation sample (n = 1234) of participants in the nested case-control studies of the Women's Health Initiative Calcium plus Vitamin D Clinical Trial.