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reverse-J-shaped, with increased risk not only at low but also at the higher levels of serum 25OHD (i.e., > 75 nmol/L).

Fiscella and Franks (2010) conducted a retrospective cohort analysis also based on NHANES III data. They examined serum 25OHD levels and CVD mortality in participants ages 18 years and older (n = 15,363). Analysis of fully adjusted data showed a U-shaped risk profile for CVD mortality, as reported by others. Without consideration of vitamin D status, after adjusting for age, gender, season, and region, non-Hispanic blacks had a 38 percent higher cardiovascular mortality than whites. Adjusting for low serum 25OHD levels reduced the racial difference in risk by about 60 percent (to 23 percent). Including both low serum 25OHD level and poverty level reduced the racial difference in risk to 1.0, suggesting that low serum 25OHD level and poverty capture much of the racial disparity in cardiovascular mortality in blacks compared with whites; however, it must be recognized that the low serum 25OHD level may be a marker for other factors (obesity, inactivity, etc.). Additionally, a cross-sectional study conducted by Freedman et al. (2010) reported a positive association between serum 25OHD level and calcified atherosclerotic plaque in the aorta and carotid arteries of African Americans.

Falls and Fractures

In a recent trial of 2,256 community-dwelling women 70 years of age and older residing in Australia and presenting with high risk of fracture, the women were treated with 500,000 IU of vitamin D annually for 3 to 5 years (Sanders et al., 2010). Sanders et al. (2010) reported that “… participants receiving annual high-dose oral cholecalciferol experienced 15% more falls and 26% more fractures than the placebo group. Women not only experienced excess fractures after more frequent falls but also experienced more fractures that were not associated with a fall. A post hoc analysis found that the increased likelihood of falls in the vitamin D group was exacerbated in the 3-month period immediately following the annual dose and a similar temporal trend was observed for fractures. An increased risk (albeit, not significant because of smaller numbers) of falls and fracture in the vitamin D group was apparent for each year of the intervention. The results were similar after adjustment for baseline calcium intake.…”

The non-physiological nature of a large one-time dose cannot be readily extrapolated to the situation in which smaller daily doses are provided. However, in view of a number of studies in the literature (e.g., Trivedi et al., 2003) in which large bolus doses have been given without apparent adverse effect, the results of the study by Sanders et al. (2010) are unexpected, but not readily dismissed. The study is notable because the adverse effect was demonstrated as a result of the intervention (which was primarily



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