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usedsearch Wesearchstudied only African American women. Our findings may not be generalizable to other ethnic groups. It should be noted that osteoporotic fractures are less common and bone density is higher in African American women than in women of other races/ethnicities, despite the lower serum 25(OH)D of African Americans (60). Heaney (61) estimated that African American women require 300 mg/d less calcium intake than do white women.
Most of the studies examining optimal vitamin D status do not control for calcium intake. Consideration of optimal vitamin D intake without knowing calcium intake is problematic. In each study in which the calcium intake exceeded 1000 mg/d, the estimated optimal serum 25(OH)D was 50 nmol/L. It is of interest that the most recent Cochrane Database of Systematic Reviews concluded that, whereas vitamin D with calcium marginally reduced hip and other nonvertebral fractures, no effect was seen when vitamin D was given alone (62). Again, the interaction between vitamin D status and calcium intake should be considered in making nutritional recommendations.
Our population had a mean age of 60 y, whereas several of the studies from the literature were done in the elderly. Renal function declines with aging, and higher concentrations of 25(OH)D are needed to prevent a rise in serum PTH in the elderly (48). Indeed, a number of studies have documented secondary hyperparathyroidism in the elderly, and calcium with vitamin D supplementation has prevented fragility fractures in some (but not all) studies. Moreover, the effect of vitamin D effects on muscle may help prevent falls in the elderly, thereby reducing fracture risk (63).
Another cogent argument against recommending a vitamin D intake based mainly on a threshold derived from the scattergram of PTH versus 25(OH)D comes from our study (5). Using various models and techniques, we were able to consistently show a threshold value in our data. Despite our finding a threshold of 40C50 nmol 25(OH)D/L, those participants above and below the putative threshold did not differ significantly in loss of bone mineral density. Another analysis attempted to associate the rate of change in bone mineral density with 25(OH)D; no correlation was found between serum 25(OH)D and rates of bone loss (5).
The whole concept of a specific threshold is suspect because such a threshold may be partly an artifact of the reported serum 25(OH)D. In a global survey, Lips et al (57) found a wide range of mean serum concentrations of 25(OH)D across and within continents. Because the threshold is directly related to the observed serum 25(OH)D, it is not surprising that there is similar wide variability in reported thresholds across the 30 studies that we reviewed. Identifying a single optimal 25(OH)D value among this variability is problematic. Furthermore, the average reported correlation across the 25 studies that reported a correlation between PTH and vitamin D was C0.30. Thus, serum 25(OH)D 'explains' 9% of the variance in PTH. A wide range in reported thresholds is found, because these thresholds are calculated from a wide range of populations, assays, and statistical techniques all applied to a weak biological phenomenon (ie, a linear r2 of 9%). The wide variability in threshold estimates is another reason for caution in using that concept in making dietary recommendations for heterogeneous populations.
There are 2 reasons for trying to identify a threshold. One reason has to do with the slope above the threshold. Several of the studies suggested that PTH concentrations above the threshold may continue to drift down with increased vitamin D (A Arabi et al, unpublished observations, 2004; 64, 65). A second reason for estimating a threshold has to do with the PTH concentrations below this point. Our theoretical concern is with the latter. As did Vieth and Fuleihan (66) and Heaney (67), we ultimately reject the clinical utility of the threshold as a way of identifying optimal vitamin D, but we first rigorously establish the statistical reality of such a point. Note that the slope of the line below the threshold is almost 10 times as big as the slope of the line above the threshold. The fact that it drifts down very slowly is not nearly as important as is the observation that, as vitamin D is reduced below the threshold, PTH increases much more rapidly. The potential conclusion that such a threshold may have implications for optimal vitamin D concentrations is one that we ultimately reject.
Finally, it must be stated that the establishment of an optimal vitamin D intake should also consider the noncalcemic effects of vitamin D that are believed to influence the prevention of some cancers, type 1 diabetes, heart disease, and falls in the elderly (17, 68). It is quite possible that African Americans (and others) may require less vitamin D for skeletal health but may require greater intake for prevention of these noncalcemic disorders. Vitamin D status and calcium intake recommendations should not be made independently but must be considered together.
ACKNOWLEDGMENTS
We thank Sharon Sprintz for her expertise as a dual-energy X-ray absorptiometry technician and Jane Moore for their expertise as the Nurse Coordinator. We also thank Lynn Maier for preparation of the typescript.
JFA, the principal investigator, designed and supervised the study and wrote the manuscript; SAT, the co-investigator, was responsible for medical supervision of the study participants; SP, the study statistician, was responsible for the data and statistical analyses and contributed to the writing of the manuscript; MF contributed to the data and statistical analyses, to the literature review, and to the writing of the manuscript; JKY, the laboratory director, was responsible for the biochemical assays. None of the authors had a personal or financial conflict of interest.
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