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D7c Discoverwomenseekingmen L Seeking Szh 1 Discover Women Seeking Men Optimal vitamin D status and serum parathyroid hormone concentrations in African American women--《美国临床营养学杂志》--医学期刊频道--首席医学网

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(2)

Part of the variability in these estimates can also be explained by the fact that different models and methods were used to estimate the threshold. These varied from the sophisticated mixed-model approach to a nave, intuitive, visual approach (5, 20, 25, 26).

Multiple regression analysis suggests that serum 25(OH)D and dietary calcium influence the reported threshold independently; together they account for 67% of the variance in reported thresholds among the 18 available studies. The overall model P value was 0.0003 (F2,15 = 15.1), and the contribution of dietary calcium to the prediction of the threshold remained significant even after control for serum 25(OH)D. Partial P values were both < 0.01. Because calcium intake was not reported in 13 studies, conclusions based on dietary calcium are only suggestive.

A nonsignificant negative correlation of C0.27 was found between PTH and dietary calcium in the 18 studies with reported dietary calcium intakes. Recently, Steingrimsdottir et al (46) reported a calcium intake x optimal 25(OH)D interaction for an effect on PTH, which we are able to confirm through our literature review. We found that, in those studies with 25(OH)D of > 50 nmol/L, calcium intake did not affect PTH. But in those studies with a mean 25(OH)D of < 50 nmol/L, dietary calcium was inversely related to PTH: within this subset, PTH was 6 pg/mL lower in the set of studies with dietary calcium > 800 mg/d than in the studies with dietary calcium < 800 mg/d (interaction F1,14 = 3.5, P = 0.08).

DISCUSSION

Our data suggest that a serum concentration of 40C50 nmol 25(OH)D/L is needed to prevent a rise in PTH concentrations in calcium-sufficient African American women in midlife. We reviewed the English-language literature that reported a threshold estimate and found that most estimates clustered between 40 and 50 nmol/L or 70 and 80 nmol/L. Indeed, almost half of the studies in our literature review reported a threshold 50 nmol/L and one-third reported thresholds between 40 and 50 nmol/L, findings that are consistent with the value we observed. Thus, we take exception to the statement of Dawson-Hughes et al (59), 'These estimates of the threshold serum 25(OH)D vary widely but there is a cluster in the 75C80 nmol range.' A equally evident cluster is found between 40 and 50 nmol/L.

The variability in the estimates for the 25(OH)D threshold may be explained by ethnic differences in calcium economy, the extent of vitamin D insufficiency, different calcium intakes, inaccuracy of 25(OH)D assays, the age and health of the populations studied, and the mathematical analyses used. We studied 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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