In this cross-sectional analysis of relatively young adults in NHANES, BMD significantly decreased with declining 25 (OH)D concentrations in whites and Mexican-Americans, but not in blacks. In addition, there were significant racial differences in the relationship between 25(OH)D and PTH above and below a 25(OH)D threshold commonly used to define vitamin D deficiency (20 ng/ml). These results may have important implications for evaluating vitamin D adequacy in minority populations. Indeed, vitamin D stores in racial minorities are routinely assessed by comparing their serum 25(OH)D concentrations against “normal” ranges that have largely been derived from the mathematical modeling of PTH and/or BMD as a function of 25(OH)D in predominantly white populations. In contrast, the results of this study suggest that optimal ranges for vitamin D among whites may not be the same as those among blacks, at least with respect to optimizing bone and mineral metabolism.
Racial differences in the relationship between 25(OH)D and BMD have been reported by previous investigators. For example, Aloia et al. analyzed the change in BMD in 208 postmenopausal African-American women randomly assigned to receive either vitamin D3
supplementation or placebo for 3 years [30
]. In contrast to analogous studies of white subjects [31
], these investigators found no significant differences in BMD loss between the intervention groups despite a significant increase in 25(OH)D concentrations in the active group as opposed to the control group [30
]. Similarly, in a study examining the relationships between 25(OH)D and BMD in elderly white, black, and Hispanic men residing in Boston, serum 25(OH)D concentrations were independently correlated with BMD in the white participants, but not the black participants [19
]. Our findings mirror these data in that we found that BMD decreased in parallel with declining serum 25(OH)D and dietary calcium intake among whites and Mexican-Americans, yet it remained remarkably preserved even within the lowest categories of calcium intake and 25(OH) D levels among blacks. These observations likely reflect known racial differences in calcium economy. Blacks are more efficient than whites in absorbing dietary sources of calcium, preserving calcium in the bones, and retaining calcium in the kidney, especially during adolescence [33
], leading some to suggest that blacks may require less dietary calcium than whites to maintain bone health [36
]. Accordingly, it is possible that blacks may also require a lower “set-point” for serum 25(OH)D to optimize calcium metabolism. Indeed, blacks maintain similar if not higher concentrations of 1,25-dihydroxyvitamin D than whites even at comparable concentrations of PTH [37
], suggesting that blacks may be able to maintain adequate calcium homeostasis at lower circulating 25(OH)D levels than whites. In addition, it is possible that higher BMI among blacks may also contribute to racial differences in the relationships between 25(OH)D and BMD [40
We observed highly significant inverse relationships between 25(OH)D and PTH above and below a 25(OH)D concentration of 20 ng/ml in whites and Mexican-Americans, but not among blacks. Indeed, while 25(OH)D and PTH were inversely related when 25(OH)D values were ≤20 ng/ml, the slope of this relationship was essentially flat above this threshold among blacks. These findings suggest that PTH concentrations may be maximally suppressed at a lower 25(OH)D concentration among blacks than among whites or Mexican-Americans. In support of this possibility is the study by Aloia et al. which found that PTH values appeared to plateau at a 25(OH)D concentration between ~16 and 20 ng/ml in African-American women [41
]. Moreover, women who began this study with 25(OH)D concentrations <17 ng/ml demonstrated significant reductions in PTH in response to vitamin D supplementation, whereas those who began the study >17 ng/ml did not, suggesting a threshold effect for PTH suppression at a 25(OH)D concentration of ~17 ng/ml, in contrast to analogous studies in white populations [3
]. Collectively, these data suggest that 25(OH)D threshold values derived from the mathematical modeling of PTH as a function of 25(OH)D in white populations may not be appropriate for blacks, potentially leading to inaccurate estimations of the prevalence of vitamin D insufficiency and deficiency in minorities.
It is important to note that numerous investigators have cautioned against the use of “bone-” or “mineral-based” 25 (OH)D thresholds as the primary determinant of optimal vitamin D levels, particularly considering the potential non-mineral benefits of vitamin D on outcomes such as hypertension, diabetes, cancer, immune function, and death [7
]. Although we agree with this concern, 25(OH)D thresholds derived from skeletal or mineral endpoints in white populations remain widely utilized for evaluating vitamin D stores in racial minorities, resulting in alarmingly high prevalence rates of vitamin D deficiency in minority populations [8
]. Indeed, 81% of blacks would have been categorized as vitamin D deficient, as compared to only 28% of whites, if one commonly used cut-off for vitamin D deficiency were indiscriminately applied to participants in this study. Yet utilizing this “one-size-fits-all” approach to assessing vitamin D stores in minority populations overlooks critical racial differences in bone and mineral metabolism as detailed above. Thus, while we cannot advocate different threshold values for vitamin D sufficiency in blacks based upon the results of this study alone, it would be similarly inappropriate to assume that standardized thresholds for vitamin D sufficiency in whites can be directly extrapolated to minority populations. Further studies are needed to test whether uniform targets for 25(OH)D adequacy result in similar or discordant outcomes by race.
Our study has limitations. First, variability in the performance of 25(OH)D assays in NHANES 2000–2006 is a potential limitation of this study. While sensitivity analyses suggested that the results of this study remained qualitatively the same when comparing the 2003–2004 sample to the 2005–2006 sample, variability from assay drift could still have impacted these results. Future studies will need to confirm these relationships when appropriate corrections for 25(OH)D results across NHANES 2000–2006 cycles are established. Second, we did not have measurements of 1,25-dihydroxyvitamin D or fibroblast growth factor 23, both of which influence 25(OH)D, PTH and bone metabolism and have been shown to differ by race [37
]. In addition, we did not have information with respect to parathyroid gland morphology, and so we could not determine whether parathyroid gland hyperplasia among blacks may have partly accounted for our results [45
]. Further studies will need to determine to what extent these factors may have impacted the findings of this study. Finally, we did not have prospective data concerning the associations between low 25(OH)D concentrations and the development of adverse health outcomes such as hypertension, diabetes, or cancer. Thus, we were unable to determine whether these relationships differ by race/ethnicity. For example, it is possible that blacks require higher 25(OH)D levels than whites for certain non-skeletal outcomes such as cardiovascular health, cancer prevention, or immune function. However, if so, this would only strengthen the case against assuming that vitamin D threshold values in whites can be extrapolated across racial and ethnic groups without first determining whether this currently widespread assumption is in fact appropriate.
In summary, we found that the relationships between 25(OH)D, BMD, and PTH varied by race among US adults. Further studies are needed to confirm these findings, and to determine whether race- and/or ethnic-specific ranges of optimal 25(OH)D are required to appropriately evaluate the adequacy of vitamin D stores in diverse populations.