Interest in vitamin d has been spurred by the observation that low 25-hydroxyvitamin D levels (25[OH]D) are associated not only with risk for osteoporosis and fracture, but also with risk for falls in seniors. Indeed, limited data suggest that supplementation of low vitamin D in frail seniors reduces falls. There is, however, some disconnect between 25(OH)D levels as determined in black vs white Americans. That is, black Americans have lower 25(OH)D levels than whites, yet blacks have both a higher bone mineral density and lower risk for osteoporotic fracture.

Current clinical practice does not typically include measurement of vitamin D-binding protein, which is the primary plasma protein carrying vitamin D in the blood, accounting for 85-90% of circulating vitamin D. Similar to the biochemistry of testosterone, it appears to be only the free 25(OH)D fraction (i.e., not bound to vitamin D-binding protein) that is active at tissue target sites. Genetic polymorphisms are responsible for variations in levels of vitamin D-binding protein, and hence the amount of bioavailable vitamin D.

Powe et al compared bioavailable vitamin D levels in subjects participating in the Healthy Aging in Neighborhoods of Diversity Across the Life Span Study (n = 2085). Overall, blacks had substantially lower 25(OH)D levels than whites (16 ng/mL vs 26 ng/mL). Similarly, levels of vitamin D-binding protein were essentially twice as high in white vs black subjects (337 mcg/mL vs 168 mcg/mL). Genetic polymorphisms more commonly seen in black Americans than whites — not ethnicity itself — explained approximately 80% of the differences in vitamin D-binding protein levels.

The greater bioavailable vitamin D in blacks compared to whites at comparable 25(OH)D levels explains most of the above-mentioned discrepant black/white fracture risk. Additionally, since polymorphisms associated with increased bioavailable vitamin D can be seen in diverse ethnicities, the authors suggest that we may soon need to be incorporating measurement of vitamin D-binding protein to accurately interpret vitamin D status.