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Effect of race and genetics on vitamin D metabolism, bone and vascular health

Nature Reviews Nephrology volume 8, pages 459–466 (2012)Cite this article

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Abstract

The pathophysiology of chronic kidney disease–mineral and bone disorder accounts for an inverse relationship between bone mineralization and vascular calcification in progressive nephropathy. Inverse associations between bone mineral density (BMD) and calcified atherosclerotic plaque are also observed in individuals of European and African ancestry without nephropathy, suggesting a mechanistic link between these processes that is independent of kidney disease. Despite lower dietary calcium intake and serum 25-hydroxyvitamin D (25(OH)D) concentrations, African Americans have higher BMD and develop osteoporosis less frequently than do European Americans. Moreover, despite having more risk factors for cardiovascular disease, African Americans have a lower incidence and severity of calcified atherosclerotic plaque formation than do European Americans. Strikingly, evidence is now revealing that serum 25(OH)D and/or 1,25 dihydroxyvitamin D levels associate positively with atherosclerosis but negatively with BMD in African Americans; by contrast, vitamin D levels associate negatively with atherosclerosis and positively with BMD in individuals of European ancestry. Biologic phenomena, therefore, seem to contribute to population-specific differences in vitamin D metabolism, bone and vascular health. Genetic and mechanistic approaches used to explore these differences should further our understanding of bone–blood vessel relationships and explain how African ancestry protects from osteoporosis and calcified atherosclerotic plaque, provided that access of African Americans to health care is equivalent to individuals of European ethnic origin. Ultimately, in our opinion, a new mechanistic understanding of the relationships between bone mineralization and vascular calcification will produce novel approaches for disease prevention in aging populations.

Key Points

  • Inverse relationships exist between bone mineral density (BMD) and calcified atherosclerotic plaque in individuals of European and African ancestry without nephropathy

  • African Americans have higher BMD and develop osteoporosis less often than do European Americans, despite lower serum 25-hydroxyvitamin D levels and dietary calcium intake

  • European Americans have higher incidence rates and severity of calcified atherosclerotic plaque relative to African Americans despite fewer cardiovascular disease risk factors

  • Inherited phenomena are likely to contribute to population-specific differences in vitamin D metabolism, vascular calcification, and bone mineralization

  • Molecular genetic approaches will enhance our understanding of bone and vascular health

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Figure 1: Relationships between bone and vascular calcium and phosphate deposition and dependence upon the environment, ethnicity, sex, and genetic factors.
Figure 2: Proposed mechanistic links between metabolic bone disease, atherosclerosis, and vascular calcification.

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Acknowledgements

The authors wish to thank D. W. Bowden, C. D. Langefeld, J. Divers, J. J. Carr, and N. Allred for their assistance with this work. This project was funded in part by NIH grant DK071891.

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  1. Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, 27157-1053, NC, USA

    Barry I. Freedman

  2. Department of Pathology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, 27157-1053, NC, USA

    Thomas C. Register

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Freedman, B., Register, T. Effect of race and genetics on vitamin D metabolism, bone and vascular health. Nat Rev Nephrol 8, 459–466 (2012). https://doi.org/10.1038/nrneph.2012.112

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