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.