Aging is associated with calcium loss from bone and increased calcium deposition in blood vessels, but whether this shift in calcium is due to common pathogenetic mechanisms shared by osteoporosis and atherosclerosis or whether these diseases are merely comorbidities of aging has been unclear. For example, women with osteoporosis have a fourfold increased risk of cardiovascular events as compared to women without osteoporosis1. But whether this is due to a true association between these diseases independent of age has been unclear, as both osteoporosis and atherosclerosis become clinically evident starting in the sixth decade, and their incidence increases further with aging. Both diseases also affect multiple ethnic groups and both sexes, although osteoporosis is more common in women than in men. A recent epidemiological study from the Multi-Ethnic Study of Atherosclerosis (MESA) by Hyder et al. 2 is of particular interest, as their results indicate that osteoporosis and atherosclerosis are closely related, independent of age and other confounders. The authors used quantitative computed tomography in 946 women and 963 men, each with a mean age of approximately 65 years, to assess lumbar spine volumetric bone mineral density (LS-vBMD), an index of skeletal mass, as well as coronary artery calcium (CAC) and abdominal aortic calcium (AAC) scores, which are indices of atherosclerosis. After adjusting the data for age, ethnicity, body mass index, hypertension, dyslipidemia, diabetes mellitus, smoking, alcohol consumption, physical activity, inflammatory biomarkers (interleukin-6 (IL-6), C-reactive protein and homocysteine) and sex hormones, decreased LS-vBMD was significantly associated with increased CAC score among women and increased AAC score among both women and men. Adjusting statistically for these multiple variables was crucial to show a potential direct link between LS-vBMD and CAC and AAC scores independent of other variables that may be affecting both bone loss and atherosclerosis.

These findings are clinically relevant, as bone density is a well-established predictor of fracture risk3, and arterial calcium content increases the risk of cardiovascular events such as myocardial infarction and stroke, as well as of death from cardiovascular disease4. Notably, the results of this study show that the relationship between vBMD and vascular calcification scores was still present after adjustment for multiple confounding variables; however, whereas epidemiological studies such as this can generate plausible hypotheses, they cannot establish causality. What, then, are the possible mechanistic links between bone loss and vascular disease? This question is best addressed after perusing the hitherto identified mechanisms underlying both bone and vascular remodeling. Bone is constantly modified through resorption by osteoclasts and formation by osteoblasts (Fig. 1), a remodeling process that is triggered by osteocytes—osteoblast-lineage cells embedded in bone—that respond to local injury, such as a microcrack occurring during normal loading, and serve an important repair function. Increasing evidence indicates that bone remodeling occurs in the bone remodeling compartment, a closed cavity covered by a canopy of bone-lining cells (probably quiescent osteoblasts) that is penetrated by a capillary that provides perivascular progenitor cells that differentiate into functional osteoblasts5. The atherosclerotic plaque shows striking similarities with the bone remodeling compartment (Fig. 1). A crucial point is that one of the outcomes of the remodeling processes