(Sub)clinical cardiovascular disease is associated with increased bone loss and fracture risk; a systematic review of the association between cardiovascular disease and osteoporosis

Cardiovascular (CV) disease and osteoporosis are both important causes of morbidity and mortality in aging men and women. They share common risk factors, such as increased age and inactivity, and are frequently found in the same individuals, suggesting a possible relationship. Results from epidemiological studies indicate an association between CV disease and osteoporosis. Prevalent CV disease and subclinical atherosclerosis have been found to be related to low bone mass and increased fracture risk [1‐4]. Similarly, low bone mineral density (BMD) has been related to increased cardiovascular risk [5‐8]. This relationship is often regarded as a result of aging; however, recent evidence suggests a direct association, independent of age and traditional cardiovascular risk factors and accumulating evidence from experimental research indicates a shared pathogenesis. A variety of factors that influence bone metabolism are involved in the development of vascular disease, for example, atherosclerosis and vascular calcification. Interestingly, several bone-related proteins are implicated in the calcification process resulting in mineral deposition [9]. This is important as calcification of the arterial wall may be a marker for CV disease and was shown to predict CV events [10]. Given the importance of identifying a person at risk for CV events or fractures, evidence for an association of CV disease with osteoporosis might have implications for screening decisions in patients with low bone mass and vice versa. This review aims to summarize all the present clinical literature about the association between CV disease and osteoporosis and to describe common pathophysiological mechanisms. The results of this review are grouped into two topics: clinical results, discussing the relationship between 1) cardiovascular disease and osteoporosis and 2) vice versa. In addition, the possible pathophysiological links of CV disease and osteoporosis will be discussed.

Our study is the first to systematically review the epidemiological literature about the association between CV disease and osteoporosis. An extensive literature search yielded 27 prospective studies addressing this relationship. Due to considerable heterogeneity in study design and outcome measurements the results could not be pooled. Focusing on the methodologically strongest studies (those with minimal selection bias and the appropriate assessments, that is, a methodological score of more than 3), our review indicates that the prevalent subclinical CV disease predicts future fractures and bone loss [2‐4, 13‐15] (Table 4).

Furthermore, there is some evidence that low bone mass predicts CV mortality and CV events [6, 62, 68, 69, 75].

Interestingly, several studies demonstrated shared risk factors, supporting the existence of a direct association between vascular calcification and bone biology.

Due to the substantial diversity of patients and study methods, pooled analysis was not considered appropriate. Although numerous efforts were made to investigate the association between CV disease and osteoporosis, a vast majority of studies used secondary outcome measurements, while a limited number of studies used primary outcome measurements such as incident CV events or osteoporosis. Furthermore, the population studied varied with respect to age, sex, baseline risk for CV events or fractures and ethnicity. Larger prospective studies in elderly persons, men and women, are needed to answer this question. To reduce heterogeneity we encourage that in new studies well-defined outcome measures should be incorporated, such as incident CV disease presented per subcategory of CV disease and measurement of BMD by DXA-scans on regular interval periods.