Bone mineral density and prediction of non-osteoporotic disease.

It is widely recognized that bone mineral density (BMD) is one of the best predictors of osteoporotic fractures. Sex hormone status clearly affects bone either directly or indirectly and a longer estrogen exposure appears to be a major determinant of postmenopausal BMD. Accordingly, several studies have led to the hypothesis that BMD might represent a marker of the accumulated lifetime exposure of estrogen and therefore be used as a predictor factor of the risk of other postmenopausal conditions such as breast cancer or cardiovascular diseases (CVD). With regard to the risk of breast cancer, there is evidence that different surrogate markers of lifetime exposure to estrogen are associated with an increased risk for breast cancer. Most of these markers are the opposite of those for the risk of fracture. Furthermore, several studies have also reported that women with higher BMD have an increased risk of breast cancer compared to women with lower BMD. On the other hand, postmenopausal women with osteoporosis are at increased risk for acute cardiovascular events and mortality independently of age and cardiovascular risk factors. BMD has been shown to inversely correlate with surrogate markers of CVD including aortic calcifications and atherosclerosis. The underlying mechanisms of such a relationship are not fully understood. Several plausible molecular links are serum lipids, pro-inflammatory cytokines or the RANK/RANK ligand/osteoprotegerin system. Interestingly, all of these factors are modulated by estrogens. It could thus be hypothesized that the intensity of postmenopausal estrogen deficiency could be also the common pathogenic factor between atherosclerosis and osteoporosis.