The most important finding in the present study is that CA IMT emerged as an independent factor that is associated significantly with Trochanter BMD, Femoral neck BMD, Ward triangle BMD and Femoral total BMD, but not with lumbar spine BMD. The association between trabecular or cortical osteoporosis and calcification in different vascular beds may vary, and should be considered when comparing the reported findings. In many studies evaluating the association between low bone mass and vascular calcification, there was an independent association between BMD at cortical sites, as represented by low hip BMD and vascular calcification [6
]. However, studies measuring BMD at predominantly trabecular sites, namely spinal sites, failed to demonstrate this association [4
]. In the past, this lack of association had been attributed to methodological pitfalls related to Dual Energy X-ray Absorptiometry (DXA) measurements. In fact, DXA measurements of the spine are confounded by the presence of calcified plaques in adjacent vessels and osteophytes [26
]. Nevertheless, the lack of an association at trabecular sites was confirmed by the Sinnot study [27
] that used highly sensitive and specific quantitative computerized tomography (QCT) measures of exclusively trabecular bone of the vertebrae. By contrast, previous studies have shown a negative association between lumbar BMD and IMT, but this lack of association has also been described in hemodialysis patients [28
Our results indicate that FA IMT is not associated significantly with BMD. Our data seem to be in contrast to the earlier findings [5
] that found a significant association between FA IMT and bone status. It is also conceivable that atherosclerotic distribution within the vascular tree may vary considerably between vascular beds, and this may explain some of the apparently conflicting findings in the literature [24
Another finding in the present study was that CA IMT is associated significantly with all femoral site BMD independently of age. Indeed, both osteoporosis and atherosclerosis increase with age, but the relationship between them has remained unclear [31
]. In some studies, the apparent association between BMD and vascular calcification disappeared after adjusting for age [25
], while in others, the association was independent of age [3
The biological explanation for the possible relationship between atherosclerosis and osteoporosis is unclear at present, but several hypotheses have been proposed. Oxidized lipids [15
], impaired vitamin K status [14
], homocysteine, and high levels of osteoprotegerin [10
] are among the factors that may contribute to the association between atherosclerosis and osteoporosis. Hamerman [34
] reviewed several possibilities, and pointed out that inflammation is likely to be one of the processes that influence atherogenesis and bone loss. Many of the inflammatory mediators driving atherogenesis in the arterial wall are known to be in the circulation as markers of cardiovascular risk. These could gain access to bone, where, together with local cytokines, they could enhance the release of osteoblastic factors, that in turn promote osteoclastogenesis.
Several researchers have suggested a role for hyperlipidemia and lipid oxidation [15
] and inflammation [34
]. In vitro
studies have shown that oxidized lipids promote osteoblastic differentiation of vascular cells and inhibit such differentiation in bone cells [35
]. One possible mechanism by which this may occur is through accumulation of oxidized lipids in tissue so as to mimic chronic infection, thereby stimulating an immune response that promotes the hardening of soft tissue (to wall off infectious agents) and the softening of hard tissue (to dissolve a substrate for growth of infectious agents). In our study, serum LDL cholesterol emerged as an independent factor that is associated significantly with femoral BMD, after adjusting for age and CA IMT.
Although several studies have shown that increasing BMD is related to a decreasing prevalence of echogenic plaque [36
], our results found no significant differences between the four groups according to the plaque echogenicity in lumbar and femoral BMD.
There are several potential limitations to this cross-sectional study. First, the subjects were not recruited from the community at large, but were selected from patients who underwent bone density determinations. This selection bias may explain the relatively high prevalence of osteoporosis in the subjects studied. In fact, we have already shown that 31 to 39% of post-menopausal women had osteoporosis [38
]. Another bias is related to the classification of plaques. Despite the fact that the reproducibility of plaque echogenicity was good, some misclassification may have occurred. Lastly, we have no direct histopathological demonstration that increased IMT is due to atherosclerosis. The arterial thickening might have been due to another, non-atherosclerotic arteriopathy. However, IMT measurements are still useful in that IMT is strongly correlated with the presence of coronary artery diseases.