**6. miRNAs in the "calcification paradox"**

Osteoporosis frequently associates with cardiovascular calcification, and the severity of aortic calcification associates positively with bone loss [2, 129, 130]. The "calcification paradox" could be explained by the shared molecular pathways in bone remodeling and cardiovascular calcification [3]. How these two processes associate with each other and whether osteoporosis leads to cardiovascular calcification - or whether both disorders just share common risk factors - is unclear. In this section, we link cardiovascular calcification and bone loss and show commonalities in the systems' miRNA pathways/patterns.

Studies of miRNA in patients with bone disease are lacking. A recent clinical study first reported miRNA as a potential biomarker for postmenopausal osteoporosis. Wang *et al*. demonstrated an association of miR-133a levels in circulating monocytes - osteoclast precur‐ sors - with postmenopausal osteoporosis [131]. Women with low bone mineral density showed higher circulating miR-133a levels [131], but the number of patients per group was small (n=10). Circulating miR-133a levels were also higher in patients with CAD [14]. Unfortunately, the study investigating bone mineral density in patients with osteoporosis did not mention characteristics of the cardiovascular patient population. miR-133a belongs to the Runx2 targeting miRNA cluster [77].

Additionally, miR-2861 contributes to osteoporosis in mice and humans by targeting histone deacethylase 5, and thereby increasing Runx2 [132]. No studies of miR-2861 in the cardiovas‐ cular system have been reported. Patients with rheumatoid arthritis also suffer from vascular calcification in different vessel beds, in addition to osteoporosis; the pathogenesis includes pro-inflammatory cytokines and site-specific inflammation (reviewed in detail elsewhere [133]). miR-146a, a negative regulator of inflammation and osteoclastogenesis, also associates with rheumatoid arthritis [134]. Similar to patients with CAD, in patients with rheumatoid arthritis, miR-146a is up-regulated in PBMCs [25].
