Beyond being epiphenomenon of shared epidemiological factors, the integration of Osteoporosis
(OP) with Cardiovascular Disease (CVD) - termed “calcification paradox” - reflects a continuum
of aberrant cardiometabolic status. The present review provides background knowledge on “calcification
paradox”, focusing on the endocrine aspect of vasculature orchestrated by the osteoblastic molecular
fingerprint of vascular cells, acquired via imbalance among established modulators of mineralization.
Osteoprotegerin (OPG), the well-established osteoprotective cytokine, has recently been shown to
exert a vessel-modifying role. Prompted by this notion, the present review interrogates OPG as the
potential missing link between OP and CVD. However, so far, the confirmation of this hypothesis is
hindered by the equivocal role of OPG in CVD, being both proatherosclerotic and antiatherosclerotic.
Further research is needed to illuminate whether OPG could be a biomarker of the “calcification paradox”.
Moreover, the present review brings into prominence the dual role of statins - cardioprotective
and osteoprotective - as a potential illustration of the integration of CVD with OP. Considering that the
statins-induced modulation of OPG is central to the statins-driven osteoprotective signalling, statins
could be suggested as an illustration of the role of OPG in the bone/vessels crosstalk, if further studies
consolidate the contribution of OPG to the cardioprotective role of statins. Another outstanding issue
that merits further evaluation is the inconsistency of the osteoprotective role of statins. Further understanding
of the varying bone-modifying role of statins, likely attributed to the unique profile of different
classes of statins defined by distinct physicochemical characteristics, may yield tangible benefits for
treating simultaneously OP and CVD.