Osteoporosis Entwined with Cardiovascular Disease: The Implication of Osteoprotegerin and the Example of Statins

Abstract

: 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 biomarker of the "calcification paradox". Moreover, the present review brings into prominence the dual role of statins−cardioprotective and osteoprotective− as 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 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.

Osteoprotegerin and Ischemic Stroke Prognosis: A Prospective Multicenter Study and Mendelian Randomization Analysis

“…It had been widely demonstrated that there was considerable downregulation of serum osteoprotegerin levels after statins and angiotensin II blockade therapy, related to beneficial changes in carotid plaque morphology. 30,31 Therefore, further clinical trials are warranted to explore whether statins or angiotensin II blocker would improve the prognosis of ischemic stroke with high plasma osteoprotegerin levels.…”

Crosstalk between bone and other organs

“…Recent work has demonstrated that regulatory hierarchies active in developing bone are also important in heart valve maturation [ 146 ]. The bone-vascular axis calcification paradox serves as a bridge between bone (osteoporosis) and vascular diseases (cardiovascular disease, CVD) [ 147 ]. CVD and cardiovascular mortality are associated with reduced bone mineral density and bone fractures.…”

Cross-Talks between the Cardiovascular Disease-Sarcopenia-Osteoporosis Triad and Magnesium in Humans

“…Deep and conceptual interactions exist between the components of the triad [2] (Figure 1). Cardiovascular disease and osteoporosis share common pathogenetic mechanisms: patients with osteoporosis have higher levels of calcification than those with normal bone mineral density, and vascular calcification is related to a higher risk of fracture [11,12,41,42]. There is a continuum of disturbed and deviant mechanisms, termed "calcification paradoxes", where aortic valve interstitial cells re-differentiate into an osteoblastlike phenotype, the pivotal cellular mechanism of aortic valve calcification [22].…”