The Emerging Role of Bone Markers in Diagnosis and Risk Stratification of Patients With Coronary Artery Disease

Abstract

Molecules that govern bone metabolism, such as osteoprotegerin (OPG) and osteopontin (OPN), have been isolated from other tissues, including blood vessels. Atherosclerosis and coronary artery disease (CAD) are leading causes of mortality worldwide. Despite novel biochemical and imaging techniques, early detection of CAD is still unsatisfactory. Experimental data indicate that bone turnover markers (BTMs) contribute to the development of atherosclerosis. This finding has sparked interest in their clinical use. This narrative review analyzed information from >50 human studies, which strongly suggest that OPG, OPN, and alkaline phosphatase (ALP) serum concentrations are altered in patients with CAD. Osteoprotegerin seems to be more useful for the detection of early disease, while OPN and ALP are recruited in vessels after the establishment of disease. Osteocalcin may be used as a flow cytometry marker for endothelial progenitor cells and can constitute a marker to monitor response to interventional treatments and risk of restenosis. However, most data derive from observational studies. Incorporation of BTMs in multifactorial computational algorithms could further determine their role in CAD diagnosis and prognosis together with other imaging techniques and biochemical markers.

Atherosclerosis in SLE: a potential role for serum parathormone levels

“…Indeed, the contribution of bone metabolism markers such as OPG or osteopontin has been previously shown to serve as surrogate markers for CVD. 4 Moreover, OPGdeficient mice displayed increased atherosclerosis, vascular calcification and osteoporosis together with heightened circulating RANKL levels. 5 A candidate molecule which attracted particular attention in recent years is 25(OH) vitamin D 3 , due to pleiotropic functions extending beyond bone mineralisation and calcium homeostasis.…”

“…Indeed, the contribution of bone metabolism markers such as OPG or osteopontin has been previously shown to serve as surrogate markers for CVD. 4 Moreover, OPG-deficient mice displayed increased atherosclerosis, vascular calcification and osteoporosis together with heightened circulating RANKL levels. 5 …”

Strong Associations between Plasma Osteopontin and Several Inflammatory Chemokines, Cytokines, and Growth Factors

“…Human studies and transgenic mouse models have shown that increased osteopontin production, especially in myocytes, was associated with increased apoptosis and myocardial dysfunction [ 13 ]. Experimental studies have indicated that osteopontin played an important role in atherosclerosis development, vascular remodeling, and restenosis [ 2 , 14 , 15 , 16 ]. It has also been shown that atherosclerosis modifying therapies with statins or angiotensin II inhibiting drugs reduced circulating osteopontin levels [ 17 , 18 ].…”

“…Therefore, osteopontin thus functions beyond those related to bone formation. Osteopontin has been implicated in several physiological and pathological processes such as bone turnover [ 2 ], cell survival [ 3 ], immune regulation and response [ 4 ], inflammation [ 5 ], ischemia [ 6 ], tissue remodeling [ 7 ], tumor progression [ 8 ], and wound healing [ 9 ]. In inflammation, osteopontin acts as a proinflammatory cytokine, modulating the immune response by enhancing expression of Th1 cytokines [ 10 ].…”

Osteoprotegerin SNP associations with coronary artery disease and ischemic stroke risk: a meta-analysis

“…In atherosclerotic plaques, elevated OPG mRNA and protein levels were observed [ 3–5 ]. Several observational studies found that serum levels of OPG were independently correlated with the presence and severity of CAD after adjusting for traditional risk factors such as hypertension and smoking in logistic regression models [ 8 , 10 , 11 ]. Moreover, increased OPG levels strongly predicted adverse clinical outcomes in patients with CAD.…”