Osteocalcin as a potential risk biomarker for cardiovascular and metabolic diseases

Abstract

Clear evidence supports a role for circulating and locally-produced osteocalcin (OC) in the pathophysiology of cardiovascular (CV) lesions and CV risk, also in combination with metabolic changes, including type 2 diabetes mellitus (T2DM). Reduced plasma OC levels are associated with greater incidence of pathological CV changes, like arterial and valvular calcification, coronary and carotid atherosclerosis and increased carotid intima-media thickness. The actual relationship between OC levels and incidence of major CV events is, however, still unclear. Moreover, reduced circulating OC levels have been mostly associated with insulin resistance, metabolic syndrome or T2DM, indicating relevant OC actions on pancreatic β-cells and insulin secretion and activity. Based on these observations, this review article will attempt to summarize the current evidence on the potential usefulness of circulating OC as a biomarker for CV and metabolic risk, also evaluating the currently open issues in this area of research.

The Impact of Osteocalcin, Osteoprotegerin and Osteopontin on Arterial Stiffness in Chronic Renal Failure Patients on Hemodialysis

“…Conflicting results are available concerning plasma OC as a predictor of cardiovascular diseases and related mortality. In general, low circulating OC concentrations were found to be associated with an increased risk of cardiovascular diseases [16, 28, 29]. In agreement with our findings inverse relationship was also seen between the risk of cardiovascular events and plasma OC levels in patients on regular HD suggesting a vasculo-protective role for OC [26, 30, 31].…”

“…Depending on the extent of its carboxylation several isoforms are formed and released into the circulation that have different biological activities including the regulation of VC and atherosclerosis, as well as the modulation of insulin secretion and insulin sensitivity. Importantly, OC is also expressed in the calcified atherosclerotic lesion where it may modulate this process [16, 23-25]. …”

Vitamin D Deficiency Is Associated with Increased Osteocalcin Levels in Acute Aortic Dissection: A Pilot Study on Elderly Patients

“…Patients evaluated in this study, in fact, displayed an acute vascular event which was the result of inflammation-related processes and alteration in the composition of the media tunica of the vascular wall. Recent reports indicated that OC is associated to arterial diseases, thus being a molecule able to exert important effects also on vascular tissues which is similar to bone tissue in term of regulation of mineral homeostatsis [21]. In addition to OC, another molecule mainly produced by the bone, osteopontin, emerged as a novel player in arterial remodeling, inflammation, and the promotion of fibrosis, thus suggesting the same ability of these bone-derived molecules to target the cardiovascular system [28, 29].…”

“…OC exists in two main form: carboxylated, promoted by vitamin K, and undercarboxylated. In this latter form, it has less affinities towards calcium and hydroxyapatite and it is easily secreted and plays important endocrine activities, such as the stimulation of insulin secretion, the increase in insulin sensitivity, and the reduction of blood glucose levels [21]. Both forms are anyway secreted.…”

“…Thus, our aim was to evaluate whether vitamin D and vitamin D-related bone markers, which have also been related to metabolic and cardiovascular diseases, namely, osteocalcin (OC), parathormone (PTH), and bone alkaline phosphatase (BAP) [20, 21], are altered in AAD, also according to dissection localization at the ascending or descending aorta. The identification of new factors and pathways potentially associated and involved in AAD may be finally helpful to identify individuals at high risk as well to study preventing strategies.…”