RANKL increases the pool of active osteoclasts by activating its specific receptor RANK located partly on osteoclastic cells, thus increasing bone resorption, whereas OPG, which neutralizes RANKL, has opposite effects. RANKL and OPG are produced by bone marrow derived stromal cells and osteoblasts and are regulated by various calcitropic cytokines, hormones, and drugs. The actions of OPG and RANKL in the vasculature and heart are still unclear but no doubt exists about the strong association of OPG with the prevalence of vascular calcifications in predialysis and HD patients. FGF23 is the main regulator of phosphate homeostasis. It is produced by osteocytes in Veratramine response to hyperphosphatemia and exerts its effects on its receptor, the Klotho-FGFR1c heterodimer, in the kidney where it inhibits the expression of Na-Pi cotransporters resulting in hyperphosphaturia. Literature data are more controversial regarding FGF23 association with vascular calcifications according to the stage of CKD. Relationships between FGF23 and aortic calcifications or peripheral vascular calcifications are well documented in HD patients. By contrast, studies in non dialysis CKD patients could not evidence any association after multivariable adjustment but rather relationships to D-Pantothenic acid sodium atherosclerosis and left ventricular hypertrophy. In this study, clinical variables such as age, diabetes mellitus and smoking habits were associated with CAC in our population of ND-CKD patients. Among biomarkers of vascular calcifications, our results clearly confirmed that both high OPG and FGF23 levels were associated with CAC in this population. Original findings of our study are that association of both markers with CAC depends on the severity of CAC extension: OPG is associated to moderate CAC while FGF23 rather represents a biomarker of severe CAC in these patients. Previous studies have reported an association between high OPG levels and CAC in CKD, HD and diabetic patients. Here, we demonstrated for the first time that high OPG is only associated to moderate rather than severe coronary calcifications. These interesting results are in total agreement with a previous study from Morony et al. in a model of atherogenic diet-fed ldlr mice. Indeed, the authors clearly showed that plasma OPG level increased with initiation of the atherogenic diet, reached a maximum value after one month of diet and did not increase further during the four following months while aortic atherosclerosis lesions were still progressing. In our study, the same pattern is observed. OPG values are significantly increased in patients with moderate compared with mild CAC, this increased level being comparable with that of patients presenting severe CAC. This clearly suggests that OPG appears as a marker of atherosclerosis/vascular calcification onset rather than its severity or progression. Considerable controversy exists regarding the role of OPG in the development and progression of vascular calcifications.