Introduction: In cases of chronic kidney disease (CKD), bone and mineral metabolism changes occur which favor soft tissue calcification. Alterations in the RANK/RANKL/OPG system could also favor vascular calcification, a major cause of morbidity and mortality in CKD. Objective: In an in vivo experimental model of chronic renal failure progression, we assess the effect of CKD on vascular calcification and bone loss correlating these changes in the RANK/RANKL/OPG pathway. An in vitro system was used to confirm findings. Material and Methods: Two models of vascular calcification were used: an in vivo rat model with chronic renal failure fed on a diet with different phosphorus content, and an in vitro model in vascular smooth muscle cells (VSMC) subjected to different calcifying stimuli. Results: At 20 weeks, 50% of animals with a diet high in phosphorus presented aortic calcification accompanied by increased aortic expression of RANKL. In contrast, OPG decreased probably as a consequence of an inflammatory component. At 20 weeks, expression of RANKL and OPG in the tibia increased, while the increase in OPG occurred at earlier stages. In VSMC, the addition of uremic serum and calcification medium increased calcium content and expression of RANKL and OPG. The addition of OPG and silencing of RANK inhibited this increase. Conclusions: Our results confirm RANK/RANKL/OPG system involvement in the vascular calcification process.
Objetive: Biochemical parameters continue to be the most widely used option for the follow-up of patients with bone metabolic disorders. The objective of our study was to assess the association of some biochemical markers of bone metabolism with the appearance and progression of aortic calcifications. Material and methods: In this study, 624 men and women older than 50 years were selected at random. The participants completed a questionnaire and underwent two lateral dorsal-lumbar x-rays and bone densitometry. Four years later, the same studies were repeated in 402 subjects along with a biochemical study. Results: Age and the proportion of men were higher in those who had "global progression" of aortic calcification (progression of the existing ones plus new ones). The serum levels of calcium and calcitriol were significantly higher and those of osteocalcin significantly lower in which "global progression" of aortic calcification was observed. Multivariate analysis showed that only osteocalcin was independently associated with "global progression" of aortic calcification, with an 18% decrease for each 1 ng/mL increase in osteocalcin levels (odds ratio (OR)=0, 82; 95% confidence interval (95% CI): 0.71-0.92). The categorization of osteocalcin into tertiles showed that the subjects of the first tertile (<4.84 ng/mL) were associated with a higher proportion of new aortic calcifications: (OR=2.45; 95% CI: 1.03-3, 56) with respect to the third tertile (>6.40 ng/mL). Conclusion: Serum levels of osteocalcin could be a biochemical marker to evaluate the appearance and/or evolution of aortic calcification. However, it is necessary to determine with greater precision how it could exert this protective effect in the process of vascular calcification.
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