Increased bone resorption in HD patients: is it caused by elevated RANKL synthesis?

Avberšek-Lužnik, Ivica; Balon, Breda Pečovnik; Rus, Igor; Marc, Janja

doi:10.1093/ndt/gfh672

Cited by 38 publications

(20 citation statements)

References 15 publications

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“…It has been assumed that the 'proinflammatory' profile of cytokines observed in atherosclerosis increases the RANKL/OPG ratio and in this way causes accumulation of calcium deposits [17]. Our in vitro findings seem to confirm numerous reports on the presence of inverse relationship between the concentration of OPG and RANKL also in vessels that are free of calcification [18].…”

Section: Discussionsupporting

confidence: 89%

Effect of unfractionated heparin, enoxaparin and sulodexide on the relations between secretion and expression of OPG, RANKL and vWF in HUVEC

Lekesiz

Naumnik

Borysewicz-Sańczyk

et al. 2013

Folia Histochem Cytobiol.

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Heparin modulates function of vascular endothelium. We studied the effects of unfractionated heparin (UFH) vs. enoxaparin vs. sulodexide on the levels and gene expression of osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kB Ligand (RANKL) and von Willebrand factor (vWF) in Human Umbilical Vein Endothelial Cells (HUVEC) culture. HUVEC were isolated from human umbilical vein by a standard method. The supernatant concentrations (ELISA) and gene expression (Real Time-PCR) of OPG, RANKL and vWF in HUVEC were determined after incubation with various concentrations of UFH, enoxaparin and sulodexide for up to 16 hours. In control HUVEC strong positive correlation between OPG and vWF levels was observed, whereas sRANKL negatively correlated with OPG and vWF levels. Only in control HUVEC a negative correlation between the supernatant level of vWF and its gene expression was found. Already the lowest concentration of UFH caused 2.5-fold increase in OPG gene expression while higher UFH concentrations substantially increased RANKL mRNA level. A negative correlation between the OPG and sRANKL concentration was noticed in supernatant HUVEC which were incubated with enoxaparine. In conclusion, the observed interrelationships between OPG, RANKL and vWF levels in unstimulated HUVEC support the presumption of the pathophysiological links between these proteins. Of the tested heparin formulas UFH seems to be the most potent in altering the OPG, RANKL and vWF axis.

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Section: Discussionsupporting

confidence: 89%

Effect of unfractionated heparin, enoxaparin and sulodexide on the relations between secretion and expression of OPG, RANKL and vWF in HUVEC

Lekesiz

Naumnik

Borysewicz-Sańczyk

et al. 2013

Folia Histochem Cytobiol.

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“…Similarly, an in vivo study showed an increased level of circulating bone-specific AlkPhos in patients with CKD in the presence of aortic calcification (45). Even though active vitamin D analogs including calcitriol may directly modulate calcifying processes leading to decreased vascular calcification, their salutary affects may also be mediated via osteopontin and AlkPhos pathways (6).…”

Section: Discussionmentioning

confidence: 99%

Association of Serum Alkaline Phosphatase with Coronary Artery Calcification in Maintenance Hemodialysis Patients

Shantouf¹,

Kövesdy²,

Kim³

et al. 2009

Clinical Journal of the American Society of Nephrology

141

115

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Background and objectives: Recent in vitro studies have shown a link between alkaline phosphatase and vascular calcification in patients with chronic kidney disease (CKD). High serum levels of alkaline phosphatase are associated with increased death risk in epidemiologic studies of maintenance hemodialysis (MHD) patients. We hypothesized that coronary artery calcification is independently associated with increased serum alkaline phosphatase levels in MHD patients.Design, setting, participants, & measurements: We examined the association of coronary artery calcification score (CACS) and alkaline phosphatase in 137 randomly selected MHD patients for whom markers of malnutrition, inflammation, and bone and mineral disorders were also measured.Results: Serum alkaline phosphatase was the only measure with significant and robust association with CACS (P < 0.003), whereas either other biochemical markers had no association with CACS or their association was eliminated after controlling for case-mix variables. Serum alkaline phosphatase >120 IU/L was a robust predictor of higher CACS and was particularly associated with the likelihood of CACS >400 (multivariate odds ratio 5.0 95% confidence interval 1.6 to 16.3; P ‫؍‬ 0.007). Serum alkaline phosphatase of approximately 85 IU/L seemed to be associated with the lowest likelihood of severe coronary artery calcification, but in the lowest tertile of alkaline phosphatase, the CACS predictability was not statistically significant.Conclusions: An association between serum alkaline phosphatase level and CACS exists in MHD patients. Given the high burden of vascular calcification in patients with CKD, examining potential therapeutic interventions to modulate the alkaline phosphatase pathway may be warranted.

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“…Avbersek-Luznik et al study showed that serum OPG levels were 6,4-fold higher in dialysis patients compared to controls, and was depended on PTH concentration [38]. Another research by Avbersek-Luznik et al support hypothesis that PTH increases bone resorbtion in HD patients through stimulating RANKL synthesis [40]. Conversely, in Doumouchtsis study, the average serum concentration of sRANKL was lower in patients on HD than in age-matched healthy controls [36] .…”

Section: Opg/rank/rankl System In Esrdmentioning

confidence: 93%

“…OPG concentrations are reported to be higher in HD patients [35][36][37][38][39], whereas RANKL level can be higher [39,40], lower [36] or within normal range [41] compared to healthy individuals. Kazama showed that serum OPG levels in uremic patients were elevated and independent of their serum PTH levels, what suggested the circulating OPG to be an independent factor affecting bone metabolism in uremic patients [42].…”

Section: Opg/rank/rankl System In Esrdmentioning

confidence: 99%

OPG/RANK/RANKL signaling system and its significance in nephrology.

Klejna

Naumnik²,

Gasowska³

et al. 2009

Folia Histochem Cytobiol.

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Increased bone resorption in HD patients: is it caused by elevated RANKL synthesis?

Cited by 38 publications

References 15 publications

Effect of unfractionated heparin, enoxaparin and sulodexide on the relations between secretion and expression of OPG, RANKL and vWF in HUVEC

Effect of unfractionated heparin, enoxaparin and sulodexide on the relations between secretion and expression of OPG, RANKL and vWF in HUVEC

Association of Serum Alkaline Phosphatase with Coronary Artery Calcification in Maintenance Hemodialysis Patients

OPG/RANK/RANKL signaling system and its significance in nephrology.

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