Active vitamin D treatment in CKD patients raises serum sclerostin and this effect is modified by circulating pentosidine levels

Background and aims: 1,25(OH) 2Vitamin D increases the expression of the sclerostin gene. Whether vitamin D receptor activation (VDRA) influences serum sclerostin in CKD and whether compounds interfering with VDRA like Advanced Glycosylation End Products (AGEs) may alter the sclerostin response to VDRA is unknown. Methods and results: Eighty-eight stage G3-4 CKD patients randomly received 2 mu g paricalcitol (PCT)/day (n = 44) or placebo (n = 44) for 12 weeks. Sclerostin, a major AGE compound like pentosidine, and bone mineral disorder biomarkers were measured at baseline, at 12 weeks and 2 weeks after stopping the treatments. At baseline, in the whole study population sclerostin correlated with male gender (P = 0.002), BMI (P < 0.001), waist circumference (P < 0.001), serum pentosidine (P = 0.002) and to aweaker extent, with diabetes (P = 0.04), 1,25(OH) 2Vitamin D (r = 0.22, P = 0.04) and serum phosphate (r = -0.26, P = 0.01). Sclerostin increased during PCT treatment (average + 15.7 pg/ml, 95% CI: -3.0 to +34.3) but not during placebo (P Z 0.03) and the PCT effect was abolished 2 weeks after stopping this drug. The increase in sclerostin levels induced by PCT was modified by prevailing pentosidine levels (P Z 0.01) and was abolished by statistical adjustment for simultaneous changes in PTH but not by FGF23 changes. Conclusions: VDRA by paricalcitol causes a moderate increase in serum sclerostin in CKD patients. Such an effect is abolished by adjustment for PTH, suggesting that it may serve to counter PTH suppression. The sclerostin rise by PCT is attenuated by pentosidine, an observation in keeping with in vitro studies showing that AGEs alter the functioning of the VDRA. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B. V. All rights reserved. Background and aims: 1,25(OH) (2)Vitamin D increases the expression of the sclerostin gene. Whether vitamin D receptor activation (VDRA) influences serum sclerostin in CKD and whether compounds interfering with VDRA like Advanced Glycosylation End Products (AGEs) may alter the sclerostin response to VDRA is unknown.