Bone geometry, density and microarchitecture in the distal radius and tibia in women with primary hyperparathyroidism - a case-control study using HR-pQCT

Abstract

Canonical Wnt-signaling stimulates osteogenesis. Sclerostin and dickkopf-1 (Dkk-1) are soluble inhibitors of Wnt-signaling. In preclinical studies parathyroid hormone (PTH) was found to increase bone turnover and bone mass by downregulation of sclerostin synthesis. We investigated whether PTH levels in chronic kidney disease (CKD) influence bone turnover through sclerostin or Dkk-1. Sclerostin and Dkk-1 were measured in serum from 64 dialysis patients and 45 healthy controls using enzyme-linked-immunosorbent assays (ELISA). Sclerostin and Dkk-1 levels were correlated with levels of intact PTH (iPTH), bone alkaline phosphatase (bAP), type I collagen c-terminal telopeptide (CTX), 25-hydroxy-cholecalciferol, calcitriol, calcium and phosphate. Sclerostin but not Dkk-1 levels were significantly higher in dialysis patients compared to controls (sclerostin: 1393 vs. 415 pg/ml, p<0.001; Dkk-1: 102 vs. 106 pmol/l, p=n.s.). There was a significant correlation between sclerostin and iPTH (ρ=-0.26), bAP (ρ=-0.27), CTX (ρ=-0.3), and calcium (ρ=0.27) in dialysis patients (p<0.05 for all) in a univariate analysis, but only the correlation with calcium remained statistically significant in a multivariate regression analysis. Dkk-1did not correlate with bone turnover markers. In healthy controls neither sclerostin nor Dkk-1 correlated with markers of bone turnover. In conclusion, sclerostin is increased in CKD and is only weakly associated with iPTH and markers of bone turnover. Disclosure of Interest: None declared