Serum dickkopf 1 levels in sclerostin deficiency

Abstract

Context: Sclerostin and Dickkopf 1 (DKK1) are antagonists of the canonicalWntsignaling pathway, both binding to the same low-density lipoprotein receptor-related protein 5/6 on osteoblasts, thereby inhibitingboneformation. It is notknownwhether there isaninteractionbetweensclerostin and DKK1. Objective: We examined whether a lack of sclerostin is compensated by increased DKK1 levels. Design, Setting, and Patients: We measured DKK1 levels in serum samples of patients and carriers of sclerosteosis (19 patients, 24 carriers) and van Buchem disease (VBD) (13 patients, 22 carriers) and 25 healthy controls. Sclerosteosis and VBD are caused by deficient sclerostin synthesis and are characterized by increased bone formation and hyperostotic phenotypes. MainOutcomeMeasures:DKK1levels were compared between patients and carriers, and between patients and healthy controls.Wealso examined associations between levels ofDKK1and the bone turnover markers procollagen type 1 amino-terminal propeptide and carboxy-terminal cross-linking telopeptide. Results: We found that DKK1 levels were significantly higher in patients with both sclerosteosis (4.28 ng/mL [95% confidence interval (CI), 3.46-5.11 ng/mL]) and VBD (5.28 ng/mL [95% CI, 3.84- 6.71 ng/mL]), compared to levels in carriers of the two diseases (sclerosteosis, 2.03 ng/mL [95% CI, 1.78-2.29 ng/mL], P