Serum Dickkopf 1 Levels in Sclerostin Deficiency

Context: Sclerostin and Dickkopf 1 (DKK1) are antagonists of the canonical Wnt signaling pathway, both binding to the same low-density lipoprotein receptor-related protein 5/6 on osteoblasts, thereby inhibiting bone formation. It is not known whether there is an interaction between sclerostin 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. Main Outcome Measures: DKK1 levels were compared between patients and carriers, and between patients and healthy controls. We also examined associations between levels of DKK1 and the bone turnover markers procollagen type 1 amino-terminal propeptide and ...