title: Serum Dickkopf 1 levels in sclerostin deficiency.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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 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 < .001; VBD, 3.47 ng/mL [95% CI, 2.97-3.97 ng/mL], P = 0.017) and to levels in healthy controls (2.77 ng/mL [95% CI, 2.45-3.08 ng/mL]; P = 0.004 and P < .001, respectively). Serum DKK1 levels were positively associated with levels of procollagen type 1 amino-terminal propeptide and carboxy-terminal cross-linking telopeptide in both disorders.
  
  
  CONCLUSIONS
  These results suggest that increased DKK1 levels observed in patients with sclerosteosis and VBD represent an adaptive response to the increased bone formation characterizing these diseases, although these increased levels do not compensate for the lack of sclerostin on bone formation.
authors.affiliation: Department of Endocrinology and Metabolic Diseases and Leiden Center for Bone Quality, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: van Lierop
authors.forename: M J C
authors.initials: MJ
authors.lastname: Moester
authors.forename: N A T
authors.initials: NA
authors.lastname: Hamdy
authors.forename: S E
authors.initials: SE
authors.lastname: Papapoulos
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019485:Bone Morphogenetic Proteins / Q000172:deficiency*; D016723:Bone Remodeling / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005819:Genetic Markers; D006801:Humans; D015576:Hyperostosis / Q000097:blood*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010009:Osteochondrodysplasias / Q000097:blood*; D013576:Syndactyly / Q000097:blood*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human