title: The effect of teriparatide on serum Dickkopf-1 levels in postmenopausal women with established osteoporosis.
abstract: OBJECTIVE
  Parathyroid hormone increases the differentiation of osteoblast precursors through canonical wingless (Wnt) signalling, resulting in an osteoanabolic effect. We aimed to evaluate serum levels of the Wnt-inhibitor Dickkopf-1 (Dkk-1) in postmenopausal women with established osteoporosis and their changes with teriparatide (TPTD - human recombinant PTH 1-34).
  
  
  METHODS
  A total of 31 postmenopausal Caucasian women with established osteoporosis (mean age 66.3 +/- 1.4 years) received daily injections of 20 microg TPTD for 18 months. Follow-up was continued for another 6 months after treatment discontinuation (total duration of treatment 24 months).
  
  
  METHODS
  Serum samples for total calcium (Ca), intact PTH (iPTH), bone-specific alkaline phosphatase, C-terminal cross-linking telopeptide of type 1 collagen (CTx) and Dkk-1 were obtained at baseline, and at 6, 18 and 24 months after TPTD initiation. Lumbar spine bone mineral density (BMD) was measured before and after 18 months of TPTD treatment. A total of 16 age- and gender-matched healthy controls were also analysed at baseline.
  
  
  RESULTS
  Serum Dkk-1 levels at baseline were significantly higher in osteoporotic women compared with that in controls (P < 0.002). Dkk-1 increased significantly during TPTD administration (P < 0.044) and decreased to baseline 6 months after TPTD discontinuation. Dkk-1 change was positively correlated to Ca (r = 0.530, P = 0.004) and negatively correlated to iPTH change (r = -0.398, P = 0.040). There was no correlation between Dkk-1 and BMD changes.
  
  
  CONCLUSIONS
  Our data suggest that Dkk-1 levels are increased in women with postmenopausal osteoporosis. TPTD therapy results in further increase of Dkk-1 that may be compensative to TPTD-induced enhanced Wnt signalling.
authors.affiliation: Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece. anastath@endo.gr
authors.forename: Athanasios D
authors.initials: AD
authors.lastname: Anastasilakis
authors.forename: Stergios A
authors.initials: SA
authors.lastname: Polyzos
authors.forename: Avraam
authors.initials: A
authors.lastname: Avramidis
authors.forename: Konstantinos A
authors.initials: KA
authors.lastname: Toulis
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papatheodorou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
mesh_terms: D000368:Aged; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008159:Lumbar Vertebrae / Q000187:drug effects; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood* / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000097:blood; D019379:Teriparatide / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D050071:Bone Density Conservation Agents; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D010281:Parathyroid Hormone; D019379:Teriparatide; D002118:Calcium