The effect of teriparatide on serum Dickkopf-1 levels in postmenopausal women with established osteoporosis

Clin Endocrinol (Oxf). 2010 Jun;72(6):752-7. doi: 10.1111/j.1365-2265.2009.03728.x. Epub 2009 Oct 15.


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).

Design and patients: 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).

Measurements: 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.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Aged
  • Bone Density / drug effects
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / pharmacology
  • Calcium / blood
  • Female
  • Follow-Up Studies
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood*
  • Lumbar Vertebrae / drug effects
  • Middle Aged
  • Osteoporosis, Postmenopausal / blood*
  • Osteoporosis, Postmenopausal / drug therapy*
  • Parathyroid Hormone / blood
  • Teriparatide / administration & dosage
  • Teriparatide / pharmacology*


  • Bone Density Conservation Agents
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Parathyroid Hormone
  • Teriparatide
  • Calcium