The effect of teriparatide on serum Dickkopf-1 levels in postmenopausal women with established osteoporosis.
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.
Anastasilakis
Athanasios D
AD
Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece. anastath@endo.gr
Polyzos
Stergios A
SA
Avramidis
Avraam
A
Toulis
Konstantinos A
KA
Papatheodorou
Athanasios
A
Terpos
Evangelos
E
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*
D050071:Bone Density Conservation Agents; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D010281:Parathyroid Hormone; D019379:Teriparatide; D002118:Calcium