Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid administration

Ersi Voskaridou; Dimitrios Christoulas; Charoula Xirakia; Konstantinos Varvagiannis; Georgios Boutsikas; Antonios Bilalis; Efstathios Kastritis; Athanasios Papatheodorou; Evangelos Terpos

doi:10.3324/haema-tol.2008.000893

Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid administration

Haematologica. 2009 May;94(5):725-8. doi: 10.3324/haema-tol.2008.000893.

Authors

Ersi Voskaridou¹, Dimitrios Christoulas, Charoula Xirakia, Konstantinos Varvagiannis, Georgios Boutsikas, Antonios Bilalis, Efstathios Kastritis, Athanasios Papatheodorou, Evangelos Terpos

Affiliation

¹ Department of Medical Research, 252 General Air Force Hospital, 3 Kanellopoulou street, Athens, Greece.

Abstract

Dickkopf-1 is an inhibitor of Wnt signaling, which is crucial for osteoblast differentiation. We evaluated serum levels of Dickkopf-1 in 66 patients with thalassemia-induced osteoporosis who received therapy with zoledronic acid in a placebo-controlled, randomized trial. At baseline, thalassemia patients had increased serum levels of Dickkopf-1 that correlated with reduced bone mineral density of the lumbar spine and the distal radius. High Dickkopf-1 also correlated with increased bone resorption and reduced bone formation markers. Zoledronic acid produced a reduction in serum Dickkopf-1, which was associated with bone mineral density increase after 12 months of therapy. On the contrary, placebo group showed a borderline increase of Dickkopf-1, which was higher in patients who showed deterioration in pain scores. These results suggest that Dickkopf-1 is implicated in the pathogenesis of osteoporosis in thalassemia and reveal Dickkopf-1 as a possible target for the development of novel agents for the management of thalassemia-induced osteoporosis.

Trial registration: ClinicalTrials.gov NCT00346242.

MeSH terms

Absorptiometry, Photon
Acid Phosphatase / blood
Adult
Alkaline Phosphatase / blood
Bone Density / drug effects
Bone Density / physiology*
Bone Density Conservation Agents / administration & dosage
Bone Density Conservation Agents / therapeutic use
Collagen Type I / blood
Diphosphonates / administration & dosage
Diphosphonates / therapeutic use
Enzyme-Linked Immunosorbent Assay
Female
Follow-Up Studies
Humans
Imidazoles / administration & dosage
Imidazoles / therapeutic use
Intercellular Signaling Peptides and Proteins / blood*
Isoenzymes / blood
Male
Middle Aged
Osteocalcin / blood
Osteopontin / blood
Osteoporosis / drug therapy
Osteoporosis / etiology
Osteoporosis / physiopathology*
Osteoprotegerin / blood
Peptides / blood
Randomized Controlled Trials as Topic
Tartrate-Resistant Acid Phosphatase
Thalassemia / blood
Thalassemia / complications*
Treatment Outcome
Young Adult
Zoledronic Acid

Substances

Bone Density Conservation Agents
Collagen Type I
DKK1 protein, human
Diphosphonates
Imidazoles
Intercellular Signaling Peptides and Proteins
Isoenzymes
Osteoprotegerin
Peptides
collagen type I trimeric cross-linked peptide
Osteocalcin
Osteopontin
Zoledronic Acid
Alkaline Phosphatase
Acid Phosphatase
Tartrate-Resistant Acid Phosphatase

Associated data

ClinicalTrials.gov/NCT00346242