title: Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid administration.
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.
authors.affiliation: Department of Medical Research, 252 General Air Force Hospital, 3 Kanellopoulou street, Athens, Greece.
authors.forename: Ersi
authors.initials: E
authors.lastname: Voskaridou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Christoulas
authors.forename: Charoula
authors.initials: C
authors.lastname: Xirakia
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Varvagiannis
authors.forename: Georgios
authors.initials: G
authors.lastname: Boutsikas
authors.forename: Antonios
authors.initials: A
authors.lastname: Bilalis
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papatheodorou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
mesh_terms: D015502:Absorptiometry, Photon; D000135:Acid Phosphatase / Q000097:blood; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D015519:Bone Density / Q000187:drug effects / Q000502:physiology*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D053495:Osteopontin / Q000097:blood; D010024:Osteoporosis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D053244:Osteoprotegerin / Q000097:blood; D010455:Peptides / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D000071681:Tartrate-Resistant Acid Phosphatase; D013789:Thalassemia / Q000097:blood / Q000150:complications*; D016896:Treatment Outcome; D055815:Young Adult; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D024042:Collagen Type I; C501126:DKK1 protein, human; D004164:Diphosphonates; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D053244:Osteoprotegerin; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D053495:Osteopontin; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase