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

• Published in: Haematologica (Roma) Vol. 94; no. 5; pp. 725 - 728
• Main Authors: Voskaridou, Ersi, Christoulas, Dimitrios, Xirakia, Charoula, Varvagiannis, Konstantinos, Boutsikas, Georgios, Bilalis, Antonios, Kastritis, Efstathios, Papatheodorou, Athanasios, Terpos, Evangelos
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01.05.2009
• Subjects: Anemias. Hemoglobinopathies; Biological and medical sciences; Diseases of red blood cells; Diseases of the osteoarticular system; Hematologic and hematopoietic diseases; Medical sciences; Osteoporosis. Osteomalacia. Paget disease; Antineoplastic agent; Human; Hemoglobinopathy; Dickkopf-1; Hematology; Diseases of the osteoarticular system; Antiresorptive agent; Diphosphonic acid derivatives; Thalassemia; Hemopathy; Bisphosphonates; Genetic disease; Osteoarticular system; Osteoporosis; Hemolytic anemia; Zoledronic acid; Osteoblast; Serum; Bone mineral density; Bone
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2008.000893

1 Thalassemia Center, Laikon General Hospital, Athens 2 Department of Medical Research, 251 General Air Force Hospital, Athens 3 Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece Correspondence: Evangelos Terpos, Department of Medical Research, 252 General Air Force Hospital, 3 Kanellopoulou street, GR-11526, Athens, Greece. E-mail: eterpos{at}hotmail.com 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 (ClinicalTrials. govIdentifier: NCT00346242 ). Key words: thalassemia, osteoporosis, Dickkopf-1, osteoblast, zoledronic acid.