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
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Absorptiometry, Photon
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Acid Phosphatase / blood
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Adult
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Alkaline Phosphatase / blood
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Bone Density / drug effects
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Bone Density / physiology*
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Bone Density Conservation Agents / administration & dosage
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Bone Density Conservation Agents / therapeutic use
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Collagen Type I / blood
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Diphosphonates / administration & dosage
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Diphosphonates / therapeutic use
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Enzyme-Linked Immunosorbent Assay
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Female
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Follow-Up Studies
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Humans
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Imidazoles / administration & dosage
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Imidazoles / therapeutic use
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Intercellular Signaling Peptides and Proteins / blood*
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Isoenzymes / blood
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Male
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Middle Aged
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Osteocalcin / blood
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Osteopontin / blood
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Osteoporosis / drug therapy
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Osteoporosis / etiology
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Osteoporosis / physiopathology*
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Osteoprotegerin / blood
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Peptides / blood
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Randomized Controlled Trials as Topic
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Tartrate-Resistant Acid Phosphatase
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Thalassemia / blood
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Thalassemia / complications*
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Treatment Outcome
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Young Adult
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Zoledronic Acid
Substances
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Bone Density Conservation Agents
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Collagen Type I
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DKK1 protein, human
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Diphosphonates
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Imidazoles
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Intercellular Signaling Peptides and Proteins
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Isoenzymes
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Osteoprotegerin
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Peptides
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collagen type I trimeric cross-linked peptide
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Osteocalcin
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Osteopontin
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Zoledronic Acid
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Alkaline Phosphatase
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Acid Phosphatase
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Tartrate-Resistant Acid Phosphatase
Associated data
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ClinicalTrials.gov/NCT00346242