Abstract
Chronic blood transfusions are responsible to cause iron overload, which leads to several complications to end organs and osteoporosis. Iron chelation is needed to remove iron excess and to contain bone-mass loss. Deferasirox is the most recent oral iron chelator that prevents transfusion related iron overload complications. Recently Eltrombopag (ELT) iron chelating properties are emerging. ELT is an agonist at Thrombopoietin receptor, used in treatment of thrombocytopenia. We tested ELT and Deferasirox in iron overloaded osteoclasts from thalassemic patients and donors measuring intracellular iron, TRAP expression and osteoclast activity. We confirmed ELT iron chelation capacity also in bone tissue and a synergic effect when used with Deferasirox. Moreover, having demonstrated its effects on osteoclast activity, we suggest for the first time that ELT could ameliorate bone tissue's health reducing bone mass loss.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Benzoates / pharmacology*
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Benzoates / therapeutic use
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Blood Transfusion
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Bone and Bones / drug effects
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Bone and Bones / metabolism
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Cell Differentiation
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Deferasirox / pharmacology
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Deferasirox / therapeutic use
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Drug Evaluation
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Female
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Ferritins / blood
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Healthy Volunteers
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Humans
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Hydrazines / pharmacology*
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Hydrazines / therapeutic use
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Iron / analysis
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Iron / metabolism
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Iron Chelating Agents / pharmacology*
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Iron Chelating Agents / therapeutic use
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Iron Overload / blood
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Iron Overload / complications
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Iron Overload / drug therapy*
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Leukocytes, Mononuclear
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Osteoclasts / drug effects
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Osteoclasts / physiology
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Osteoporosis / etiology
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Osteoporosis / prevention & control*
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Primary Cell Culture
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Pyrazoles / pharmacology*
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Pyrazoles / therapeutic use
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Receptors, Thrombopoietin / antagonists & inhibitors
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Thalassemia / complications
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Thalassemia / therapy*
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Transfusion Reaction / blood
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Transfusion Reaction / complications
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Transfusion Reaction / drug therapy*
Substances
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Benzoates
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Hydrazines
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Iron Chelating Agents
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Pyrazoles
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Receptors, Thrombopoietin
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MPL protein, human
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Ferritins
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Iron
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eltrombopag
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Deferasirox
Grants and funding
The study was supported by PRIN (Progetti di Rilevante Interesse Nazionale) 2015. 20153NBRS3_002 to FR, and the Department of Woman, Child and General and Special Surgery of the University of Campania “Luigi Vanvitelli”. There was no additional external funding received for this study. Moreover, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.