Iron chelating properties of Eltrombopag: Investigating its role in thalassemia-induced osteoporosis

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.

长期输血可引发铁过载，进而导致终末器官出现多种并发症，并诱发骨质疏松。临床需通过铁螯合疗法清除体内过量铁元素，以抑制骨量丢失。地拉罗司（Deferasirox）是目前最新的口服铁螯合剂，可预防输血相关性铁过载并发症。近期研究显示，艾曲波帕（Eltrombopag，ELT）亦具备铁螯合活性：ELT作为血小板生成素受体激动剂，临床常用于治疗血小板减少症。本研究以地中海贫血患者及健康供者的铁过载破骨细胞为模型，检测了ELT与地拉罗司对细胞内铁含量、TRAP表达及破骨细胞活性的影响。实验证实，ELT在骨组织中同样具备铁螯合能力，且与地拉罗司联用时可产生协同效应。此外，基于其对破骨细胞活性的调控作用，我们首次提出ELT可通过减少骨量丢失改善骨组织健康状况。