Impact of iron overload on bone remodeling in thalassemia
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REVIEW
Impact of iron overload on bone remodeling in thalassemia Pokpong Piriyakhuntorn 1 & Adisak Tantiworawit 1 & Mattabhorn Phimphilai 2 & Krekwit Shinlapawittayatorn 3,4,5 & Siriporn C. Chattipakorn 3,4 & Nipon Chattipakorn 3,4,5 Received: 26 June 2020 / Accepted: 1 September 2020 # International Osteoporosis Foundation and National Osteoporosis Foundation 2020
Abstract Introduction Iron overload, a state with excessive iron storage in the body, is a common complication in thalassemia patients which leads to multiple organ dysfunctions including the bone. Iron overload-induced bone disease is one of the most common and severe complications of thalassemia including osteoporosis. Currently, osteoporosis is still frequently found in thalassemia even with widely available iron chelation therapy. Study selection Relevant publications published before December 2019 in PubMed database were reviewed. Both pre-clinical studies and clinical trials were obtained using iron overload, thalassemia, osteoporosis, osteoblast, and osteoclast as keywords. Results Increased ROS production is a hallmark of iron overload-induced impaired bone remodeling. At the cellular level, oxidative stress affects bone remodeling by both osteoblast inhibition and osteoclast activation via many signaling pathways. In thalassemia patients, it has been shown that bone resorption was increased while bone formation was concurrently reduced. Conclusion In this review, reports on the cellular mechanisms of iron overload-associated bone remodeling are comprehensively summarized and presented to provide current understanding this pathological condition. Moreover, current treatments and potential interventions for attenuating bone remodeling in iron overload are also summarized to pave ways for the future discoveries of novel agents that alleviate this condition. Keywords Iron overload . Osteoblast . Osteoclast . Bone remodeling . Osteoporosis . Thalassemia
Introduction Iron overload, or hemochromatosis, is a state with excessive iron storage in the body. Primary or hereditary hemochromatosis is defined as an abnormality in iron-regulating genes, resulting in uncontrolled iron absorption [1]. Secondary, or acquired form, hemochromatosis is found in the conditions
* Nipon Chattipakorn [email protected] 1
Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
2
Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
3
Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
4
Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
5
Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
that usually have anemia such as thalassemia, myelodysplastic syndrome, aplastic anemia, and end-stage renal disease.
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