Bone loss caused by iron overload in a murine model: importance of oxidative stress

Osteoporosis is a frequent problem in disorders characterized by iron overload, such as the thalassemias and hereditary hemochromatosis. The exact role of iron in the development of osteoporosis in these disorders is not established. To define the effect of iron excess in bone, we generated an iron-...

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Bibliographic Details
Published in:	Blood 2010-10, Vol.116 (14), p.2582-2589
Main Authors:	Tsay, Jaime, Yang, Zheiwei, Ross, F. Patrick, Cunningham-Rundles, Susanna, Lin, Hong, Coleman, Rhima, Mayer-Kuckuk, Philipp, Doty, Stephen B., Grady, Robert W., Giardina, Patricia J., Boskey, Adele L., Vogiatzi, Maria G.
Format:	Article
Language:	eng
Subjects:	Acetylcysteine - therapeutic use Animals Antioxidants - therapeutic use Biological and medical sciences Bone and Bones - drug effects Bone and Bones - metabolism Bone and Bones - pathology Diseases of the osteoarticular system Hematologic and hematopoietic diseases Iron Overload - chemically induced Iron Overload - complications Iron Overload - metabolism Iron-Dextran Complex Male Medical sciences Mice Mice, Inbred C57BL Osteoporosis - drug therapy Osteoporosis - etiology Osteoporosis - metabolism Osteoporosis - pathology Osteoporosis. Osteomalacia. Paget disease Oxidative Stress Red Cells, Iron, and Erythropoiesis
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Summary:	Osteoporosis is a frequent problem in disorders characterized by iron overload, such as the thalassemias and hereditary hemochromatosis. The exact role of iron in the development of osteoporosis in these disorders is not established. To define the effect of iron excess in bone, we generated an iron-overloaded mouse by injecting iron dextran at 2 doses into C57/BL6 mice for 2 months. Compared with the placebo group, iron-overloaded mice exhibited dose-dependent increased tissue iron content, changes in bone composition, and trabecular and cortical thinning of bone accompanied by increased bone resorption. Iron-overloaded mice had increased reactive oxygen species and elevated serum tumor necrosis factor-α and interleukin-6 concentrations that correlated with severity of iron overload. Treatment of iron-overloaded mice with the antioxidant N-acetyl-L-cysteine prevented the development of trabecular but not cortical bone abnormalities. This is the first study to demonstrate that iron overload in mice results in increased bone resorption and oxidative stress, leading to changes in bone microarchitecture and material properties and thus bone loss.
ISSN:	0006-4971 1528-0020 1528-0020