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-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.
Tsay
Jaime
J
Department of Pediatrics, Weill Cornell Medical College, New York, NY 10065, USA.
Yang
Zheiwei
Z
Ross
F Patrick
FP
Cunningham-Rundles
Susanna
S
Lin
Hong
H
Coleman
Rhima
R
Mayer-Kuckuk
Philipp
P
Doty
Stephen B
SB
Grady
Robert W
RW
Giardina
Patricia J
PJ
Boskey
Adele L
AL
Vogiatzi
Maria G
MG
D000111:Acetylcysteine / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019190:Iron Overload / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D007505:Iron-Dextran Complex; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress
D000975:Antioxidants; D007505:Iron-Dextran Complex; D000111:Acetylcysteine