Bone abnormalities in young male rats with iron intervention and possible mechanisms

Studies suggest iron overload may cause bone lesion. The mechanisms are not well understood at present. Therefore, this study was designed to observe the effect of iron overload on bone metabolism in young male rats and explore its possible mechanism. Eighteen SD rats were randomly assigned to iron-loading and control groups. Fe-dextran (250 mg/kg of body weight) was injected intraperitoneally into the rats from iron-loading group, every other day for 5 weeks. The bone mineral density (BMD) of femur, length and diameter of tibia, and histological microstructure of femur and vertebra was determined. The concentrations of serum superoxide dismutase (SOD) and malondialdehyde (MDA) were assayed by ELISA. The mRNA expression of cytokines was detected by real-time PCR. The results showed an obvious bone abnormality after iron intervention, such as significantly decreased content of Ca in bone tissue, shorter length of tibia, lower BMD of femur, and obvious lesion of bone microarchitecture. At the same time, with iron intervention, the concentrations of serum SOD decreased but MDA increased; the mRNA expression of osteocalcin and osteoprotegerin (OPG) decreased, whereas that of receptor activator of nuclear factor kappa B ligand (RANKL) and IL-6 increased significantly. In summary, iron overload indeed give rise to the abnormal changes of bone metabolism independently. Increased bone resorption, and probably decreased bone formation are involved in the process of bone lesion caused by iron overload. Oxidative stress and RANKL participate in the pathological process, and IL-6 may play a supporting role.