Excess iron undermined bone load-bearing capacity through tumor necrosis factor-alpha-dependent osteoclastic activation in mice

Iron overload has been associated with bone mass loss. To elucidate the effects of excess iron on bone metabolism, an iron-overloading mouse model was established by administering iron-dextran at 250 mg/kg to female BALB/c mice. After 4 weeks, the mice were sacrificed and the biomechanical properties of the femurs were examined. The results suggested a notable decrease of the maximal bending stress and the modulus of bending elasticity in the femurs obtained from the excess iron-treated mice compared to the control mice. The levels of the serum osteocalcin, C-telopeptide of type I collagen (CTX-1) and tumor necrosis factor-alpha(TNF-alpha) were measured in order to investigate the underlying mechanism responsible for the excess iron-induced bone strength reduction. Overall, the results suggested that iron overload resulted in a marked reduction of bone load-bearing capacity through a TNF-triggered osteoclast differentiation and resorption mechanism.