Bone structural and mechanical properties are affected by hypotransferrinemia but not by iron deficiency in mice

Hypotransferrinemia is a genetic defect in mice resulting in <1% of normal plasma transferrin (Tf) concentrations; heterozygotes for this mutation (+/hpx) have low circulating Tf concentrations. We used this mutant mouse in conjunction with dietary iron deficiency to study the influence of Tf and iron on bone structural and mechanical properties. Twenty-one weanling wild-type BALB/cj +/+ mice and 21 weanling +/hpx mice were fed iron-deficient or iron-adequate diets for 8 weeks. Twelve hpx/hpx mice were fed the iron-adequate diet. Hypotransferrinemia resulted in increased tibia iron and calcium concentrations, lower femur failure load, and extrinsic stiffness. Because the femurs of the hpx/hpx mice were disproportionately small, these bones actually had increased tissue material properties (ultimate stress [US] and modulus of elasticity) than those of wild-type mice. This is the first report on the effect of dietary iron deficiency on bone structural and mechanical properties. Dietary iron deficiency in +/+ and +/hpx mice decreased tibia iron concentrations but had no effect on tibia calcium and phosphorus concentrations or femur structural or mechanical properties. Because the bones of the hpx/hpx mice were small, but had superior tissue mechanical properties, we conclude that Tf is important for normal bone mineralization.