BONE DEFICITS IN RESPONSE TO IRON ADMINISTRATION BETWEEN HFE HEMOCHROMATOSIS AND WILDTYPE MICE

HFE-hemochromatosis (HH) is a hepcidin dysregulation disorder resulting in systemic iron overload. Associative studies in patients and preclinical models reported a correlation between HFE/Hfe-HH and bone dysfunction such as osteoporosis, osteopenia, and arthropathy. Interestingly, removal of iron via phlebotomy does not appear to improve bone anomalies, suggesting that additional triggers of bone loss are present. Moreover, we previously showed systemic iron overload in Hfe-HH mice is insufficient to cause bone loss. 



Our study investigates if Hfe-/- mice are more susceptible to bone deficits than wildtype mice (Wt), when additional triggers of bone loss are present. Parenteral administration of iron is known to cause bone loss in Wt mice. We intraperitoneally injected Hfe-/- and Wt mice (sex/age-matched, C57Bl/6J background) with iron dextran at 1g/kg and 0.1g/kg for 8 weeks, and assessed bone status.



µCT analysis revealed a strong bone deficit in both trabecular and cortical bone of Hfe-/- and Wt male mice femurs after 8 weeks of injection with 1g/kg. Of particular interest, are however the effects of the lower iron dose (0.1g/kg). We show bone deficits in Hfe-/- mice that are not replicated in the Wt mice: Femoral and L5 vertebra BT/TV were decreased, and cortical bone was also unilaterally impacted, with thickness decreasing only in Hfe-/-. These effects were observed despite the lack of expected liver impairment such as fibrosis.



Our data implies that Hfe-/- mice are more prone to disruption of bone status than wild-type counterparts. Deciphering the underlying mechanism(s) of this discrepancy is our current goal.