Grant: Catalyst Grant: Bone Health

Low bone mass density (BMD) with osteoporosis is commonly observed in patients with haemolytic anaemia (HA), but its causes remain unknown. The enhanced destruction of red blood cells (RBC) responsible for HA leads to the release and accumulation of free haemoglobin and heme in the plasma. Heme and haemoglobin are iron-containing molecules with important oxidant properties, and generate systemic oxidative stress in patients with HA. We want to understand the links between free heme, oxidative stress and bone fragility in these patients. For this, we aim to set up an in vivo experimental model in mice to study the effects of heme injection on their bone structure. In parallel, we will also study whether free heme further contributes to the destruction of oxidised RBC, whether free heme leads to inflammation, and whether these factors act in combination to render bones more fragile. As the capacity of our tissues to defend themselves against oxidants diminishes with age, with hormonal changes or with disease, and as all these conditions may lead to bone fragility, we believe that our study will contribute to understand how failure in antioxidant defences progressively modifies the function of bone cells.