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Impact of iron and anemia on bone metabolism and fractures

Subject Area Endocrinology, Diabetology, Metabolism
Term since 2020
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 436298031
 
Anemia and osteoporosis are both frequent diseases and often coincide, especially among the aging population where low-grade inflammation is common. Hereditary hemochromatosis is the most frequent, inherited autosomal-recessive disease in Europe. It has become evident that disturbances in iron metabolism are associated with bone disease. In addition, inflammation is a major cause of anemia and bone loss. Considering the clinical relevance of these diseases, the overall goal of this project is to investigate the mutual interactions between inflammation, iron homeostasis and bone metabolism in mice and men. To that end we will focus on two main aims: 1) Determine the association of anemia/hemochromatosis and fractures in humans using the UK CPRD database, and 2) unravel the impact of anemia of inflammation on bone metabolism and in particular, the role of bone morphogenetic protein (BMP) type I receptor ALK3 in preclinical models. In preliminary analyses, we have shown that the cohort data is representative to the German population and that cohort analyses are feasible. A particular interest will be the analysis of co-morbidities, co-medication and fracture outcomes. In the second aim, we will use established murine animal models of anemia of inflammation and address the effects on bone homeostasis by comprehensive phenotyping. The contribution of ALK3 to anemia of inflammation-induced bone loss will be determined using conditional knockout mice. Thus, this project will provide novel outcomes and insights into the occurrence of fractures with iron disorders and their associated co-morbidities and co-medications, as well as provide insights in the mechanisms that link anemia, inflammation, and bone loss.
DFG Programme Research Units
International Connection Switzerland
 
 

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