Anemia 2013 July-7


PLoS One. 2012;7(9):e46101

Alterations in bone and erythropoiesis in hemolytic anemia: comparative study in bled, phenylhydrazine-treated and Plasmodium-infected mice.

Moreau R, Tshikudi Malu D, Dumais M, Dalko E, Gaudreault V, Roméro H, Martineau C, Kevorkova O, Dardon JS, Dodd EL, Bohle DS, Scorza T.

Department of Biological Sciences, Université du Québec à Montreal, 141 Avenue du Président Kennedy, Montréal, QC, H2X1Y4.


Osteoporosis is frequent in people suffering from chronic hemolytic pathologies as thalassemias and sickle cell disease, and it is proposed that sustained erythropoiesis and concurrent bone marrow hyperplasia affect bone remodelling. Considering that a deficient bone marrow erythropoiesis is also frequent in these disorders, we hypothesized that the release and accumulation of free heme concurrent to haemolysis, affects marrow and bone physiology in these disorders. To address this hypothesis, we studied the bone status and bone marrow erythropoiesis in mice with acute hemolytic anemia caused by phenylhydrazine administration or Plasmodium infection and used phlebotomized mice as controls for non hemolytic stress erythropoiesis.


Although significant drops in hemoglobin concentrations, enhanced erythropoiesis in the spleen and enhanced reticulocytosis occurred in all three experimental groups, anemia was relatively more severe in mice with acute haemolysis. The latter also developed high levels of free heme and reactive oxygen species in the bone marrow, and reduced numbers of bone marrow erythroid precursors. In addition, low concentrations of serum bone forming markers, and impaired ability of progenitor cells to differentiate into osteoclasts ex vivo were found in these mice. In contrast, no major changes in erythroid cell numbers occurred in the bone marrow of bled mice, which generated higher numbers of erythroid blast forming units in response to erythropoietin, and higher numbers of osteoclasts. Importantly, the alterations in bone metabolism were accompanied by reduced trabecular bone volume, enhanced trabecular spacing and lower trabecular numbers in mice with hemolytic anemia, altogether indicating enhanced bone resorption.


Taken together our data suggests that through the release and accumulation of free heme, haemolysis exerts distinct effects to bleeding in the marrow and bone and may contribute to osteoporosis through a mechanism independent of erythropoietic stress.


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