ECTS Abstracts (2015) 1 P410

Impaired Intestinal Calcium Absorption and Bone Formation in Male and Female Beta-Thalassemic Mice

Narattaphol Charoenphandhu1,2, Kanogwun Thongchote1, Kamonshanok Kraidith1,2, Saovaros Svasti3 & Nateetip Krishnamra1,2

1Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand; 2Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; 3Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.

A decrease in beta-globin protein synthesis leads to a hereditary anaemia known as beta-thalassemia. In addition to haematological symptoms, beta-thalassemic patients and rodents usually manifest aberrant bone metabolism and growth retardation, but the underlying mechanism remains elusive. Here we demonstrated in hemizygous beta-globin knockout mice (BKO) that beta-thalassemia was associated with a marked decrease in the duodenal calcium absorption, which could be alleviated by long-term 1,25-dihydroxyvitamin D3 supplementation. Further investigation of bone mineral density in two beta-thalassemic mouse models, namely BKO and beta-IVSII654 knockin with abnormal splicing of beta-globin gene, showed that beta-thalassemia led to low bone mineral density, as determined by ex vivo dual-energy X-ray absorptiometry and computed tomography, in sex- and age-dependent manner. Specifically, the thalassemia-associated osteopenia appeared to be more severe in female mice than male mice. Bone histomorphometric analysis in male beta-IVSII654 thalassemic mice revealed a marked decrease in bone formation rate with modest change in osteoclast-mediated bone resorption (as indicated by osteoclast surface and eroded surface), whereas both decreased bone formation and accelerated bone resorption contributed to osteopenia in female beta-IVSII654 mice. It could be concluded that beta-thalassemia-associated osteopenia resulted, in part, from the impaired duodenal calcium absorption and bone formation as well as a sex-dependent increase in bone resorption. This study has been approved by the animal ethics committee of Faculty of Science, Mahidol University.

Disclosure: The authors declared no competing interests. This work was supported by Mahidol University (to N. Charoenphandhu), and the Thailand Research Fund (TRF)–Mahidol University through the TRF Senior Research Scholar Grant (RTA5780001 to N. Charoenphandhu).

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