Murine Model for Cystic Fibrosis Bone Disease Demonstrates Osteopenia and Sex-Related Differences in Bone Formation

Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida 32610, USA.
Pediatric Research (Impact Factor: 2.31). 12/2008; 65(3):311-6. DOI: 10.1203/PDR.0b013e3181961e80
Source: PubMed


As the incidence of cystic fibrosis (CF) bone disease is increasing, we analyzed CF transmembrane conductance regulator (CFTR) deficient mice (CF mice) to gain pathogenic insights. In these studies comparing adult (14 wk) CF and C57BL/6J mice, both bone length and total area were decreased in CF mice. Metaphyseal trabecular and cortical density were also decreased, as well as diaphyseal cortical and total density. Trabecular bone volume was diminished in CF mice. Female CF mice revealed decreased trabecular width and number compared with C57BL/6J, whereas males demonstrated no difference in trabecular number. Female CF mice had reduced mineralizing surface and bone formation rates. Conversely, male CF mice had increased mineralizing surface, mineral apposition, and bone formation rates compared with C57BL/6J males. Bone formation rate was greater in males compared with female CF mice. Smaller bones with decreased density in CF, despite absent differences in osteoblast and osteoclast surfaces, suggest CF transmembrane conductance regulator influences bone cell activity rather than number. Differences in bone formation rate in CF mice are suggestive of inadequate bone formation in females but increased bone formation in males. This proanabolic observation in male CF mice is consistent with other clinical sex differences in CF.

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Available from: Terence Flotte, Jul 15, 2014
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    • "Despite the absence of these confounding factors, both CFTR knockout and F508del-CFTR mouse models recapitulate the human CFBD phenotype of reduced trabecular bone volume and cortical thickness, and impaired bone formation and enhanced bone resorption [8], [9], [12], [16]. Similarly, “gut corrected” CFTR knockout mice also demonstrate a similar bone phenotype further suggesting that CF bone disease is not solely due to intestinal obstruction [17]. "
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