| First Author | Haston CK | Year | 2008 |
| Journal | Am J Respir Crit Care Med | Volume | 177 |
| Issue | 3 | Pages | 309-15 |
| PubMed ID | 18006890 | Mgi Jnum | J:323253 |
| Mgi Id | MGI:7262762 | Doi | 10.1164/rccm.200705-659OC |
| Citation | Haston CK, et al. (2008) Persistent osteopenia in adult cystic fibrosis transmembrane conductance regulator-deficient mice. Am J Respir Crit Care Med 177(3):309-15 |
| abstractText | RATIONALE: A loss of function mutation in the cystic fibrosis transmembrane conductance regulator gene is believed to be an independent risk factor for bone disease in patients with cystic fibrosis. OBJECTIVES: The objective of this work was to use congenic mice as a preclinical model to examine the bone phenotype of Cftr(-/-) mice and control littermates at 8, 12, and 28 weeks of age. METHODS: The bone phenotype of control and Cftr(-/-) mice was evaluated by quantitative imaging, histologic and histomorphometric analyses, and serum levels of bone biomarkers. MEASUREMENTS AND MAIN RESULTS: At 12 weeks of age, Cftr(-/-) mice were smaller, had lower bone mineral density, cortical bone thinning, and altered trabecular architecture compared with Cftr(+/+) or Cftr(+/-) control mice. In skeletally mature 28-week-old mice, there were persistent deficits in cortical and trabecular bone structure in Cftr(-/-) mice despite significant, quantifiable improvements. Cftr(-/-) mice also had lower serum insulin-like growth factor-I levels at 12 weeks of age than did control mice, whereas parathyroid hormone and 25-hydroxyvitamin D levels were not significantly different. CONCLUSIONS: Persistent osteopenia and structural abnormalities in adult Cftr(-/-) mice, in the absence of overt respiratory and gastrointestinal disease, suggest that loss of Cftr function has a direct impact on bone metabolism in Cftr(-/-) mice that is not sex specific or subject to haplotype insufficiency. |
