Persistent osteopenia in adult cystic fibrosis transmembrane conductance regulator-deficient mice.
BACKGROUND
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.


OBJECTIVE
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.


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.
Haston
Christina K
CK
Meakins-Christie Laboratories, 3626 rue St. Urbain, Montreal, PQ, H2X 2P2 Canada. christina.haston@mcgill.ca
Li
Wei
W
Li
Ailian
A
Lafleur
Melanie
M
Henderson
Janet E
JE
D000367:Age Factors; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000209:etiology / Q000503:physiopathology*; D002113:Calcification, Physiologic / Q000502:physiology*; D003550:Cystic Fibrosis / Q000150:complications / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D018181:Mice, Inbred CFTR; D012737:Sex Factors
D019005:Cystic Fibrosis Transmembrane Conductance Regulator