Age-related bone loss in the LOU/c rat model of healthy ageing.
Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder.
Duque
Gustavo
G
Aging Bone Research Program, Nepean Clinical School, University of Sydney, Nepean Hospital, NSW, Australia. gduque@med.usyd.edu.au
Rivas
Daniel
D
Li
Wei
W
Li
Ailian
A
Henderson
Janet E
JE
Ferland
Guylaine
G
Gaudreau
Pierrette
P
D050154:Adiposity; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001835:Body Weight; D015519:Bone Density / Q000502:physiology; D001853:Bone Marrow; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism*; D024042:Collagen Type I / Q000097:blood; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D005260:Female; D005269:Femur; D008297:Male; D010006:Osteoblasts / Q000166:cytology; D015675:Osteocalcin / Q000097:blood; D010010:Osteoclasts / Q000166:cytology; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000097:blood; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains; D014807:Vitamin D / Q000097:blood; D055114:X-Ray Microtomography
D015415:Biomarkers; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D014807:Vitamin D