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Am J Physiol Regul Integr Comp Physiol (October 26, 2006). doi:10.1152/ajpregu.00302.2006
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Submitted on May 4, 2006
Accepted on October 19, 2006

Aging Alters the Skeletal Response to Disuse in the Rat

Daniel S. Perrien1, Nisreen S. Akel2, Esther E. Dupont-Versteegden3, Robert A. Skinner4, Eric R Siegel5, Larry J. Suva6, and Dana Gaddy1*

1 Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States; Center for Orthopaedic Research, Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
2 Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
3 Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States; Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
4 Center for Orthopaedic Research, Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
5 Division of Biometry College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
6 Center for Orthopaedic Research, Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States; Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

* To whom correspondence should be addressed. E-mail: gaddydana{at}uams.edu.

Disuse has been shown to cause a rapid and dramatic loss of skeletal mass and strength in the load bearing bones of young and mature animals and humans. However, little is known about the skeletal effects of disuse in aged mammals. The current study was designed to determine whether the skeletal effects of disuse are maintained with extreme age. Fisher 344/Brown Norway male rats (6-months (Y) or 32-months (O)) were hindlimb suspended (HS) (HSY or HSO) or housed individually (CONY or CONO) for 2 weeks. Trabecular volume and microarchitecture in the proximal tibia were significantly decreased by HS only in young rats. HS significantly reduced cortical bone mineral density and increased cortical porosity only in old rats, by inducing new pore formation. Cortical pore diameter was also increased in old rats, regardless of loading condition. Ex vivo osteogenic and adipogenic cultures established from each group demonstrated that both age and HS decreased osteoblastogenesis. Age, but not HS, decreased sensitivity to endogenous BMP stimulation, as measured by treatment with exogenous noggin. Adipocyte development increased with age, while HS suppressed sensitivity to PPAR-gamma induced differentiation. Serum IGF-1 levels were reduced with HS in young rats, and with age in both control and HS. These results suggest that the site of bone loss due to disuse is altered with age, and that the loss of osteogenic potential with disuse in the old rats may be due to the combined effects of decreased IGF-1 levels and sensitivity as well as diminished BMP production.




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