Abstract

Exercise is a key determinate of fracture risk and provides a clinical means to promote bone formation. However, the efficacy of exercise to increase bone mass declines with age. The purpose of this study was to identify age-related differences in the anabolic response to exercise at the cellular and tissue level. To this end, young (8-weeks of age) and adult (36-weeks of age) male mice were subjected to a moderate exercise regimen of running on a treadmill. As a result, exercise had a significant effect on PTHrP and SOST gene expression during the first week that was dependent upon age. In particular, young mice displayed an increase in PTHrP expression and decrease in SOST expression, both of which remained unaffected by exercise in the adult mice. After 5-weeks of exercise, a significant decrease in the percentage of osteocytes expressing sclerostin at the protein level was found in young mice, but not adult mice. Mechanical testing of the tibia found exercise to have a significant influence on tissue-level mechanical properties, specifically ultimate-stress and modulus that was dependent on age. Adult mice in particular experienced a significant decrease in modulus despite an increase in cortical area and cortical thickness compared to sedentary controls. Altogether, this study demonstrates a shift in the cellular response to exercise with age, and that gains in bone mass at the adult stage fail to improve bone strength.

Highlights

  • The aging process predisposes individuals to increased fracture risk due to continual bone loss

  • Results from a two-way analysis of variance (ANOVA) found exercise had a significant effect on cortical area, cortical thickness, and the periosteal perimeter that were dependent on age

  • The present study demonstrates that exercise in adult mice fails to improve the mechanical strength of bone despite relative gains in bone mass

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Summary

Introduction

The aging process predisposes individuals to increased fracture risk due to continual bone loss. Exercise and physical activity provide a means to increase peak bone mass in children and adolescents (Greene et al, 2005; Kontulainen et al, 2003; Ward et al, 2005), while allowing adults and elderly to maintain bone mass later in life (Bielemann et al, 2013; Forwood and Burr, 1993; Nikander et al, 2010; Nguyen et al, 2000; Marques et al, 2012; Karlsson, 2002). The gain in bone strength following exercise is often limited to vertebrate bodies, while long bones present little to no improvements in fracture rates, especially in the lower limb (Nguyen et al, 2000; Marques et al, 2012; Gomez-Cabello et al, 2012). Understanding how the anabolic response to exercise and physical activity change with age plays key role in developing preventative strategies that can compensate for such deficiencies to promote bone formation in an aging population

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