To investigate the controversial issue whether exercise-induced positive effects on bone can be maintained after cessation of exercise, 100 5-week-old male Sprague-Dawley rats were used to assess the effects of long-term exercise (EX, treadmill running) and subsequent deconditioning (DC, free cage activity) on the femoral neck and femoral midshaft. At entry, the rats were randomly assigned into eight groups: four control groups (C 14 , C 28 , C 42 , and C 56 ), and four exercise groups (EX, EX ؉ DC 14 , EX ؉ DC 28 , and EX ؉ DC 42 ). Rats in the exercise groups were first subjected to a 14-week period of progressively intensifying running, after which the rats of group EX were killed and the remaining exercise groups (EX ؉ DC 14 , EX ؉ DC 28 , and EX ؉ DC 42 ) were allowed to move freely in their cages for a subsequent deconditioning period of 14, 28, or 42 weeks, whereas control rats were kept free in their cages for the entire study period (0 -56 weeks) and killed with their respective exercise group. At each time point, a comprehensive analysis of the femoral neck and midshaft characteristics (peripheral quantitative computed tomography analysis and fracture load [F max ]) was performed. In comparison with their age-matched controls, 14 weeks of treadmill training resulted in significant (p < 0.05) increases in all measured femoral neck parameters of the growing male rats (i.e., ؉25% in total cross-sectional area [tCSA], ؉28% in total bone mineral content [tBMC], ؉11% in total bone mineral density [tBMD], and ؉30% in F max ). On the contrary, no exercise-induced positive effects were seen in femoral midshaft. The exercise-induced benefits in the femoral neck were partially maintained during the deconditioning period of 14 weeks, the tCSA being ؉17%, tBMC ؉18% (both p < 0.05), and the F max ؉11% (p ‫؍‬ 0.066) higher in the exercised group than control group. However, after 42 weeks of deconditioning, these benefits were eventually lost. In conclusion, exercise through the period of the fastest skeletal growth results in significant improvements in size, mineral mass, and strength of the femoral neck of male rats. However, these exercise-induced bone benefits are eventually lost if exercise is completely ceased, and thus, continued training is probably needed to maintain the positive effects of youth exercise into adulthood. Further studies should focus on assessing the minimal level of activity needed to maintain the exercise-induced bone gains. (J Bone Miner Res 2003;18:544 -552)

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Mediolateral three-point bending of the rat midfemur was developed to enable the assessment of the mechanical competence of the elliptic bone cross-section in terms of its widest diameter, the apparent primary direction of bone adaptation to loading.Introduction: Today, the most commonly used method to characterize the biomechanical properties of appendicular long bones is the three-point bending testing of the midfemur in the anteroposterior (AP) direction. However, as the diameter of the elliptic cross-section of femoral diaphysis is widest in the orthogonal mediolateral (ML) direction, the femoral diaphysis should also show the highest resistance to bending along this direction. The objective of this study was thus to introduce and validate a mechanical testing protocol for femoral midshaft along the ML direction. Materials and Methods: To determine the repeatability of the novel testing protocol, 38 pairs of rat femora underwent a comprehensive structural analysis by pQCT followed by ML three-point bending. For comparison of the repeatability, corresponding tests were performed on the femoral neck. To validate the novel testing direction, the left hindlimb of 24 rats was neurectomized for 6 months, whereas the right limb served as an intact control. After excision, one half of these pairs of femora were randomly subjected to three-point bending test in the conventional AP direction and the remaining in the orthogonal ML direction. Results: The precision (CV rms ) of breaking load, stiffness, and energy absorption of the femoral midshaft in the ML direction was 3.8%, 6.6%, and 14.5%, respectively. The corresponding values for femoral neck compression test were 7.6%, 17.9%, and 18.7%, respectively. The loading-induced effect on the femoral midshaft (difference between the neurectomized [nonloaded] and contralateral intact [loaded] femur) was +2.2%, +1.9%, and +2.1% in the AP direction and −18.9%, −17.6%, and −20.3% in the ML direction (p < 0.01 for all comparisons), respectively. Conclusions: Our results show that testing of rat femoral midshaft in the ML direction is a precise and biologically valid method to determine the structural strength of this widely used skeletal site in experimental bone research.

Aged bones have been considered to have reduced capacity to respond to changes in incident loading. By subjecting young and adult rats to increased loading and subsequent deconditioning, we observed quantitatively similar adaptive responses of bone in these two groups, but young skeletons adapted primarily through geometric changes and adult bones through increased volumetric density. Loss of the exercise-induced bone benefits did not depend on age.Introduction: Aging has been shown to decrease the sensitivity of the mechanosensory cells of bones to loadinginduced stimuli, presumably resulting in not only reduced capacity but also different adaptive mechanism of the aged skeleton to altered loading, as well as poorer capacity to preserve exercise-induced bone benefits. Materials and Methods: Fifty young (5-week-old) and 50 adult (33-week-old) male rats were randomized into control and exercise (ϩdeconditioning) groups. After a 14-week progressively intensified running program, one-half of the exercised rats (both young and adult) were killed, and the remaining rats underwent subsequent 14-week period of deconditioning (free cage activity). A comprehensive analysis of the femoral neck was performed using peripheral quantitative computed tomography and mechanical testing. Results: In comparison with the controls, both young and adult exercised rats had significant increases in almost all measured parameters: ϩ25% (p Ͻ 0.001) and ϩ10% (not significant [NS]) in the cross-sectional area; ϩ28% (p Ͻ 0.001) and ϩ18% (p Ͻ 0.001) in bone mineral content; ϩ11% (p Ͻ 0.05) and ϩ23% (p Ͻ 0.001) in bone mineral density; and ϩ30% (p Ͻ 0.01) and ϩ28% (p Ͻ 0.01) in the breaking load, respectively. The skeletal responses were not statistically different between the young and adult rats. After the 14-week period of deconditioning, the corresponding exercised-to-controls differences were ϩ17% (p Ͻ 0.05) and ϩ10% (NS), ϩ18% (p Ͻ 0.05) and ϩ13% (p Ͻ 0.05), ϩ2% (NS) and ϩ2% (NS), and ϩ11% (NS) and ϩ6% (NS), respectively. Again, the response differences were not significant between the age groups. Conclusion: Quantitatively, the capacity of the young and adult skeleton to adapt to increased loading was similar, but the adaptive mechanisms appeared different: growing bones seemed to primarily display geometric changes (increase in bone size), whereas the adult skeleton responded mainly through an increase in density. Despite this apparent difference in the adaptive mechanism, aging did not modulate the ability of the skeleton to preserve the exercise-induced bone gain, because the bone loss was similar in the young and adult rats after cessation of training.