Seventy 9 to 11-week-old Sprague-Dawley male rats were divided into seven groups [baseline, 3-week, 11-week control groups; a group with a left limb immobilization for 3 weeks; and three groups with a similar immobilization and subsequent 8-week free (FR), low-intensity running (LR) or high-intensity running (HR) remobilization] to determine the site-specific effects of decreased mechanical loading and subsequent increased activity on rat femur. Bone mineral content of the proximal femur (PBMC), femoral midshaft (SBMC) and distal femur (DBMC) and the histomorphometry of the distal femur were used as outcome variables. The 3-week immobilization period resulted in significant bone loss in the proximal and distal ends of the immobilized left limb, the deficit being -5.9% in PBMC and -14.7% in DBMC. Immobilization also led to marked microarchitectural changes in the distal femur, the left-side deficit in trabecular bone volume (BV/TV) being -23.9%. After remobilization, there was a clear indication for dose-dependent response; i.e., immobilization-induced left-to-right side differences in BV/TV persisted in the FR animals (-23.8%), while these left limb deficits were significantly reduced in the LR group (-15.0%) and virtually absent in the HR group (-3.1%). The left limb deficit in PBMC was still significant in all groups after the 8-week period of remobilization [-9.6% in the FR group; -13.4% in the LR group; and -7.2% in the HR group]. The left-limb deficit in SBMC was significant in the HR11 group only (-7.2%), and, contrary to histomorphometric data, virtually absent in DBMC in all remobilization groups. As compared with the age-matched control data, the weight-adjusted BMCs of both limbs of the LR and HR groups were comparable or even higher (right limbs) than those of the controls. In conclusion, this study indicates that remobilization-induced bone recovery depends on the intensity of the remobilization so that during the 8-week period of remobilization, high-intensity running results in better recovery than low-intensity running, both of which are more efficient than free-cage activity only. Immobilization-induced changes in rat femur are also restored in a site-specific fashion, the most trabecular distal region of the femur showing more complete recovery than the more cortical proximal and midshaft regions.

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