Cortical and Trabecular Bone Benefits of Mechanical Loading Are Maintained Long Term in Mice Independent of Ovariectomy

Abstract

Skeletal loading enhances cortical and trabecular bone properties. How long these benefits last after loading cessation remains an unresolved, clinically relevant question. This study investigated long-term maintenance of loading-induced cortical and trabecular bone benefits in female C57BL/6 mice and the influence of a surgically induced menopause on the maintenance. Sixteen-week-old animals had their right tibia extrinsically loaded 3 days/week for 4 weeks using the mouse tibial axial compression loading model. Left tibias were not loaded and served as internal controls. Animals were subsequently detrained (restricted to cage activities) for 0, 4, 8, 26, or 52 weeks, with ovariectomy (OVX) or sham-OVX surgery being performed at 0 weeks detraining. Loading increased midshaft tibia cortical bone mass, size, and strength, and proximal tibia bone volume fraction. The cortical bone mass, area, and thickness benefits of loading were lost by 26 weeks of detraining because of heightened medullary expansion. However, loading-induced benefits on bone total area and strength were maintained at each detraining time point. Similarly, the benefits of loading on bone volume fraction persisted at all detraining time points. The long-term benefits of loading on both cortical and trabecular bone were not influenced by a surgically induced menopause because there were no interactions between loading and surgery. However, OVX had independent effects on cortical bone properties at early (4 and 8 weeks) detraining time points and trabecular bone properties at all detraining time points. These cumulative data indicate loading has long-term benefits on cortical bone size and strength (but not mass) and trabecular bone morphology, which are not influenced by a surgically induced menopause. This suggests skeletal loading associated with physical activity may provide long-term benefits by preparing the skeleton to offset both the cortical and trabecular bone changes associated with aging and menopause.

Ontogenetic changes to bone microstructure in an archaeologically derived sample of human ribs

“…Subsequent bone growth is more obviously related to changes in physiologic demand or the mechanical loading environment (Frost & Jee, ; Martin et al ; Carter & Beaupre, ; Currey, ). BV/TV, in particular, has been shown to be highly responsive to dynamic loading (Goldstein et al ; Van Rietbergen et al ; Warden et al ; Prot et al ). Ryan et al () describe divergent ontogenetic patterns in the humerus and femur, in which the latter demonstrates significantly higher BV/TV after about 1 year of age.…”

Biomechanical Aspects of the Muscle-Bone Interaction

“…For example, mechanical loading during growth preferentially deposits new bone on the outer periosteal surface to increase bone size [66, 67], whereas the loss of bone mass during aging primarily occurs via intracortical bone loss adjacent to the endocortical surface [68]. The discordant bone surface effects of loading and its cessation enables the bone size benefits of loading when young to persist and have lasting benefits on bone strength, as the latter is most influenced by the distance of its material from the neutral axis (i.e., bone size) [64, 65]. …”

Physical activity when young provides lifelong benefits to cortical bone size and strength in men

“…We demonstrated that mechanical loading during a period of rapid skeletal growth conferred lifelong benefits in bone size and strength in rodent models (18,19). To explore whether the same phenomenon occurs in humans, the current study used a uniquely controlled cross-sectional study design that compared differences in humeral…”