Elsevier

Bone

Volume 36, Issue 3, March 2005, Pages 454-464
Bone

Mechanosensitivity of the rat skeleton decreases after a long period of loading, but is improved with time off

https://doi.org/10.1016/j.bone.2004.12.001Get rights and content

Abstract

After the initial adaptation to large mechanical loads, it appears as though the skeleton's responsiveness to exercise begins to wane. To counteract the waning effects of long-term mechanical loading, “time off” may be needed to improve the responsiveness of bone cells to future mechanical signals and reinitiate bone formation. The aim of this study was to determine whether bone becomes less sensitive to long-term mechanical loading and whether time off is needed to improve mechanosensitivity. Fifty-seven female Sprague–Dawley rats (7–8 months of age) were randomized to one of following groups: Group 1 loading was applied for 5 weeks followed by 10 weeks of time off (1 × 5); Group 2 loading was applied for 5 weeks, followed by time off for 5 weeks and loading again for 5 weeks (2 × 5); Group 3 loading was applied continuously for 15 weeks (3 × 5); Group 4 age-matched control group; and Group 5 baseline control group. An axial load was applied to the right ulna for 360 cycles/day, at 2 Hz, 3 days/week at 15 N. At the end of the intervention, all three loaded groups showed similar increases in bone mass, cortical area, and IMIN in response to mechanical loading. Bone formation rate of the loaded ulna was increased in the first 5 weeks of loading for all three loaded groups; however, during the last 5 weeks, it was only significantly increased in the group that had time off (2 × 5) (P < 0.05). The group that had time off (2 × 5) also showed greater improvements in work to failure compared to the group loaded for 5 weeks (1 × 5) and the entire 15 weeks (3 × 5). A second experiment showed that the waning effect of long-term loading on the skeleton is not a result of aging. In conclusion, mechanical loading of the rat ulna results in large improvements in bone formation during the first 5 weeks of loading, but continual loading decreases the osteogenic response. Having time off increases bone formation and improves the resistance to fracture.

Introduction

The size, shape, and internal structure of the skeleton are greatly affected by the mechanical loads imposed upon it by muscle contraction and gravity. Mechanical loads greater than those habitually encountered by the skeleton can significantly increase bone mass and bone size by increasing bone formation on cortical and trabecular surfaces, and/or reducing the rate of bone turnover [1]. These changes may then result in large improvements in bone strength and reduce the risk of future fracture. In support of this notion, both human and animal studies have shown moderate to high impact loads can add a significant amount of new bone to the skeleton [2], [3], [4].

After the initial adaptation to large mechanical loads, it appears as though the skeleton's responsiveness to exercise begins to wane. In rats, new bone formation has been detected as early as 5 days after the onset of loading, the amount of new bone formed then reaches a peak around 15 days, after which the new bone begins to consolidate [5]. After 14 weeks, the new bone is fully mineralized and bone formation had completely stopped. Thus, in accordance with the principle of bone adaptation, bone appears to adapt to a new load in order to normalize the strain level in bone tissue. When the strain is reduced, the bone is considered adapted and bone formation ceases [6]. The exact time at which bone formation begins to decrease is not known. Cullen et al. [7] and Yeh et al. [8] reported that bone formation was elevated after 6 to 12 weeks of loading, but by 16 to 18 weeks, bone adaptation was complete [7], [8]. Whereas a recent study by Kim et al. [9] suggests that bone formation reaches a peak as early as 2 weeks after the onset of loading and diminishes to levels found in controls after 4 weeks [9].

To counteract the waning effects of long-term mechanical loading, “time off” may be needed to improve the responsiveness of bone cells to future mechanical signals and reinitiate bone formation [10]. Previous investigations on short-term loading studies in rats suggest that rest periods ranging from 10 to 14 s in between individual loading cycles, and from 1 to 8 h in between bouts of loading enhance the osteogenic response more than continuous uninterrupted loading [10], [11], [12]. For instance, separating 360 loading cycles into 4 by 60 cycles with a 1-h rest in between has a greater osteogenic affect than applying all the loads in one bout [11], [13]. Short rest periods appear to help re-stimulate bone cells so that they are more receptive to mechanical signals. To investigate the benefit of having a long period of time off, we compared the skeletal effects of mechanical loading for 15 weeks with mechanical loading for 5 weeks followed by 5 weeks of time off and 5 weeks of loading again.

The reduced skeletal response to long-term mechanical loading has also been attributed to aging. Over time, mechanosensory bone cells may become less sensitive to changes in their loading environment and a higher load may be needed to initiate a response [14], [15]. However, the findings are inconclusive; a recent study on cultured human bone cells found no evidence for the loss of mechanosensitivity with donor age [16]. Moreover, current findings in the literature have shown that the responsiveness of the aged skeleton is either increased [17], reduced [14], [15], or unaffected [18], [19], [20] compared to the younger skeleton. Therefore, to determine whether aging effects explain a change in the responsiveness to long-term mechanical loading, we also compared the osteogenic response of the skeleton to 2 weeks of loading in rats 6 months and 10 months of age.

We hypothesized that: (1) cortical bone will become less responsive to mechanical loading after several weeks; (2) time off is necessary to re-establish mechanosensitivity; and (3) age does not affect mechanosensitivity. To address our hypotheses, we asked the following questions in Experiment 1: Does 5 weeks of mechanical loading followed by a 10-week break result in a similar gain in bone mass and bone strength compared to 15 weeks of loading? Does partitioning two 5-week sessions of mechanical loading with a 5-week break increase the bone cells' response to loading? For Experiment 2 we asked: Does the responsiveness of cortical bone to 2 weeks of mechanical loading differ at 6 months compared to 10 months of age?

Section snippets

Animals

Eighty-four female Sprague–Dawley rats (6 to 8 months of age) were purchased from Harlan (Indianapolis, IN). The rats were housed two per cage for 2 weeks before the experiment began and provided standard rat chow and water ad libitum during the acclimatization and experimental period. All procedures performed in this experiment were in accordance with the Institutional Animal Care and Use Committee guidelines of Indiana University.

Experiment 1

To investigate the effect long-term mechanical loading and time

Experiment 1

One animal from the age-matched control group died during the 15-week experiment due to unknown causes. There were no differences in body weight between the study groups at the end of the study and all groups showed a similar increase in body weight throughout the experiment (5.4 ± 2.2 g; range 3.6 to 11.4 g). There were no differences in bone length between the loaded and unloaded ulna in any of the groups at the end of the study.

Mechanical loading imposed a strain of 3288 ± 83 μɛ at the

Discussion

The key findings of this study are (1) 15 weeks of loading results in similar improvements in bone mass and bone geometry as a single 5-week session and two 5-week sessions of loading with time off in between, (2) bone formation rate can be improved if a 5-week break is introduced between loading sessions compared to continuously applying mechanical loads, (3) time off for 5 weeks between sessions of loading increases the bones' resistance to fracture, and (4) age does not decrease

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