Simulated resistance training, but not alendronate, increases cortical bone formation and suppresses sclerostin during disuse

Dept. of Health and Kinesiology, MS 4243, Texas A&M Univ., College Station, TX 77843-4243, USA.
Journal of Applied Physiology (Impact Factor: 3.06). 12/2011; 112(5):918-25. DOI: 10.1152/japplphysiol.00978.2011
Source: PubMed


Mechanical loading modulates the osteocyte-derived protein sclerostin, a potent inhibitor of bone formation. We hypothesized that simulated resistance training (SRT), combined with alendronate (ALEN) treatment, during hindlimb unloading (HU) would most effectively mitigate disuse-induced decrements in cortical bone geometry and formation rate (BFR). Sixty male, Sprague-Dawley rats (6-mo-old) were randomly assigned to either cage control (CC), HU, HU plus either ALEN (HU+ALEN), or SRT (HU+SRT), or combined ALEN and SRT (HU+SRT/ALEN) for 28 days. Computed tomography scans on days -1 and 28 were taken at the middiaphyseal tibia. HU+SRT and HU+SRT/ALEN rats were subjected to muscle contractions once every 3 days during HU (4 sets of 5 repetitions; 1,000 ms isometric + 1,000 ms eccentric). The HU+ALEN and HU+SRT/ALEN rats received 10 μg/kg ALEN 3 times/wk. Compared with the CC animals, HU suppressed the normal slow growth-induced increases of cortical bone mineral content, cortical bone area, and polar cross-sectional moment of inertia; however, SRT during HU restored cortical bone growth. HU suppressed middiaphyseal tibia periosteal BFR by 56% vs. CC (P < 0.05). However, SRT during HU restored BFR at both periosteal (to 2.6-fold higher than CC) and endocortical (14-fold higher than CC) surfaces (P < 0.01). ALEN attenuated the SRT-induced BFR gains during HU. The proportion of sclerostin-positive osteocytes in cortical bone was significantly higher (+121% vs. CC) in the HU group; SRT during HU effectively suppressed the higher proportion of sclerostin-positive osteocytes. In conclusion, a minimum number of high-intensity muscle contractions, performed during disuse, restores cortical BFR and suppress unloading-induced increases in sclerostin-positive osteocytes.

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    • "In skeletally mature rats, mechanical loads that are applied in an intermittent and dynamic pattern different from normal activity, as well as high intensity simulated resistance training exercise, lead to increases in bone mass [18] [19], density [20], trabecular bone microarchitecture [21], and increased bone formation rate on the endocortical surface [22]. Therefore, given concerns with incomplete recovery, exercise may be a promising approach to investigate for adding bone on the endocortical surface and restoring trabecular morphology. "
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    ABSTRACT: Spaceflight provides a unique environment for skeletal tissue causing decrements in structural and densitometric properties of bone. Previously, we used the adult hindlimb unloaded (HU) rat model to show that previous exposure to HU had minimal effects on bone structure after a second HU exposure followed by recovery. Furthermore, we found that the decrements during second HU exposure were milder than the initial HU cycle. In this study, we used a moderate intensity resistance exercise protocol as an anabolic stimulus during recovery to test the hypothesis that resistance exercise following an exposure to HU will significantly enhance recovery of densitometric, structural, and, more importantly, mechanical properties of trabecular and cortical bone. We also hypothesized that resistance exercise during recovery, and prior to the second unloading period, will mitigate the losses during the second exposure. The hypothesis that exercise during recovery following hindlimb unloading will improve bone quality was supported by our data, as total BMC, total vBMD, and cancellous bone formation at the proximal tibia metaphysis increased significantly during exercise period, and total BMC/vBMD exceeded age-matched control and non-exercised values significantly by the end of recovery. However, our results did not support the hypothesis that resistance exercise prior to a subsequent unloading period will mitigate the detrimental effects of the second exposure, as the losses during the second exposure in total BMC, total vBMD, and cortical area at the proximal tibia metaphysis for the exercised animals were similar to those of the non-exercised group. Therefore, exercise did not mitigate effects of the second HU exposure in terms of pre-to-post HU changes in these variables, but it did produce beneficial effects in a broader sense.
    Bone 06/2014; 71. DOI:10.1016/j.bone.2014.06.005 · 3.97 Impact Factor
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    • "The tail suspended hindlimb unloaded (HU) rodent has become a well-established ground-based analogue for investigating the skeletal adaptations of spaceflight [17]. The HU model simulates spaceflight conditions by reducing mechanical loads to the hindlimbs and inducing a cephalic shift of fluids, both deleterious to bone [14] [22] With the National Aeronautics and Space Administration's (NASA) growing interest in returning to the Moon, a near-Earth asteroid, or Mars, it is becoming increasingly important to determine if added resistance exercise protects the musculoskeletal unit during space missions. Results from our lab using a novel partial weight bearing suspension apparatus have demonstrated that partial weight bearing, and in particular 3/8th body weight (Martian gravity) and 1/6th body weight (Lunar gravity), does not protect against bone loss observed with the full unloading of traditional tail suspension [26]. "
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