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

Macias BR, Swift JM, Nilsson MI, Hogan HA, Bouse SD, Bloomfield SA. Simulated resistance training, but not alendronate, increases cortical bone formation and suppresses sclerostin during disuse. J Appl Physiol 112: 918-925, 2012. First published December 15, 2011; doi: 10.1152/japplphysiol. 00978.2011.-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 disuseinduced 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 mu g/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 SRTinduced 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.