title: Simulated resistance training, but not alendronate, increases cortical bone formation and suppresses sclerostin during disuse.
abstract: 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.
authors.affiliation: Dept. of Health and Kinesiology, MS 4243, Texas A&M Univ., College Station, TX 77843-4243, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Macias
authors.forename: J M
authors.initials: JM
authors.lastname: Swift
authors.forename: M I
authors.initials: MI
authors.lastname: Nilsson
authors.forename: H A
authors.initials: HA
authors.lastname: Hogan
authors.forename: S D
authors.initials: SD
authors.lastname: Bouse
authors.forename: S A
authors.initials: SA
authors.lastname: Bloomfield
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005819:Genetic Markers; D019417:Hindlimb Suspension / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055070:Resistance Training / Q000379:methods; D013977:Tibia / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C486031:Sost protein, rat; D019386:Alendronate