Previously, we have demonstrated that high intensity muscle contractions and the anti-resorptive agent alendronate (ALEN) independently abolish or mitigate, respectively, reductions in cancellous bone mass during rodent hindlimb unloading (HU).
PURPOSE: To assess the separate and combined effects of a reduced frequency and intensity of muscle contractions simulating resistance training (SRT) and ALEN.
METHODS: Male, Sprague-Dawley rats (6-mo-old) were randomly assigned to cage control (CC, n=12), HU (HU, n=12), HU plus either ALEN (HU+ALEN, n=12), SRT (HU+SRT, n=12), or ALEN and SRT (HU+SRT/ALEN, n=12). HU+SRT and HU+SRT/ALEN rats were subjected to muscle contractions while anesthetized once every 3 days during 28-d HU (75% peak isometric strength; 4 sets of 5 reps; 1000ms isometric + 1000ms eccentric). Additionally, HU+ALEN and HU+SRT/ALEN rats received 0.01 mg/kg BW ALEN 3×/week.
RESULTS: Standard histomorphometry revealed a 56% reduction in periosteal bone formation rate (BFR) at mid-shaft tibia after 28-d HU, which was not rescued by ALEN treatment. However, we observed a 2.6- and 14-fold increase periosteal and endocortical (BFR), respectively, in HU+SRT vs. CC rats. These increases in diaphyseal BFR were significantly blunted (∼35-56%) in HU+SRT/ALEN rats. At the proximal tibia metaphysis (PTM), HU reduced cancellous BFR 80%, with no effect of ALEN treatment (-85% vs. CC). Similar to diaphyseal results, SRT during HU significantly increased cancellous BFR 123% vs. CC, whereas HU+SRT/ALEN inhibited the anabolic effect of SRT and reduced BFR (-33% vs. CC). SRT prevented negative effects of HU on PTM cancellous microarchitecture, resulting in increased bone volume (+19%) and trabecular thickness (+9%), respectively vs. CC. Additionally, osteoclast surface (OcS/BS) was reduced (-57%) and osteoid surface (OS/BS) significantly increased in HU+SRT rats vs. CC (32%). Adding ALEN to SRT during HU reduced OcS/BS (-75%), ObS/BS (-72%), and OS/BS (-61%) vs. CC, but did not affect microarchitecture.
CONCLUSION: These results demonstrate the anabolic effect of high intensity muscle contractions during disuse and suggest that both bone resorption and formation are suppressed when SRT is combined with bisphosphonate treatment during HU.
Funded by NSBRI through NASA Cooperative Agreement NCC 9-58.