Short bouts and long-term exercise reduce sedentary-induced bone loss and microstructural changes by modulating bone formation and resorption in healthy young male rats.

Although the toxic effect of Sedentary behavior (SED) on bone health has been demonstrated in the previous study, the underlying mechanisms of SED, or break SED to bone health remain unclear. In this study, we aim to investigate the effects of sedentary behavior (SED) on bone health, as well as the potential favor effects of moderate to vigorous physical activity (MVPA) and periodic interruptions of SED. To simulate SED, we used small Plexiglas cages (20.0 × 9.0 × 10.0 cm) to restrict animal movement. Short bursts of exercise to break SED and continuous long-term exercise were also designed. After an 8-weeks period of SED, we observed decreased bone mass and bone microstructure. Specifically, there was a notable decrease in the bone mineral density (BMD), bone surface (BS) and cortical thickness (Ct.Th) significantly reduced in cortical bone. In the trabecular bone, parameters such as trabecular separation (Tb.Sp), trabecular number (Tb.N), BS, connectivity density (Conn.D), BS/BV, bone volume/tissue volume (BV/TV), degree of anisotropy (DA), and structural model index (SMI) were also significantly reduced. In addition, we detected an increase in serum tartrate-resistant acid phosphatase (TRAP) levels in SED rats at both 4 and 8 weeks. At 8 weeks, the osteoclast number and surface with TRAP-staining were significantly increased, however, the OPG mRNA and proteins level were significantly decreased. After daily short bouts exercise and long-term exercise, we observed improvements in bone mass and microstructure. These improvements included increasing BMD and BV/TV of cortical bone, and improving Conn.D, BV/TV, DA and SMI of trabecular. Meanwhile, we found that, at 4 and 8 weeks, there was an increase in serum ALP. At 8 weeks, the mineralized nodules surface with Alizarin Red S-staining, and OPG mRNA and proteins level in bone tissue were significantly increased. Our findings suggest that SED leads to alterations in the bone mass and microstructure, which are associated with the changes in the OPG protein and bone remodeling. Exercise, whether in short daily bouts or continuous long-term sessions, can ameliorate the harmful effects of SED. Similarly, the changes in bone mass and microstructure from exercise are also associated with the changes in the OPG protein and bone remodeling by upregulated osteoblast activity to bone formation. Overall, our findings indicate the importance of physical activity in maintaining bone health and preventing the negative impacts of prolonged SED.