Chronic stress can cause psychiatric disorders, e.g., anxiety and depression, and has been shown to induce bone loss in humans and rodents, all of which are intractable to conventional anxiolytic drugs. Regular exercise has been reported to alleviate chronic stress and enhance bone gain in non-stressed rodents, but forced exercise can aggravate stress, thereby increasing bone loss in stressed individuals. We, therefore, hypothesised that voluntary exercise, such as voluntary running in a wheel with minimal physical stress due to forced training, could alleviate bone loss after exposure to 4-week restraint stress. Herein, male rats were divided into 4 groups, i.e., non-stressed sedentary controls, non-stressed rats subjected to 4-week wheel running exercise, sedentary stressed rats, and stressed rats subjected to wheel running exercise. After the 4-week experiment, tibiae were collected for bone microstructural analyses by using micro-computed tomography (micro-CT) and bone histomorphometry. Heart and adrenal weights were recorded to confirm successful exercise and stress induction protocols. This study has been approved by the animal ethics committee of the Faculty of Medicine, Thammasat University. The micro-CT results showed that stressed rats exhibited lower trabecular mineral density than control rats with no change in moment of inertia (MMI). Voluntary running exercise significantly increased polar MMI and MMI in the y-axis in stressed rats as compared with sedentary stressed rats, suggesting that voluntary running increased bone strength. In bone histomorphometric study, stressed rats subjected to voluntary wheel running tended to have greater bone volume fraction (bone volume normalised by tissue volume; BV/TV), and had greater osteoblast surface without changes in osteoclast surface or eroded surface. It could be concluded that long-term exposure to repetitive stress deteriorated bone microstructure, while voluntary running exercise could alleviate stress-induced bone loss in male rats, presumably by inducing bone formation rather than diminishing osteoclast-mediated bone resorption.
Disclosure: The authors declared no competing interests. This work was supported by the Thailand Research Fund (TRF)Mahidol University through the TRF Senior Research Scholar Grant (RTA5780001 to N. Charoenphandhu), and Faculty of Medicine, Thammasat University (to J. Charoenphandhu).