Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

Azuma K1, Furuzawa M2, Fujiwara S2, Yamada K3, Kubo KY4.
  • 1Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Fukuoka, 807-8555, Japan.
  • 2Department of Prosthodontics, Asahi University School of Dentistry, Mizuho, 501-0296, Japan.
  • 3Department of Anatomy and Physiology, Faculty of Domestic economy, Nagoya Women’s University, Nagoya, 467-8610, Japan.
  • 4Seijoh University Graduate School of Health Care Studies, Tokai, 478-8588, Japan.



Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

KEYWORDS: Chewing; Corticosterone; Osteoporosis; Psychologic stress; X-ray microtomography

PMID: 26664256



Osteoporosis is the most common metabolic skeletal disease. It is associated with menopause, increasing age, physical inactivity, smoking and other risk factors. Recent studies suggest that chronic psychological stress can also affect bone mass and bone quality.

Active mastication, or chewing is an effective stress-coping behavior. Recent basic and clinical investigations have shown that chewing may alleviate stress-induced responses, such as increases in noradrenaline turnover in rat hypothalamus, and impaired spatial memory due to an increase in glucocorticoid receptor expression in the hippocampus. Chewing could rescue the stress-related hippocampal dysfunction. Chewing also could ameliorate sympathetic hyperactivity during stress. Our research group was interested in examining whether chewing under chronic psychological stress prevents stress-induced bone loss in mice.

The study involved experiments on three groups of mice bred to mimic age-related osteoporosis in humans. Two groups of mice were placed in stressful conditions for an hour twice a day. One group was allowed to chew on wooden sticks (Fig. 1). The third, control group of mice wasn’t subjected to stress. After four weeks, the adrenal glands, which secrete hormones in response to stress, were significantly heavier in the stressed mice that weren’t given wooden sticks, compared with the control group. But chewing under chronic stress prevented increases in stress hormones and adrenal gland weight in the group of mice given sticks.

This study suggests biting strength and bone health are closely related, especially in frail, older people at risk of tooth and bone loss. Chewing may help to maintain strong bones by suppressing the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system, which regulates the body’s response to stress in rodents. Human studies are necessary to validate the hypothesis that active mastication is effective in preventing bone loss induced by chronic psychological stress in older people.


Related articles published in our research group:

  1. Azuma K, Adachi Y, Hayashi H, Kubo KY. Chronic psychological stress as a risk factor of osteoporosis. J UOEH 37:245-253, 2015
  2. Chen H, Iinuma M, Onozuka M, Kubo KY. Chewing maintains hippocampus-dependent cognitive function. Int. J. Med. Sci. 12:502-509, 2015
  3. Kubo KY, Iinuma M, Chen H. Mastication as a stress-coping behavior. BioMed Research International 2015:876409, 2015
  4. Kondo H, Kurahashi M, Mori D, Iinuma M, Tamura Y, Mizutani K, Shimpo K, Sonoda S, Azuma K, Kubo KY. Hippocampus-dependent spatial memory impairment due to molar tooth loss is ameliorated by an enriched environment. Arch. Oral Biol. 61:1-7, 2016