Cause or Effect? The Link Between Psychological Stress and Osteoporosis

An osteoporosis diagnosis may affect a patient’s mental health because of diminished quality of life, fear of falling, embarrassment about posture changes, or general depression about the diagnosis; however, several recent studies have found that mental health disorders may significantly affect bone loss, contributing to osteoporosis.

Although osteoporosis and psychological stress occur via different mechanisms, several potential molecular links exist between a pathological response to stress and the development of bone disease. Anxiety has been found to contribute to lower hip bone mineral density (BMD), and several studies have shown that depression is a predictor for osteoporosis and fracture. Also germane to the discussion is that pharmacological interventions designed to improve mental health, such as those for major depressive disorder or posttraumatic stress disorder, may affect bone health.¹

In one study, postmenopausal women with depression presented with lower lumbar vertebra and femur dual-energy X-ray absorptiometry scores when compared with women without depression.² Another study compared the bones of 2327 patients with depression with 21,141 patients without depression. The patients with depression had lower BMD and higher bone resorption markers than the patients without depression. In fact, lower BMD was observed in the vertebra, proximal femur, and distal radius, and was found to involve multiple trabecular bone sites throughout the body.³

Sex, Stress, and Osteoporosis

Studies involving both sexes have revealed a negative association between depression and BMD.² More specifically, researchers have found that women are more sensitive to stress, and depressed women, in particular, respond more strongly to stressors. Both osteoporosis and depression are ~3× more common in women than in men, and women are more vulnerable to depression-related low bone mass.³

Several studies have examined the relationship between osteoporosis and depression in men. In a study of 80 patients with depression, about one-third of which were men, the spinal BMD was 15% lower than in the control participants. In general, studies showed that bone mass was lower in men with depression when compared with men without depression, and bone loss in men with depression was greater than in women with depression.³

A Closer Look at the Link

Bone tissue is continuously lost and regenerated to maintain a healthy balance and adapt to changing environmental factors. Disturbances in these processes can result in reduced bone mass and an increased risk for fractures. The aging process, particularly in postmenopausal women, further affects bone health.²

Stressful situations can provoke physiological responses, and each person responds differently to these situations, depending on their interpretation, resources, and adaptation strategies.² Psychological or mental stress can occur in response to an acute event, as in a fight-or-flight response to a traumatic or life-threatening event, or it can be chronic, as in the case of caregivers, service members, and other high-stress occupations.

In times of acute psychological and physical stress, stress signaling begins through the hypothalamic-pituitary-adrenal (HPA) axis and the sympathomedullary pathway through the secretion of stress hormones, which include glucocorticoids (cortisol) and catecholamines (epinephrine and norepinephrine). Immune cells (leukocytes) release receptors for these stress hormones and quickly respond by altering the inflammatory immune response; however, in chronic stress and chronic stress-associated mental health conditions, the HPA axis becomes poorly regulated, resulting in hypercortisolism or glucocorticoid resistance.¹

Anxiety or depression disorders can develop as a result of acute or chronic stress, and depression is often coupled with anxiety. Both conditions can alter the HPA response.¹ Aging further activates the HPA, producing more glucocorticoids and stronger feelings of stress, anxiousness, and depression.²

The key molecular mediators between psychological stress and bone health are believed to be growth hormones, glucocorticoids, and inflammatory cytokines. Stress alters the levels of growth hormones by modifying the HPA axis, growth hormone-releasing hormones, and growth hormone-inhibiting hormones. When this balance is upset by chronic stress, a decrease in growth hormones can develop, leading to bone loss.²

Chronic stress, long known to affect the body’s physical health, has been associated with obesity, atherosclerosis, lung conditions, and diabetes. How psychological stress affects disease is not well understood, but several studies have shown that stress hormone signaling via the brain-immune connection is a significant contributor. Chronic stress can alter blood cell and platelet production and increase systemic inflammation, which can, in turn, negatively affect osteoclasts and osteoblasts; however, researchers caution that the roles of inflammatory factors in osteoporosis and in psychological stress are highly complex, context-dependent, and dose-dependent.¹

Shared Risk Factors

Lifestyle-related risk factors for developing osteoporosis, such as smoking, alcohol use, and substance abuse, may be influenced by stress. Smoking, in particular is a strong risk factor for developing osteoporosis, although the link is not well understood. Alcohol consumption is a significant risk factor for developing osteoporosis as well. Substance abuse, such as opioid addiction, occurs more often in persons with psychological stress-associated mental health disorders. Research has found that women addicted to opioids have increased rates of osteopenia and osteoporosis. Obesity also may be a risk factor for osteoporosis because of increased inactivity, as exercise can increase bone mass and decrease risk of fracture. In addition, obesity can increase systemic inflammation and the risk for type 2 diabetes, another known risk factor associated with developing osteoporosis-related fractures.¹

Treatment Considerations

In the United States alone, osteoporosis accounts for >1.5 million fractures/y, and by 2025, treatment costs are estimated to eclipse $25 billion. An in-depth understanding of the mechanisms that affect stress and bone health is essential for determining a patient’s risk and providing treatment recommendations. It is important to note that pharmacological therapies used for mental health disorders and osteoporosis may have interacting effects, so interventions should be carefully weighed when making treatment recommendations.²

Treatments for osteoporosis include the following, but their possible effect on psychological stress should be considered before prescribing:

• Bisphosphonates

• Statins

• Denosumab

• Teriparatide

• Estrogen/selective estrogen receptor modulator

• Strontium ranelate

• Beta-blockers

• Exercise

Complementary, alternative, and integrative remedies, such as fish oil, calcium, magnesium, and vitamin D supplements, may offer benefits with fewer risks than traditional pharmacological interventions.¹

Researchers concluded that further study is warranted to understand the “whole-health effects” of chronic psychological stress on osteoporosis and to develop a more personalized plan of care for patients.¹

References

1. Wippert PM, Rector M, Kuhn G, Wuertz-Kozak K. Stress and alterations in bones: an interdisciplinary perspective. Front Endocrinol (Lausanne). 2017;8:96.

2. Kelly RR, McDonald LT, Jensen NR, Sidles SJ, Larue AC. Impacts of psychological stress on osteoporosis: clinical implications and treatment interactions. Front Psychiatry. 2019;10.

3. Azuma K, Adachi Y, Hayashi H, Kubo KY. Chronic psychological stress as a risk factor of osteoporosis. J UOEH. 2015;37(4):245-253.