Depression as a risk factor for osteoporosis

Abstract

Osteoporosis is a major public health threat. Multiple studies have reported an association between depression and low bone mineral density, but a causal link between these two conditions is disputed. Here we review the endocrine and immune alterations secondary to depression that might affect bone mass. We also discuss the possible role of poor lifestyle in the etiology of osteoporosis in subjects with depression and the potential effect of antidepressants on bone loss. We propose that depression induces bone loss and osteoporotic fractures, primarily via specific immune and endocrine mechanisms, with poor lifestyle habits and use of specific antidepressants also potential contributory factors. Unrecognized link between depression and osteoporosisOsteoporosis is a public health threat. In 2005, more than 2 million fractures occurred in the United States, 70% of which occur in women, with a healthcare system financial strain of 17 billion dollars [1]. This burden is predicted to increase and by 2020, it is predicted that 14 million women and men will be affected by osteoporosis in the US with a projected 50% increase in fractures at a cost of 25 billion dollars per year [1].Recognized risk factors for osteoporosis include menopause, Caucasian or Asian race, a thin frame, physical inactivity, smoking, alcohol use, inadequate calcium and vitamin D intake, corticosteroid use, and certain medical conditions. We suggest depression as another risk factor for osteoporosis. Major depressive disorder (MDD) is an important cause of disability in the US and one of the leading causes of disability worldwide [2]. Despite a large body of evidence, however, depression is not listed among the risk factors for osteoporosis [3]. We suggest a causal link between MDD and osteoporosis, analyze the clinical consequences of this relationship, and propose potential mechanisms. Relationship between depression, bone mass, and osteoporotic fracturesSchweiger et al. reported a 15% deficit in spine bone mass measured by computed tomography (CT) in patients with major depression, spurring a growing number of reports. Many of these relevant reports investigating a potential relationship between depression and osteoporosis were described in detail in our previous review article [4] and are listed in Table 1. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Determining whether decreased bone mass in subjects with depression translates into increased fracture risk is critical. Bone mineral density (BMD) is considered a reliable predictor for fractures, accounting for approximately 70% of the risk v...

Chronic Psychological Stress as a Risk Factor of Osteoporosis

“…Recently, the association between chronic psychological stress and osteoporosis has been the subject of a growing body of research. The published literature, especially recent animal and human studies, showed that chronic psychological stress is a risk factor for developing osteoporosis [11][12][13][14][15]. In the present review, we aim to provide the current understanding of the relationship between chronic psychological stress and osteoporosis.…”

“…Recent studies implicated chronic stress, such as depression in bone loss and osteoporosis, showing there is a link between chronic stress and osteoporosis [11,[31][32][33][34]. Epidemiological studies indicate that depression is an important risk factor for osteoporosis [32][33][34].…”

Bone-brain crosstalk and potential associated diseases

“…One of them, the Nasu-Hakola syndrome, is a genetically heterogeneous disease characterized by a unique combination of systemic bone cysts and dementia with psychotic symptoms similar to schizophrenia. This syndrome is the result of a loss of function mutation in the DAP12 gene located in chromosome 19 [115]. MRI and neuropathological studies of Nasu-Hakola patients have demonstrated the development of calcifications in the basal ganglia and also that frontal lobe syndrome and that dementia begins to develop by age 30.…”

The antidepressant bupropion exerts alleviating properties in an ovariectomized osteoporotic rat model

“…The activity and level of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), are also increased in depression [21] . Moreover, as potent stimulators of the hypothalamo-pituitary-adrenal (HPA) axis, these inflammatory mediators might contribute to hypercortisolism in depression [22] . The use of antidepressants that have the potential to affect either bone strength or risk of fracture is a possible confounding factor in the association between depression and bone mineral density (BMD).…”

“…In prospective analyses, current and baseline use of SSRI, but not tricyclic antidepressants (TCAs), have been associated with decreased hip BMD after 5 years of administration [25,26] . Most SSRIs associated with a dose-dependent increase in fracture risk and TCAs, such as amitriptyline and clomipramine, are also associated with the same level of fractures [22] . Animal studies also indicated that serotonin may influence bone mass.…”