Major depressive disorder has been associated with low bone mineral density. The strength of this association, however, varies greatly among studies; the direction of the causative link is still controversial, and the etiology remains unclear. We aimed to confirm this association, assess its magnitude and estimate its clinical relevancy. A total of 535 articles were initially identified and the research synthesis was based on 33 qualified articles. Of these, 25 articles (or 76 %) showed an inverse relationship between major depression or minor depression or depressive symptoms and bone mineral density or bone turnover. Meta-analysis could be performed on 20 of the initially selected 33 articles. Standardized weighted differences in mean AP spine, total femur and femoral neck bone mineral density, each from at least 10 studies, were computed in g/cm 2 and transformed into percent differences. At each site, bone mass was lower in subjects with depression as compared to controls: AP spine bone mineral density was 4.73 % lower (95 % CI −7.28 % to −2.19 %, p < 0.0001; n = 16 studies), total femur bone mineral density was 3.53 % lower (95 % CI −5.66 % to −1.41 %, p < 0.001; n = 13 studies), and femoral neck bone mineral density was 7.32 % lower (95 % CI −10.67 % to −3.96 %; p < 0.0005; n = 8 studies). In conclusion, major depressive disorder was associated with lower bone mineral density at the AP spine, femoral neck, and total femur. The deficits in bone mineral density in subjects with depression are of clinical significance and likely to increase fracture risk over the lifetime of these subjects.

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...