Depression and osteoporosis: a research synthesis with meta-analysis

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.