Depression and osteoporosis: a research synthesis with meta-analysis

Abstract

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.

Fig. 1

Disposition diagram for bone density/depression studies.

Fig. 2

Meta-analysis forest plots for AP spine BMD, total femur BMD, and femoral neck BMD. a : AP spine BMD: Most studies show lower AP spine BMD in depressed subjects, with 3 studies indicating that BMD was higher in controls. b : Total femur: Most studies show lower total femur BMD in depressed subjects, with 3 studies indicating that BMD was higher in controls, and 2 studies showing no difference. c : Femoral neck BMD: Most studies show lower femoral neck BMD in depressed subjects, with 3 studies indicating that BMD was higher in controls. Note: although reportedly measured, no data were provided for the femoral neck in reference [8]. For each one of these 3 graphs under the first column are listed in chronological order the studies included and the year of publication; these studies are subdivided in studies conducted only in women, only in men, and studies conducted in men and women. Studies that utilized DSM criteria to characterize depression are indicated with a dagger. In the last column the relative weight of each individual study is reported.

Fig. 3

Funnel plots for AP spine BMD, total femur BMD and femoral neck. a: AP Spine BMD: Funnel plot shows slight asymmetry with several outliers, which may be due to different effect sizes of depression in men and women, or depression treatment effects. To further analyze publication bias, we computed the estimated number of studies that in theory would bring p-value to a number greater than alpha. For AP spine that number is 228, giving more weight to the results despite the presence of several outliers on the funnel plot. b: Total femur BMD: Funnel plot is fairly symmetrical, but several outliers were still present. In this case, the number of studies that would bring p-value to a number greater than alpha is 133. c: Femoral neck: Funnel plot shows slight asymmetry with several significant outliers. This, however, may be simply accounted by the small number of studies that reported on the association between the femoral neck BMD and depression (n = 8). However, the number of studies that would bring p-value to a number greater than alpha is n = 130.