Major Depression Is a Risk Factor for Low Bone Mineral Density: A Meta-Analysis

Background: The role of depression as a risk factor for low bone mineral density (BMD) and osteoporosis is not fully acknowledged, mainly because the relevant literature is inconsistent and because information on the mechanisms mediating brain-to-bone signals is rather scanty. Methods: Searching databases and reviewing citations in relevant articles, we identified 23 studies that quantitatively address the relationship between depression and skeletal status, comparing 2327 depressed with 21,141 nondepressed individuals. We subjected these studies to meta-analysis, assessing the association between depression and BMD as well as between depression and bone turnover markers. Results: Overall, depressed individuals displayed lower BMD than nondepressed subjects, with a composite weighted mean effect size (d) of -.23 (95% confidence interval: -.33 to -.13; p < .001). The association between depression and BMD was similar in the spine, hip, and forearm. It was stronger in women (d = -.24) than men (d = -.12) and in premenopausal (d = -.31) than postmenopausal (d = -.12) women. Only women individually diagnosed for major depression by a psychiatrist with DSM criteria displayed significantly low BMD (d = -.36); women diagnosed by self-rating questionnaires did not (d = -.06). Depressed subjects had increased urinary levels of bone resorption markers (d = .52). Conclusions: The present findings portray depression as a significant risk factor for low BMD. Premenopausal women who are psychiatrically diagnosed with major depression are particularly at high-risk for depression-associated low BMD. Hence, periodic BMD measurements and antiosteoporotic prophylactic and curative measures are strongly advocated for these patients.