Depression, fracture risk, and bone loss: a meta-analysis of cohort studies

Whether depression can increase the risk of bone fractures is uncertain. This meta-analysis, which pooled results from 14 qualifying individual cohort studies, found that depression was associated with a significantly increased risk of fractures and bone loss. The effect of depression on the risk of bone fractures is controversial. We conducted a meta-analysis of prospective studies that examined the risk of osteoporotic fractures and bone loss associated with depression. We searched databases and reviewed citations in relevant articles to identify cohort studies that met prestated inclusion criteria; 14 studies were identified. Information on study design, participant characteristics, exposure and outcome measures, control for potential confounders, and risk estimates was abstracted independently by two investigators using a standardized protocol. Data were pooled by use of a random-effects model. In studies that reported fracture outcomes as hazard ratios (HRs) (six studies [n = 108,157]), depression was associated with a 17% increase in fracture risk (HR = 1.17; 95% confidence interval [CI], 1.00-1.36; P = 0.05); in studies that reported risk ratios as fracture outcomes (four studies [n = 33,428]), depression was associated with a 52% increase in risk (risk ratio, 1.52; 95% CI, 1.26-1.85; P < 0.001). In studies that reported bone mineral density as an outcome (five studies [n = 8,931]), depression was associated with a reduced annualized bone loss rate of 0.25% (0.05-0.45%; P = 0.02) at the hip and 0.29% (-0.07-0.64%; P = 0.11) at the spine. The HR for the three studies (n = 14,777) that did not adjust for antidepressant treatment was 1.30 (95% CI, 1.11-1.52; P = 0.01), and the HR for the three studies (n = 93,380) that did adjust for antidepressant treatment was 1.05 (95% CI, 0.86-1.29; P = 0.6). Evidence supports an association between depression and increased risk of fracture and bone loss that may be mediated by antidepressants.