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

Osteoporos Int. 2010 Oct;21(10):1627-35. doi: 10.1007/s00198-010-1181-x. Epub 2010 Mar 4.


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.

Introduction: 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.

Methods: 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.

Results: 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).

Conclusion: Evidence supports an association between depression and increased risk of fracture and bone loss that may be mediated by antidepressants.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antidepressive Agents / adverse effects
  • Depression / complications*
  • Depression / epidemiology
  • Depressive Disorder / complications*
  • Depressive Disorder / epidemiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoporosis / epidemiology
  • Osteoporosis / etiology*
  • Osteoporotic Fractures / epidemiology
  • Osteoporotic Fractures / etiology*
  • Risk Assessment / methods


  • Antidepressive Agents