The Role of Stress-induced Cortisol in the Relationship Between Depression and Decreased Bone Mineral Density

Background: This study was designed to test the hypothesis that cortisol mediates the relationship between bone density and depression in postmenopausal women.

Methods: Nineteen women aged 52-79 who had been assessed for bone mineral density by dual-energy x-ray absorptiometer (DEXA) were evaluated for depression and anxiety. Diurnal and stress-induced measures of salivary cortisol were obtained during the following week and at a laboratory session involving a speech task.

Results: Nine volunteers reported depression while 10 were never depressed. Ever depressed women had significantly lower total lumbar and right femur DEXA Z scores than never depressed (t(17) = 2.5, p = .019 and t(17) = 2.06, p = .05, respectively). Ever depressed women demonstrated a significant increase in salivary cortisol (area under the curve (AUC) = 27.83, SD = 37.64) compared to never depressed women (AUC = -13.34, SD = 19.55) (t(17) = -3.041, p = .007) during a psychological challenge. There were significant inverse relationships between salivary cortisol AUC values and bone density Z scores at every measured bone site. Mediation analyses suggest that 51 - 67% of the association between depression and bone density could be attributed to stress-induced changes in cortisol.

Conclusions: Cortisol hypersecretion in response to stress may, in part, explain the impact of depression on bone density in post-menopausal women.