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Table 1.  

The Demographic Data of Patients and Controls

Table 2.  

The Demographic Data of Patients and Controls

Table 3.  

The Clinical Data of Patients and Controls

Relation of Cortisol Levels and Bone Mineral Density Among Premenopausal Women With Major Depression

Authors: Abdurrahman Altindag, MD ; Ozlem Altindag, MD ; Mehmet Asoglu, MD ; Zehra Deveci, MD ; Minna Gunes, MD ; N Soran, MDFaculty and Disclosures


Summary and Introduction


We aimed to investigate the relationship between cortisol levels and bone mineral density (BMD) among premenopausal women with major depression. We compared BMD, plasma cortisol, osteocalcin and C-telopeptide (CTx) levels of 36 premenopausal women with major depression with 41 healthy women who were matched for age and body mass index. Osteocalcin and CTx were used for the evaluation of bone turnover. The clinical diagnosis of major depression was made by using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The 21-item Hamilton Rating Scale for Depression was used for the assessment of depressive symptoms. In comparison with the controls, the mean BMD of the depressed women was significantly lower at the lumbar spine and at all sites of the proximal femur (p = 0.02, 0.01). Plasma cortisol levels were significantly higher in depressive patients than in controls (p = 0.001). Osteocalcin was lower and CTx was higher in the patient group than in controls (p = 0.04, p = 0.008). Lumbar and femur BMD scores were negatively correlated with cortisol levels in the patient group. Major depression had important effects on BMD and bone turnover markers. Depression should be considered among risk factors for osteoporosis in premenopausal women.


Osteoporosis is the most prevalent metabolic bone disease characterised by bone fragility and increased risk of bone fracture.[1] It is known that diagnosis of osteoporosis should be considered when one or more risk factors are present such as poor nutrition, certain medical disorders, history of previous fracture, thinness and smoking.[2,3]

There are several studies which have investigated the unrecognised risk factors for bone loss.[4-6] For example, the administration of steroids to treat medical disorders or excessive production of cortisol can lead to diminished bone metabolism and altered bone architecture.[7]

A dysregulation of the hypothalamic-pituitary-adrenal (HPA) system, with higher concentrations of serum cortisol in major depressive disorder (MDD), has been frequently reported.[8] The available data suggest that corticotropin releasing hormone (CRH) overdrive and cortisol overproduction may play a pathogenic role in the occurrence of certain types of depression, directly and/or indirectly, i.e. by induction or exacerbation of disturbances in monoaminergic transmission.[9] More refined analysis of the HPA system revealed that corticosteroid receptor signalling is impaired in major depression, resulting, among other changes, in increased production and secretion of CRH in various brain regions postulated to be involved in the causality of depression.[10] Another possible explanation is that MDD patients have a reduced number of glucocorticoid receptors.[11] Furthermore, a dysregulation of pro- and anti-inflammatory cytokines in MDD has been reported, including increased serum levels of interleukin-1β, interleukin-2 (IL-2), interleukin-6 (IL-6), tumour necrosis factor-, and the soluble IL-2 and IL-6 receptors.[12]

Given the reports of osteoporosis in patients who are chronically treated with glucocorticoids or who suffer from Cushing's syndrome, higher serum cortisol concentrations have been hypothesised to be one mechanism by which depression might induce bone loss.[13] Increased level of endogenous or exogenous corticosteroids is associated with decreased bone mineral content because of decreased bone formation and increased bone resorption.[14] Recent studies have suggested that bone mass is affected by hypercortisolism.[6,15] Despite the increased levels of plasma cortisol results in decreased bone mineral density (BMD), the exact mechanism by which osteoporosis develops in depressive patients still remains to be determined. The study was planned to investigate the relationship between cortisol levels and BMD among premenopausal women with major depression.

What's Known. The association of major depression and osteoporosis is a controversial issue. There were several inconsistent reports on this issue in the literature. The hypothesis that major depression leads to osteoporosis was discussed first in 1994. Later it has been proposed that major depressive disorder leads to lower BMD without a change in cortisol level. Recently, a study reported that there were no differences between depressive patients and healthy controls with regard to cortisol levels and BMD.

What's new. We found that patients with major depressive disorder have higher cortisol levels and lower BMD values than healthy controls. To our knowledge, this is the first report investigating the association between cortisol levels and BMD values in patients with major depressive disorder. We thought major depression had important effects on BMD and bone turnover markers and it may be useful to assess BMD values of depressive patients, and to treat them in cases of lower BMD values.

Table of Contents

  1. Summary and Introduction
  2. Methods
  3. Results
  4. Discussion