Bone Density in Postmenopausal Women Swayed by Mood Changes

Women with diagnoses of depression and low bone mineral density (BMD) are presented with a problematic situation, because antidepressant drugs are associated with decreased BMD and a risk of fractures. Psychotherapy for management of depression may be a solution.

Primary care physicians need to be aware of the relationship between mood and BMD in postmenopausal women, especially because the incidence of mood changes and depression in older women is high.

My colleagues and I addressed these points in a study that appeared recently in Archives of Osteoporosis. Accumulating Evidence
In the past decade, researchers have begun to study the relationship between decreased BMD and depression. One line of research has found numerous symptoms of depression among women with osteoporosis, compared with healthy women.¹ Women who have osteoporosis may have difficulties in executing routine, fairly simple daily tasks, and these difficulties may result in feelings of incapacity, low self-esteem, and an impaired sense of well-being and quality of life, which, in turn, leads to depression.²

A second line of research has focused on psychiatric populations. Researchers have found an association with substantially decreased BMD among women with different levels of depression.³ This effect has been explained by hormonal and immunological processes that evolved during depression and affected bone condition. What’s more, this relationship was found even when mediating lifestyle variables related to depression were controlled.⁴

Antidepressant drugs, such as selective serotonin reuptake inhibitors, appear to have negative effects on BMD, in some studies leading to at least 4% lower BMD.^5,6

A few studies have directly examined the effect of depression on markers of bone condition. These studies found an increase in bone turnover markers, hormones affecting osteoblast activity (cortisol and parathyroid hormone), and proinflammatory markers among patients with diagnoses of clinical depression compared with a control group.^7-10

In sum, the accumulating body of evidence from numerous studies, including meta-analyses and longitudinal studies, indicates a relationship of depression with low BMD. However, a number of studies have found evidence contradicting this relationship. Our study aimed to address the inconsistencies.

Depression and Hip BMD
In our study, we found significant negative correlations between depression and BMD variables in 3 areas of measurement. Depression explained 4% to 6% of the variation in 6 BMD variables, beyond background variables. Depression also was found to make a unique significant contribution to the explained variance in right and left hip BMD, after controlling risk factors for osteoporosis and other mood variables, such as anxiety and stress.

Depression triggers the sympathetic nervous system, which, in turn, releases the neurotransmitter noradrenalin. This may play a role in bone loss. The sympathetic nervous system may mediate the skeletal effects of stress-induced depression, and serotonin also may be a factor in bone conditions because it enhances bone formation and limits bone resorption. Depression also affects proinflammatory cytokines and the hypothalamic-pituitary-adrenal axis.

The effects of depression include increased smoking, excessive alcohol use, and physical inactivity. Impaired function resulting from osteoporosis (difficulties in functioning physically and a sense of incapacity, low self-esteem, and impairment in sense of well-being and quality of life) may in turn lead to deterioration in mood.
 
The addition of more measurement variables could have increased the validity of our study. For example, laboratory tests (blood or urine) that measure substances secreted by bone during dismantling or construction could serve as additional sources for evaluating bone condition. We also could measure mood variables (cortisol) in further empirical testing and directly investigate the effect of mood on bone density.

Future studies should further examine the complex relationship between depression, antidepressant drugs, and osteoporosis and the effects of psychotherapy on depression, anxiety, stress, and bone condition.

References
1. Coelho R, Silva C, Maia A, et al. Bone mineral density and depression: a community study in women. J Psychosom Res. 1999;46:29-35.
2. Lips P, Agnusdei D, Caulin F, et al. The development of a European questionnaire for quality of life in patients with vertebral osteoporosis. Scand J Rheumatol Suppl. 1996;103:84-85.
3. Wu Q, Magnus JH, Liu J, et al. Depression and low bone mineral density: a meta-analysis of epidemiologic studies. Osteoporos Int. 2009;20:1309-1320.
4. Williams LJ, Pasco JA, Jacka FN, et al. Depression and bone metabolism: a review. Psychother Psychosom. 2009;78:16-25.
5. Cauley J, Fullman RL, Stone KL. Factors associated with the lumbar spine and proximal femur bone mineral density in older men. Osteoporos Int. 2005;16:1525-1537.
6. Diem SJ, Blackwell TL, Stone KL, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med. 2007;167:1240-1245.
7. Yirmiya R, Bab I. Major depression is a risk factor for low bone mineral density: a meta-analysis. Biol Psychiatry. 2009;66:423-432.
8. Altindag O, Altindag A, Asoglu M, et al. Relation of cortisol levels and bone mineral density among premenopausal women with major depression. Int J Clin Pract. 2007;61:416-420.
9. Herran A, Amado JA, Garcia-Unzueta MT, et al. Increased bone remodeling in first-episode major depressive disorder. Psychosom Med. 2000;62:779-782.
10. Kahl KG, Rudolf S, Stoeckelhuber BM, et al. Bone mineral density, markers of bone turnover, and cytokines in young women with borderline personality disorder with and without comorbid major depressive disorder. Am J Psychiatry. 2005;162:168-174.