Depression Associated With Low Bone Mineral Density

December 3, 2007 — A new study shows that low bone mineral density (BMD) is more prevalent in premenopausal women with major depressive disorder (MDD) than among health control women. The risk associated with MDD was similar in magnitude to other risk factors for osteoporosis such as smoking or low calcium intake.
The study is published in the November 26 issue of the Archives of Internal Medicine.
Giovanni Cizza, MD, PhD, MHSc, from the National Institute of Diabetes, Digestive, and Kidney Diseases in Bethesda, Maryland, told Medscape Psychiatry that he hopes their findings will underline the need to test women with depression for bone loss.
"I think the practical message is depression is a risk factor for osteoporosis," he said. "The novelty of this study is the fact that these women were not severely depressed. They were mildly depressed, and yet they had bone loss of clinical significance, so the threshold to prescribe the test within the population of women with depression should be to almost everybody, not only the more severely depressed women, or those with a long duration of depression."
First author on the paper is Farideh Eskandari, MD, MHSc, from Case Western Reserve University in Cleveland, Ohio for the Premenopausal, Osteoporosis Women, Alendronate, Depression (POWER) Study Group.
A Disease of Chronic Stress
Depression is considered a disease of chronic stress, Dr. Cizza said, with attendant increases in the stress hormone cortisol, and cytokines produced by the immune system. "Those substances are helpful to fight stress, but if there is too much cortisol or cytokines, there are side effects," he said. "One of the side effects is bone loss, so it was obvious to ask the question, 'do women with depression have low bone mass?'"
In this study, they examined BMD in 89 premenopausal women with current or recent MDD, and 44 healthy control women enrolled in the POWER study, a prospective study of bone turnover carried out at the National Institutes of Health Clinical Center.
MDD was defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV); women were enrolled if they met the criteria for MDD and had had a depressive episode within the last 3 years.
BMD was measured with dual energy x-ray absorptiometry at the spine, hip, and forearm. Mean hourly levels of plasma 24-hour cytokines and 24-hour urinary free cortisol and catecholamine excretion were measured in a subset of women.
They found that the prevalence of low BMD, defined as a T score of less than –1, was statistically significantly greater in women with MDD vs the control women at the femoral neck and total hip, and showed a trend to be greater at the lumbar spine.
In addition, women with MDD had increased mean levels of 24-hour proinflammatory cytokines and decreased levels of anti-inflammatory cytokines.
Dr. Cizza noted that the difference in BMD they saw of approximately 3% at the spine and 2% to 3% at the hip in these premenopausal women with depression is comparable to the loss seen in the first year after menopause. "The bone loss experienced past the menopause is very rapid and very severe, so it is a clinically significant loss," he said.
More Data to Come
The data published here represent cross-sectional baseline data for the POWER study, a prospective study that observed these women for 3 years. Bone mass has been measured every 6 months, and participants have been assessed clinically for depression.
Dr. Cizza is currently analyzing these data. "The next step is to see what happened to them over time. Did they lose more bone mass than controls? Did the ones who are more severely depressed lose more bone than the ones not severely depressed? It's going to be very interesting."
In the meantime, though, he added, psychiatrists should think about having women with depression assessed for bone loss, and internists seeing women with bone loss should consider whether these women might have depression. "It goes both ways," he said.
The diagnosis is critical because it can be treated with lifestyle modification, increased calcium intake, smoking cessation, increased exercise, or increased medication. "The test is available, noninvasive and the amount of radiation is minimal," he noted. "There really is no good reason this condition should go undiagnosed."
The study was supported in part by the Intramural Research Programs of the National Institute of Mental Health; the National Institute of Diabetes, Digestive, and Kidney Diseases; the National Center for Complementary and Alternative Medicine; and the Warren Magnuson Clinical Center of the National Institutes of Health. Three of the study authors have received funding. The remaining study authors have disclosed no relevant financial relationships.
Arch Intern Med. 2007;167:2329-2336.