Depression May Contribute to Bone Loss in Younger Women

Many studies have linked depression to bone loss in older women. Now a new study links the two in younger women as well.

The study was conducted by Giovanni Cizza, M.D., a principal investigator at the National Institute of Mental Health, and colleagues.

The study included 44 healthy control subjects and 89 premenopausal women, aged 21 to 45, who had experienced a major depression within the previous three years. Some of the 89 subjects were currently depressed as well.“ The idea,” Cizza explained in an interview, “was that the cumulative damage of depression on their bones would remain whether they were currently depressed or not.”

Some possibly confounding factors, such as calcium intake, coffee and alcohol intake, smoking, physical fitness, and oral contraceptive use, were similar between depressed subjects and controls.

The bone mineral density of all subjects was measured at various points at the spine and hip. Bone-mineral-density results for the depressed subjects were then compared with those for the controls, taking body mass index into consideration.

The prevalence of low bone mineral density, defined as a T score of less than one standard deviation below that of the controls, was significantly greater in depressed women than in control subjects at the hip. The prevalence of low bone mineral density also tended to be greater in the depressed group than the controls at the spine, although this difference was not statistically significant.

Also, the bone-mineral-density deficits found in depressed subjects were clinically meaningful and comparable to those resulting from established risk factors for osteoporosis, such as reduced calcium intake and smoking. For example, 25 of the 89 depressed subjects had a T score more than one standard deviation below that of the healthy control subjects at the hip and spine, indicating considerable erosion in bone mineral density, and two had a T score more than 2.5 standard deviations below that of the controls at the hip and spine, indicating osteoporosis.

Thus, “low bone mineral density is more prevalent in premenopausal women with major depressive disorder,” Cizza and his colleagues concluded in their study report, which appeared in the November 26, 2007, Archives of Internal Medicine.

Depression Probably the Culprit

The researchers believe that depression reduces bone mineral density in premenopausal women, not that reduced bone mineral density causes depression. One reason why, they pointed out, is because osteoporosis remains mostly asymptomatic and undiagnosed until a fracture ensues and thus is unlikely to cause depression. Another reason why, they explained, is that they observed a striking difference in plasma cytokine concentrations between depressed subjects and controls—proinflammatory cytokine levels were substantially higher in the former. One of these cytokines, interleukin 6, is a potent bone-resorption factor and could contribute to bone loss in depressed women.

And indeed, if depression can erode bone mineral density in premenopausal women by increasing cytokines or via other means, then it poses a salient question: What effect might antidepressant treatment have on such erosion?

Two recent studies found an increased rate of bone loss in older men and women taking SSRI antidepressants, suggesting that antidepressants might contribute to bone loss (Psychiatric News, August 3, 2007). However, these studies did not take depression into consideration as a possible confounding factor, so it was unclear whether antidepressants or depression itself might have been responsible for the loss. Then, 73 of the 89 depressed subjects in the current study were taking antidepressants. But when Cizza and his colleagues took antidepressant use by these subjects into consideration, he still found a link between depression and low bone mineral density in them. So it looks as if depressed subjects' low bone mineral density could not be attributed to antidepressants.

Antidepressants May Even Help

In fact, it is possible that antidepressants might counter bone loss due to depression, Cizza and his group speculated, and that “the usefulness of antidepressants for bone loss in major depressive disorder should be evaluated.” But such a study would have to be large and long, and it would therefore be expensive, Cizza admitted.

“This was a well-conducted prospective study,” Ladi Kukoyi, M.D., told Psychiatric News. Kukoyi is an assistant clinical professor of psychiatry at the University of California-Davis and has studied this subject. “It is probably the largest study to date looking at this issue. It [also] adds to the extant literature with... the thorough nature of its biochemical inflammatory data collection. I think clinical psychiatrists will welcome its results as another reason to aggressively treat depression if prospective studies can confirm that we can reverse the reduction in bone mineral density with effective depression treatment.”

The study was funded by the National Institutes of Health.

An abstract of “Low Bone Mass in Premenopausal Women With Depression” is posted at<http://archinte.ama-assn.org/cgi/content/abstract/167/21/2329>.▪