Normal bone
Bone with osteoporosis

Depression can cause a loss of bone mass, leading to osteoporosis and fractures, say researchers at the Hebrew University of Jerusalem in an article published in the Proceedings of the National Academy of Sciences.

The researchers say their findings constitute a significant step forward in understanding the interaction between the mind and the skeletal system. Based on their findings, the researchers have already been able to demonstrate the efficacy of anti-depressant drugs in preventing bone mass loss.

Participants in the project were researchers from the university's Brain and Behavior Laboratory, headed by Prof. Raz Yirmia; from the Bone Laboratory, headed by Prof. Itai Bab; and from the Brain Trauma Laboratory, headed by Prof. Esther Shohami. Also participating were doctoral students Inbal Goshen, Alon Bajayo , Tirza Kreisel, Sharon Feldman and Yosef Tam

Loss of bone mass is the leading cause of osteoporosis and bone fractures among the aged in general and among post-menopausal women in particular. Several studies indicate that people with major depression generally have a lower bone mass density compared to control samples; however, no direct link between these two conditions has been established.

In order to examine the connection between depression and bone mass loss, the researchers used a model involving laboratory mice. Following the induction of a depression-like condition, the mice developed behavioral symptoms mirroring those seen in depressed humans, including a reduction in pleasurable activity and in social interaction.

After four weeks in a depressed state, the laboratory animals showed a dramatic bone mass loss, including in the hip bone and vertebrae. This loss was caused by impairment in the bone renewal process, which is essential to maintaining normal bone density. This impairment was caused by a reduction in the number of bone-building cells, which are called osteoblasts.

The laboratory tests showed that chronic use of an anti-depressant drug halted not only the depression itself but also the loss of bone density.

The researchers were also able to describe the process connecting depression to the skeletal structure. They found that depression sets off a neural system connecting the brain to the internal organs, including the skeleton. This system is called the "sympathetic nervous system." Its activation causes the secretion within the bone of a chemical compound called noradrenaline, which has a detrimental effect on the bone-building cells. The researchers were able to show that chronic treatment with a drug that blocks noradrenaline in the bone also blocks the detrimental influence of depression on the bone.

This research serves as the basis for new, efficient drugs for treatment of osteoporosis, which is the most prevalent degenerative disease in western society. The Hebrew University's technology transfer company, Yissum, has applied for a patent for treatment of osteoporosis through anti-depressants.

"The connection between the brain and the skeleton in general, and the influence of depression on bone mass in particular is a new area of research about which we still know very little," said Prof. Yirmiya. "The new findings, which we have discovered in the Hebrew University laboratories, point for the first time to depression as an important element in causing bone mass loss and osteoporosis."

The research was funded by the Bikura program of the Israel National Science Foundation.

Yirmiya R, Goshen I, Bajayo A, Kreisel T, Feldman S, Tam J, Trembovler V, Csernus V, Shohami E, Bab I.
Depression induces bone loss through stimulation of the sympathetic nervous system
PNAS published 2006 Oct 30; 10.1073/pnas.0604234103   [Abstract]