Exploring the Depression-Bone Connection

Content provided by the Faculty of the Harvard Medical School

A new study finds that antidepressant use doubles fracture risk. Other research points to links between depression and bone loss.

Most of us can tick off the major risk factors for osteoporosis: age, gender, race, family history, smoking, inactivity, low body weight, and inadequate calcium and vitamin D. Depression isn't on the list, but some evidence suggests that it should be. In particular, a study in the Jan. 22, 2007, Archives of Internal Medicine found that people ages 50 and over who regularly took the widely prescribed antidepressants known as selective serotonin reuptake inhibitors (SSRIs) had double the rate of fractures as people not using such medications. Other research points to depression itself as a source of endocrine changes that can damage bone.

Whether the danger comes from depression, the drugs used to treat it, or something else, this is a problem that researchers and clinicians are paying more attention to. The implications for women, particularly older women, are enormous: As many as one woman in 10 suffers from depression, and more than 30 million women ages 50 and over have osteoporosis or are at risk for it. Identifying depression as a risk factor could improve the diagnosis and treatment of this potentially devastating condition.

Making the Connection

The idea that osteoporosis and depression might be linked goes back at least to the 1980s, when observational studies concluded that depression was an emotional response to living with the pain and disability of osteoporosis. But during the 1990s, depression began to emerge as a possible cause of bone loss, rather than a result. Scientists studied women who didn't have osteoporosis symptoms or even know they had the condition. Using new technologies, they found lower bone mineral density (BMD) — a risk factor for osteoporosis and fractures — in those who were depressed. Moreover, the link was found in both younger women (where such bone loss is uncommon) and women past menopause.

A controlled study in the Oct. 17, 1996, New England Journal of Medicine involving mostly premenopausal women found that those with a history of major depression had bone densities that were 10% to 15% lower at the hip and 6.5% lower at the spine than those without depression, regardless of physical activity levels. The depressed women also had higher levels of cortisol, a stress hormone known to cause bone loss.

Since then, many studies have found a similar relationship, so investigators have been looking at hormones and brain chemicals that could be involved in both depression and bone loss. For example, Israeli researchers working with an animal model of depression found that depression activates the sympathetic nervous system and triggers the release of noradrenaline, which interferes with bone-building cells. (The sympathetic nervous system connects the brain to the internal organs and skeleton.) Moreover, they found that imipramine, one of an older class of drugs called tricyclic antidepressants, reversed both depression and depression-induced bone loss. These findings were published in the November 2006 Proceedings of the National Academy of Sciences.

A National Institute of Mental Health (NIMH) study of bone loss in premenopausal women with and without major depression showed that those who were depressed had unfavorable levels of cytokines that specifically affect bone mass. (Cytokines are chemical messengers that interact with the immune, nervous, and endocrine systems.) Studies have also found brain-bone connections involving other substances, including the hormone leptin. Dr. Giovanni Cizza, who directed the NIMH study and has been investigating depression and bone loss for several years, says these discoveries herald a new discipline, which he calls "the neuropsychoendocrinology of bone regulation."

Depression may be a risk factor for osteoporosis in other ways: "If you're very depressed, you may not be taking care of yourself — not eating right, for example — and you're more likely to have bone loss," says Dr. Jessica Gören, a clinical psychiatric pharmacist at Harvard Medical School–affiliated Cambridge Health Alliance. She believes that depressed patients need more aggressive counseling about osteoporosis, "because regardless of whether depression is an independent factor, lifestyle is."

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Women ages 19 to 50 need at least 1,000 milligrams of calcium every day. Younger women and women older than 50 need even more.