The National Institute of Mental Health (NIMH) has launched a new study of women ages 21 to 45 who are suffering from major depression to find out whether low bone mass is related to depression or stress hormones, such as cortisol. During a 12-month period, researchers will monitor bone loss and the effects of depression and stress on physical health. The trial involves 6 visits to NIMH, where participants will receive a psychological evaluation, a bone mineral density test, and measurements of stress hormones.

In a review of published research, NIMH-funded scientists report a strong association between depression and osteoporosis. The literature suggests that depression may be a significant risk factor for osteoporosis, a progressive decrease in bone density that makes bones fragile and more likely to break. Low bone mineral density (BMD), a major risk factor for fracture, is more common in depressed people than in the general population.

"Using different data, all of the studies point to the same conclusion," said NIMH researcher and first author Giovanni Cizza, M.D.,Ph.D. "Depression is not only a disease of the brain, but it also has long-term consequences for other medical conditions, such as osteoporosis." Dr. Cizza and Philip Gold, M.D., NIMH, George Chrousos, M.D., National Institute of Child Health, and Pernille Ravn, M.D, Center for Clinical and Basic Research, Ballerup, Denmark, present a summary of the findings in the July issue of "Trends in Endocrinology & Metabolism".

Both the clinical trial and research review underscore the seriousness of depression, a treatable illness that affects 5 to 9 percent of women and 1 to 2 percent of men. Depression symptoms include loss of interest or pleasure in activities that were once enjoyed, including sex; fatigue, decreased energy; difficulty concentrating, remembering, making decisions; insomnia, early-morning awakening, or oversleeping; appetite and weight loss or overeating and weight gain; thoughts of death or suicide; suicide attempts; restlessness, irritability; and persistent symptoms that do not respond to treatment, such as headaches, digestive disorders, and chronic pain.

Although its causes are unclear, major depression is associated with hormonal abnormalities that can lead to changes in tissue, such as bone. Research suggests that higher cortisol levels, often found in depressed patients, may contribute to bone loss and changes in body composition. Fragile bones and increased risk of fracture are signs of osteoporosis. When one or more risk factors occur, such as low BMD, family history, previous fracture, thinness, or smoking, a clinical evaluation for osteoporosis is recommended. Identifying depression as a risk factor would improve patient diagnosis and treatment.

In one study, evidence revealed that bone density at the lumbar spine was 15% lower in 80 men and women older than 40 with major depression compared to 57 men and women who were not depressed. Factors such as smoking, a history of excessive or inadequate exercise, or estrogen treatment did not affect the study, implying that depression per se had an effect on bone mass.

Another study measured bone mineral density at the spine, hip, and radius in 22 pre-and 2 postmenopausal women with previous or current major depression. The 24 controls were matched by age, menopausal status, race, and body mass index. BMD was 6% lower at the spine and 14% lower at the hip in the depressed women. No premenopausal women in the control group had such a deficit.

The association between depression, BMD, falls, and risk of fracture was examined in a study of 7,414 elderly women. Depression prevalence was 6%. Depressed women were more likely to fall (70% versus 59%) and had more vertebral (11% versus 5%) and non-vertebral (28% versus 21%) fractures compared with controls. This research underlines depression as a risk factor for osteoporotic fractures.

The relationship between osteoporosis and mental health was evaluated in a sample of 102 middle-aged Portuguese women. Osteoporosis had a 47% prevalence, and depression was significantly more common in women with osteoporosis than in women without it (77% versus 54%). Women with the disorder had depressive scores 25-35% higher than those with normal bone mass. This study did not find a link between depressive symptoms and low BMD, suggesting that only fully developed depression is a risk factor for osteoporosis.

In their summary, the researchers show a consistent association between depression and osteoporosis, suggesting that depression is a substantial risk factor. Some bone-loss studies combined actively depressed subjects with those who had a previous diagnosis, so it is unknown whether current depression and past diagnoses affect bone loss equally. With major depression as the threshold, most studies revealed a clear association between depression and osteoporosis.

Cizza and colleagues concluded that a clinical evaluation of subjects with unexplained bone loss, especially premenopausal women and young or middle-aged men, should include an assessment of depression. Conversely, non-traumatic fractures in a depressed patient should alert the physician to the possibility of osteoporosis.

The current NIMH study will determine whether women with major depression and normal BMD lose bone mass faster than women without depression and if the drug alendronate (Fosamax) can maintain or increase bone mass in premenopausal women with major depression and low bone mass. It is open to women 21 to 45 years old in treatment for major depression within the year and no history of schizophrenia, bipolar or eating disorders, or suicide risk and to healthy control women with no history of major depression or major organ disease.