Bone Mineral Density in Women With Major Depression

Osteoporosis is a condition that is underdiagnosed and undertreated, and often goes
unnoticed until a fragility fracture occurs after many years of progressive loss of bone
quality. Risk factors for osteoporosis include glucocorticoid excess and a pro-inflammatory
state, both of which we and others have observed in a substantial proportion of patients
with Major Depressive Disorder.

We have found statistically and clinically significant reductions in bone mineral density
(BMD) in a group of 24 depressed but otherwise healthy pre-menopausal women, as compared to
24 healthy, closely matched controls. The difference was significant at several trabecular
bone sites (e.g., 13.6% at the femoral neck, 13.6% at the Ward's triangle, and 10.8% at the
trochanter). Epidemiological studies indicate that losses in trabecular bone mineral density
of these magnitudes are associated with an increased lifetime risk for fracture up to 50%.

Although the mechanism(s) of the lower bone mineral density in our patients with past or
current depression has not yet been elucidated, these subjects showed significantly higher
24-hour urinary free cortisol excretion than their matched controls. However, the extent of
the lower bone mineral density in women with past or current depression cannot be accounted
for strictly on the basis of hypercortisolism alone, but is likely to require other hormonal
or biochemical factors as well.

Preliminary data in subjects recruited from a large study of mothers with or without mood
disorders and their offspring indicate that a disproportionate number of young adult
offspring of mothers with Major Depressive Disorder show reduced BMD, 2/3 of whom had not
yet manifested clinical signs or symptoms of mood disorder.

In the light of the fact that major depression affects between 5% and 9% of the female
population, the depression-associated lower bone mineral density potentially predisposes
millions of women to enhanced susceptibility to osteoporosis. We therefore wish to continue
our assessment of bone mineral density in subjects with past or current depression to
further document the incidence of lower bone mineral density in a larger series. We also
wish to identify subjects with past or present depression who have reduced bone mineral
density to offer them the possibility of participating in other studies designed to clarify
pathophysiologic mechanisms involved in low bone mineral density, identify any clinical
characteristics of depressive illness that may predict increased risk of osteopenia or
osteoporosis, examine the association of low BMD with other endocrine and metabolic
disturbances seen in depressive illness, and to identify those who may require therapeutic
intervention.

INCLUSION CRITERIA:

A history of current or past major depression of at least four months duration, or a
history of two or more brief depressive episodes will be the primary criterion for
inclusion.

Patients with Bipolar Disorder will be eligible if they meet the depressive episode
criterion.

No specific inclusion criteria are set for normal volunteers.

EXCLUSION CRITERIA:

DEPRESSED SUBJECTS:

Pregnant women will not be eligible to participate.

Known medical causes of osteoporosis, other than depression.

Current or past history of eating disorders, or schizophrenia, as per DSM-IV.

Chronic use of oral or parenteral steroids (daily use for 3 months or longer).

HEALTHY SUBJECTS:

Pregnant women will not be eligible to participate.

Known medical causes of osteoporosis.

Any history of DSM-IV diagnosis, including depression, eating disorders, and alcohol or
drug abuse.

History or current evidence of any significant clinical or laboratory abnormalities.