Healthy Clinical Trial
Official title:
Bone Mineral Density in Patients With Major Depression With Melancholic and Atypical Features: Relation to Stress-System Neurohormonal Function
The purpose of this study is to examine calcium absorption and bone mineral density in women
with depression.
Research indicates that pre-menopausal women with depression have significantly lower bone
mineral density (BMD) than pre-menopausal women without depression. Although the mechanisms
of BMD loss are unclear, researchers believe that individuals with depression have impaired
calcium absorption. However, it is unknown whether the abnormal absorption is a result of
depression or a side effect of the drugs used to treat it. This study will compare calcium
absorption in women with depression and in healthy women without depression.
Participants in this study will be given two non-radioactive calcium isotopes. One can be
taken by mouth and the other must be injected. Participants will have the level of isotopes
in their urine measured to estimate true fractional calcium absorption (TFCA). Participants
may also have a dual X-ray absorptiometry (DEXA) scan to measure total body adiposity and
lean body mass.
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.
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