Bone Mineral Density in Patients With Major Depression With Melancholic and Atypical Features: Relation to Stress-System Neurohormonal Function

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.