We have recently found that premenopausal women with past or current depression show clinically significant decrements in bone mineral density in the hip and spine, rendering more than 40% at present risk for osteoporotic fracture. Recent pharmacologic advances provide the opportunity to ameliorate or reverse this clinically significant loss of bone mineral density. Available agents such as bisphosphonates or growth hormone are each preferentially effective in the contexts of increased and decreased bone turnover, respectively. It is currently not known whether the decrease in bone mineral density in depression is associated with increased or decreased bone turnover because the many endocrine changes associated with depression of possible relevance to decreased bone mineral density have disparate effects on bone turnover dynamics. At present, the only definitive way to determine the status of bone turnover in humans is via bone biopsy and histomorphometric evaluation. In addition, bone marrow routinely obtained during standard bone biopsy would provide the opportunity to culture osteoblast and osteoclast progenitor cells to determine possible abnormalities in differentiation and function as a means of exploring the cellular and molecular mechanisms of decreased bone mineral density in depression. In light of the high incidence of depression in women, decreased bone mineral density in patients with past or current depression has considerable public health implications.