In the early 1980s, researchers studying osteoporosis noted that depression was one of the major negative consequences of bone loss and fractures. These researchers believed that osteoporosis and fractures occurred first, causing a reactive depression. Meanwhile, a similar but distinct psychiatry literature noted that osteoporosis or bone loss appeared to be an undesirable consequence of major depression. Here, depression was seen as the causal factor, and osteoporosis was the outcome. The psychiatric perspective is more biological, based on the presence of hypercorticoidism in depressed individuals. Those who believe that osteoporosis leads to depression point out that depression is a consequence of many chronic illnesses. Regardless of the correct causal order, the strong positive relationship between osteoporosis and depression merits further clinical and research attention in the future.