In 161 ambulatory rheumatic disease patients receiving long-term prednisone therapy, diaphyseal mass (DM) and metaphyseal mass (MM) of the forearm were measured by single photon absorptiometry, and bone radiographs were reviewed when available. Multivariate analysis of treatment and patient characteristics demonstrated that glucocorticoid-induced osteopenia (defined as an elevated DM:MM ratio) and bone fractures occurred with similar frequency in patients of each sex, in whites and blacks, in patients with various rheumatic diseases, and in patients receiving different regimens of prednisone therapy. However, large cumulative doses of prednisone were associated with elevated DM:MM ratios as well as with bone fractures, and menopause or age greater than or equal to 50 years (males or females) was associated with bone fractures. We conclude that long-term therapy with various prednisone regimens results in glucocorticoid-induced osteopenia and fractures. This affect is cumulative, occurs in all patient groups, and results in more bone fractures in certain groups.