A tetracycline (doxycycline) was administered daily by oral intubation to adult diabetic rats to assess the effect on skeletal tissue; the rationale--osteopenia is a complication of diabetes and tetracyclines (TCs) were recently found to inhibit pathologic collagen loss (e.g. in diabetic rat skin) by a mechanism independent of their antimicrobial efficacy. Osteopenia was induced by streptozotocin-diabetes as indicated by physical (e.g. specific gravity), chemical (e.g. calcium (Ca) content) and ultrastructural characteristics of the femurs, and TC administration (including treatment with a chemically-modified non-antimicrobial analog) appeared to prevent the development of the bone deficiency disease without affecting the severity of hyperglycemia.