Total parenteral nutrition (TPN) may affect bone metabolism in a variety of ways. These may include potential indirect effects such as on gastrointestinal hormone secretion, liver function, especially cytochrome P450 isoenzymes, metabolic biorhythms where established, and the continuous compared with the intermittent supply of nutrients. More substantial evidence exists for the reduction of bone formation, parathyroid hormone secretion, and calcitriol production in TPN patients along with high urinary calcium excretion. This review considers both aluminum loading and vitamin D sensitivity as etiologic factors and suggests that aluminum may have played a primary role in the pathogenesis of these abnormalities in bone and mineral metabolism, but that vitamin D may have potentiated the deleterious actions of aluminum. While the sources of aluminum contamination of TPN solutions have been identified and efforts are under way to reduce its contamination of TPN solutions, the persistence of low bone mass measurement in TPN patients is a problem that has been identified repeatedly, does not have a current explanation, and requires further study.