A syndrome of bone pain and fractures has been described in patients receiving long-term support from parenteral nutrition containing large quantities of aluminium or vitamin D2. Whether this same syndrome occurs in patients supported by current therapeutic regimens is controversial. In this study, bone health was longitudinally evaluated over 7 to 61 months in 14 subjects maintained on long-term parenteral nutrition. The parameters of bone health evaluated included bone mass as measured by single and dual photon absorptiometry and quantitative histomorphometry of bone biopsies. There was a striking heterogeneity in baseline measures of bone health. Mean bone density of parenteral nutrition patients was significantly below expected values on entry into the study at both the distal radius (z score = -0.76 +/- 0.27) and the lumbar spine (z score = -1.17 +/- 0.27). Mean areal density at the forearm was less severely depressed (z score = -0.62 +/- 0.34). The longitudinal changes in bone density and morphology were heterogeneous, with some subjects showing deterioration, others improvement, and still others no change. We conclude that patients already established on parenteral nutrition frequently have osteopenia. The group as a whole did not demonstrate normalization of the osteopenia, but our results also suggest that current parenteral nutrition formulations low in aluminum and vitamin D2 do not necessarily cause worsening of bone health. The etiology of this clinical syndrome merits additional study.