Glucocorticoids have been suggested to play a major role in transplantation-related osteopenia. In this study we assess the long-term changes and the effect of steroid withdrawal from the standard immunosuppressive regimen on bone mineral density (BMD) after orthotopic liver transplantation (OLT). Sixty-nine non-osteoporotic patients (20 women, 49 men), aged 48 +/- 9.5 years (mean +/- SD), and with a follow-up of 58.3 +/- 23.2 months (range 24-121 months) were studied. Immunosuppressive treatment consisted of prednisone, cyclosporin A and azathioprine. In 41 patients (group A), prednisone was tapered and withdrawn after 36.2 +/- 19.3 months (range 13-79 months), whereas in 28 patients (group B) prednisone was maintained. BMD in the spine (L1-L4) was serially measured by dual-energy X-ray absorptiometry (Hologic QDR 1,000w) at baseline, before steroid withdrawal and at the end of study. Age- and sex-matched Z-scores of BMD were calculated. No differences were found in age, body mass index, time since OLT, or baseline BMD between the two groups. BMD had significantly increased in both groups at the end of follow-up period (group A, +8.1 +/- 8.7%; group B, +3.2 +/- 8.0%, p < 0.05). However, the Z-score was significantly higher in group A than in group B at the end of study (-0.44 +/- 1.05 vs -0.99 +/- 0.77; p<0.05). BMD recovery was lower in pre-OLT biliary cirrhosis patients. Bone mass improvement was independent of the time since OLT in both groups, and of the time of steroid withdrawal in group A. Our data confirm that steroid withdrawal accelerates the recovery of bone mass in patients who have undergone a successful liver transplantation.