The longevity of recipients of liver transplant may be compromised by spinal osteoporosis and vertebral fractures. However, femoral neck fractures are associated with a higher morbidity and mortality than spine fractures. As there is little information on bone loss at this clinically important site of fracture, the aim of this study was to determine whether accelerated bone loss occurs at the proximal femur following transplantation. Bone mineral density and body composition were measured at the femoral neck, lumbar spine and total body, using dual x-ray absorptiometry in 22 men and 19 women, age 46 +/- 1.4 y (mean +/- SEM) before and at a mean of 19 mo after surgery (range 3-44). Results were expressed in absolute terms (g/cm2) and as a z score. Before transplantation, z scores for bone mineral density were reduced at the femoral neck (-0.47 +/- 0.21 SD), trochanter (-0.56 +/- 0.19 SD), Ward's triangle (-0.35 +/- 0.14 SD), lumbar spine (-0.76 +/- 0.13 SD), and total body (-0.78 +/- 0.15 SD) (all P < 0.01 to < 0.001). Following transplantation, bone mineral density decreased by 8.0 +/- 1.7% at the femoral neck (P < or = 0.01) and by 2.0 +/- 1.2% at the lumbar spine (P < or = 0.05). Total weight increased by 12.2 +/- 2.3%, lean mass decreased by 5.7 +/- 1.4%, while fat mass increased from 24.1 +/- 2.0% to 35.1 +/- 1.8% (all P < or = 0.001). Patients with end-stage liver disease have reduced bone mineral density. Liver transplantation is associated with a rapid decrease in bone mineral density at the proximal femur, further increasing fracture risk and a reduction in lean (muscle) mass, which may also predispose to falls. Prophylactic therapy to prevent further bone loss should be considered in patients after liver transplantation.