BONE LOSS AFTER LIVER-TRANSPLANTATION

We studied 35 adult patients (mean age = 43 yr) referred for orthotopic liver transplantation. Spinal bone mineral density was measured by quantitative computed tomography scanning before transplantation (n = 35) and at 3 mo (n = 21) and 12 mo (n = 11) after orthotopic liver transplantation. The readings were corrected to age 50 yr, using the regression equations derived from normal control subjects. Quantitative bone histological studies were performed in 17 patients before orthotopic liver transplantation and 3 mo after orthotopic liver transplantation. Before orthotopic liver transplantation, the corrected spinal bone mineral density in men was 108 +/- 20 mg/cm3, less than in male control subjects (129 +/- 22 mg/cm3, p < 0.005). In women patients the value was 117 +/- 27 mg/cm3, and in female control subjects 126 +/- 19 mg/cm3 (NS). However, women patients with primary biliary cirrhosis had lower spinal bone mineral density (106.5 +/- 14.8) than female control subjects (p < 0.005). Histologically, the resorbing surface was near the normal mean, whereas the osteoblast surface, tetracycline surface and bone formation rate was lower in men (p < 0.05) but not women. Spinal bone mineral density decreased by 24% in the first 3 mo after orthotopic liver transplantation with no further decrease at 12 mo. Five patients had vertebral fractures within 6 mo of orthotopic liver transplantation. One patient fractured a wrist and three had osteonecrosis of the hip or knee. Bone histological studies 3 mo after orthotopic liver transplantation showed no change in resorbing surface but an increase in osteoblast surface from 2.1% +/- 3.0% to 6.0% +/- 7.0% (p < 0.05), increased bone formation in men (21 +/- 31 to 80 +/- 96-mu-m2/mm2 p < 0.05) and serum osteocalcin increased from 2.3 +/- 0.3 pg/ml before transplantation to 5.9 +/- 1.8 pg/ml (p < 0.05). Bone loss was related to the number of hospital days after orthotopic liver transplantation (r = 0.79, p < 0.001) but not to any other factor, including prednisone and cyclosporin dose. The study shows that bone mass is reduced in men with end-stage liver failure and that considerable bone loss occurs in the first 3 mo after orthotopic liver transplantation, frequently resulting in vertebral fractures. The exact cause of the bone loss is not clear, although immobilization appears to be important, probably in combination with corticosteroid therapy. The cellular changes causing this bone loss must occur very early after orthotopic liver transplantation because by 3 mo after transplantation, increased bone formation had begun to occur.