Effects of a single infusion of pamidronate prior to liver transplantation: a bone histomorphometric study

Osteoporosis is a common and serious complication of solid organ transplantation. Effective therapeutic regimens have not been established but evidence that increased bone turnover is responsible for bone loss early after transplantation provides a rationale for the use of anti-resorptive agents in the peri-operative period. We have examined the effects of a single preoperative infusion of pamidronate, 60 mg, on bone remodelling and turnover in a prospective study of 12 patients, four male and eight female aged 19-61 years, with chronic liver disease, who formed a subgroup of a larger randomised controlled single-blind study. Iliac-crest biopsies were obtained before and 3 months after liver transplantation and histomorphometry performed using image analysis. In untreated patients (n = 5) a significant increase in bone formation rate at tissue level was demonstrated at 3 months in comparison to pre-operative values (0.035 +/- 0.013 vs. 0.161 +/- 0.12 mum(2)/mum/day; mean +/- SD, P = 0.003). In patients treated with pamidronate (n = 7) no significant increase in bone formation rate was demonstrated at 3 months, although there was a trend towards an increase in indices of bone turnover. In this group there was also a significant reduction in erosion cavity length (210.4 +/- 63.8 vs. 179.8 +/- 67.5 mum; P = 0.03) and non-significant reductions in other indices of erosion cavity size. These results indicate that pre-operative administration of pamidronate in patients with chronic liver disease prevents, at least in part, the increase in bone turnover which occurs in untreated patients after transplantation.