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 pre-operative 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 microm(2)/microm/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 microm; 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.

Lack of effect of intravenous pamidronate on fracture incidence and bone mineral density after orthotopic liver transplantation.

BACKGROUND/AIMS: Increased rates of bone loss and fracture have been reported after liver transplantation. The aim of this study was to investigate the effects of a pre-transplant infusion of pamidronate on fracture incidence and bone loss during the first year after transplantation. METHODS: Ninety-nine adults awaiting orthotopic liver transplantation (OLT) were randomised to pamidronate or no treatment. Spinal X-rays were obtained at baseline and after 12 months. Bone mineral density (BMD) was measured at the lumbar spine (L1-4) and femoral neck at baseline, and 3, 6, and 12 months after OLT. RESULTS: The incidence of fractures in the first year after OLT was 8%, four patients within the pamidronate treated group and two in the untreated group developing fractures (P=0.40). No significant spinal bone loss occurred in either group during the first year. However, significant and sustained bone loss occurred at the femoral neck in both groups. No significant differences were seen between pamidronate treated or untreated groups at either site. CONCLUSIONS: Pamidronate in the regimen used had no significant effect on fracture rate or BMD post-transplant. The low incidence of fracture and absence of spinal bone loss indicate that bone disease after liver transplantation may be less common than previously reported.