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

Abstract

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 singleblind 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 k0.12 pm2/ pmlday; 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 pm; 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.

Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long‐term follow‐up of a prospective study

“…Osteoporosis and increased risk of fragility fractures have been reported among long-term survivors of solidorgan transplantation (Henderson et al, 1995;Ninkovic et al, 2000;Kreig et al, 2001). Analysis of bone markers and bone histomorphometric assessment have demonstrated a state of high bone turnover following organ transplantation (Bishop et al, 1999;Vedi et al, 2002), although results of studies using antiresorptive drugs to prevent or retard bone loss have been conflicting (Kreig et al, 2001;Ninkovic et al, 2002). Following either autoSCT or alloSCT, we observed a significant and persistent loss in BMD at the femoral neck, associated with an initial decrease in serum markers of bone formation.…”

Posttransplantation Bone Disease

“…Intravenous pamidronate was clearly more effective than nasal calcitonin plus calcitriol in patients following cardiac transplantation (38). Intravenous ibandronate has been effective in liver transplant recipients (39) and in a study of a single dose of intravenous pamidronate given at the time of liver transplantation, the characteristic rise in bone turnover was largely prevented (16,40). Studies with the first generation bisphosphonate, etidronate, have yielded variable results.…”

Prophylactic Bisphosphonate Treatment Prevents Bone Fractures After Liver Transplantation

“…Many of these studies have been small and most have not been randomized or controlled (7). Beneficial effects of pamidronate on indirect parameters, such as bone mineral density (BMD), have been shown in patients undergoing heart, liver, lung and kidney transplantation (8)(9)(10)(11)(12). One investigator suggested that aledronate is efficacious in preventing the natural course of bone loss associated with LT (13).…”