Osteoporosis is common in patients with chronic cholestatic liver disease, and atraumatic spinal fracture is a recognized complication after orthotopic liver transplantation. Bisphosphonates are potent inhibitors of osteoclast bone resorption and have been successfully used to treat postmenopausal osteoporosis. We examined whether preoperative bone mineral density can predict the risk of fracture after orthotopic liver transplantation and whether intravenous bisphosphonate can prevent fractures in high-risk patients. Beginning in February 1993, standard bone mineral density measurements of the lumbar spine were performed as part of routine pretransplantation assessment. On the basis of a preliminary analysis from January 1995, patients with a lumbar spine bone mineral density of <0.84 g/cm2, or <84% of the predicted value (age/sex), were treated with intravenous bisphosphonate (pamidronate disodium) every 3 months before and for 9 months after liver transplantation. Bone mineral density measurements were available in 90 of 136 consecutive first transplants performed in our unit from February 1993 to September 1996. Before the use of pamidronate, 7 patients sustained symptomatic vertebral fractures. Their mean spine bone mineral density was lower than in the 38 patients with no clinical evidence of fracture (81.8% +/- 12.3% v 94.2% +/- 10.2%; P = .006). Since the introduction of pamidronate, no symptomatic vertebral fractures have occurred. Of 29 surviving patients with bone mineral density <0.84 g/cm2 before transplantation, 38% who did not receive treatment with pamidronate suffered spontaneous fracture, whereas 0 of 13 who received treatment suffered such a complication. A low lumbar spine bone mineral density is associated with a high risk of symptomatic vertebral fracture after liver transplantation. These results suggest that this risk is considerably reduced by the administration of intravenous bisphosphonate before and after transplantation.