Better late than never? Experience with intravenous pamidronate treatment in patients with low bone mass or fractures following cardiac or liver transplantation

Abstract

 Organ transplantation is associated with a high turnover of bone metabolism, and an increased loss of bone mass and incidence of osteoporotic fractures. Established therapies for osteoporosis after organ transplantation are still lacking, however. We report on an intravenous bisphosphonate therapy initiated in transplant patients because of a high rate of bone loss or incident osteoporotic fractures. Twenty-one patients after liver transplantation and 13 patients after heart transplantation received 30 mg pamidronate intravenously every 3 months, combined with 1000 mg calcium and 1000 IU vitamin D per day. The median time interval between transplantation and start of pamidronate treatment was 1.9 years in cardiac patients and 2.3 years in liver patients. Lumbar spine bone mineral density (LS BMD) and femoral neck BMD (FN BMD) were measured before and every 6 months after pamidronate therapy was initiated. Spinal radiographs were performed annually. Biochemical markers of bone metabolism were determined every 3 months, immediately before pamidronate administration. From a previous observational study, 58 patients treated only with calcium and vitamin D were matched for age, sex, pretransplantation LS BMD and time interval between transplantation and the first pamidronate treatment. In the pamidronate-treated patients, the mean increase in LS BMD adjusted for baseline values amounted to 0.080 ± 0.038 g/cm² (8.6 ± 4.0 %) after 1 year and 0.091 ± 0.058 g/cm² (10.4 ± 6.1%) after 2 years compared with 0.001 ± 0.037 g/cm² (0.26 ± 4.0%) after 1 year and 0.015 ± 0.057 g/cm² (1.8 ± 6.0%) after 2 years in the historical control group (absolute LS BMD changes pamidronate group vs historical group p < 0.0001 after 1 and 2 years). The changes of FN BMD were 0.024 ± 0.043 g/cm² (3.2 ± 6.1%) after 1 year and 0.046 ± 0.052 g/cm² (7.0 ± 6.1%) after 2 years in the pamidronate group compared with −0.012 ± 0.043 g/cm² (−1.6 ± 6.1%) after 1 year and −0.013 ± 0.052 g/cm² (−1.1 ± 6.1%) after 2 years in the historical control group (absolute FN BMD changes pamidronate group vs historical group p=0.003 after 1 year and p=0.001 after 2 years). From a total of 287 application cycles of pamidronate treatment, no severe side effects were observed and non-severe side effects were seen in only 39 cycles (13.6%). We conclude that cyclic intravenous pamidronate treatment is beneficial to patients with low bone mass or osteoporotic fractures following transplant, even when not immediately initiated.