Intravenous Pamidronate as Treatment for Osteoporosis after Heart Transplantation: A Prospective Study

Abstract

Fractures due to osteoporosis are one of the major complications after heart transplantation, occurring mostly during the first 6 months after the graft, with an incidence ranging from 18% to 50% for vertebral fractures. Bone mineral density (BMD) decreases dramatically following the graft, at trabecular sites as well as cortical sites. This is explained by the relatively high doses of glucocorticoids used during the months following the graft, and by a long-term increase of bone turnover which is probably due to cyclosporine. There is some evidence for a beneficial effect on BMD of antiresorptive treatments after heart transplantation. The aim of this study was to assess prospectively the effect on BMD of a 3-year treatment of quarterly infusions of 60 mg of pamidronate, combined with 1 g calcium and 1000 U vitamin D per day, in osteoporotic heart transplant recipients, and that of a treatment with calcium and vitamin D in heart transplant recipients with no osteoporosis. BMD of the lumbar spine and the femoral neck was measured by dual-energy X-ray absorptiometry in all patients every 6 months for 2 years and after 3 years. Seventeen patients, (1 woman, 16 men) aged 46+/-4 years (mean +/- SEM) received only calcium and vitamin D. A significant decrease in BMD was observed after 6 months following the graft, at the lumbar spine (- 6.6%) as well as at the femoral neck (-7.8%). After 2 years, BMD tended to recover at the lumbar spine, whereas the loss persisted after 3 years at the femoral neck. Eleven patients (1 woman and 10 men) aged 46+/-4 years (mean +/- SEM) started treatment with pamidronate on average 6 months after the graft, because they had osteoporosis of the lumbar spine and/or femoral neck (BMD T-score below -2.5 SD). Over the whole treatment period, a continuous increase in BMD at the lumbar spine was noticed, reaching 18.3% after 3 years (14.3% compared with the BMD at the time of the graft). BMD at the femoral neck was lowered in the first year by -3.4%, but recovered totally after 3 years of treatment. In conclusion, a 3-year study of treatment with pamidronate given every 3 months to patients with existing osteoporosis led to a significant increase in lumbar spine BMD and prevented loss at the femoral neck. However, since some of these patients were treated up to 14 months after the transplant, they may already have passed through the phase of most rapid bone loss. In patients who were not osteoporotic at baseline, treatment with calcium and vitamin D alone was not able to prevent the rapid bone loss that occurs immediately 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

“…In agreement with findings after solid-organ transplantation (Henderson et al, 1995;Ninkovic et al, 2000;Kreig et al, 2001), our results demonstrated a significant early decline in BMD at the femoral neck (but not the lumbar spine), which persisted for at least 2 years in recipients following autoSCT. There was also a significant early reduction in BMD at the trochanter but, by 2 years, the BMD at this site had returned to baseline values.…”

“…Significant reductions in vertebral and non-vertebral fracture rates in postmenopausal women have been reported after only 1 year of treatment (Ensrud et al, 1997;Harris et al, 1999;Pols et al, 1999). 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).…”

“…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.…”

Post-transplantation osteoporosis

“…In the second year after cardiac transplantation, BMD remained stable, although alendronate and calcitriol were discontinued (44). Similarly, studies demonstrated the efficacy of intravenous ibandronate, zolendronic acid and of pamidronate in the prevention of bone loss after renal, heart, lung, liver and bone marrow transplant recipients, independent of the time following transplantation (23, 40,41,45,46).…”

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).…”