Efficacy of Pamidronate for Osteoporosis in Patients with Cystic Fibrosis following Lung Transplantation

Abstract

Lung transplantation with its attendant life-long immunosuppression contributes to bone loss and its sequelae, fractures and kyphosis, in patients with lung disease, many of whom already suffer from severe osteoporosis. Patients with cystic fibrosis (CF) are one of the most severely affected groups. We conducted a controlled, randomized, nonblinded trial of pamidronate (30 mg intravenously every 3 mo) with vitamin D (800 IU/d) and calcium (1 g/d) (n = 16) compared with vitamin D and calcium alone (n = 18, the control subjects) for 2 yr in 34 patients after lung transplant to improve bone mineral density (BMD). The treatment groups were similar in age, sex, baseline T-scores, renal function, hospitalization rates, immunosuppressant levels, change in lung function, and body mass index (BMI) over the study period. The patients treated with pamidronate gained 8.8 +/- 2.5% and 8.2 +/- 3.8% in spine and femur BMD after 2 yr in comparison to control subjects, who gained, on average (+/- SD), 2.6 +/- 3.2 and 0.3 +/- 2.2%, respectively (p </= 0.015 for both). Seven and six fractures occurred in the control and pamidronate groups, respectively (p > 0.2). Measures of bone resorption were highest immediately after lung transplant and improved with both pamidronate and time. Measures of bone formation were very poor after lung transplant, but recovered in the first post-lung transplant year irrespective of therapy. We conclude that pamidronate was more effective than control in improving bone mineral density after lung transplantation in patients with CF and appears to be one of the most promising agents studied to date for posttransplant osteoporosis.

Glucocorticoid-induced osteoporosis: a systematic review and cost-utility analysis

“…14,55 In a meta-analysis of 66 studies with BMD estimates in 2891 patients, bone loss at the spine and the hip was 11% greater than that expected for age and sex and 12% greater at the forearm.…”

“…In a third, 56 although patients received pamidronate prior to transplant, some already had vertebral fractures at baseline. In the fourth study, 55 at study entry the mean time since transplant was 4 months; 68% of subjects were osteoporotic by the WHO definition, and they were evenly distributed between treatment groups. In the study which compared pamidronate with calcitriol, 5 the mean baseline T-score was substantially lower in the calcitriol group (see Appendix 9, Table 124).…”

“…In the study which compared pamidronate with calcitriol, 5 the mean baseline T-score was substantially lower in the calcitriol group (see Appendix 9, Table 124). In three studies, all subjects received supplementary calcium at a daily dose of either 800 6 or 1000 mg. 5,55 In one study, 55 all subjects also received 800 IU of ergocalciferol (vitamin D 2 ) daily (see Appendix 9, Tables 122-124 for details).…”

Osteoporosis in chronic obstructive pulmonary disease

“…Another randomised, controlled, nonblinded trial compared the effect of 30 mg i.v. pamidronate every 3 months for 2 yrs with vitamin D (800 IU?day -1 ) and calcium supplements (1000 mg?day -1 ) with the same doses of vitamin D and calcium in 34 adults with cystic fibrosis following lung transplantation [134]. Post-transplantation patients received immunosuppressants which included cyclosporin A, prednisolone and azathioprine.…”

Medical complications of lung transplantation

“…More limited data exist supporting the benefits of bisphosphonates in the lung transplant population. A prospective, randomised, controlled trial comparing the efficacy of pamidronate, calcium and vitamin D with calcium and vitamin D alone, in CF patients with osteoporosis who had undergone LTx, demonstrated greater BMD at the end of 2 yrs in the pamidronate-treated group but no difference in fracture rates [61]. A second prospective, uncontrolled trial involving 45 lung transplant recipients showed that the addition of pamidronate to calcium, vitamin D and hormonal replacement therapy (as indicated), stabilised BMD more effectively and reduced the rate of fractures compared with historical controls [62].…”