Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):941-6.

Randomised controlled trial, parallel design, trial duration 2 years.

Single centre, university hospital, USA; Inclusion criteria:- CF, 1 to 12 months post-lung transplantation, ambulatory; Exclusion criteria:- primary graft failure or other post-operative morbidities that precluded long-term survival, renal insufficiency (serum creatinine > 3.0 mg/dl), or pregnancy; N = 34 (16 in treatment group); 17 female (7 in treatment group). Groups similar in age, gender, baseline T-scores, renal function, hospitalisation rates, immunosuppressant levels, change in lung function and body mass index over study period. 13 in treatment group and 12 controls had baseline T-scores < -2.5 at a minimum of one site; all other -1 < T < -2.5 at a minimum of one site. Treatment group: mean (SD) age 27.5 years (6.6 years); control group mean (SD) age 29.1 years (6.4 years).

Intravenous pamidronate (30 mg every 3 months) for study duration of 2 years; All participants received oral vitamin D (800IU/day) and oral calcium (1g/day).

Primary outcome: BMD (spine; 0, 6, 12, 18, 24 months; DXA Hologic QDR 1000/W Waltham MA). Bone biomarkers (serum osteocalcin, urine cross-linked N-telopeptides of type 1 collagen, urine free deoxypyridinoline; 0, 3, 12, 24 months; also 2, 14 days after first pamidronate infusion in intervention group); Serum calcium, vitamin D (25-hydroxyvitamin D, 1,25-dihydroxyvitamin D) and PTH levels (0, 3, 12, 24 months); Survival. Withdrawals; Secondary outcomes: BMD (femur; 0, 6, 12, 18, 24 months; DXA Hologic QDR 1000/W Waltham MA); Kyphosis angles (degrees; 0, 24 months; thoracic spine curvature using lateral chest radiographs using a modification of method of Cobb); Adverse events (number during study; thrombophlebitis, cellulitis, bone pain, fever, hypocalcaemia defined as serum calcium < 7.8 mg/dl, hypervitaminosis defined as serum 25-hydroxyvitamin D > 55 ng/ml); New fractures (number of fractures during study; long bone using clinical data, rib using posteroanterior chest radiographs, vertebral using lateral chest radiographs);

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 0.2). 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

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.