Prevention of bone loss after heart transplantation with antiresorptive therapy: A pilot study

Background: Heart transplantation, with its attendant glucocorticoid and cy closporine therapy, has deleterious effects on the skeleton. We have previo usly reported rapid bone loss and high fracture rates (36% of patients) dur ing the first year after heart transplantation. The bone loss was accompani ed by declines in serum 1,25-dihydroxyvitamin D and osteocalcin levels and increased urinary excretion of markers of bone resorption (hydroxyproline, pyridinoline, and deoxypyridinoline). We therefore investigated whether bon e loss could be prevented by bisphosphonates, agents that inhibit bone reso rption. Methods: Serial measurements of bone mineral density (BMD) and biochemical indexes of mineral metabolism were compared in 18 group A patients who rece ived a single intravenous infusion of pamidronate (60 mg) within 2 weeks of heart transplantation, followed by 4 cycles of oral etidronate (400 mg dai ly for 14 days every 3 months) and oral calcitriol 0.25 mu g daily, to thos e of 52 patients who previously underwent transplantation (group B) who did not receive antiresorptive therapy. Both groups received elemental calcium 1000 mg and vitamin D 400 IU daily Results: At 12 months after transplantation, there was virtually no lumbar spine bone loss in group A patients, whereas lumbar spine BMD had declined significantly in group B patients (0.2% +/- 0.9% vs 6.8% +/- 1.0%, respecti vely; P < .0001). Similarly, femoral neck BMD fell by 10.6% +/- 1.1% in gro up B patients and by only 2.7% +/- 1.4% in group A patients (P < .0001). Th ree incident vertebral fractures occurred in two group A patients, whereas 17 group B patients sustained 30 incident vertebral fractures, one hip frac ture and three episodes of rib fractures (P < .02; test of proportions). Wi th respect to markers of bone resorption, urinary deoxypyridinoline fell by 51% +/- 9% in group A patients and increased by 65% +/- 22% in group B pat ients by 3 months after transplantation (P < .0001). Conclusion: In summary, heart transplant recipients treated with bisphospho nates and replacement doses of calcitriol sustained less bone loss and fewe r fractures than those treated with calcium and vitamin D. We conclude that bisphosphonate therapy, in conjunction with calcitriol, shows promise for prevention of transplantation-related osteoporosis.