CYCLOSPORINE INDUCES HIGH BONE TURNOVER AND MAY CONTRIBUTE TO BONE LOSS AFTER HEART-TRANSPLANTATION

Cardiac transplantation has become a successful therapy for end-stage heart disease. However, increased bone loss has been observed in heart transplant recipients, sometimes being responsible for osteoporotic f ractures. Glucocorticoids cause dose-related bone loss, particularly i n the first 6-12 months of use, but cyclosporine might play a role as well. The evolution of bone mineral density (BMD) and biochemical para meters was prospectively assessed in 24 patients (mean age 52 years) f rom cardiac transplantation. All patients received cyclosporin A (CsA) and prednisone, the latter at decreasing dosage. The mean current dai ly dose of CsA was 321 mg and serum levels of CsA were constant. All p atients received calcium (500 mg day(-1)) and vitamin D (1000 U day(-1 )) for prevention of bone loss. BMD (g cm(-2)) was measured in 17 pati ents at the lumbar spine, femoral neck and total hip with dual energy X-ray absorptiometry every 6 months. Spinal BMD as well as neck and to tal hip BMD decreased at 6 and 12 months after transplantation, being statistically significant at the three sites: -5.6 and -3.4% for the l umbar spine, -9.3 and -8.5% for the femoral neck, -4.8% and -6.0% for the total hip respectively. Parathyroid hormone (PTH) and osteocalcin (BGP) increased by 90% and 800% respectively between pretransplantatio n values and 18 months after transplantation. BGP levels measured ever y 2 months from transplantation increased continuously from 8.7 mu g L (-1) (mean +/- SEM) before transplantation to 31.3 +/- 10.1 (P<0.05) a t 4 months, to 59.1 +/- 8.8 (P < 0.01) at 6 months and to 72.2 +/- 9.9 (P < 0.01) at 18 months (Kruskal-Wallis analysis: P<0.0001). PTH show ed a biphasic pattern with an initial decrease from 39.3 +/- 4.1 ng L( -1) baseline to at 22.0 +/- 2.8 ng L(-1) at 2 months, but increasing t hereafter to 45.9 +/- 5.7 at 6 months and 74.2 +/- 8.9 at 18 months (K ruskal-Wallis analysis: P<0.001). These variations represent a biochem ical profile remarkably different from that of glucocorticoid-induced osteoporosis. In summary, cardiac transplant patients lose bone immedi ately after transplantation at the spine and the hip. Later on, the lo ss in BMD discontinues at all sites of the skeleton, but predominantly at the spine, and a few patients still lose bone at the hip. This is probably a result of the high bone turnover either due to secondary hy perparathyroidism or induced by cyclosporin A.