Cyclosporine bone remodeling effect prevents steroid osteopenia after kidney transplantation

Background It is well established that prednisone above 7.5 mg/day may indu ce osteopenia in association with decreased bone formation. In contrast, th e effect of cyclosporine on bone remodeling and bone mineral density (BMD) is controversial. Multiple confounding factors explain this controversy, es pecially after renal transplantation. Methods. Fifty-two renal transplanted patients never exposed to aluminum wh ile on dialysis were selected because they had no rejection and no hypercal cemia for 24 months while being treated with low dose prednisone/cyclospori ne A (daily dose at 10 mg and 4.8 mg/kg, respectively, beyond 3 months). Bo ne remodeling markers (BRMs; plasma osteocalcin, bone and total alkaline ph osphatases for formation, and urinary pyridinolines for resorption) were se quentially measured together with plasma creatinine, intact parathyroid hor mone (PTH) and 25 OH vitamin D and cyclosporine from day 0 to 24 months. BM D was measured at 3, 6, 12, and 24 months by quantitative computerized tomo graphy (QCT) at the lumbar spine and by double-energy x-ray absorptiometry (DEXA) at this site, as well as at the femoral neck, radius shaft, and ultr adistal (UD) radius. Results. Plasma concentrations of creatinine, PTH, and 25 OH vitamin D init ially decreased and stabilized beyond three months at 137 mu mol/L, 1.5 the upper limit of normal (ULN) and 11 ng/mL, respectively. All BRM increased significantly above the ULN at six months and then decreased. The BMD Z sco re at three months was low at all sites measured by DEXA and QCT. Follow-up measurements showed stability of absolute value and of Z score at all site s measured by DEXA. A comparison of the lumbar QCT Z score, which was avail able in 42 patients at 3 and 24 months, showed an increase in 28 and a decr ease in 14, so that the increase for the whole group was significant (P < 0 .04). Compared with patients with a decreased Z score, those with an increa sed Z score had significantly higher cyclosporine and lower prednisone dosa ges and a greater BRM increase at six months, whereas age, sex ratio, and p lasma creatinine, PTH and 25 OH vitamin D were comparable and stable from m onths 3 through 24. The mean trough level of cyclosporine for the first six months was positively correlated to osteocalcin and total alkaline phospha tase increase at six months, and both bone formation and resorption marker increases were significantly correlated to the lumbar QCT Z score increase at 24 months. Conclusions. Combined low-dose prednisone and cyclosporine immunosuppressio n are associated with a stabilization of BMD measured at all sites with DEX A 3 to 24 months after renal transplantation and with a prevention of age-r elated loss of vertebral trabecular bone, as shown by the significant incre ase in lumbar spine QCT Z score. It is suggested that cyclosporine, togethe r with the decrease of prednisone dosage but independent of renal function, PTH, and vitamin D status, contributes to a transient stimulation of bone remodeling at six months, which counterbalances the deleterious effect of p rednisone on bone formation and BMD.