[Long-term stability of bone mineral density in patients with renal transplant treated with cyclosporine and low doses of corticoids. Protective role of cyclosporine?]

Abstract

Objectives: Cyclosporine has been thought to have a deleterious effect on bone in transplant recipients because of high turnover osteopenia observed in humans after transplantation. However, varying confounding factors such as renal and parathyroid function, cumulative steroid doses and previous exposure to aluminium, also play a role and hinder interpretation of the cyclosporine effect on bone mineral density (BMD).

Patients and methods: A 2-year prospective study was conducted to measure BMD starting 3 months after transplantation and bone remodeling markers from the first post-transplantation day in 52 kidney recipients with no prior exposure to aluminum. None of the patients experienced rejection and at 3 months all had good stable renal function (serum creatinine 137 mumol/l) and mildly elevated parathyroid hormone levels (1.5 times the upper limit of normal). All patients were given the same low dose steroid treatment (10 mg/day) and at 6 months cyclosporine was decreased from 7 to 4.8 mg/kg/day.

Results: BMD measured by double energy X-ray absorptiometry, (DEXA) and expressed in Z score, was moderately decreased at 3 months for the vertebrae (-1.40), the femoral neck (-1.34) and the ultradistal radius (-0.95) which have predominantly cancellous bone and was significantly less decreased (p < 0.05) for the lower third of the radius (-0.6) which is mainly cortical bone. BMD measurements were comparable at 6, 12 and 24 months. When measured by axial computerized tomography (ACT) BMD of the vertebrae showed a non-significant increase of Z score from -1.37 to -1.19 at 2 years. Bone remodeling markers was observed up to month 6 (from month 3 for osteocalcine and from month 1 for total and bone alkaline phosphatase and urinary pyridinoline), then returned to baseline levels at 2 years in parallel with decreased cyclosporine dosage. The increase of vertebral BMD measured by ACT at 1 year was correlated both to cyclosporine dose at 1 year and to bone alkaline phosphatase at 6 months.

Conclusion: Our data confirm the presence of moderate osteopenia 3 months after transplantation, predominantly in trabecular bone, logically linked to the initial high doses of corticosteroids. The long-term stability of BMD measured by DEXA and the correlation of vertebral BMD increase measured by ACT with cyclosporine dose and bone alkaline phosphate suggest that cyclosporine had a beneficial immunosuppressor effect by stimulating bone remodeling and thus counterbalancing the suppressive effect of corticosteroids.