Immunosuppressant use without bone loss - Implications for bone loss aftertransplantation

Cyclosporine A (CsA) is associated with posttransplantation bone disease. I mmunosuppressant drugs such as sirolimus (SRL), which are more potent and l ess deleterious than CsA, are being developed. Previous experiments have sh own that SRL although immunosuppressive, is relatively bone sparing. The us e of low doses of CsA and SRL in combination has displayed in vivo synergis m, This study was initiated to examine the effect of low-dose CsA and SRL o n bone metabolism, thereby hopefully providing a bone sparing immunosuppres sive regimen for transplant recipients. One hundred and nineteen rats were divided into groups: basal, vehicle, CsA high dose, CsA low dose, SRL low d ose, and combination low-dose CsA and SRL, The basal group was killed on da y 0 for histomorphometry, The experimental groups were weighed and bled on days 0, 28, 56, and 84 and were killed on day 84 for histomorphometry. Seri al assays for blood urea nitrogen (BUN), creatinine, and osteocalcin were p erformed. Osteocalcin was raised on days 28 and 56 in the high dose CsA gro up. Histomorphometry showed osteopenia with high-dose CsA, Low-dose CsA was relatively bone sparing, while low-dose SRL and combined low-dose CsA did not cause bone loss. In conclusion, the synergistic combination of low-dose CsA and SRL has the potential of providing both bone sparing and immunosup pressive benefits.