Bone metabolism in renal transplant patients treated with cyclosporine or sirolimus.
Sirolimus is a new immunosuppressive agent used as treatment to prevent acute renal allograft rejection. One of the complications of renal transplantation and subsequent long-term immunosuppression is bone loss associated with osteoporosis and consequent fracture. Two open-label, randomized, phase 2 studies comparing sirolimus versus cyclosporine (CsA) included indices of bone metabolism as secondary end-points. Markers of bone turnover, serum osteocalcin and urinary N-telopeptides, were measured over a 1-year period in 115 patients receiving either CsA or sirolimus as a primary therapy in combination with azathioprine and glucocorticoids (study A) or mycophenolate mofetil (MMF) and glucocorticoids (study B). Urinary excretion of N-telopeptides and the concentrations of serum osteocalcin were consistently higher in the CsA-treated patients and significantly different at week 24 for N-telopeptides and at weeks 12, 24, and 52 for osteocalcin. In conclusion, future trials are warranted to test whether a sirolimus-based regimen conserves bone mineral density compared with a CsA-based regimen.
Campistol
Josep M
JM
Unidad de Transplante Renal, Hospital Clinic I Provincial, Barcelona, Spain. jmcampis@medicina.ub.es
Holt
David W
DW
Epstein
Solomon
S
Gioud-Paquet
Martine
M
Rutault
Karine
K
Burke
James T
JT
D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000097:blood; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010455:Peptides / Q000097:blood; D020123:Sirolimus / Q000009:adverse effects*
D024042:Collagen Type I; D007166:Immunosuppressive Agents; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D016572:Cyclosporine; D003094:Collagen; D002118:Calcium; D020123:Sirolimus