What is the role of rapamycin in the pathogenesis of organ transplantation-related osteoporosis?

Updated: Jul 02, 2020
  • Author: Carmel M Fratianni, MD, FACE; Chief Editor: George T Griffing, MD  more...
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Answer

Answer

Rapamycin inhibits downstream signaling from the mammalian target of rapamycin (mTOR) proteins, a signaling pathway promoting tumor growth. Rapamycin binds to the FK506 binding protein, and this complex then binds to mTOR and prevents interaction of mTOR with target proteins in the signaling pathway. Short-term administration of rapamycin causes no trabecular bone loss and potentially has bone-sparing effects. [62]

Two open-label, randomized, phase-2 studies comparing sirolimus versus cyclosporine examined bone metabolism with markers of bone turnover, osteocalcin, and urinary N-telopeptides measured over a 1-year period in 115 patients receiving CsA or sirolimus with azathioprine and glucocorticoids or mycophenolate with glucocorticoids. In the patients treated with CsA, serum osteocalcin and urine N-telopeptides were consistently higher compared with those receiving sirolimus. [63]


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