Impact of sirolimus, tacrolimus and mycophenolate mofetil on osteoclastogenesis--implications for post-transplantation bone disease.
Nephrol Dial Transplant
; 26(12): 4115-23, 2011 Dec.
Article
en En
| MEDLINE
| ID: mdl-21622987
BACKGROUND: Post-transplantation bone disease is associated with a high degree of morbidity including pain and fractures. Glucocorticoid-induced osteoporosis on top of pre-existing renal osteodystrophy is considered the major pathogenic factor, while the role of non-glucocorticoid immunosuppressants is less well defined. METHODS: In this study, we investigated the influence of sirolimus (SRL) versus calcineurin inhibitor (CI)-based immunosuppressive regimens on biomarkers of bone resorption in renal transplant patients. In addition, the impact of SRL, tacrolimus and mycophenolate mofetil (MMF) on osteoclast activation and function was assessed in cell culture systems. RESULTS: Using this approach, we demonstrated reduced serum levels of bone resorption markers in patients treated with SRL after kidney transplantation compared to a CI-based regimen. In line with this observation, we detected profoundly reduced osteoclast differentiation and subsequently diminished hydroxyapatite resorption in the presence of SRL compared to MMF and tacrolimus in vitro. Moreover, SRL significantly reduced osteoclast precursor proliferation in vitro compared to tacrolimus and led to augmented apoptosis in osteoclast precursors. CONCLUSIONS: Taken together, SRL was shown to inhibit osteoclast formation in vivo and in vitro. SRL thus may have the potential to balance osteoclast promoting effects of glucocorticoids and CI, thereby counteracting the development of accelerated osteoporosis in renal transplant recipients.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoclastos
/
Trasplante de Riñón
/
Tacrolimus
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Sirolimus
/
Inmunosupresores
/
Ácido Micofenólico
Tipo de estudio:
Etiology_studies
/
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Límite:
Adult
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Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Nephrol Dial Transplant
Asunto de la revista:
NEFROLOGIA
/
TRANSPLANTE
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Reino Unido