title: Sirolimus and tacrolimus rather than cyclosporine A cause bone loss in healthy adult male rats.
abstract: The aim of this work was to study the effects of cyclosporine (CsA), tacrolimus (FK-506), and rapamycin (RAPA) on bone mass, femoral microstructure, femoral biomechanical properties, and bone remodeling in healthy adult male rats. Forty-eight 5-month-old male Wistar rats were used. CsA (2 mg/kg/day), FK-506 (3 mg/kg/day), RAPA (1.25 mg/kg/day), or water (0.5 ml/rat/day, control group) were administered orally for 3 months. After sacrifice, mean values of immunosuppressants in blood were: CsA (670.4 ng/ml), FK-506 (19.2 ng/ml), and RAPA (4.8 ng/ml). Levels of biochemical parameters were normal in all groups. Femoral BMD was decreased in FK-506 and RAPA groups and lumbar BMD in FK-506 group. Trabecular volume fraction (BV/TV) decreased only in FK-506 group. RAPA and CsA affected femoral cortical structure, but FK-506 did not. FK-506 produced an increase in bone remodeling, and CsA a decrease. FK-506 group showed a decrease in biomechanical parameters relative to all groups. RAPA group showed a decrease in ultimate stress vs control group, and CsA group presented an increase in biomechanical parameters versus control group. We found that administration of both RAPA and FK-506 as monotherapy for healthy rats produced osteopenia. CsA treatment only produces slight damages in the cortical zone of the femur.
authors.affiliation: Bioquímica Investigación, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rubert
authors.affiliation: Bioquímica Investigación, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Montero
authors.affiliation: Trabeculae, Technology Based Firm, Technological Park of Galicia, Ourense, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Guede
authors.affiliation: Traumatology and Orthopedic Surgery, University Hospital Complex of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Jose-Ramón
authors.initials: JR
authors.lastname: Caeiro
authors.affiliation: Bioquímica Investigación, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Martín-Fernández
authors.affiliation: Medicina Interna, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Curiel
authors.affiliation: Bioquímica Investigación, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: de la Piedra
keywords: Bone quality; Cyclosporine; Immunosuppressants; Osteopenia; Rapamycin; Tacrolimus