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Conversion of Immunosuppressive Monotherapy from Cyclosporin A to Tacrolimus Reverses Bone Loss in Rats

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Abstract

Tacrolimus is used for transplant patients with refractory graft rejection and those with intolerance to cyclosporin (CsA), without the disfiguring adverse effects frequently attributed to CsA therapy. Since we have shown that CsA-associated bone loss can also affect alveolar bone, the purpose of this study was to evaluate the effects of conversion of monotherapy from CsA to tacrolimus on alveolar bone loss in rats. Groups of rats were treated with either CsA (10 mg/kg/day, s.c.), tacrolimus (1 mg/kg/day, s.c.), or drug vehicle for 60 and 120 days, and an additional group received CsA for 60 days followed by conversion to tacrolimus for a further 60-day period. Bone-specific alkaline phosphatase (BALP), tartrate-resistent acid phosphatase (TRAP-5b), calcium (Ca2+), interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) concentrations were evaluated in the serum. Analyses of bone volume, bone surface, number of osteblasts, and osteoclasts were performed. Treatment with CsA for either 60 or 120 days was associated with bone resorption, represented by lower bone volume and increased number of osteoclasts; serum BALP, TRAP-5b, IL-1β, IL-6, and TNF-α were also higher in these animals. After conversion from CsA to tacrolimus, all the altered serum markers returned to control values in addition to a significant increase of bone volume and a lower number of osteoclasts. This study shows that conversion from CsA to tacrolimus therapy leads to a reversal of the CsA-induced bone loss, which can probably be mediated by downregulation of IL-1β, IL-6, and TNF-α production.

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Authors and Affiliations

  1. Department of Physiology and Pathology, Dental School of Araraquara, State University of São Paulo, Rua Humaitá 1680, CEP 14901-803, Araraquara, São Paulo, Brazil

    Luís C. Spolidorio & Denise M. P. Spolidorio

  2. Department of Diagnostics and Surgery, Dental School of Araraquara, State University of São Paulo, Rua Humaitá 1680, CEP 14901-803, Araraquara, São Paulo, Brazil

    Patricia O. Nassar & Carlos A. Nassar

  3. Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, CEP 05508-900, São Paulo, São Paulo, Brazil

    Marcelo N. Muscará

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  1. Luís C. Spolidorio
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  2. Patricia O. Nassar
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  3. Carlos A. Nassar
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  4. Denise M. P. Spolidorio
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  5. Marcelo N. Muscará
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Correspondence to Luís C. Spolidorio.

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Spolidorio, L.C., Nassar, P.O., Nassar, C.A. et al. Conversion of Immunosuppressive Monotherapy from Cyclosporin A to Tacrolimus Reverses Bone Loss in Rats. Calcif Tissue Int 81, 114–123 (2007). https://doi.org/10.1007/s00223-007-9040-2

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