title: Bone quality in swine composite tissue allografts: effects of combination immunotherapy.
abstract: BACKGROUND
  Tacrolimus (FK506)/mycophenolate mofetil (MMF)/prednisone combination immunosuppression therapy has been found to effectively prevent composite tissue allograft (CTA) rejection with minimal toxicity in a preclinical porcine model. These findings have been reproduced in 24 human hands transplanted in 18 patients. In CTAs containing bone, adequate bone quality and healing are essential for long-term functional success. The purpose of this study was to determine the effect FK506/MMF/prednisone immunotherapy has on bone quality and healing.
  
  
  METHODS
  Forelimb CTA-flaps were transplanted in nine pigs. Recipient animals received FK506/MMF/prednisone therapy for 3 months. Bone quality was studied pre- and posttransplant by measuring acoustic velocity and density and by calculating elastic coefficients. Additional bone quality analyses were performed on unoperated limbs, and in bone grafts from two pigs that had autograft procedures performed. Bone healing was assessed using radiographic analysis.
  
  
  RESULTS
  Three animals were lost to immunosuppression-related complications before the endpoint of the study. The bone component of all six CTA-flaps showed normal healing. Although results of the bone density measurements were not significantly different when comparing pre- to posttransplant values, acoustic velocity and elastic coefficient measurements showed a significant decrease posttransplant indicating a decrease in bone quality.
  
  
  CONCLUSIONS
  FK506/MMF/prednisone combination therapy prevented rejection, did not adversely affect bone quality, and showed normal bone healing. The transplant procedure itself decreased bone quality more than the immunosuppression regimen did over the observation period in this study. Based on these findings, we conclude to prevent CTA failure it is important to monitor bone quality posttransplant.
authors.affiliation: Department of Surgery, University of Louisville, and Jewish Hospital, Louisville, KY 40202, USA.
authors.forename: Marieke
authors.initials: M
authors.lastname: Vossen
authors.forename: Ramsey K
authors.initials: RK
authors.lastname: Majzoub
authors.forename: Jean
authors.initials: J
authors.lastname: Edelstein
authors.forename: Gustavo
authors.initials: G
authors.lastname: Perez-Abadia
authors.forename: Michael
authors.initials: M
authors.lastname: Voor
authors.forename: Claudio
authors.initials: C
authors.lastname: Maldonado
authors.forename: Taskin
authors.initials: T
authors.lastname: Tecimer
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Jevans
authors.forename: Marty
authors.initials: M
authors.lastname: Zdichavsky
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Frank
authors.forename: Cedric
authors.initials: C
authors.lastname: Francois
authors.forename: Moshe
authors.initials: M
authors.lastname: Kon
authors.forename: John H
authors.initials: JH
authors.lastname: Barker
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005552:Forelimb / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D005938:Glucocorticoids / Q000494:pharmacology*; D006084:Graft Rejection / Q000000981:diagnostic imaging / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007167:Immunotherapy / Q000379:methods*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011241:Prednisone / Q000494:pharmacology; D011859:Radiography; D013552:Swine; D016559:Tacrolimus / Q000494:pharmacology; D014184:Transplantation, Homologous; D014463:Ultrasonography; D014945:Wound Healing / Q000187:drug effects
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus