Bone quality in swine composite tissue allografts: effects of combination immunotherapy.
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.
Vossen
Marieke
M
Department of Surgery, University of Louisville, and Jewish Hospital, Louisville, KY 40202, USA.
Majzoub
Ramsey K
RK
Edelstein
Jean
J
Perez-Abadia
Gustavo
G
Voor
Michael
M
Maldonado
Claudio
C
Tecimer
Taskin
T
Jevans
Anthony W
AW
Zdichavsky
Marty
M
Frank
Johannes M
JM
Francois
Cedric
C
Kon
Moshe
M
Barker
John H
JH
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
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus