Influence of tacrolimus and short-duration prednisone on bone mineral density following liver transplantation.
BACKGROUND
Osteoporosis is a known complication of chronic prednisone use. Patients with end stage liver disease (ESLD) are prone to develop osteopenia and osteoporosis, and additional bone loss may occur with the use of immunosuppression agents after orthotopic liver transplant (OLT). The aim of this study was to determine the effect of tacrolimus (FK506) and short-duration (4 month) prednisone immunosuppression therapy on bone mineral density (BMD) after OLT of patients with cirrhotic ESLD.


METHODS
Forty-nine patients with cirrhotic ESLD (26 men, 23 women; median age 54 years) had dual energy x-ray absorptiometry preformed at baseline and 4 and 12 months after OLT. Immunosuppression therapy after OLT included a standard transplant protocol of daily tacrolimus to maintain plasma levels between 0.2 to 0.5 ng/mL and daily oral prednisone tapered over 4 months. BMD was measured at the lumbar spine (L-BMD) and left hip (hip BMD) and reported as raw density (g/cm2) and T score (standard deviations from gender-matched young healthy subjects). Results represent total hip measurements. Two-sided paired t test and analysis of variance methods were used for statistical comparisons.


RESULTS
Significant improvement in L-BMD was seen at 4 and 12 months. Hip BMD declined at 4 months but was stable thereafter between 4 and 12 months. BMD results did not differ between gender and liver disease types.


CONCLUSIONS
Tacrolimus and short-duration prednisone administration after OLT was not associated with bone loss at the lumbar spine at either 4 or 12 months. Significant bone loss occurred at the hip during the 4 months of prednisone administration after OLT but was stable thereafter. These findings suggest that immunosuppression protocols that use lower doses of prednisone administration over shorter time intervals may help prevent bone loss after OLT.
Scolapio
James S
JS
Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA. scolapio.james@mayo.edu
DeArment
Jennifer
J
Hurley
Daniel L
DL
Romano
Michele
M
Harnois
Denise
D
Weigand
Stephen D
SD
D015502:Absorptiometry, Photon; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000503:physiopathology; D006615:Hip; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008107:Liver Diseases / Q000503:physiopathology* / Q000628:therapy*; D016031:Liver Transplantation; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use; D012189:Retrospective Studies; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D013223:Statistics as Topic; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014815:Vitamins / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D020845:Selective Estrogen Receptor Modulators; D014815:Vitamins; D020849:Raloxifene Hydrochloride; D002118:Calcium; D011241:Prednisone; D016559:Tacrolimus