Secondary osteoporosis in liver transplant recipients: a longitudinal study in patients with and without cholestatic liver disease.
BACKGROUND
Metabolic bone disease is one of the major long-term complications in liver transplant recipients, but it remains unclear which patients are at highest risk for developing severe bone disease following transplantation.


METHODS
A total of 46 consecutive, adult patients with chronic liver disease accepted for a liver transplantation waiting list were prospectively included in the study. The patients were classified into two groups: group A--chronic cholestatic liver disease (n = 28), and group B--chronic non-cholestatic liver disease (n = 18). Bone mineral density (BMD) was measured at acceptance for the waiting list and at 3, 12 and 36 months following transplantation. Markers of bone turnover (serum-bone specific alkaline phosphatases (bALP), s-osteocalcin, s-1-collagen-C-terminal telopeptide (1-CTP) and urine N-terminal telopeptides u-Ntx) were measured at acceptance and at 3, 6, 12, 24 and 36 months following transplantation. BMD and markers of bone turnover were compared with similar values in a matched control group of 42 healthy individuals.


RESULTS
BMD decreased significantly during the early post-transplantation period (median bone loss femoral neck (FN) 3 months post-transplant 8.5%). BMD levels declined slightly from 3 to 12 months following transplantation and increased thereafter. The relative bone loss was greatest among group B patients (relative bone loss FN 3 months post-transplant: group A, 8% versus group B, 13%; P = 0.04). At 36 months, 8/17 group A and 2/9 group B patients had BMD levels that exceeded the pretransplant levels (P = 0.12). The early bone loss was positively correlated with an increase in resorption markers (s-1-CTP and u-Ntx). Group B had higher levels of both s-1-CTP and u-Ntx at 3 and 6 months post-transplant than group A patients (P = 0.03). Bone formation markers increased slowly from 6 months post-transplant and onwards. Relative bone loss was positively correlated to total glucocorticoid dose during the first 3 months post-transplant. There were no differences in BMD between patients receiving tacrolimus versus those receiving cyclosporin A.


CONCLUSIONS
Bone loss following liver transplantation is considerable in patients with both cholestatic and non-cholestatic liver disease, the first group has the poorest starting-point while the latter group has the greatest bone loss following transplantation. Bone loss is closely correlated with biochemical markers of bone resorption and total dose of glucocorticoids given post-transplant.
Section of Hepatology and Gastroenterology, Dept. of Medicine, Rikshospitalet, NO-0027 Oslo, Norway. kristian.bjoro@labmed.uio.no
K
K
Bjøro
B
B
Brandsaeter
K
K
Wiencke
T
T
Bjøro
K
K
Godang
J
J
Bollerslev
E
E
Schrumpf
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D002779:Cholestasis / Q000097:blood / Q000453:epidemiology / Q000628:therapy; D003094:Collagen / Q000097:blood / Q000187:drug effects; D024042:Collagen Type I; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005272:Femur Neck / Q000187:drug effects; D005500:Follow-Up Studies; D005542:Forearm; D050723:Fractures, Bone / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008107:Liver Diseases / Q000097:blood / Q000453:epidemiology / Q000628:therapy; D016031:Liver Transplantation; D008137:Longitudinal Studies; D008159:Lumbar Vertebrae / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D015675:Osteocalcin / Q000097:blood / Q000187:drug effects; D010024:Osteoporosis / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects; D010455:Peptides / Q000097:blood / Q000187:drug effects; D011183:Postoperative Complications / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D016019:Survival Analysis; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome; D014850:Waiting Lists
D015415:Biomarkers; D024042:Collagen Type I; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; C110762:glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine; D015675:Osteocalcin; D016572:Cyclosporine; D003094:Collagen; D000469:Alkaline Phosphatase; D016559:Tacrolimus