OSTEOPOROSIS AND BONE-MINERAL METABOLISM DISORDERS IN CIRRHOTIC-PATIENTS REFERRED FOR ORTHOTOPIC LIVER-TRANSPLANTATION

The purpose of this study was to determine the prevalence of osteoporo sis, to estimate the bone turnover and hormonal status, and to identif y the factors associated with bone disease in patients with end-stage liver disease who were referred for orthotopic liver transplantation. A prospective study was performed on 58 cirrhotic patients (6 with pri mary biliary cirrhosis, 14 with alcoholic cirrhosis, and 38 with posth epatitic cirrhosis), who were referred for orthotopic liver transplant ation. Patients, excluding those with primary biliary cirrhosis, were classified in Child-Pugh groups according to the severity of liver dis ease (class B [28 patients], class C [24 patients]). Biochemical param eters of bone mineral metabolism and standard liver function tests wer e measured in all patients. Additionally, serum osteocalcin, urinary h ydroxyproline/creatinine ratio, serum intact parathyroid hormone, seru m 25-hydroxy-vitamin D, serum 1,25-dihydroxyvitamin D, follicle-stimul ating hormone, and luteinizing hormone levels were determined in patie nts and controls within the same age range. Plasma testosterone, sex h ormone-binding globulin levels, and free testosterone index were obtai ned for all men included in the study. Bone mass of the lumbar spine a nd femur were measured by dual X-ray absorptiometry (DPX-L), and were expressed as a standard deviation of mean values (Z-score) from a sex and age-matched control group. Spinal X-rays were obtained to assess v ertebral fractures. Osteoporosis was considered as a factor in spinal bone mineral density with a Z-score below 2 or at least one vertebral fracture.Twenty-five patients (43%) had osteoporosis, with lower bone mass measurements in the lumbar spine than in the femoral neck (P < 0. 005). Alcoholic and Child-Pugh C patients showed the lowest femoral bo ne mineral density values. Cirrhotic patients showed lower osteocalcin levels than controls (14.3 +/- 5.9 vs. 18.2 +/- 8.1 ng/ml; P < 0.05) and showed increased urinary hydroxyproline (125.1 +/- 51.5 vs. 107.9 +/- 26.6 nM/mg creatinine; P < 0.05). Serum 25-hydroxyvitamin D, 1,25- dihydroxyvitamin D and parathyroid hormone levels were significantly l ower in cirrhotic patients than in controls (10.3 +/- 9.1 vs. 23.1 +/- 26.6 ng/ml; P = 0.000), (12.9 +/- 9.1 vs. 48.3 +/- 11.5 pg/ml; P = 0. 000), (16.6 +/- 9.2 vs. 27.9 +/- 8.2 pg/ml; P = 0.000), with no differ ences between Child-Pugh groups. Alcoholic Child-Pugh C patients showe d the lowest 25-hydroxyvitamin D serum values (4.5 +/- 2.2 ng/ml; P < 0.05). Male patients had lower testosterone levels than controls (302. 5 +/- 229.4 vs. 556.7 +/- 146.5 ng/dl; P = 0.000), with increased sex hormone-binding globulin values. Levels of testosterone and gonadotrop in were related to Child-Pugh classification. No correlation was found between bone mass and hormonal values. A significant decrease in bone mass, particularly in the lumbar spine, is seen in end-stage cirrhoti c patients. Reduced bone formation and significant disorders of bone m ineral metabolism, such as vitamin D deficiency, reduced parathyroid h ormone levels, and hypogonadism are involved. Moreover, severity and e tiology of the liver disease are the main risk factors for developing bone loss and mineral metabolism disorders in patients referred for or thotopic liver transplantation.