Osteoporosis and Bone Mineral Metabolism Disorders in Cirrhotic Patients Referred for Orthotopic Liver Transplantation

Abstract

The purpose of this study was to determine the prevalence of osteoporosis, to estimate the bone turnover and hormonal status, and to identify 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 primary biliary cirrhosis, 14 with alcoholic cirrhosis, and 38 with posthepatitic cirrhosis), who were referred for orthotopic liver transplantation. Patients, excluding those with primary biliary cirrhosis, were classified in Child-Pugh groups according to the severity of liver disease (class B [28 patients], class C [24 patients]). Biochemical parameters of bone mineral metabolism and standard liver function tests were measured in all patients. Additionally, serum osteocalcin, urinary hydroxyproline/creatinine ratio, serum intact parathyroid hormone, serum 25-hydroxyvitamin D, serum 1,25-dihydroxyvitamin D, follicle-stimulating hormone, and luteinizing hormone levels were determined in patients and controls within the same age range. Plasma testosterone, sex hormone-binding globulin levels, and free testosterone index were obtained for all men included in the study. Bone mass of the lumbar spine and 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 vertebral 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 bone 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 lower 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 differences between Child-Pugh groups. Alcoholic Child-Pugh C patients showed 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 gonadotropin 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 cirrhotic patients. Reduced bone formation and significant disorders of bone mineral metabolism, such as vitamin D deficiency, reduced p...

Disturbances of parathyroid hormone–vitamin D axis in non-cholestatic chronic liver disease: a cross-sectional study

“…This finding is similar to the observations of other studies [15,20]. In our series, 61 patients with CLD had vitamin D levels less than 80 nmol/l, but only in 6 (9.8%) patients the serum PTH level was increased ([6.8 pmol/l).…”

“…Previous studies have shown inconsistent results about the correlation between serum vitamin D level and the severity of liver dysfunction. Our results are in line [3,19] with some studies, and in contradiction to some other studies [16,20]. Our study also showed a significant correlation between low serum vitamin D level and markers of liver function insufficiency including coagulopathy, hypoalbuminemia, hyperbilirubinemia, and thrombocytopenia, in agreement with other studies [21][22][23].…”

Osteoporosis after liver transplantation

“…51 There have been relatively few studies of changes in sex hormone status following liver transplantation and those that exist are confined to men. An increase in free testosterone following transplantation has been a common finding in these studies, although recovery to normal levels is not achieved in all patients.…”

“…Although this may occur in patients with chronic liver disease, it is rare. 52 Conversely vitamin D insufficiency, in which lesser degrees of deficiency result in secondary hyperparathyroidism and bone loss, 53 is commonly associated with chronic liver disease 50,51,54,55 and may contribute to post-transplantation osteoporosis. Prospective studies indicate that serum 25-hydroxyvitamin D levels, which reflect vitamin D status, tend to increase with time after transplantation, 15,23,33 and in the study of Feller et al 27 significantly higher serum 25-hydroxyvitamin D levels were noted at a mean of 85 months follow-up than prior to transplantation; however, serum 1,25-dihydroxyvitamin D levels, which were normal at baseline, did not change during the follow-up period.…”

“…Thus in some studies, the changes were predominantly those of low bone turnover and reduced bone formation at the cellular level, 30,59,60 whilst others have also reported evidence of increased turnover and resorption. [61][62][63][64] Biochemical markers of bone formation have been reported to be decreased 51 or normal 55 and resorption markers increased. 51,55 The heterogeneity observed in the histological characteristics is likely to reflect a number of factors including differences in the underlying liver disease and its severity, the prevalence of vitamin D deficiency and secondary hyperparathyroidism, and the presence or absence of glucocorticoid therapy.…”