Objectives.  The prevalence of osteoporosis amongst patients with primary biliary cirrhosis (PBC) is high and may be a serious clinical problem. Hormone replacement therapy (HRT) is effective in preventing bone loss but has not been evaluated in randomized trials in PBC. The primary aim was to study the effect of transdermal HRT in combination with daily vitamin D and calcium supplementation on bone loss compared with vitamin D and calcium supplementation only in postmenopausal women with PBC. The secondary aim was to study the safety of transdermal HRT.

OBJECTIVE:Patients with chronic liver disease (CLD) have an increased prevalence of osteoporosis. The aim of this study was to evaluate prospectively the rate of bone loss and potential predictors of increased bone loss in a cohort of patients with CLD. DESIGN:Bone mineral density (BMD) was measured at baseline and at follow-up by dual-energy X-ray absorptiometry at the lumbar spine and the femoral neck. RESULTS:Forty-three patients (31 female, 12 male) were available for a second measurement of BMD, with a median of 25 months (range 18-41) between the measurements. Mean annual bone loss at the lumbar spine and the femoral neck, respectively, was 0.6 +/- 2.0% and 1.5 +/- 2.4% in females and 0.8 +/- 1.9% and 2.9 +/- 2.0% in males. The BMD Z score decreased significantly over time at the femoral neck (P = 0.005 and P = 0.02 for females and males, respectively). Bone loss was increased significantly at the lumbar spine in patients classified as Child-Pugh B + C compared with those classified as Child-Pugh A (P = 0.04). Serum levels of bilirubin correlated independently and positively, and 25-hydroxy vitamin D3 levels negatively, with bone loss at the femoral neck. CONCLUSIONS:Patients with CLD have increased bone loss at the femoral neck. Advanced liver disease is associated with increased bone loss, and hyperbilirubinaemia and low levels of vitamin D3 are predictors of increased bone loss.

OBJECTIVES/DESIGN:Increased rate of bone loss has been reported in women with primary biliary cirrhosis (PBC) and varying degree of liver dysfunction. Whether bone loss is increased in patients without liver dysfunction is unclear. The aim of this study was to estimate retrospectively the rate of bone loss in postmenopausal women with PBC and well-preserved liver function.SUBJECTS/INTERVENTIONS:Forty-three women with PBC, and classified as Child-Pugh class A, were included. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry at the lumbar spine and the femoral neck.RESULTS:Median time between measurements of BMD was 26 months (range, 12-48 months). Twenty women were not receiving any bone protective treatment, i.e. hormone replacement therapy (HRT), bisphosphonates or vitamin D/calcium supplementation, whilst 23 women received such treatment. Mean annual bone loss in the former group was 0.38 +/- 2.56% and 0.42 +/- 2.29% at the lumbar spine and the femoral neck, respectively. Women receiving treatment, however, increased their BMD by 1.92 +/- 3.76% and 0.15 +/- 2.75% at the lumbar spine and the femoral neck, respectively. At the lumbar spine the difference with regard to changes in BMD between untreated and treated women was statistically significant (P = 0.02). Women who received HRT (n = 11) increased their BMD at the lumbar spine by 2.95 +/- 3.91%, P = 0.03 when compared with untreated women.CONCLUSION:Bone loss in postmenopausal women with PBC and well-preserved liver function is not increased above normal. Treatment with bone protective treatment, mainly HRT, improves BMD at the lumbar spine.

Background and Aim: The pathophysiology of osteoporosis complicating chronic liver disease is unknown. Recent animal studies have found leptin to be a potent inhibitor of bone formation. The aim of this study was to investigate the relationship between serum leptin levels and bone mineral density in patients with chronic liver disease.

BACKGROUND/AIMS:Insulin-like growth factor-I (IGF-I) levels are low in patients with chronic liver disease (CLD) and have been found to correlate with measurements of bone mineral density (BMD) in men with viral cirrhosis. The aim of this study was to investigate the relationship between circulating IGF-I levels and BMD in patients with CLD of other causes.METHODS:Fifty-eight patients with CLD were included. Age- and sex-matched normal individuals served as controls. Serum levels of IGF-I and IGF-II and their binding proteins (IGFBP-1-3) were measured by radioimmunoassay. BMD was measured by dual energy X-ray absorptiometry.RESULTS:IGF-I levels were 57+/-33 and 136+/-48 ng/ml; p<0.0001 in patients and controls, respectively. IGF-II and IGFBP-3 levels were lower (p<0.0001) and IGFBP-1 and IGFBP-2 levels were higher in patients compared with controls (p<0.0005 and p<0.0001, respectively). All growth factors, except for IGFBP-2, correlated with parameters of liver function. In a multiple regression analysis, adjusting for age, no correlation was found between IGF-I, IGF-II, IGFBP-1-3 and BMD in either patients or controls.CONCLUSION:Patients with CLD have low levels of IGF-I, IGF-II and IGFBP-3 that correlate with liver function. No relationship was found between low levels of growth factors and BMD.

Background/Aims: Metabolic bone disease is known to complicate chronic liver disease. In a cross-sectional, controlled study we have studied the prevalence of osteoporosis in patients with various types of chronic liver disease. We also identified risk factors predisposing to osteoporosis in this patient group.Methods: Seventy-two hospitalised patients, 46 females and 26 males, were included. Age- and sex-matched individuals from the background population served as controls. Bone mineral density was measured by dual energy X-ray absorptiometry at the lumbar spine and femoral neck,Results: Bone mineral density was significantly lower in patients with chronic liver disease than in controls at the lumbar spine (Z-score: -0.35 SD+/-1.36 vs, 0.26 SD+/-1.19, p<0.01) but not at the femoral neck (Z-score: -0.18 SD+/-1.48 vs. 0.17 SD+/-1.08, NS). Patients with cholestatic chronic liver disease did not have lower bone mineral density compared with patients with non-cholestatic chronic liver disease (Z-score: -0.35 SD+/-1.30 vs. -0.34 SD+/-1.45). Osteoporosis was found in 30% of the patients and 15% of the controls, respectively. In a multivariate regression analysis on risk factors in the patient group, the following factors were associated with osteoporosis: use of corticosteroids (odds ratio=18.9; p<0.01), low body mass index (odds ratio=14,1; p=0,001), high age and female sex,Conclusion: Patients with chronic liver disease are at risk of developing osteoporosis. Risk factors for osteoporosis in chronic liver disease are low body mass index and corticosteroid therapy, in addition to high age and female sex, Cholestatic liver disease per se is not associated with an increased risk for osteoporosis.