Project:

Metabolic bone diseases in patients with advanced liver disease

Mentor (Advisor):

Assoc. Prof. Ludmila Brunerová M.D. Ph.D.

Department:

Internal Department, Faculty Hospital Kralovske Vinohrady and 3rd Faculty of Medicine, Charles University, Prague

Contact information:

Ludmila.brunerova@fnkv.cz, 26716 2758

Project Narrative:

Introduction

Liver diseases represent an established risk factor for low bone mineral density (BMD) and fractures. Osteoporosis is frequent complication in patients with chronic liver diseases, particularly liver cirrhosis, chronic cholestasis, hemochromatosis and alcoholic liver disease and affects up to 30% of this population. The mechanism of bone involvement is complex with negative impact of cholestasis, alcohol, iron overload, low vitamin D, malnutrition and steroids on bone formation. In accordance with current EASL guidelines (European Association for Study of the Liver), all the patients with liver disease should be examined by densitometry in case they have history of fragility fracture, more than 3 months treatment with ≥ 5 mg prednison/equivalent, cholestatic liver disease (bilirubin ≥ 3 UNL for more than 6 months), liver cirrhosis or any other risk factor for osteoporosis (postmenopausal, premature menopause/before 45 years of age, secondary amenorhea for more than 6 months, male hypogonadism, low BMI (less than 19kg/m²), smoking), hemochromatosis, alcohol abuse and finally before and after liver transplantation.

Currently, no data on the occurrence of bone disease in patients with liver diseases in Czechia is available.

Therapeutic effect (increase in BMD) of bisphosphonates and denosumab was confirmed only in small cohorts, however, limited data is available for teriparatide and romosozumab. The aim of the study is:

1. To assess the prevalence of densitometry-derived osteoporosis/osteopenia in patients from hepatologic outpatient with significant fibrosis (METAVIR/fibroscan > 2) and of other metabolic bone diseases (osteomalacia etc).

2. To compare the occurrence of osteoporosis/osteopenie according to ethiology of liver disease with regards to METAVIR score and steroid treatment.

3. To assess the effect of antiosteoporotic treatment started in a randomized manner (BMD, fractures, adverse effects, quality of life ) in 1 and 2 years resp.

Hypotheses:

1. Prevalence of osteoporosis will reach 30%.

2. Confirmation of expected efficacy and safety of anti-resorptive and anabolic antiosteoporotic treatment.

Inclusion criteria: Signed informed consent. Liver disease (METAVIR > 2)

Exclusion criteria: unable to undergo DXA, contraindication of antiosteoporotic treatment

Grant: GAUK, standard care

Estimated number of involved patients: 350

Requirements for student applicants:

Specialization in endocrinology (and bone diseases)