Cholestasis and metabolic bone disease - a clinical review

Abstract

Metabolic bone disease, mainly osteopenia/osteoporosis and occasionally osteomalacia, is a major extrahepatic manifestation of chronic cholestatic liver disease (synonym: hepatic osteodystrophy). Reduced bone mineral density is found in up to 60% and atraumatic fractures in about 20% of patients with chronic liver disease. Hepatic osteodystrophy is characterized by reduced formation and increased resorption of bone; major risk factors are chronic cholestasis and advanced cirrhosis. Pathogenetic mechanisms include genetic factors, abnormalities of calcium, vitamin D, vitamin K and bilirubin metabolism, IGF-1 deficiency, the RANKL/OPG-system, hypogonadism, drugs harmful to bone, lifestyle factors (smoking, alcoholism, immobility), malnutrition and low body mass index. Screening for osteopenia should be performed and reversible risk factors must be corrected. At present, bisphosphonates are the predominantly used specific drugs for the treatment of osteoporosis in chronic liver disease. After orthotopic liver transplantation bone mineral density improves in long-term follow-up. Studies are needed for fracture prevention in chronic liver disease.