Osteoporosis is a common complication observed in patients with primary biliary cirrhosis (PBC), with a prevalence of around 25%. The pathogenesis of bone loss in PBC is not well understood, since low bone formation and high resorption have been described. Bone disease is influenced by the duration and severity of the disease and oestrogen deficiency secondary to menopause. Genetic susceptibility has also been considered for osteoporosis in PBC, including vitamin D receptor genotypes, the gene encoding collagen type I alpha1 and insulin growth factor 1 gene microsatellite repeat polymorphism. Based on current evidence, the proposed genotypes either do not influence the development of osteoporosis in PBC or play only a minor role in it. The duration as well the severity of cholestasis are the main factors for such a disturbance since they are associated with the degree of bone loss. These features may exceed the potential effect of gene polymorphisms on osteoporosis in PBC.