High osteoprotegerin serum levels in primary biliary cirrhosis are associated with disease severity but not with the mRNA gene expression in liver tissue

The influence of osteoprotegerin and RANKL as regulators of osteoclastogenesis and bone remodeling in liver disease and in the development of osteoporosis in primary biliary cirrhosis (PBC) is uncertain. Therefore, 68 women with PBC and 20 healthy females were studied by assessing circulating osteoprotegerin and RANKL. Bone mineral density and markers of bone turnover were measured as well. Osteoprotegerin-mRNA expression was also assessed in liver tissue from 16 patients and 5 controls. Osteoprotegerin was higher in PBC than in controls (5.4 ± 0.2 vs. 2.9 ± 0.2 pM/l, P < 0.0001), whilst RANKL was lower in patients than in controls (0.39 ± 0.06 vs. 1.40 ± 0.16 pM/l, P < 0.0001). Osteoprotegerin was more elevated in patients with more advanced disease, as defined by bilirubin above 1.2 mg/dl (6.6 ± 0.6 vs. 5.2 ± 0.2 pM/l, P = 0.02) or by Mayo over 4 (5.9 ± 0.3 vs. 4.8 ± 0.2 pM/l, P = 0.02). Osteoprotegerin and RANKL were unrelated with osteoporosis, and no associations were found with markers of bone remodeling, except for RANKL, which was particularly decreased in patients with low osteocalcin. This marker of bone formation was also higher in patients with elevated circulating osteoprotegerin. Liver osteoprotegerin gene expression was similar in patients and controls, and no correlation was found between liver osteoprotegerin-mRNA and patients’ respective circulating levels. In conclusion, osteoprotegerin and RANKL are abnormal in patients with PBC, regardless of osteoporosis. The elevated circulating osteoprotegerin is associated with the severity of disease, but not with gene expression in the liver.