Sclerostin is involved in the regulation of osteoblastogenesis and little is known about its role in the development of bone disease in primary biliary cirrhosis (PBC), characterised by low bone formation. Therefore, we have assessed the circulating levels and the liver expression of sclerostin in this cholestatic disease. Serum sclerostin levels were measured in 83 women with PBC (mean age: 60±12 years) and 101 control women. Lumbar and femoral BMD as well as parameters of mineral metabolism and bone remodeling were measured. Moreover, sclerostin gene expression in the liver was assessed in samples of liver tissue taken by biopsy in 11 PBC patients and five healthy controls by real time PCR, and presence and distribution of sclerostin was evaluated in liver slices from 11 patients by immunohistochemistry. The presence and severity of histologic lesions were assessed semiquantitatively in the same liver samples. 77% of patients had low BMD (22% osteoporosis and 55% osteopenia). PBC patients had higher sclerostin levels than controls (76.7±38.6 vs 32.5±14.7 pmol/l, P<0.001). Serum sclerostin correlated inversely with markers of bone formation and resorption. Sclerostin mRNA in the liver was overexpressed as compared with control samples (2.7±0.3-fold vs healthy liver). Sclerostin was detected by immunohistochemistry in seven of the 11 liver samples and mainly located in the bile ducts. Sclerostin was associated with the severity of cholangitis (P=0.02) and indirectly with the degree of lobular inflammation (P=0.03). Sclerostin mRNA expression was higher in samples positive by immunohistochemistry (2.9±0.4 vs 2.5±0.3, p:NS), and particularly in those with lobular granuloma (3.6±0.6 vs 2.4±0.2, P=0.02). The increased expression of sclerostin in the liver and the association with histologic cholangitis may explain the high serum levels of this protein in patients with PBC, thus suggesting that sclerostin influences the decreased bone formation in this cholestatic disease.
Disclosure: The authors declared no competing interests.