Background and aims: Low bone formation is the main pathogenic mechanism of osteoporosis in primary biliary cirrhosis (PBC). Sclerostin, an inhibitor of the Wnt pathway, is involved in the regulation of osteoblastogenesis and little is known about its role in the development of bone disease in PBC. Thus, we evaluated the circulating levels of sclerostin and its relationship to bone mass, the parameters of mineral metabolism and liver disease severity.
Methods: Serum sclerostin levels were measured in 83 women with PBC (mean age: 60±12 years) treated with ursodeoxycolic acid and 101 control women of the same age. In patients with PBC, we assessed the degree of cholestasis, lumbar and femoral BMD (DXA), as well as parameters of mineral metabolism (Ca/P, PTH, 25OHD, PINP, bone ALP, sCTX, NTX, and osteocalcin). In 20 PBC patients sclerostin levels were measured again after 5 years.
Results: 77% had low BMD (22% osteoporosis and 55% osteopenia). Patients with PBC showed higher sclerostin levels than controls (76.7±38.6 vs 32.5±14.7 pmol/l, P<0.001). Sclerostin levels were higher in patients with less severe cholestasis. A direct correlation between sclerostin and lumbar (r=0.354, P=0.002) and femoral BMD (r=0.336, P=0.003) and age (r=0.256, P=0.002) was observed. In the 65 patients not receiving bisphosphonates at the time of the evaluation, there was an inverse correlation of sclerostin with bone formation markers, PINP (P=0.05) and osteocalcin (P=0.037) and bone resorption, NTX (P=0.01) and sCTX (P=0.03). Sclerostin was significantly decreased in patients who were evaluated at 5 years (99.5±35.9 vs 60.1±30.9 pmol/l, P=0.001).
Conclusion: In primary biliary cirrhosis there is an increase in sclerostin, related to bone mass and liver disease severity. The inverse association with bone formation markers indicates that high sclerostin plays a role in the decreased bone formation in this liver disease.
17 May 2014 - 20 May 2014