Risk of secondary osteoporosis due to lobular cholestasis in non‐cirrhotic primary biliary cholangitis

• Published in: Journal of gastroenterology and hepatology Vol. 32; no. 9; pp. 1611 - 1616
• Main Authors: Seki, Anna, Ikeda, Fusao, Miyatake, Hirokazu, Takaguchi, Koichi, Hayashi, Shosaku, Osawa, Toshiya, Fujioka, Shin‐ichi, Tanaka, Ryoji, Ando, Masaharu, Seki, Hiroyuki, Iwasaki, Yoshiaki, Yamamoto, Kazuhide, Okada, Hiroyuki
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01-09-2017
• Subjects: Aged; Alkaline phosphatase; Bone Density; Bone growth; Bone mineral density; Bone Remodeling; Bone Resorption; Bone turnover; bone turnover marker; Case-Control Studies; Cholangitis; Cholangitis - complications; Cholangitis - metabolism; Cholangitis - pathology; Cholestasis; Cholestasis - complications; Cholestasis - metabolism; Cholestasis - pathology; Cirrhosis; Collagen (type I); Female; Fibrosis; Gallbladder diseases; Hepatocytes; Humans; Keratin; keratin 7; Liver; Liver Cirrhosis; Middle Aged; Osteogenesis; Osteoporosis; Osteoporosis - epidemiology; Osteoporosis - etiology; Osteoporosis - metabolism; Post-menopause; Postmenopause; Prevalence; primary biliary cholangitis; Propensity Score; Risk; Risk Factors; secondary osteoporosis; Urine; bone mineral density; bone turnover marker; secondary osteoporosis; keratin 7; primary biliary cholangitis
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/jgh.13746

Background and Aim
It remains unclear whether primary biliary cholangitis (PBC) represents a risk factor for secondary osteoporosis.
Methods
A case–control study was conducted to examine bone mineral density and bone turnover markers in middle‐aged postmenopausal PBC patients without liver cirrhosis. We compared the incidence of low bone mineral density between propensity‐score matched subgroups of PBC patients and healthy controls and investigated the mechanisms underlying unbalanced bone turnover in terms of the associations between bone turnover markers and PBC‐specific histological findings.
Result
Our analysis included 128 consecutive PBC patients, all postmenopausal women aged in their 50s or 60s, without liver cirrhosis or fragility fracture at the time of PBC diagnosis. The prevalence of osteoporosis was significantly higher in the PBC group than in the control group (26% vs 10%, P = 0.015, the Fisher exact probability test). In most PBC patients (95%), the level of bone‐specific alkaline phosphatase was above the normal range, indicating increased bone formation. On the other hand, the urine type I collagen‐cross‐linked N‐telopeptide showed variable levels among our PBC patients, indicating unbalanced bone resorption. Advanced fibrosis was associated with low bone turnover. Lobular cholestasis, evaluated as aberrant keratin 7 expression in hepatocytes, showed significant negative correlations with bone formation and resorption, indicating low bone turnover.
Conclusion
Our results show that, compared with healthy controls, even non‐cirrhotic PBC patients have significantly higher risk of osteoporosis. Moreover, lobular cholestasis was associated with low bone turnover, suggesting this feature of PBC may itself cause secondary osteoporosis in PBC patients.