title: Risk of secondary osteoporosis due to lobular cholestasis in non-cirrhotic primary biliary cholangitis.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Seki
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Fusao
authors.initials: F
authors.lastname: Ikeda
authors.affiliation: Department of Internal Medicine, Hiroshima City Hospital, Hiroshima, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Miyatake
authors.affiliation: Department of Internal Medicine, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takaguchi
authors.affiliation: Department of Internal Medicine, Ritsurin General Hospital, Takamatsu, Japan.
authors.forename: Shosaku
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Osawa
authors.affiliation: Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Fujioka
authors.affiliation: Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Department of Internal Medicine, Mitoyo General Hospital, Kanonji, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ando
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Seki
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okada
mesh_terms: D000368:Aged; D015519:Bone Density; D016723:Bone Remodeling; D001862:Bone Resorption; D016022:Case-Control Studies; D002761:Cholangitis / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D002779:Cholestasis / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis; D008875:Middle Aged; D010012:Osteogenesis; D010024:Osteoporosis / Q000453:epidemiology* / Q000209:etiology* / Q000378:metabolism; D017698:Postmenopause; D015995:Prevalence; D057216:Propensity Score; D012306:Risk; D012307:Risk Factors
keywords: bone mineral density; bone turnover marker; keratin 7; primary biliary cholangitis; secondary osteoporosis