Anna Seki1, Fusao Ikeda1, Hirokazu Miyatake2, Koichi Takaguchi3, Shosaku Hayashi4, Toshiya Osawa5, Shin-Ichi Fujioka5, Ryoji Tanaka5, Masaharu Ando6, Hiroyuki Seki1, Yoshiaki Iwasaki1, Kazuhide Yamamoto5, Hiroyuki Okada1. 1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. 2. Department of Internal Medicine, Hiroshima City Hospital, Hiroshima, Japan. 3. Department of Internal Medicine, Kagawa Prefectural Central Hospital, Takamatsu, Japan. 4. Department of Internal Medicine, Ritsurin General Hospital, Takamatsu, Japan. 5. Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan. 6. Department of Internal Medicine, Mitoyo General Hospital, Kanonji, Japan.
Abstract
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.
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.
Authors: Nicola Pugliese; Ivan Arcari; Alessio Aghemo; Andrea G Lania; Ana Lleo; Gherardo Mazziotti Journal: World J Gastroenterol Date: 2022-04-14 Impact factor: 5.374