Association between non-alcoholic fatty liver disease-associated hepatic fibrosis and bone mineral density in postmenopausal women with type 2 diabetes or impaired glucose regulation

Xiaopeng Zhu; Hongmei Yan; Xinxia Chang; Mingfeng Xia; Linshan Zhang; Liu Wang; Xiaoyang Sun; Xinyu Yang; Xin Gao; Hua Bian

doi:10.1136/bmjdrc-2019-000999

Association between non-alcoholic fatty liver disease-associated hepatic fibrosis and bone mineral density in postmenopausal women with type 2 diabetes or impaired glucose regulation

BMJ Open Diabetes Res Care. 2020 Aug;8(1):e000999. doi: 10.1136/bmjdrc-2019-000999.

Authors

Xiaopeng Zhu^{1

2}, Hongmei Yan^{1

2}, Xinxia Chang^{1

2}, Mingfeng Xia^{1

2}, Linshan Zhang^{1

2}, Liu Wang^{1

2}, Xiaoyang Sun^{1

2}, Xinyu Yang^{1

2}, Xin Gao^{3

2}, Hua Bian^{3

2}

Affiliations

¹ Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China.
² Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China.
³ Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China zhongshan_bh@126.com zhongshan_endo@126.com.

Abstract

Introduction: To evaluate the association of non-alcoholic fatty liver disease (NAFLD)-associated hepatic fibrosis with bone mineral density (BMD) in postmenopausal women with type 2 diabetes mellitus (T2DM) or impaired glucose regulation (IGR).

Research design and methods: Two cohorts including 46 subjects with biopsy-proven NAFLD and 445 subjects with proton magnetic resonance spectrum-proven NAFLD were enrolled in this study. All subjects were postmenopausal women with T2DM or IGR. BMD at the lumbar spine L1-L4 and hip was measured using dual-energy X-ray absorptiometry. NAFLD fibrosis stage and NAFLD fibrosis score were used to evaluate the severity of liver fibrosis.

Results: In subjects with liver biopsy-proven NAFLD, BMD (T-score, Z-score and BMD value) in the advanced fibrosis group were significantly lower than that in the non-advanced fibrosis group (p<0.05). Fibrosis stage was negatively associated with T-score, Z-score and BMD value after adjusting for age, body mass index (BMI) and fasting plasma glucose (FPG). Additionally, fibrosis stage was independently associated with T-score, Z-score and BMD value after adjusting for age, BMI and FPG. These results were validated in a large cohort of 445 subjects. Additionally, bone metabolism-associated factors, including calcium and phosphate, were associated with liver fibrosis, indicating that bone metabolism may play a critical role in the association between liver fibrosis and BMD. Mechanically, parathyroid hormone and biomarkers of bone formation (osteocalcin and procollagen type 1 N-terminal propeptide) and bone resorption (procollagen type I carboxy terminal peptide β special sequence) were increased in subjects with advanced liver fibrosis than in subjects without advanced liver fibrosis, indicating that liver fibrosis decreased BMD probably via increasing bone turnover.

Conclusions: NAFLD-associated hepatic fibrosis was negatively associated with decreased BMD in postmenopausal women with T2DM or IGR. Liver fibrosis decreased BMD probably via increasing bone turnover. Severe liver fibrosis may represent high risk for osteoporosis in postmenopausal women with T2DM or IGR.

Keywords: biopsy; bone density; liver disease; type 2 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bone Density
Diabetes Mellitus, Type 2* / complications
Female
Glucose
Humans
Liver Cirrhosis / etiology
Non-alcoholic Fatty Liver Disease* / complications
Non-alcoholic Fatty Liver Disease* / diagnostic imaging
Postmenopause

Substances

Glucose