Bone Turnover Markers and Probable Advanced Nonalcoholic Fatty Liver Disease in Middle-Aged and Elderly Men and Postmenopausal Women With Type 2 Diabetes

Ningjian Wang,Wen Zhang,Yi Chen,Yuying Wang,Fangzhen Xia,Bin Hu,Qing Li,Heng Wan,Yingli Lu,Boren Jiang,Xiaoman Chen

doi:10.3389/fendo.2019.00926

Ningjian Wang, Wen Zhang + Show 9 more

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https://doi.org/10.3389/fendo.2019.00926

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Abstract

Objective: Type 2 diabetic patients have a higher incidence of nonalcoholic steatohepatitis (NASH) and advanced stages of fibrosis, and nonalcoholic fatty liver disease (NAFLD) is associated with impaired bone health. We aimed to investigate whether bone turnover is associated with the probable presence of NASH and fibrosis.Methods: In total, 4,937 diabetic participants from Shanghai, China were enrolled in 2018. Subjects with NAFLD were categorized into simple NAFLD and probable NASH groups based on the presence of a metabolic syndrome. The NAFLD fibrosis score was used to identify patients with a higher likelihood of advanced fibrosis.Results: In postmenopausal women, large N-mid fragment of osteocalcin (N-MID osteocalcin) was negatively associated with probable NASH (P for trend < 0.001). β-C-terminal cross-linked telopeptides of type I collagen (β-CTX) and procollagen type I N-terminal propeptide (P1NP) were positively associated with the probable presence of significant fibrosis in postmenopausal women (P for trend 0.015 and <0.001). However, in men, N-MID osteocalcin and β-CTX were negatively associated with the probable presence of significant fibrosis (P for trend 0.029 and 0.027).Conclusions: Significant associations among N-MID osteocalcin, β-CTX and P1NP, and probable advanced NAFLD were observed. Further prospective and animal studies are warranted to understand the causal relationship and underlying mechanism.

Highlights

Nonalcoholic fatty liver disease (NAFLD) encompasses a histological spectrum from nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH) to fibrosis and cirrhosis and can even develop into hepatocellular carcinoma [1]
Angulo et al describe it as a scoring system that accurately separates patients with NAFLD with and without advanced fibrosis [14]. In this large community-based study, we aimed to investigate whether bone turnover markers (β-CTX, N-MID osteocalcin, and procollagen type 1 N-peptide (P1NP)) are associated with the probable presence of NASH and significant fibrosis evaluated using the above noninvasive measurements in Chinese men and postmenopausal women with type 2 diabetes
After adjusting for demographic and metabolic parameters and diabetes medications in men, we found that none of the P1NP, NMID osteocalcin, and β-CTX quartiles showed a significant trend associated with simple NAFLD and probable NASH, but some of the quartiles, such as the Q3 of P1NP and the Q2 of β-CTX, were significantly associated with probable NASH compared with the corresponding Q1 (Figure 2)

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) encompasses a histological spectrum from nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH) to fibrosis and cirrhosis and can even develop into hepatocellular carcinoma [1]. A relatively small sample study in postmenopausal women with diabetes found that the presence of NAFLD and significant fibrosis was significantly associated with lower bone turnover [9]. Bone turnover markers, such as β-C-terminal telopeptide (β-CTX), N-MID osteocalcin, and procollagen type 1 N-peptide (P1NP), were reported to be associated with chronic liver injury, inflammation, and fibrosis [10,11,12]. To the best of our knowledge, there are limited studies with a large sample size that have provided information on the association between advanced NAFLD status (NASH and significant fibrosis) and bone turnover markers in diabetic patients of both genders

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