The association of liver fat content and serum alanine aminotransferase with bone mineral density in middle-aged and elderly Chinese men and postmenopausal women

Abstract

BackgroundRecent studies have linked non-alcoholic fatty liver disease (NAFLD) to a reduced bone mineral density (BMD). We aimed to detect the quantitative association of liver fat content (LFC) and serum alanine aminotransferase (ALT) with BMD in a middle-aged and elderly Chinese population.MethodsThe lumbar spine, hip and whole body BMDs were measured using dual-energy x-ray absorptiometry (Lunar iDXA, GE Healthcare) in 1659 Chinese (755 men and 1028 postmenopausal women) from Shanghai Changfeng community. Liver fat content was quantified via an ultrasound quantitative method. Multivariate linear regression analyses were carried out to determine the independent association of LFC and serum ALT with BMD and bone metabolic biomarkers. We also attempted to investigate the synergistic association between LFC and ALT as risk factors for bone mineral loss in Chinese.ResultsSubjects with higher LFC had significantly lower BMD at all skeletal sites. Univariate correlation analysis showed that both LFC and ALT were inversely associated with BMD at the spine (r = −0.116, P < 0.001 and r = −0.102, P = 0.005), hip (r = −0.095, P = 0.014 and r = −0.075, P = 0.041) and whole body sites (r = −0.134, P < 0.001 and r = −0.164, P < 0.001) in men. After confounders were controlled for, LFC and ALT remained associated with BMD and bone formation biomarkers in men, but not postmenopausal women. When both NAFLD and elevation of ALT were present, there was a significant synergistic worsening of the BMDs at all bone sites.ConclusionsLiver fat content and serum ALT were inversely correlated with BMD in middle-aged and elderly men. The underlying mechanism might relate to a reduction in osteoblast activity. Elevation of the hepatotoxic biomarker ALT may indicate high risk for osteoporosis in patients with NAFLD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0766-3) contains supplementary material, which is available to authorized users.

Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases

“…The association between NAFLD and BMD was modest, however, and remained significant in these studies even after adjusting for several potential confounding factors, including age, weight, alcohol intake, smoking and metabolic risk factors. Increasing ultrasonographic severity of hepatic steatosis as well as serum alanine-aminotransferase levels correlated inversely with BMD 153. A further cohort study of 7797 Chinese adults aged >40 years confirms the existence of a sex-specific association with a higher rate of recent osteoporotic fractures in men with NAFLD compared with those without (3.6% vs 1.7%, p=0.003), with no difference seen in women 156.…”

Systematic review with meta‐analysis: non‐alcoholic fatty liver disease is associated with a history of osteoporotic fractures but not with low bone mineral density

“…Figure summarises the results of the literature search and study selection. After excluding duplicates, based on titles and abstracts of 148 citations (in accordance with the aforementioned exclusion criteria of the meta‐analysis), we initially identified 17 potentially relevant studies from PubMed, Web of Science, and Scopus databases prior to 31 August 2018 (last date searched). After examining the full text of these 17 publications, we further excluded five studies, because of unsatisfactory inclusion criteria (ie, use of fatty liver index for diagnosing NAFLD or inclusion of patients with end‐stage liver disease awaiting liver transplantation) or unavailability of extractable data for BMD, as specified in the PRISMA flow diagram.…”

“…Overall, 12 studies were eligible for inclusion in the meta‐analysis and were then assessed for quality . The main characteristics of the included studies are summarised in Table .…”

“…The diagnosis of NAFLD was based on liver biopsy (n = 1 study), ultrasonography (n = 10 studies), or vibration‐controlled transient elastography (Fibroscan) (n = 2 study), in the absence of excessive alcohol consumption and other known causes of chronic liver disease. In 10 of eligible studies, the outcome measure was BMD (as measured by DEXA at different skeletal sites) between patients with and without NAFLD, whereas in the remaining two studies the outcome measure was the history of osteoporotic fractures in patients with NAFLD compared with those without the disease . Most eligible studies were carried out in Asia (n = 10 studies mostly from China and South Korea); one study was carried out in the United States, and another one was carried out in Italy (including only post‐menopausal women with non‐insulin treated type 2 diabetes) .…”

“…Recently, the existence of a possible association between NAFLD and osteoporosis has created considerable scientific interest . Several observational cross‐sectional or case‐control studies have examined the association between imaging‐defined or biopsy‐proven NAFLD and BMD measurement in middle‐aged and elderly individuals . However, the findings from such studies have been inconsistent or conflicting so far, with some studies reporting a significant association between NAFLD and reduced BMD, especially in Chinese men, some studies reporting a significant association between NAFLD and increased BMD, and with others failing to find any significant association between NAFLD and BMD .…”