Correlation Between Non-alcoholic Fatty Liver Disease And Low Bone Mineral Density

Objective:Recently,a large number of evidence-based clinical studies have shown that non-alcoholic fatty liver disease(NAFLD)is a risk factor associated with low BMD(bone mineral density).The present study aims to explore the influencing factors of low BMD and the effect of NAFLD and its severity on low BMD by reviewing the clinical data of the population undergoing physical examination.Methods:This study is divided into two parts,including cross-sectional study and retrospective cohort study.The included 1720 subjects underwent abdominal ultrasound and BMD examination in annual comprehensive health examinations from 2013 to 2018.In the baseline survey,demography,past medical history,living habits,glucose and serum lipids and other clinical data were collected,and the occurrence of low BMD events was taken as the outcome of the retrospective cohort study.We conducted univariate analysises of the association between NAFLD and low BMD events and multivariate analysises that adjusting multiple baseline characteristics.The main methods were Logistic regression,COX regression and Propensity Score Matching(PSM)and so on.Results:A total of 1720 subjects(1064 subjects with normal BMD and 656 subjects with low BMD)were included at baseline.The first part of the study was cross-sectional study and we showed that the average age,the proportion of men,the proportion of smokers and the prevalence rate of NAFLD in the low BMD group were significantly higher than those in the normal BMD group,but the body mass index(BMI)was lower than that in the normal BMD group.Multivariate Logistic regression indicated that age(OR=1.02,95%CI: 1.01-1.03,P=0.001),male gender(OR=1.90,95%CI: 1.45-2.50,P<0.001),level of triglyceride(OR=1.12,95%CI: 1.02-1.23,P=0.018)and the prevalence rate of NAFLD(OR=1.70,95%CI: 1.33-2.16,P<0.001)were independent risk factors for low BMD.However,BMI(OR=0.86,95%CI: 0.83-0.90,P=0.001)is its independent protective factor.The second part is retrospective cohort study,in which 1064 subjects with normal BMD were followed up and 399(37.5%)subjects had low BMD events after follow up.The incidence of low BMD events in NAFLD patients was significantly higher than that in the control group(33.8% vs.14.8%,P<0.001).COX regression analysis showed that NAFLD was a risk factor for the occurrence of end-point events of low BMD(HR=1.62,95%CI: 1.32-2.00,P<0.001).After adjusting for age,sex,BMI and other influencing factors(including smoking,exercise,blood pressure,serum lipid,etc.),NAFLD was still an independent risk factor for the occurrence of low BMD(HR=2.44,95%CI: 1.91-3.12,P<0.001).Then the fibrosis stage and severity of NAFLD were evaluated with the non-invasive serological index(APRI).Further analysis showed that the risk of low BMD events in NAFLD patients with middle-high grade APRI was significantly higher than that in patients with NAFLD with low grade APRI(HR=1.57 vs 2.11,P<0.05 between groups).Conclusion:Compared with the normal BMD group,the prevalence of NAFLD in the low BMD group was significantly higher.Aging,male,high level of triglyceride and the prevalence rate of NAFLD were independent risk factors for low BMD,while low BMI was independent protective factors.Among people without previous low BMD events,NAFLD can significantly increase the risk of low bone mass events.Increased non-invasive fibrosis markers of NAFLD were positively associated with an increased incidence of low BMD in a graded manner.Our findings indicated NAFLD can be a significant contributor to low BMD pathogenesis,requiring further studies to elucidate the potential mechanisms.