非酒精性脂肪性肝病与血清维生素D及骨密度的关系

目的探讨非酒精性脂肪性肝病(NAFLD)与维生素D及骨密度的关系。方法选取2018年5月-2019年3月于大连大学附属中山医院住院及门诊就诊的NAFLD患者180例为NAFLD组,另选取年龄及性别相匹配的健康体检者180例为对照组。比较2组维生素D、骨密度、骨代谢生化标志物β胶原降解产物(β-CTX)、Ⅰ型胶原氨基端延长肽(P1NP)、骨钙素(OC)]的差异。正态分布的计量资料2组间比较采用独立样本t检验,非正态分布采用Mann-Whitney U检验;计数资料2组间比较采用χ^2检验。相关性采用Spearman秩相关分析;采用二项分类logistic回归分析NAFLD的相关危险因素。结果 NAFLD组25(OH) D13.06(10.73~19.77) ng/ml vs 19.88(12.56~22.60) ng/ml,Z=-1.37,P=0.041]、L1-4骨密度0.87(0.83~1.05) g/cm^2vs1.05(0.92~1.21) g/cm^2,Z=-2.17,P=0.034]、股骨颈骨密度(0.76±0.21) g/cm^2vs(0.84±0.51) g/cm^2,t=2.02,P=0.015]、P1NP45.40(33.35~58.02) ng/ml vs 67.39 (48.09~87.49) ng/ml,Z=-0.83,P=0.044]和OC14.79 (11.64~18.87) ng/ml vs17.29(15.16~21.04) ng/ml,Z=-2.09,P=0.037]水平均明显低于对照组;β-CTX354.75(186.32~526.57) pg/ml vs 287.67(164.10~497.76) pg/ml,Z=-1.04,P=0.027]水平明显高于对照组。NAFLD患者25(OH) D(13.51±3.20) ng/ml vs(18.86±3.70) ng/ml,t=3.02,P=0.038]及L1-4骨密度(0.75±0.24) g/cm^2vs(1.05±0.31) g/cm^2,t=2.17,P=0.035]、股骨颈骨密度(0.71±0.18) g/cm^2vs(0.82±0.21) g/cm^2,t=2.25,P=0.042]在ALT>2倍正常值上限(ULN)组明显低于≤2×ULN组;25(OH) D、L1-4骨密度、股骨颈骨密度在CT诊断不同程度脂肪肝组间比较差异均无统计学意义(P值均> 0.05)。骨密度与HDL-C(r=0.232,P<0.05)呈正相关,与BMI(r=-0.271,P<0.05)、GLU(r=-0.242,P<0.05)、ALT(r=-0.375,P<0.05)、AST(r=-0.312,P<0.05)、LDL-C(r=-0.247,P<0.05)呈负相关。logistic回归分析结果显示,25(OH) D比值比(OR)=1.113,95%可信区间(95%CI):1.023~1.210,P=0.013]、BMI(OR=0.676,95%CI:0.522~0.877,P=0.003)、GLU(OR=0.350,95%CI:0.139~0.882,P=0.026)是NAFLD的影响因素。结论 NAFLD患者血清维生素D及骨密度明显低于正常人,通过血清维生素D及骨密度的分析可进一步阐明NAFLD的骨代谢特征,对NAFLD并发骨质疏松症进行合理的早期筛查,以提高NAFLD患者的预后及生活质量。

Association of nonalcoholic fatty liver disease with vitamin D and bone mineral density

Objective To investigate the association of nonalcoholic fatty liver disease( NAFLD) with vitamin D and bone mineral density.Methods A total of 180 patients with NAFLD who were hospitalized or visited the outpatient service of Zhongshan Hospital Affiliated to Dalian University from May 2018 to March 2019 were enrolled as NAFLD group,and 180 healthy individuals matched for age and sex who underwent physical examination were enrolled as control group.The two groups were compared in terms of vitamin D,bone mineral density,and biochemical markers for bone metabolism β isomer of C-terminal telopeptide of type I collagen(β-CTX),type 1 procollagen amino terminal peptide( P1 NP),and osteocalcin( OC)].The independent samples t-test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data.The chi-square test was used for comparison of categorical data between groups.A Spearman correlation analysis was performed,and a binary logistic regression analysis was used to investigate the risk factors for NAFLD.Results Compared with the control group,the NAFLD group had significantly lower levels of 25( OH) D 13.06( 10.73-19.77) ng/ml vs 19.88( 12.56-22.60) ng/ml,Z =-1.37,P = 0.041],L1-4 bone mineral density0.87( 0.83-1.05) g/cm^2 vs 1.05( 0.92-1.21) g/cm^2,Z =-2.17,P = 0.034],bone mineral density of the femoral neck( 0.76 ±0.21 g/cm^2 vs 0.84 ± 0.51 g/cm^2,t = 2.02,P = 0.015),P1 NP 45.40( 33.35-58.02) ng/ml vs 67.39( 48.09-87.49) ng/ml,Z =-0.83,P = 0.044],and OC 14.79( 11.64-18.87) ng/ml vs 17.29( 15.16-21.04) ng/ml,Z =-2.09,P = 0.037],as wellas a significantly higher level of β-CTX 354.75( 186.32-526.57) pg/ml vs 287.67( 164.10-497.76) pg/ml,Z =-1.04,P =0.027].Compared with those with alanine aminotransferase( ALT)≤2 × upper limit of normal( ULN),the NAFLD patients with ALT >2 × ULN had significantly lower levels of 25( OH) D( 13.51 ± 3.20 ng/ml vs 18.86 ± 3.70 ng/ml,t = 3.02,P = 0.038),L1-4 bone mineral density( 0.75 ± 0.24 g/cm^2 vs 1.05 ± 0.31 g/cm^2,t = 2.17,P = 0.035),and bone mineral density of the femoral neck( 0.71 ± 0.18 g/cm^2 vs 0.82 ± 0.21 g/cm^2,t = 2.25,P = 0.042).There were no significant differences in 25( OH) D,L1-4 bone mineral density,and bone mineral density of the femoral neck between the groups of patients with different degrees of fatty liver disease on CT( all P>0.05).Bone mineral density was positively correlated with high-density lipoprotein cholesterol( r = 0.232,P<0.05) and was negatively correlated with body mass index( BMI)( r =-0.271,P<0.05),blood glucose( Glu)( r =-0.242,P<0.05),ALT( r =-0.375,P<0.05),aspartate aminotransferase( r =-0.312,P<0.05),and low-density lipoprotein cholesterol( r =-0.247,P<0.05).The logistic regression analysis showed that 25( OH) D( odds ratio OR]= 1.113,95% confidence interval CI]: 1.023-1.210,P =0.013),BMI( OR = 0.676,95% CI: 0.522-0.877,P = 0.003),and Glu( OR = 0.350,95% CI: 0.139-0.882,P = 0.026) were influencing factors for NAFLD.Conclusion Patients with NAFLD have significantly lower levels of vitamin D and bone mineral density than healthy individuals.An analysis of serum vitamin D and bone mineral density can further clarify the features of bone metabolism in NAFLD,and early screening of NAFLD with osteoporosis should be performed to improve the prognosis and quality of life of patients with NAFLD.