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Liu A, Sun Y, Qi X, Zhou Y, Zhou J, Li Z, Wu X, Zou Z, Lv X, Li H, Li Y. Nonlinear association between liver fat content and lumbar bone mineral density in overweight and obese individuals: evidence from a large-scale health screening data in China. Endocrine 2025; 88:446-456. [PMID: 39869295 DOI: 10.1007/s12020-025-04168-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 01/14/2025] [Indexed: 01/28/2025]
Abstract
BACKGROUND The impact of fatty liver disease on lumbar bone mineral density (BMD) represents an intriguing area of study, particularly in light of established research linking obesity to bone metabolism. However, there remains limited investigation into the correlation between quantifying liver fat content (LFC) and lumbar BMD among overweight and obese populations, particularly within the Chinese demographic. This study aims to accurately quantify LFC and investigate its association with lumbar BMD in overweight or obese individuals. METHODS This cross-sectional study was conducted at the Health Management Center of Henan Provincial People's Hospital from January 2019 to February 2023, involving 6996 participants with a body mass index (BMI) of 24 kg/m² or higher. LFC and lumbar BMD were assessed using computed tomography. The study utilized one-way ANOVA, subgroup analysis, multifactor regression analysis, smooth curve fitting, and threshold and saturation effect analysis to explore the relationship between LFC and lumbar BMD. Furthermore, inflammatory cell analysis was included to investigate the potential mediating role of inflammatory cells in the association between LFC and lumbar BMD. RESULTS After adjusting for confounding variables, multivariate regression analysis revealed a significant negative association between LFC and lumbar BMD (β = -0.323, 95% CI: -0.464 to -0.183, P < 0.001). Particularly, participants in the highest baseline LFC quartile (Q4 group) exhibited a more pronounced negative impact on lumbar BMD compared to those in the lowest quartile (Q1 group) (β = -5.026, 95% CI: -7.040 to -3.012, P < 0.001). Threshold saturation effect analysis identified a turning point in the LFC-BMD relationship (K = 5.4). Below this point, LFC showed a positive correlation with lumbar BMD (β = 0.962, 95% CI: 0.016-1.907, P < 0.05), whereas above it, LFC was significantly negatively correlated with lumbar BMD (β = -0.405, 95% CI: -0.558 to -0.253, P < 0.001). Additionally, mediation analysis indicated that leukocytes and monocytes potentially mediated the association between LFC and lumbar BMD, with mediation ratios of -5.78 and -6.68%, respectively. CONCLUSION Among individuals categorized as overweight or obese, elevated levels of LFC were associated with reduced lumbar BMD, particularly noticeable above a threshold of 5.4%. Additionally, various types of inflammatory cells are presumed to exert a substantial mediating influence on the correlation between LFC and lumbar BMD.
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Affiliation(s)
- Ao Liu
- Department of Medical Imaging, People's Hospital of Zhengzhou University, #7 Wei Wu Road, Zhengzhou, 450003, China
| | - Yongbing Sun
- Department of Medical Imaging, People's Hospital of Zhengzhou University, #7 Wei Wu Road, Zhengzhou, 450003, China
| | - Xin Qi
- Department of Medical Imaging, Henan Provincial People's Hospital, Xinxiang Medical College, Zhengzhou, 450003, China
| | - Yang Zhou
- Department of Medical Imaging, People's Hospital of Zhengzhou University, #7 Wei Wu Road, Zhengzhou, 450003, China
| | - Jing Zhou
- Department of Health Management, Chronic Health Management Laboratory, Henan Provincial People's Hospital, Zhengzhou, 450003, China
| | - Zhonglin Li
- Henan Provincial People's Hospital, Zhengzhou, 450003, China
| | - Xiaoling Wu
- Department of Nuclear Medicine, Henan Provincial People's Hospital, Zhengzhou, 450003, China
| | - Zhi Zou
- Henan Provincial People's Hospital, Zhengzhou, 450003, China
| | - Xue Lv
- Department of Health Management, Chronic Health Management Laboratory, Henan Provincial People's Hospital, Zhengzhou, 450003, China
| | - Hao Li
- Department of Health Management, Fuwai Central China Cardiovascular Hospital, #1 Fuwai Avenue, Zhengzhou, 451464, China
| | - Yongli Li
- Department of Health Management, Chronic Health Management Laboratory, Henan Provincial People's Hospital, Zhengzhou, 450003, China.
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Zhang WJ, Xu XP, Song XH, Zhang ZR, Zhang XR, Yang B, Tao ZB, Zhang Z, Zhou XH. Liver function linked to bone health: A bibliometric of the liver-bone axis. World J Hepatol 2025; 17:103016. [PMID: 40027553 PMCID: PMC11866138 DOI: 10.4254/wjh.v17.i2.103016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 01/01/2025] [Accepted: 01/21/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND The liver exerts profound influence on skeletal health, while osseous tissues reciprocally modulate hepatic function. This bidirectional metabolic axis between these two organ systems plays a pivotal role in both physiological homeostasis and pathological states. AIM To investigate and analyze the literatures on liver-bone axis using bibliometrics. METHODS A comprehensive literature search pertaining to the liver-bone axis was conducted using the Science Citation Index Expanded within the Web of Science Core Collection. Subsequently, visualization and bibliometric analyses were performed utilizing VOSviewer (version 1.6.20), Citespace (version 6.2.R4), and the R programming language. RESULTS This comprehensive analysis encompasses 855 publications, comprising 694 articles and 161 reviews, authored by 4988 researchers from 425 institutions across 61 countries. The United States and China emerge as the leading nations in terms of publication volume. The University of California system stands out as the most influential institution in liver-bone axis research. Guanabens N is identified as the most prolific author in this field. The annual increase in publications related to the liver-bone axis underscores its growing prominence as a research focus. The study highlights key areas of investigation, including osteoporosis, bone metabolism, non-alcoholic fatty liver disease, and insulin-like growth factor-1, which represent both current and prospective hot topics within this domain. CONCLUSION This investigation employs bibliometric methodologies to conduct a systematic analysis of liver-bone axis literature spanning from 2001 to 2024. The exponential growth in publications over the past two decades underscores the significance of synthesizing research outcomes in this domain. Through rigorous statistical analyses, we delineate fundamental contributions to the field while providing strategic direction for emerging scholars. Furthermore, we illuminate current research trajectories and identify promising future investigative directions. Investigation of the liver-bone axis enhances our comprehension of inter-organ communication networks. Conceptualizing these organs as an integrated system provides profound insights into pathophysiological mechanisms and disease management strategies. This paradigm not only facilitates the development of sophisticated diagnostic modalities but also catalyzes the discovery of novel therapeutic agents targeting these mechanistic pathways, thereby advancing our capacity to diagnose and treat hepatic and skeletal disorders.
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Affiliation(s)
- Wei-Jin Zhang
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China
| | - Xun-Pei Xu
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China
| | - Xin-Hua Song
- Department of Pharmacy, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China
| | - Zhan-Rong Zhang
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China
| | - Xuan-Rui Zhang
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China
| | - Biao Yang
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China
| | - Zheng-Bo Tao
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China
| | - Zheng Zhang
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China
- Department of Orthopedic Rehabilitation, Qingdao Special Servicemen Recuperation Center of People's Liberation Army Navy, Qingdao 266000, Shandong Province, China
| | - Xu-Hui Zhou
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China
- Translational Research Center of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China.
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Zheng M, Xu J, Feng Z. Association between nonalcoholic fatty liver disease and bone mineral density: Mendelian randomization and mediation analysis. Bone Rep 2024; 22:101785. [PMID: 39220175 PMCID: PMC11363625 DOI: 10.1016/j.bonr.2024.101785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 06/24/2024] [Accepted: 06/25/2024] [Indexed: 09/04/2024] Open
Abstract
Background Observational studies have reported significant association between non-alcoholic fatty liver disease (NAFLD) and bone mineral density (BMD), a critical indicator of bone health. We aimed to investigate whether NAFLD is a cause for changes in BMD. Methods We selected 29 independent SNPs as instrumental variables for NAFLD. A range of Mendelian randomization (MR) methods, namely the inverse variance-weighted (IVW) method, weighted-median, weighted-mode, and MR-Egger regression, were utilized to determine the causal effects of NAFLD on BMD. Two-step MR analysis was conducted to determine the mediating effect of fasting glucose, insulin, glycosylated hemoglobin, low-density cholesterol, and body-mass index on the association between NAFLD and BMD. False-discovery-rate (FDR) was used to correct for multiple testing bias. Results The IVW-method indicated a significantly inverse association between genetically predicted NAFLD and total body BMD (β = -0.04, 95 % CI -0.07 to -0.02, FDR = 0.010). Notably, the relationship was more pronounced in participants over 60 years of age (β = -0.06, 95 % CI -0.11 to -0.02, FDR = 0.030). Inverse associations were observed in other subpopulations and in site-specific BMD, though they were not statistically significant after correcting for multiple testing. We observed a significantly positive association between NAFLD and the risk of osteoporosis. Consistency in results was observed across multiple MR methods and in the repeated analysis. Fasting glucose, insulin, and glycosylated hemoglobin mediated 25.4 % (95 % CI 17.6-31.5 %), 18.9 % (12.0-24.9 %), and 27.9 % (19.9-36.7 %) of the effect of NAFLD on BMD, respectively. Conclusion Our findings underscore a probable causal negative link between NAFLD and BMD, indicating that NAFLD might detrimentally affect bone health, especially in older individuals.
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Affiliation(s)
- Minzhe Zheng
- Department of Orthopedics, the Affiliated Lihuili Hospital, Ningbo University, Ningbo City, China
| | - Junxiang Xu
- Department of Orthopedics, the Affiliated Lihuili Hospital, Ningbo University, Ningbo City, China
| | - Zongxian Feng
- Department of Orthopedics, the Affiliated Lihuili Hospital, Ningbo University, Ningbo City, China
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Pan B, Zhao Y, Chen C, Cai J, Li K, Wang Y, Liu J. The relationship between advanced liver fibrosis and osteoporosis in type 2 diabetes patients with MAFLD. Endocrine 2024; 85:206-221. [PMID: 38367145 DOI: 10.1007/s12020-024-03724-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 02/02/2024] [Indexed: 02/19/2024]
Abstract
PURPOSE To investigate the relationship between advanced liver fibrosis and osteoporosis in metabolic-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS A total of 1144 T2DM patients were divided into the MAFLD and non-MAFLD groups, 460 T2DM patients with MAFLD (277 males aged ≥50 years and 183 postmenopausal females) were divided into N1 (advanced liver fibrosis excluded), N2 (indeterminate advanced liver fibrosis), and N3 (advanced liver fibrosis) groups according to the non-alcoholic fatty liver fibrosis score (NFS), the differences in bone mineral density (BMD) levels and prevalence of osteoporosis were compared. Based on the tertile levels of BMD of the lumbar spine (L), T2DM patients were divided into three groups (T1, T2, and T3), and the differences in the prevalence of advanced liver fibrosis were compared. RESULTS The BMD levels of the L4, and L1-4 in the MAFLD group were lower than those of the non-MAFLD groups in male and female T2DM patients .The BMD levels of the total hip, L4, and L1-4 in the N3 group were lower than those of the N2 and N1 groups in male and female T2DM patients with MAFLD, and the prevalence of osteoporosis in the N3 group of males was higher than that in the N1 group. The BMD levels of the total hip, L4, and L1-4 were negatively correlated with NFS in both males and females. The BMD levels of the total hip and L4 in males, and the BMD level of L4 in females were negatively associated with NFS. The prevalence of advanced liver fibrosis was higher in the T1 group than in the T2 and T3 groups in T2DM patients with MAFLD. CONCLUSION The BMD levels in male aged ≥50 years or postmenopausal female diabetic patients with MAFLD were negatively correlated with the degree of advanced liver fibrosis, which means an increased risk of liver fibrosis with decreasing BMD.
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Affiliation(s)
- Binjing Pan
- The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | - Yangting Zhao
- The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | - Chongyang Chen
- The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | - Jing Cai
- The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | - Kai Li
- The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | - Yawen Wang
- The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | - Jingfang Liu
- The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.
- Department of Endocrinology, the First Hospital of Lanzhou University, Lanzhou, Gansu, China.
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Drapkina OM, Kontsevaya AV, Kalinina AM, Avdeev SN, Agaltsov MV, Alekseeva LI, Almazova II, Andreenko EY, Antipushina DN, Balanova YA, Berns SA, Budnevsky AV, Gainitdinova VV, Garanin AA, Gorbunov VM, Gorshkov AY, Grigorenko EA, Jonova BY, Drozdova LY, Druk IV, Eliashevich SO, Eliseev MS, Zharylkasynova GZ, Zabrovskaya SA, Imaeva AE, Kamilova UK, Kaprin AD, Kobalava ZD, Korsunsky DV, Kulikova OV, Kurekhyan AS, Kutishenko NP, Lavrenova EA, Lopatina MV, Lukina YV, Lukyanov MM, Lyusina EO, Mamedov MN, Mardanov BU, Mareev YV, Martsevich SY, Mitkovskaya NP, Myasnikov RP, Nebieridze DV, Orlov SA, Pereverzeva KG, Popovkina OE, Potievskaya VI, Skripnikova IA, Smirnova MI, Sooronbaev TM, Toroptsova NV, Khailova ZV, Khoronenko VE, Chashchin MG, Chernik TA, Shalnova SA, Shapovalova MM, Shepel RN, Sheptulina AF, Shishkova VN, Yuldashova RU, Yavelov IS, Yakushin SS. Comorbidity of patients with noncommunicable diseases in general practice. Eurasian guidelines. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2024; 23:3696. [DOI: 10.15829/1728-8800-2024-3996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024] Open
Abstract
Создание руководства поддержано Советом по терапевтическим наукам отделения клинической медицины Российской академии наук.
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Drapkina OM, Martynov AI, Arutyunov GP, Bakulin IG, Livzan MA, Maev IV, Egorov IV. Resolution of the Expert Forum "New therapeutic horizons of NAFLD". TERAPEVT ARKH 2024; 96:186-193. [DOI: 10.26442/00403660.2024.02.202648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
Aim. To present the materials of the Expert Forum "New therapeutic horizons of NAFLD," held on December 19, 2023, on the updated nomenclature of fatty liver disease (FLD), its main issues of diagnosis and treatment, the burden of cardiovascular risk in FLD patients. Executive Summary of the Resolution. It is recommended that the latest update of the FLD nomenclature be considered for adaptation to the clinical practice of doctors of all therapeutic specialties. Due to the high prevalence of a combination of non-alcoholic fatty liver disease (NAFLD) and an alcoholic component in the Russian Federation, it is essential to distinguish this subgroup of patients. Numerous clinical conditions associated with NAFLD include cardiovascular disease, pre-diabetes/type 2 diabetes mellitus, polycystic ovary syndrome, obstructive sleep apnea, sarcopenic obesity, cholelithiasis, and chronic kidney disease. Once a diagnosis of NAFLD has been made, further examination of patients should be aimed at detecting the presence of fibrosis using non-invasive methods such as transient liver elastography, FibroTest, and calculation of the FIB-4 fibrosis index. The original ademethionine can be considered a universal drug in treating NAFLD due to reducing oxidative stress and correcting concomitant fatigue and asthenia.
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Ansari MD, Majid H, Khan A, Sultana Y. Clinical frontiers of metabolic bone disorders: a comprehensive review. METABOLISM AND TARGET ORGAN DAMAGE 2023; 4. [DOI: 10.20517/mtod.2023.38] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Metabolic bone disease (MBD)encompasses various conditions that adversely impact bone health, such as osteoporosis, primary hyperparathyroidism, osteomalacia, and fluorosis disease. Effectively managing these disorders requires early detection and a focus on maintaining healthy nutritional habits. Dietary adjustments serve as a cornerstone, but supplementation of essential minerals like calcium, phosphate, and vitamin D is often necessary to support bone reabsorption and regeneration, and reduce fracture risk. Despite the effectiveness of these measures in many cases, hereditary bone diseases pose distinctive challenges due to genetic factors. Emerging technologies that provide higher-resolution insights into bone architecture and quality are now complementing traditional diagnostic tools like dual-energy X-ray absorptiometry (DXA). Moreover, the therapeutic landscape has transformed with the introduction of newer agents that not only halt bone loss but also stimulate bone formation. These agents promise better outcomes with reduced side effects, catering to a wider patient population. However, the management of MBDs remains multifaceted, necessitating individualized approaches based on the patient’s clinical profile. As the global prevalence of MBDs, especially osteoporosis, continues to soar, it becomes imperative for clinicians to stay abreast with the evolving paradigms. This review serves as a bridge between historical knowledge and recent discoveries, offering a holistic perspective on the challenges and opportunities in the domain of MBDs.
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Zhang G, Zhao Y, Wang S, Gong Q, Li H. Relationship between nonalcoholic fatty liver disease and bone mineral density in elderly Chinese. J Orthop Surg Res 2023; 18:679. [PMID: 37705028 PMCID: PMC10498582 DOI: 10.1186/s13018-023-04168-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 09/07/2023] [Indexed: 09/15/2023] Open
Abstract
OBJECTIVE As our society grows older, both bone loss and fatty liver have become important issues. However, the relationship between reduced bone mineral density and fatty liver remains controversial. The purpose of this study was to investigate the relationship between nonalcoholic fatty liver disease and less bone mineral density in the ankles of Chinese people over 65. METHODS The research included 716 older adults over the age of 65 who underwent a comprehensive health screening. A logistic regression model was used to investigate the relationship between nonalcoholic fatty liver disease (NAFLD) and ankle bone mineral density. RESULTS A logistic regression model was used to analyze the odds ratios of reduced bone mineral density between patients with fatty liver and controls. In the adjusted model, adjustments were made for age, sex, systolic blood pressure, diastolic blood pressure, overweight rate, history of hypertension, history of diabetes, history of smoking, history of alcohol consumption, fasting glucose, hemoglobin, urea, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, waist circumference, total protein, albumin, and globulin. The adjusted OR (aOR) for reduced bone mineral density was 0.66 [95% confidence interval (CI) = 0.45-0.97, P = 0.034 < 0.05]. In subgroup analysis by age, sex, and BMI, women, age > 75 years, and BIM < 25 were statistically significant. CONCLUSION This study suggested that NAFLD is associated with a reduced risk of reduced heel bone mass. More research needs to be done to back up the results of this study and look into possible problems.
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Affiliation(s)
- Guangheng Zhang
- Department of Orthopaedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430077, China
| | - Yingsong Zhao
- Department of Orthopaedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430077, China
| | - Siyuan Wang
- Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430077, China
| | - Qing Gong
- Department of Gastroenterology, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, No. 1677 Wutaishan Road, Huangdao District, Qingdao, 266000, China
| | - Hewei Li
- Department of Orthopaedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430077, China.
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Liu F, Wu Y, Chen J, Zou T, Qin Y, Teng Z, Su Y, Wu R, Huang J. Risk factors for osteoporosis in chronic schizophrenia on long-term treatment with antipsychotics: a cross-sectional study. BMC Psychiatry 2023; 23:454. [PMID: 37344770 DOI: 10.1186/s12888-023-04951-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 06/11/2023] [Indexed: 06/23/2023] Open
Abstract
BACKGROUND Little is known about the laboratory variable risks with bone mineral density (BMD) in patients with schizophrenia. This study was designed to fully investigate the related risk factors for decreased BMD in schizophrenia, as well as evaluate the gender difference of BMD. METHOD The BMD of the forearm of 211 patients (males/females = 140/71) who met the diagnostic criteria for DSM-5 schizophrenia was measured by dual-energy X-ray absorptiometry. Basic demographic information, clinical assessments, and laboratory variables (regarding nutrition, hormones, metabolism, and inflammatory markers) were comprehensively collected. RESULTS Among 211 subjects, seventy-four (35%) patients had low BMD. Males had a significantly lower BMD T-score than females (P = 0.002). Multiple regression analyses showed that the independent risks with low BMD were lower folate, glycosylated hemoglobin levels, higher age, serum ferritin, and follicle-stimulating hormone (FSH) levels. In female patients, the BMD was mainly associated with age and serum hormones (FSH and testosterone), while the BMD of male patients was primarily related to age, microelements (serum ferritin and 25-OH-VD), and parathyroid hormone. CONCLUSION Our study found several meaningful correlations between osteoporosis and schizophrenia, especially regarding laboratory measures, which may provide new clues to identifying or preventing osteoporosis in clinical patients.
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Affiliation(s)
- Furu Liu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central, South University, 410011, Changsha, Hunan, China
| | - Ying Wu
- Department of Intensive Care Unit, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China
| | - Jindong Chen
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central, South University, 410011, Changsha, Hunan, China
| | - Tianxiang Zou
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central, South University, 410011, Changsha, Hunan, China
| | - Yue Qin
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central, South University, 410011, Changsha, Hunan, China
| | - Ziwei Teng
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central, South University, 410011, Changsha, Hunan, China
| | - Yuhan Su
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central, South University, 410011, Changsha, Hunan, China
| | - Renrong Wu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central, South University, 410011, Changsha, Hunan, China
| | - Jing Huang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central, South University, 410011, Changsha, Hunan, China.
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Hassan AM, Haridy MA, Shoaeir MZ, Abdel-Aziz TM, Qura MK, Kenawy EM, Mansour TMM, Salaheldin Elsayed S, Ali WE, Abdelmeguid MM, Abdel-Gawad M. Non-alcoholic fatty liver disease is associated with decreased bone mineral density in upper Egyptian patients. Sci Rep 2023; 13:4353. [PMID: 36928441 PMCID: PMC10020438 DOI: 10.1038/s41598-023-31256-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 03/08/2023] [Indexed: 03/18/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has been linked with a number of extra hepatic diseases and could be a potential risk factor of decreasing bone mineral density. To determine whether Upper Egyptian patients with NAFLD are at risk of developing osteoporosis. Cross sectional study was done on a total 100 individuals; 50 patients diagnosed with NAFLD (based on ultrasound imaging) crossed-matched with 50 individuals without NAFLD based on age, sex and body mass index. Bone mineral density, serum calcium and phosphorus levels, serum parathyroid hormone, serum vitamin D and fasting insulin level were assessed. Osteoporosis was prevalent in NAFLD patients versus to controls (19/50 vs. 0/50; P < 0.001). There was significant decrease in bone mineral density in NAFLD patients than controls (- 2.29 ± 0.4 vs. - 1.53 ± 0.1; P < 0.001). There was a statistical significance decrease in serum vitamin D and calcium levels in NAFLD patients than controls. Furthermore, vitamin D levels in the NAFLD group was a predictor for osteoporosis (OR 0.614; 95% CI 0.348-0.825). Patients with NAFLD tend to have a significant decrease in bone density, vitamin D, and serum calcium levels than controls.
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Affiliation(s)
- Amro M Hassan
- Hepatology, Gastroenterology and Infectious Diseases Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt.
| | - Mustafa Ahmed Haridy
- Hepatology, Gastroenterology and Infectious Diseases Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
| | - Mohamed Z Shoaeir
- Rheumatology and Rehabilitation Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
| | - Tarek M Abdel-Aziz
- Rheumatology and Rehabilitation Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
| | - Mohamed Khairy Qura
- Rheumatology and Rehabilitation Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
| | - Eglal M Kenawy
- Internal Medicine Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
| | | | | | - Wael Esmat Ali
- Clinical Pathology Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
| | | | - Muhammad Abdel-Gawad
- Hepatology, Gastroenterology and Infectious Diseases Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
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Tsutsumi T, Nakano D, Hashida R, Sano T, Kawaguchi M, Amano K, Kawaguchi T. The Inter-Organ Crosstalk Reveals an Inevitable Link between MAFLD and Extrahepatic Diseases. Nutrients 2023; 15:nu15051123. [PMID: 36904122 PMCID: PMC10005526 DOI: 10.3390/nu15051123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 02/19/2023] [Accepted: 02/21/2023] [Indexed: 02/25/2023] Open
Abstract
Fatty liver is known to be associated with extra-hepatic diseases including atherosclerotic cardiovascular disease and extra-hepatic cancers, which affect the prognosis and quality of life of the patients. The inter-organ crosstalk is mediated by metabolic abnormalities such as insulin resistance and visceral adiposity. Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed as a new definition for fatty liver. MAFLD is characterized by the inclusion criteria of metabolic abnormality. Therefore, MAFLD is expected to identify patients at high risk of extra-hepatic complications. In this review, we focus on the relationships between MAFLD and multi-organ diseases. We also describe the pathogenic mechanisms of the inter-organ crosstalk.
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Affiliation(s)
- Tsubasa Tsutsumi
- Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan
| | - Dan Nakano
- Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan
| | - Ryuki Hashida
- Department of Orthopedics, School of Medicine, Kurume University, Kurume 830-0011, Japan
| | - Tomoya Sano
- Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan
| | - Machiko Kawaguchi
- Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan
| | - Keisuke Amano
- Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan
- Correspondence: ; Tel.: +81-942-31-7627
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12
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Khan S, Kalkwarf HJ, Hornung L, Siegel R, Arce-Clachar AC, Sheridan R, Ippisch HM, Xanthakos SA. Histologic Severity of Nonalcoholic Fatty Liver Disease Associates with Reduced Bone Mineral Density in Children. Dig Dis Sci 2023; 68:644-655. [PMID: 35672623 PMCID: PMC10042591 DOI: 10.1007/s10620-022-07563-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 05/09/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Lower whole body bone mineral density (BMD) has been reported in children with nonalcoholic fatty liver disease (NAFLD), but potential mediators remain uncertain. AIMS To assess BMD at multiple skeletal sites in children with confirmed NAFLD and controls with obesity, adjusting for known determinants of BMD, and examine potential mediators. METHODS We assessed age-, sex-, and race-specific, and height-adjusted BMD z-scores of whole body, lumbar spine, hip, femoral neck and forearm by dual-energy-x-ray absorptiometry in 79 children, 8-19 years old: 46 with biopsy-confirmed NAFLD [29 steatohepatitis (NASH)/17 fatty liver (NAFL)] and 33 controls without liver disease. We compared BMD z-scores by multivariable regression, adjusting for known BMD determinants and potential mediators (inflammatory and insulin resistance measures). RESULTS Unadjusted mean BMD z-scores in NAFLD were similar to controls, but significantly lower in NASH vs. NAFL at all sites. After covariate adjustment, mean forearm BMD z-score was higher in NAFL (β 0.60 ± SE 0.30, p < 0.05) and lower in NASH (β - 0.49 ± SE 0.26, p = 0.06) vs. controls (p = 0.002 for group), with similar trends at whole body and total hip; hs-CRP negatively associated with whole body and forearm BMD z-scores (p < 0.05), while visceral fat area negatively associated with femoral neck (p < 0.05). Only three children had clinically low whole body BMD z-scores (< - 2), one per group (control, NAFL and NASH). CONCLUSIONS NASH, but not NAFL, may be associated with increased risk of reduced BMD in children. Systemic inflammation, independent of body composition and load bearing, may mediate reduction in BMD in NASH.
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Affiliation(s)
- Soofia Khan
- Division of Gastroenterology, Phoenix Children's, Phoenix, AZ, USA
| | - Heidi J Kalkwarf
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center Cincinnati, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Lindsey Hornung
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, USA
| | - Robert Siegel
- The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Ana Catalina Arce-Clachar
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center Cincinnati, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Rachel Sheridan
- Department of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Holly M Ippisch
- The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Stavra A Xanthakos
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center Cincinnati, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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13
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Kim MJ, Kim MS, Lee HB, Roh JH, Jeon JH. Relationship between the High Fatty Liver Index and Risk of Fracture. Gut Liver 2023; 17:119-129. [PMID: 35892266 PMCID: PMC9840917 DOI: 10.5009/gnl210571] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 04/15/2022] [Accepted: 05/03/2022] [Indexed: 02/01/2023] Open
Abstract
Background/Aims The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased rapidly as a consequence of more sedentary lifestyles and a Westernized diet. Fracture is a major clinical problem in older people, but few large-scale cohort studies have evaluated the relationship between NAFLD and fracture. Therefore, we aimed to determine whether the fatty liver index (FLI), which represents the severity of NAFLD, can predict fracture risk. Methods We analyzed the relationship between the FLI and incident fracture using multivariate Cox proportional hazards models and data for 180,519 individuals who underwent National Health check-ups in the Republic of Korea between 2009 and 2014. Results A total of 2,720 participants (1.5%) were newly diagnosed with fracture during the study period (median 4.6 years). The participants were grouped according to FLI quartiles (Q1, 0 to <5.653; Q2, 5.653 to <15.245; Q3, 15.245 to <37.199; and Q4 ≥37.199). The cumulative fracture incidence was significantly higher in the highest FLI group than in the lowest FLI group (Q4, 986 [2.2%] and Q1, 323 [0.7%]; p<0.001). The adjusted hazard ratio indicated that the highest FLI group was independently associated with a higher incidence of fracture (hazard ratio for Q4 vs Q1, 2.956; 95% confidence interval, 2.606 to 3.351; p<0.001). FLI was significantly associated with a higher incidence of fracture, independent of the baseline characteristics of the participants. Conclusions Our data imply that the higher the FLI of a Korean patient is, the higher their risk of osteoporotic fracture, independent of key confounding factors. (Gut Liver, Published online July 27, 2022).
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Affiliation(s)
- Min-Ji Kim
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - Min-Su Kim
- Department of Internal Medicine, Chungnam National University Sejong Hospital, Chungnam National University College of Medicine, Sejong, Korea
| | - Han-Byul Lee
- Department of Statistics, Kyungpook National University, Daegu, Korea
| | - Jae-Hyung Roh
- Department of Internal Medicine, Chungnam National University Sejong Hospital, Chungnam National University College of Medicine, Sejong, Korea
| | - Jae-Han Jeon
- Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
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14
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Bott KN, Feldman E, de Souza RJ, Comelli EM, Klentrou P, Peters SJ, Ward WE. Lipopolysaccharide-Induced Bone Loss in Rodent Models: A Systematic Review and Meta-Analysis. J Bone Miner Res 2023; 38:198-213. [PMID: 36401814 PMCID: PMC10107812 DOI: 10.1002/jbmr.4740] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 10/27/2022] [Accepted: 11/03/2022] [Indexed: 11/21/2022]
Abstract
Osteoporosis has traditionally been characterized by underlying endocrine mechanisms, though evidence indicates a role of inflammation in its pathophysiology. Lipopolysaccharide (LPS), a component of gram-negative bacteria that reside in the intestines, can be released into circulation and stimulate the immune system, upregulating bone resorption. Exogenous LPS is used in rodent models to study the effect of systemic inflammation on bone, and to date a variety of different doses, routes, and durations of LPS administration have been used. The study objective was to determine whether systemic administration of LPS induced inflammatory bone loss in rodent models. A systematic search of Medline and four other databases resulted in a total of 110 studies that met the inclusion criteria. Pooled standardized mean differences (SMDs) and corresponding 95% confidence intervals (CI) with a random-effects meta-analyses were used for bone volume fraction (BV/TV) and volumetric bone mineral density (vBMD). Heterogeneity was quantified using the I2 statistic. Shorter-term (<2 weeks) and longer-term (>2 weeks) LPS interventions were analyzed separately because of intractable study design differences. BV/TV was significantly reduced in both shorter-term (SMD = -3.79%, 95% CI [-4.20, -3.38], I2 62%; p < 0.01) and longer-term (SMD = -1.50%, 95% CI [-2.00, -1.00], I2 78%; p < 0.01) studies. vBMD was also reduced in both shorter-term (SMD = -3.11%, 95% CI [-3.78, -2.44]; I2 72%; p < 0.01) and longer-term (SMD = -3.49%, 95% CI [-4.94, -2.04], I2 82%; p < 0.01) studies. In both groups, regardless of duration, LPS negatively impacted trabecular bone structure but not cortical bone structure, and an upregulation in bone resorption demonstrated by bone cell staining and serum biomarkers was reported. This suggests systemically delivered exogenous LPS in rodents is a viable model for studying inflammatory bone loss, particularly in trabecular bone. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Affiliation(s)
- Kirsten N Bott
- Department of Kinesiology, Brock University, St. Catharines, ON, Canada.,Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
| | - Evelyn Feldman
- Lakehead University Library, Lakehead University, Thunder Bay, ON, Canada
| | - Russell J de Souza
- Department of Health Research Methods, Evidence, and Impact, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.,Population Health Research Institute, Hamilton Health Sciences Corporation, Hamilton, ON, Canada
| | - Elena M Comelli
- Department of Kinesiology, Brock University, St. Catharines, ON, Canada.,Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.,Joannah and Brian Lawson Centre for Child Nutrition, University of Toronto, Toronto, ON, Canada
| | - Panagiota Klentrou
- Department of Kinesiology, Brock University, St. Catharines, ON, Canada.,Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
| | - Sandra J Peters
- Department of Kinesiology, Brock University, St. Catharines, ON, Canada.,Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
| | - Wendy E Ward
- Department of Kinesiology, Brock University, St. Catharines, ON, Canada.,Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada.,Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.,Department of Health Sciences, Brock University, St. Catharines, ON, Canada
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15
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Yu Z, Wu Y, Zhang R, Li Y, Zang S, Liu J. Increased risk of non-alcoholic fatty liver disease fibrosis is closely associated with osteoporosis in women but not in men with type 2 diabetes. Endocr Connect 2022; 11:e220174. [PMID: 36129166 PMCID: PMC9578104 DOI: 10.1530/ec-22-0174] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 08/10/2022] [Indexed: 11/30/2022]
Abstract
Background This study aimed to investigate the association of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis with osteoporosis in postmenopausal women and men over 50 years of age with type 2 diabetes (T2DM). Methods In this study, 1243 patients with T2DM (T2DM with coexistent NAFLD, n = 760; T2DM with no NAFLD, n = 483) were analysed. Non-invasive markers, NAFLD fibrosis score (NFS) and fibrosis index based on four factors (FIB-4), were applied to evaluate NAFLD fibrosis risk. Results There was no significant difference in bone mineral density (BMD) between the NAFLD group and the non-NAFLD group or between males and females after adjusting for age, BMI and gender. In postmenopausal women, there was an increased risk of osteoporosis (odds ratio (OR): 4.41, 95% CI: 1.04-18.70, P = 0.039) in the FIB-4 high risk group compared to the low risk group. Similarly, in women with high risk NFS, there was an increased risk of osteoporosis (OR: 5.98, 95% CI: 1.40-25.60, P = 0.043) compared to the low risk group. Among men over 50 years old, there was no significant difference in bone mineral density between the NAFLD group and the non-NAFLD group and no significant difference between bone mineral density and incidence of osteopenia or osteoporosis among those with different NAFLD fibrosis risk. Conclusion There was a significant association of high risk for NAFLD liver fibrosis with osteoporosis in postmenopausal diabetic women but not men. In clinical practice, gender-specific evaluation of osteoporosis is needed in patients with T2DM and coexistent NAFLD.
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Affiliation(s)
- Zhiyan Yu
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Yueyue Wu
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Rui Zhang
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Yue Li
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Shufei Zang
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Jun Liu
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
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16
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Wester A, Hagström H. Risk of fractures and subsequent mortality in non-alcoholic fatty liver disease: A nationwide population-based cohort study. J Intern Med 2022; 292:492-500. [PMID: 35373876 PMCID: PMC9545244 DOI: 10.1111/joim.13497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Studies suggest an association between osteoporosis and non-alcoholic fatty liver disease (NAFLD), but whether patients with NAFLD are at increased risk of fractures is unknown. OBJECTIVES The aim was to determine the rate and risk of fractures and the mortality rate after fracture in patients with NAFLD compared to the general population. METHODS This was a nationwide population-based cohort study using data from the Swedish National Patient Registry on 10,678 patients with NAFLD from 1987 to 2016. Patients were matched for sex, age, and municipality with 99,176 controls from the Swedish Total Population Registry. Cox regression was used to estimate fracture rates. The risk of fractures was assessed while accounting for competing risks (death and liver transplantation). RESULTS A total of 12,312 fractures occurred during 761,176 person-years of follow-up. Patients with NAFLD (17.5 per 1000 person-years) had a slightly higher fracture rate than controls (16.1 per 1000 person-years; adjusted hazard ratio 1.11, 95% confidence interval [CI] 1.05-1.19), although the 5-year risk of fractures was similar (8.0%, 95% CI 7.4-8.6 versus 7.3%, 95% CI 7.2-7.5). Additionally, 1-year mortality after fracture was similar in NAFLD and controls. CONCLUSIONS Patients with NAFLD have a slightly higher rate of fractures but long-term risk of fractures comparable to the general population. This suggests that broad surveillance of risk factors for fractures in patients with NAFLD is not motivated.
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Affiliation(s)
- Axel Wester
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Hannes Hagström
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.,Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden.,Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
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17
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The association of nonalcoholic fatty liver disease with bone mineral density in type 2 diabetes. Eur J Med Res 2022; 27:143. [PMID: 35934712 PMCID: PMC9358869 DOI: 10.1186/s40001-022-00775-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 07/26/2022] [Indexed: 11/10/2022] Open
Abstract
Objective We examined the association between nonalcoholic fatty liver disease and lumbar spine bone mineral density in individuals with and without type 2 diabetes. Methods The lumbar BMD of 1088 subjects was measured using dual-energy X-ray absorptiometry (DXA). Liver fat content was quantified via B-mode ultrasound. Multivariable linear regression was used to study the association between NAFLD and lumbar BMD in participants with and without T2DM. Results The lumbar BMD in the T2DM group and the non-diabetes group was higher in the NAFLD group than in the non-NAFLD group (P < 0.001). Multivariate regression analysis in the T2DM group showed that after adjusting for confounders, the positive association between lumbar spine BMD and NAFLD remained (P = 0.027). In the non-diabetes group, after adjusting for confounders, the association between NAFLD and lumbar spine BMD disappeared. Conclusions The relationship between nonalcoholic fatty liver disease and lumbar bone mineral density may differ in individuals with and without diabetes. The effect of nonalcoholic fatty liver disease on bone mineral density needs to be evaluated in different clinical contexts.
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18
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Rahimpour Z, Hoseini R, Behpour N. Alterations of liver enzymes and lipid profile in response to exhaustive eccentric exercise: vitamin D supplementation trial in overweight females with non-alcoholic fatty liver disease. BMC Gastroenterol 2022; 22:372. [PMID: 35927637 PMCID: PMC9354270 DOI: 10.1186/s12876-022-02457-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 07/31/2022] [Indexed: 11/10/2022] Open
Abstract
Background Eccentric exhaustive exercise (EEE) training has been known as a promising training modality to enhance performance and stimulate adaptation in healthy individuals or patients that might also cause abnormal liver enzymes and lipid profiles. Vitamin D (Vit D) supplementation is believed to improve the condition of Non-Alcoholic Fatty Liver Disease (NAFLD) patients. However, there is limited evidence on the effect of Vit D supplementation on the EEE-induced alterations. This study aimed to investigate the effect of short-term supplementation of Vit D on the liver enzymes and lipid profile alterations following EEE in overweight women with NAFLD. Methods In this clinical trial, 22 overweight women with NAFLD were randomly divided into experimental and control (n = 11 in each). The experimental group consumed 2000 IU of Vit D per day for six weeks; the control group consumed a lactose placebo daily with the same color, shape, and warmth percentage. Two treadmill EEE sessions were performed before and after the six-week Vit D supplementation. Blood was taken from the antecubital vein to measure the liver enzymes, lipid profile, and Vit D at four stages: Pre 1(before the first EEE session), Post 1(after the first EEE session), Pre 2 (before the second EEE session), and Post 2 (after the second EEE session). Results The results indicate that Vit D supplementation significantly reduced Bodyweight (BW; P = 0.047), Body Mass Index (BMI; P = 0.044), Body Fat Percentage (BFP; P = 0.001), and Waist Hip Ratio (WHR; P = 0.001) in the experimental group. Additionally, the results showed increased liver enzymes (ALT, AST, and GGT) and lipid profile (TC, TG, and LDL) following EEE. While the HDL levels decreased significantly after EEE. Compared with control, the results of the independent t-test showed significantly lower ALT (P = 0.001; P = 0.001), AST (P = 0.001; P = 0.001), and GGT (P = 0.001; P = 0.001); while significantly higher Vit D (P = 0.001, P = 0.001) in the experimental in both Pre 2 and Post 2; receptively. Also, significantly lower TC (P = 0.001; P = 0.001), TG (P = 0.048; P = 0.001), and LDL (P = 0.001; P = 0.001); while significantly higher HDL (P = 0.001, P = 0.001) were observed in the experimental group compared to the control in both Pre 2 and Post 2; receptively. Conclusions Vit D supplementation reduces the liver enzymes and improves lipid profile alterations following EEE in overweight women with NAFLD. Thus, Vit D supplementation can be considered a functional supplement to improve the EEE-induced alteration. Trial registration: The trial was in the Iranian Clinical Trial Registration Center under the (IRCT20201130049538N1) on 05/07/2021.
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Affiliation(s)
- Zahra Rahimpour
- Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran
| | - Rastegar Hoseini
- Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran.
| | - Nasser Behpour
- Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran
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19
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Liu Y, Shuai P, Liu Y, Li D. Association between non-alcoholic fatty liver disease and bone turnover markers in southwest China. J Bone Miner Metab 2022; 40:712-719. [PMID: 35639173 DOI: 10.1007/s00774-022-01340-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 05/03/2022] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is not considered only a liver disease but also associated with an increased risk of extra-hepatic diseases including bone metabolism disorders. In our study, we aim to explore the changes of several bone turnover markers (BTMs) under different fat deposition and stiffness levels of the liver. MATERIALS AND METHODS We analyzed the physical examination data of 3353 subjects from February 2018 to June 2021 in this study. The steatosis and stiffness of liver were quantitatively detected using the fat attenuation parameter (FAP) and liver stiffness measurements (LSM) of transient elastography (TE). Serum 25-hydroxyvitamin D3 (25(OH)D3), osteocalcin, carboxy-terminal collagen crosslinks (CTX), amino terminal elongation peptide of total type 1 procollagen (P1NP) were tested. Clinical and other biochemical data were also collected. RESULTS With the increasing of FAP, the levels of 25(OH)D3 and osteocalcin decreased, the difference was statistically significant. No correlation was found between LSM and all the four BTMs. Logistic regression analysis revealed that FAP ≥ 244 dB/m was negatively correlated with 25(OH)D3 (in both males and females) and osteocalcin (only in males). No correlation was found between FAP ≥ 244 dB/m and P1NP or CTX. CONCLUSION The degree of liver adipose deposition was found to be negatively associated with the serum levels of 25(OH)D3 (in both males and females) and osteocalcin (only in males) in southwest China.
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Affiliation(s)
- Ying Liu
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan Province, China
- Department of Health Management Center and Institute of Health Management, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 Section 2, West 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China
| | - Ping Shuai
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan Province, China
- Department of Health Management Center and Institute of Health Management, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 Section 2, West 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China
| | - Yuping Liu
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan Province, China
- Department of Health Management Center and Institute of Health Management, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 Section 2, West 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China
| | - Dongyu Li
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan Province, China.
- Department of Health Management Center and Institute of Health Management, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 Section 2, West 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China.
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20
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Von-Hafe M, Borges-Canha M, Vale C, Leite AR, Sérgio Neves J, Carvalho D, Leite-Moreira A. Nonalcoholic Fatty Liver Disease and Endocrine Axes-A Scoping Review. Metabolites 2022; 12:298. [PMID: 35448486 PMCID: PMC9026925 DOI: 10.3390/metabo12040298] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 03/20/2022] [Accepted: 03/27/2022] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD often occurs associated with endocrinopathies. Evidence suggests that endocrine dysfunction may play an important role in NAFLD development, progression, and severity. Our work aimed to explore and summarize the crosstalk between the liver and different endocrine organs, their hormones, and dysfunctions. For instance, our results show that hyperprolactinemia, hypercortisolemia, and polycystic ovary syndrome seem to worsen NAFLD's pathway. Hypothyroidism and low growth hormone levels also may contribute to NAFLD's progression, and a bidirectional association between hypercortisolism and hypogonadism and the NAFLD pathway looks likely, given the current evidence. Therefore, we concluded that it appears likely that there is a link between several endocrine disorders and NAFLD other than the typically known type 2 diabetes mellitus and metabolic syndrome (MS). Nevertheless, there is controversial and insufficient evidence in this area of knowledge.
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Affiliation(s)
- Madalena Von-Hafe
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; (M.V.-H.); (C.V.); (A.R.L.); (J.S.N.); (A.L.-M.)
| | - Marta Borges-Canha
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; (M.V.-H.); (C.V.); (A.R.L.); (J.S.N.); (A.L.-M.)
- Serviço de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal;
| | - Catarina Vale
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; (M.V.-H.); (C.V.); (A.R.L.); (J.S.N.); (A.L.-M.)
| | - Ana Rita Leite
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; (M.V.-H.); (C.V.); (A.R.L.); (J.S.N.); (A.L.-M.)
| | - João Sérgio Neves
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; (M.V.-H.); (C.V.); (A.R.L.); (J.S.N.); (A.L.-M.)
- Serviço de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal;
| | - Davide Carvalho
- Serviço de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal;
- Investigação e Inovação em Saúde (i3s), Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal
| | - Adelino Leite-Moreira
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; (M.V.-H.); (C.V.); (A.R.L.); (J.S.N.); (A.L.-M.)
- Serviço de Cirurgia Cardiotorácica do Centro Hospitalar Universitário de São João, 4200-319 Porto, Portugal
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21
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Xie R, Liu M. Relationship Between Non-Alcoholic Fatty Liver Disease and Degree of Hepatic Steatosis and Bone Mineral Density. Front Endocrinol (Lausanne) 2022; 13:857110. [PMID: 35360054 PMCID: PMC8964007 DOI: 10.3389/fendo.2022.857110] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 02/22/2022] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The liver and bones are both active endocrine organs that carry out several metabolic functions. However, the link between non-alcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) is still controversial. The goal of this study was to discover if there was a link between non-alcoholic fatty liver disease and bone mineral density in US persons aged 20 to 59 years of different genders and races. METHODS Using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, multivariate logistic regression models were utilized to investigate the association between NAFLD and lumbar BMD. Fitted smoothing curves and generalized additive models were also used. RESULTS The analysis included a total of 1980 adults. After controlling for various variables, we discovered that NAFLD was negatively linked with lumbar BMD. The favorable connection of NAFLD with lumbar BMD was maintained in subgroup analyses stratified by sex, race and age in men, other race and aged 20-29 years. The relationship between NAFLD and lumbar BMD in blacks and people aged 40-49 years was a U-shaped curve with the inflection point: at 236dB/m and 262dB/m. Furthermore, we discovered that liver advanced fibrosis and liver cirrhosis were independently connected with higher BMD, while no significant differences were detected in severe liver steatosis and BMD. CONCLUSIONS Our study found an independently unfavorable relationship between NAFLD and BMD in persons aged 20 to 59. We also discovered a positive link between BMD and advanced fibrosis and cirrhosis. More research is needed to back up the findings of this study and to look into the underlying issues.
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Affiliation(s)
| | - Mingjiang Liu
- Department of Hand Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
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22
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Zheng CS, Wen HQ, Lin WS, Luo XW, Shen LS, Zhou X, Zou FY, Li QL, Hu HJ, Guo RM. Quantification of lumbar vertebral fat deposition: Correlation with menopausal status, non-alcoholic fatty liver disease and subcutaneous adipose tissue. Front Endocrinol (Lausanne) 2022; 13:1099919. [PMID: 36714601 PMCID: PMC9878446 DOI: 10.3389/fendo.2022.1099919] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 12/27/2022] [Indexed: 01/15/2023] Open
Abstract
PURPOSE To assess abdominal fat deposition and lumbar vertebra with iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) and investigate their correlation with menopausal status. MATERIALS AND METHODS Two hundred forty women who underwent routine abdominal MRI and IDEAL-IQ between January 2016 and April 2021 were divided into two cohorts (first cohort: 120 pre- or postmenopausal women with severe fatty livers or without fatty livers; second cohort: 120 pre- or postmenopausal women who were obese or normal weight). The fat fraction (FF) values of the liver (FFliver) and lumbar vertebra (FFlumbar) in the first group and the FF values of subcutaneous adipose tissue (SAT) (FFSAT) and FFlumbar in the second group were measured and compared using IDEAL-IQ. RESULTS Two hundred forty women were evaluated. FFlumbar was significantly higher in both pre- and postmenopausal women with severe fatty liver than in patients without fatty livers (premenopausal women: p < 0.001, postmenopausal women: p < 0.001). No significant difference in the FFlumbar was observed between obese patients and normal-weight patients among pre- and postmenopausal women (premenopausal women: p = 0.113, postmenopausal women: p = 0.092). Significantly greater lumbar fat deposition was observed in postmenopausal women than in premenopausal women with or without fatty liver and obesity (p < 0.001 for each group). A high correlation was detected between FFliver and FFlumbar in women with severe fatty liver (premenopausal women: r=0.76, p<0.01; postmenopausal women: r=0.82, p<0.01). CONCLUSION Fat deposition in the vertebral marrow was significantly associated with liver fat deposition in postmenopausal women.
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Affiliation(s)
- Chu-Shan Zheng
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hui-Quan Wen
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wu-Sheng Lin
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiao-Wen Luo
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Li-Shan Shen
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiang Zhou
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Feng-Yun Zou
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qing-Ling Li
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of VIP Medical Center, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- *Correspondence: Qing-Ling Li, ; Hui-Jun Hu, ; Ruo-Mi Guo,
| | - Hui-Jun Hu
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- *Correspondence: Qing-Ling Li, ; Hui-Jun Hu, ; Ruo-Mi Guo,
| | - Ruo-Mi Guo
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- *Correspondence: Qing-Ling Li, ; Hui-Jun Hu, ; Ruo-Mi Guo,
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23
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Loosen SH, Roderburg C, Demir M, Qvartskhava N, Keitel V, Kostev K, Luedde T. Non-alcoholic fatty liver disease (NAFLD) is associated with an increased incidence of osteoporosis and bone fractures. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 60:1221-1227. [PMID: 34710938 DOI: 10.1055/a-1482-9236] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and osteoporosis are common diseases with a rising incidence worldwide. Both diseases occur in similar patient populations, however, data on their mutual influence are conflicting. Here, we aimed to evaluate the impact of NAFLD on the incidence of osteoporosis and fractures by using the Disease Analyzer database featuring data on diagnoses, prescriptions, and demographic aspects of 7.49 million cases followed in general practices in Germany. METHODS A total of 50,689 patients with NAFLD diagnosed between 2000 and 2015 were matched by age, sex, index year, and 3 comorbidities (obesity, diabetes mellitus, and vitamin D/calcium deficiency) to a cohort of equal size without NAFLD. Incidence of osteoporosis and bone fractures were compared between both groups within 10 years from the index date. RESULTS Within the observation period, the incidence of osteoporosis was significantly higher in the NAFLD group (6.4%) compared to patients without NAFLD (5.1%; log-rank, p < 0.001). Similar results were observed for bone fractures (12.6 vs. 10.3 %; log-rank p < 0.001). The difference was more pronounced in women compared to men and observed in all age groups >50 years of age. CONCLUSION Our data show that NAFLD is significantly associated with osteoporosis as well as bone fractures in a large cohort of patients followed in German general practices. This finding suggests that NAFLD patients might benefit from improved monitoring for the occurrence of bone demineralization and osteoporosis, which in turn could trigger preventive therapeutic measures.
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Affiliation(s)
- Sven H Loosen
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty of Heinrich Heine University Düsseldorf, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Christoph Roderburg
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty of Heinrich Heine University Düsseldorf, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Münevver Demir
- Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, Germany
| | - Natalia Qvartskhava
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty of Heinrich Heine University Düsseldorf, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Verena Keitel
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty of Heinrich Heine University Düsseldorf, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Karel Kostev
- Epidemiologie, IQVIA Germany, Frankfurt, Germany
| | - Tom Luedde
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty of Heinrich Heine University Düsseldorf, University Hospital Düsseldorf, Düsseldorf, Germany
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Hepatic fibrosis is associated with an increased rate of decline in bone mineral density in men with nonalcoholic fatty liver disease. Hepatol Int 2021; 15:1347-1355. [PMID: 34608587 DOI: 10.1007/s12072-021-10254-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 09/11/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND There is still controversy about the association between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD). The aim of this study was to clarify the association between NAFLD and the decline in BMD in healthcare examinees. METHODS Participants who underwent regular health check-ups with BMD and hepatic ultrasonography from 2006 to 2015 with more than one follow-up until 2020 were included. Propensity score matching was performed between the NAFLD group and the control group, and mixed linear regression models were used for the longitudinal analysis. RESULTS Of 2623 eligible participants (mean age 58.7 ± 7.3 years; males 31.3%), 888 (33.9%) had NAFLD. At baseline, the NAFLD group had a higher total hip BMD than the non-NAFLD group in men (0.988 vs. 1.015 g/cm2, p = 0.007); however, there was no difference in baseline BMD in women (p = 0.253). In longitudinal analysis during a follow-up period of 7.1 years, there was no significant difference in the BMD decline rate between the two groups in the PS-matched cohort (p = 0.816 in men and p = 0.827 in women). However, among men with NAFLD, those with a high and intermediate probability of advanced fibrosis by the FIB-4 showed a significantly increased rate of decline in total hip BMD compared to those with low scores (0.01 vs. - 0.19% change/year, p = 0.011). CONCLUSIONS NAFLD was not associated with the total hip BMD decline rate. However, hepatic fibrosis was significantly associated with an increased rate of decline in total hip BMD in men with NAFLD. CLINICAL TRIAL REGISTRATION This study is a retrospective observational study and is not a drug trial. There was no need for clinical trial registration.
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25
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Kang SH, Lee HW, Yoo JJ, Cho Y, Kim SU, Lee TH, Jang BK, Kim SG, Ahn SB, Kim H, Jun DW, Choi JI, Song DS, Kim W, Jeong SW, Kim MY, Koh H, Jeong S, Lee JW, Cho YK. KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease. Clin Mol Hepatol 2021; 27:363-401. [PMID: 34154309 PMCID: PMC8273632 DOI: 10.3350/cmh.2021.0178] [Citation(s) in RCA: 166] [Impact Index Per Article: 41.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Affiliation(s)
- Seong Hee Kang
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, SoonChunHyang University Bucheon Hospital, Bucheon, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul Korea
| | - Tae Hee Lee
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea
| | - Byoung Kuk Jang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, SoonChunHyang University Bucheon Hospital, Bucheon, Korea
| | - Sang Bong Ahn
- Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Joon-Il Choi
- Department of Radiology, Seoul St.Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Do Seon Song
- Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hong Koh
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Korea
| | - Sujin Jeong
- Division of Pediatric Gastroenterology Hepatology and Nutrition, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Jin-Woo Lee
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Yong Kyun Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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Xiu L, Jiang T, Yao XA, Wen Z. Correlation Between 25 Hydroxyvitamin D Levels and Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study. Int J Gen Med 2021; 14:3099-3107. [PMID: 34234538 PMCID: PMC8257066 DOI: 10.2147/ijgm.s319449] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 06/15/2021] [Indexed: 12/20/2022] Open
Abstract
Purpose We aimed to analyze the serum vitamin D level in Chinese patients with type 2 diabetes mellitus (T2DM) and discuss its correlation with nonalcoholic fatty liver disease (NAFLD). Patients and Methods A total of 300 patients with T2DM (92 patients without NAFLD and 208 patients with NAFLD) were enrolled, and 25-hydroxyvitamin D [25-(OH)D] levels were compared between the two groups. Second, the NAFLD fibrosis score (NFS) and fatty liver index (FLI) were used to group patients with T2DM complicated by NAFLD, and the differences in serum 25-(OH)D in patients with different degrees of liver fibrosis were compared. Third, multiple regression analysis was used to analyze the independent predictors of liver fibrosis in patients with T2DM complicated by NAFLD. Results The level of 25-(OH)D in patients with T2DM complicated by NAFLD was significantly lower than that in patients with T2DM alone. Based on the NFS and FLI, the 25-(OH)D level of the hepatic fibrosis subgroup was significantly lower than that of the subgroup without liver fibrosis. 25-(OH)D was found to be an independent predictor of liver fibrosis in patients with T2DM complicated by NAFLD. Conclusion The serum 25-(OH)D level in patients with T2DM complicated by NAFLD was significantly reduced, and the 25-(OH)D level showed a gradual downward trend with the degree of liver fibrosis. Low concentrations of 25-(OH)D may be indicative of the degree of liver fibrosis in diabetic patients.
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Affiliation(s)
- Lei Xiu
- Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China
| | - Tao Jiang
- Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China
| | - Xiao-Ai Yao
- Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China
| | - Zhen Wen
- Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China
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Mahmoudi L, Asadi S, Al-Mousavi Z, Niknam R. A randomized controlled clinical trial comparing calcitriol versus cholecalciferol supplementation to reduce insulin resistance in patients with non-alcoholic fatty liver disease. Clin Nutr 2021; 40:2999-3005. [PMID: 33341312 DOI: 10.1016/j.clnu.2020.11.037] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 11/17/2020] [Accepted: 11/27/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world with no definite treatment. Insulin resistance (IR) and low serum vitamin D are closely linked to NAFLD. Since there is no comparative study on the effect of calcitriol with cholecalciferol on NAFLD based on homeostasis model of insulin resistance (HOMA-IR) as an IR indicator, so we designed this research. METHODS A double blind randomized clinical trial was conducted on patients with NAFLD with concomitant vitamin D deficiency/insufficiency at two referral tertiary teaching medical centers, from July 2017 to January 2019. Patients were randomly divided into two groups: calcitriol (1 mcg/day) and cholecalciferol (50,000 IU/week) for 8 weeks. Before and after the intervention, anthropometric and laboratory data were measured and HOMA-IR was calculated for each patient. RESULTS 54 patients completed the trial. In total, calcitriol supplementation improved serum insulin levels as well as IR based on the HOMA-IR index, significantly compared to the cholecalciferol group. HOMA-IR decreased 1.8 times more in patients receiving calcitriol than in those receiving cholecalciferol, which was clinically meaningful. The observed changes were more pronounced in patients with higher baseline body mass index. Moreover, calcitriol was more associated with a significant decrease in liver enzymes and cholesterol levels comparing to cholecalciferol. CONCLUSION Based on the findings of this study, the use of calcitriol supplementation significantly reduced HOMA-IR as an IR indicator in NAFLD patients, compared to cholecalciferol. To confirm this findings, further studies with larger sample sizes are recommended.
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Affiliation(s)
- Laleh Mahmoudi
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sara Asadi
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Al-Mousavi
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ramin Niknam
- Department of Internal Medicine, School of Medicine, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
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Imamura Y, Mawatari S, Oda K, Kumagai K, Hiramine Y, Saishoji A, Kakihara A, Nakahara M, Oku M, Hosoyamada K, Kanmura S, Moriuchi A, Miyahara H, Akio Ido. Changes in body composition and low blood urea nitrogen level related to an increase in the prevalence of fatty liver over 20 years: A cross-sectional study. Hepatol Res 2021; 51:570-579. [PMID: 33675676 DOI: 10.1111/hepr.13631] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 02/13/2021] [Accepted: 02/28/2021] [Indexed: 02/08/2023]
Abstract
AIM Qualitative body composition (BC) change, characterized by the combination of visceral fat gain and muscle loss, is drawing attention as a risk factor for fatty liver (FL). The present study aimed to describe trends in BC change and its association with FL in the Japanese population. METHODS Data from medical checkups carried out on 56 639 Japanese participants every 5 years from 1997 to 2017 were analyzed. Fat mass index (FMI) and fat-free mass index (FFMI) were calculated using body mass index and body fat percentage. Subjects were divided into two groups according to deviations from the correlation line of FMI and FFMI as the reference: FMI-predominant BC and FFM-dominant BC. Fatty liver was determined using abdominal ultrasonography. RESULTS The prevalence of FL significantly increased from 27.3% to 42.7% in men and from 18.0% to 25.5% in women. The prevalence of FMI predominance significantly increased from 33.6% to 43.9% in men and from 29.1% to 47.0% in women. Fat mass index predominance was independently associated with FL in men and women (odds ratio: 1.96 and 1.94, respectively). Serum blood urea nitrogen level was inversely associated with FL in men and women (0.958 and 0.961, respectively) and significantly decreased from 15.8 to 14.9 mg/dl in men and from 15.1 to 14.0 mg/dl in women. CONCLUSIONS Increasing FMI-predominant BC and decreasing serum blood urea nitrogen level could account for the increase in the prevalence of FL over 20 years. We believe that these factors stem from current lifestyle habits in Japan.
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Affiliation(s)
- Yasushi Imamura
- Department of Hepatology, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Seiichi Mawatari
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kohei Oda
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kotaro Kumagai
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Yasunari Hiramine
- Department of Hepatology, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Akiko Saishoji
- Department of Hepatology, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Atsuko Kakihara
- Department of Hepatology, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Mai Nakahara
- Department of Nephrology, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Manei Oku
- Department of Nephrology, Kajikionsen Hospital, Aira, Japan
| | - Kaori Hosoyamada
- Department of Diabetes, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Shuji Kanmura
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Akihiro Moriuchi
- Department of Gastroenterology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan
| | - Hironori Miyahara
- Medical Health Care Center, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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On the Relationship Between Non-alcoholic Fatty Liver Disease with Body Composition and Bone Mineral Density in Overweight/Obese Adolescents. HEPATITIS MONTHLY 2021. [DOI: 10.5812/hepatmon.112184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: Nonalcoholic fatty liver disease (NAFLD) is a health problem growing in line with the rising prevalence of obesity in children and adolescents, which may be correlated with different metabolic abnormalities such as osteoporosis. Objectives: This study aimed to evaluate the possible relationship between NAFLD with body composition and bone mineral density (BMD) in obese and overweight adolescents. Methods: This cross-sectional study encompassed 70 adolescents aged 11 - 18 years and was conducted during March 2016 and September 2016 in Mashhad, Iran. Anthropometric parameters and blood biomarkers were measured. Fat mass, fat-free mass, and BMD were determined using dual-energy X‐ray absorptiometry (DXA) scans, and NAFLD was also assessed using Fibroscan. All statistical data were analyzed using SPSS software version 21. Multivariate linear regression assessed the relationship between liver fat content with bone-related indicators, and multivariate logistic regression detected the relationship between body composition and NAFLD. Results: Total and trunk fat mass were significantly correlated with higher NAFLD even after controlling for intervening factors (total fat mass, OR = 1.27; 95% CI, 1.016 to 1.59, P = 0.036; trunk fat mass, OR = 1.35; 95% CI, 0.97 to 1.88, P = 0.045). Moreover, liver fat content was significantly correlated with lower BMD Z-score after adjusting for gender, BMI Z-score, ALT, fat mass index, total lean mass, and physical activity (β = -0.285, P = 0.048). Conclusions: The findings of the present study suggest that excess adipose tissue is correlated with higher NAFLD. Moreover, liver steatosis may be correlated with decreased BMD Z-score in overweight/obese adolescents.
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Li BT, Simon TG, Wang N, Chung RT, Corey KE, Dichtel LE, Samelson EJ, Kiel DP, Long MT. Association Between Liver Fat and Bone Density is Confounded by General and Visceral Adiposity in a Community-Based Cohort. Obesity (Silver Spring) 2021; 29:595-600. [PMID: 33528915 PMCID: PMC7904629 DOI: 10.1002/oby.23100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 10/27/2020] [Accepted: 11/11/2020] [Indexed: 12/20/2022]
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is associated with low bone mineral density (BMD); however, it is not known whether early-stage NAFLD may be associated with BMD after accounting for BMI or visceral adipose tissue (VAT). METHODS This was a cross-sectional study of 3,462 Framingham Heart Study participants who underwent computed tomographic measurement of liver fat, VAT volume, volumetric spine BMD, vertebral cross-sectional area (CSA), and vertebral compressive strength. This study excluded heavy alcohol consumers. Multivariable linear regression models were used to assess the association between NAFLD and volumetric BMD, CSA, and vertebral compressive strength after accounting for covariates, including BMI or VAT. RESULTS A total of 2,253 participants (mean age, 51.2 [SD 10.7] years; 51.1% women) were included. In multivariable-adjusted models, positive associations between NAFLD and integral BMD, trabecular BMD, and vertebral compressive strength were observed. However, results were attenuated and no longer significant after additionally adjusting for BMI or VAT. NAFLD was observed to be weakly associated with a lower vertebral CSA in adjusted models. CONCLUSIONS In a community-based cohort, the associations between NAFLD and BMD and vertebral strength were confounded by BMI and VAT. However, NAFLD was associated with a reduced vertebral CSA in adjusted models.
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Affiliation(s)
- Belinda T. Li
- Boston University School of Medicine, Boston, MA, USA
| | - Tracey G. Simon
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Na Wang
- Biostatistics & Epidemiology Data Analytics Center, School of Public Health, Boston University, Boston, MA, USA
| | - Raymond T. Chung
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Kathleen E. Corey
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Laura E. Dichtel
- Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Elizabeth J. Samelson
- Hebrew SeniorLife, Hinda and Arthur Marcus Institute for Aging Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Douglas P. Kiel
- Hebrew SeniorLife, Hinda and Arthur Marcus Institute for Aging Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Michelle T. Long
- Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
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Bott KN, Yumol JL, Comelli EM, Klentrou P, Peters SJ, Ward WE. Trabecular and cortical bone are unaltered in response to chronic lipopolysaccharide exposure via osmotic pumps in male and female CD-1 mice. PLoS One 2021; 16:e0243933. [PMID: 33544708 PMCID: PMC7864436 DOI: 10.1371/journal.pone.0243933] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 11/30/2020] [Indexed: 12/05/2022] Open
Abstract
Chronic low-grade inflammation has been identified as an underlying cause of many diseases including osteoporosis. Lipopolysaccharide (LPS) is a potent inducer of the inflammatory response that can negatively affect bone outcomes by upregulating bone resorption and inhibiting bone formation. The objective of this study was to assess the longitudinal response of trabecular and cortical bone structure and bone mineral density to LPS continuously administered for 12 weeks in male and female CD-1 mice. Mice were assigned to one of four LPS groups at 8-weeks of age: placebo (0.0 μg/d), low (0.9 μg/d), mid (3.6 μg/d) and high (14.4 μg/d) dose. Trabecular and cortical bone outcomes were measured at 8, 12, 16, and 20 weeks of age using in vivo micro-computed tomography. The anticipated serum LPS dose-dependent response was not observed. Therefore, the low, mid, and high LPS groups were combined for analysis. Compared to the placebo group, endpoint serum LPS was elevated in both males (p < 0.05) and females (p < 0.05) when all LPS treatment groups were combined. However, there was no significant change in trabecular or cortical bone outcomes in the combined LPS groups compared to the placebo following the 12-week LPS intervention for either sex. This suggests that although serum LPS was elevated following the 12-week LPS intervention, the dosages administered using the osmotic pumps was not sufficient to negatively impact trabecular or cortical bone outcomes in either male or female CD-1 mice.
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Affiliation(s)
- Kirsten N. Bott
- Department of Kinesiology, Brock University, St. Catharines, ON, Canada
- * E-mail:
| | - Jenalyn L. Yumol
- Department of Kinesiology, Brock University, St. Catharines, ON, Canada
| | - Elena M. Comelli
- Department of Kinesiology, Brock University, St. Catharines, ON, Canada
- Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada
- Joannah and Brian Lawson Centre for Child Nutrition, University of Toronto, Toronto, ON, Canada
| | - Panagiota Klentrou
- Department of Kinesiology, Brock University, St. Catharines, ON, Canada
- Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
| | - Sandra J. Peters
- Department of Kinesiology, Brock University, St. Catharines, ON, Canada
- Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
| | - Wendy E. Ward
- Department of Kinesiology, Brock University, St. Catharines, ON, Canada
- Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada
- Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
- Department of Health Sciences, Brock University, St. Catharines, ON, Canada
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Lee HJ, Lee DC, Kim CO. Association Between 10-Year Fracture Probability and Nonalcoholic Fatty Liver Disease With or Without Sarcopenia in Korean Men: A Nationwide Population-Based Cross-Sectional Study. Front Endocrinol (Lausanne) 2021; 12:599339. [PMID: 33868162 PMCID: PMC8044878 DOI: 10.3389/fendo.2021.599339] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 03/16/2021] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) and sarcopenia, which are common in elderly men, are known as risk factors of fracture. However, few studies have examined the association with fracture in these patients. Therefore, we aimed to investigate the association between NAFLD with or without sarcopenia and 10-year fracture probability in Korean men aged ≥50 years. MATERIALS AND METHODS Data of 2,525 individuals from the 2010-2011 Korea National Health and Nutrition Examination Survey were analyzed. NAFLD was defined using the fatty liver index (FLI) and comprehensive NAFLD score (CNS), and liver fibrosis using the fibrosis 4 calculator. Sarcopenia was defined as the lowest quintile for sex-specific sarcopenia index cutoff; values. The Fracture Risk Assessment (FRAX) tool was used to predict the 10-year probability of major osteoporotic and hip fractures. RESULTS Compared to the no NAFLD group, the 10-year major osteoporotic fracture probability was significantly associated with the FLI-defined (β = 0.16, P = 0.002) and CNS-defined (β = 0.20, P < 0.001) NAFLD groups with liver fibrosis. Similarly, the 10-year hip fracture probability was significantly associated with the FLI- and CNS-defined NAFLD with liver fibrosis groups compared to the group without NAFLD (FLI-defined group, β = 0.04, P = 0.046; CNS-defined group, β = 0.05, P = 0.048). Furthermore, in the group with sarcopenia, the 10-year major osteoporotic fracture probability was significantly associated with the FLI- and CNS-defined NAFLD with liver fibrosis groups compared to the group without NAFLD (FLI-defined group, β = 0.29, P = 0.003; CNS-defined group, β = 0.38, P < 0.001). CONCLUSIONS NAFLD with liver fibrosis is significantly associated with a higher 10-year major osteoporotic and hip fracture probability in Korean men aged ≥50 years, and this positive association was more profound in patients with sarcopenia. Therefore, screening middle-aged to elderly men who have NAFLD combined with liver fibrosis and sarcopenia may help prevent fractures.
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Affiliation(s)
- Hye Jun Lee
- Department of Family Medicine, College of Medicine, Yonsei University, Seoul, South Korea
| | - Duk Chul Lee
- Department of Family Medicine, College of Medicine, Yonsei University, Seoul, South Korea
- *Correspondence: Duk Chul Lee, ; Choon Ok Kim,
| | - Choon Ok Kim
- Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, South Korea
- *Correspondence: Duk Chul Lee, ; Choon Ok Kim,
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Sylvester FA. Effects of Digestive Diseases on Bone Metabolism. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:1023-1031.e7. [DOI: 10.1016/b978-0-323-67293-1.00091-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Zhai T, Chen Q, Xu J, Jia X, Xia P. Prevalence and Trends in Low Bone Density, Osteopenia and Osteoporosis in U.S. Adults With Non-Alcoholic Fatty Liver Disease, 2005-2014. Front Endocrinol (Lausanne) 2021; 12:825448. [PMID: 35126317 PMCID: PMC8807487 DOI: 10.3389/fendo.2021.825448] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 12/28/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is suggested to be associated with bone mineral density (BMD) alterations; however, this has not been ascertained. The current study aimed to investigate the changes in BMD and the prevalence of osteopenia/osteoporosis in US adults with or without NAFLD and to evaluate their association. METHODS The study was conducted based on data collected from the U.S. National Health and Nutrition Examination Survey (NHANES) during the period 2005-2014. A total of 13 837 and 6 177 participants aged > 20 years were eligible for conducting the Hepatic Steatosis Index (HSI) and the US Fatty Liver Index (USFLI) analysis, respectively. RESULTS From 2005-2014, a downward trend in femoral neck BMD was observed in subjects with NAFLD aged ≥ 40. After adjustment for potential confounders, an upward shift occurred in the prevalence of osteopenia/osteoporosis at the femoral neck in adults aged ≥ 40, particularly in women ≥ 60 years old and men below the age of 60. Moreover, a negative association was found between BMD and NAFLD markers (USFLI, HSI), whereas NAFLD with advanced fibrosis was positively associated with the prevalence of spine fractures. CONCLUSIONS There was a trend toward lower BMD and higher prevalence of osteopenia/osteoporosis at the femoral neck in US adults with NAFLD aged ≥ 40 years during the period of 2005-2014. NAFLD with advanced fibrosis was positively associated with a higher risk of spine fracture. More research is required to fully investigate the mechanism and consequence of poor bone health in NAFLD patients and consider optimum management of osteopenia/osteoporosis for this population.
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Affiliation(s)
- Tianyu Zhai
- Department of Endocrinology and Metabolism, Zhongshan Hospital, and Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China
| | - Qi Chen
- Department of Endocrinology and Metabolism, Zhongshan Hospital, and Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China
| | - Jing Xu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, and Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China
| | - Xi Jia
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Pu Xia
- Department of Endocrinology and Metabolism, Zhongshan Hospital, and Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China
- *Correspondence: Pu Xia,
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Sung J, Ryu S, Song YM, Cheong HK. Relationship Between Non-alcoholic Fatty Liver Disease and Decreased Bone Mineral Density: A Retrospective Cohort Study in Korea. J Prev Med Public Health 2020; 53:342-352. [PMID: 33070506 PMCID: PMC7569013 DOI: 10.3961/jpmph.20.089] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 06/23/2020] [Indexed: 01/01/2023] Open
Abstract
Objectives The aim of this retrospective cohort study was to investigate whether non-alcoholic fatty liver disease (NAFLD) was associated with incident bone mineral density (BMD) decrease. Methods This study included 4536 subjects with normal BMD at baseline. NAFLD was defined as the presence of fatty liver on abdominal ultrasonography without significant alcohol consumption or other causes. Decreased BMD was defined as a diagnosis of osteopenia, osteoporosis, or BMD below the expected range for the patient’s age based on dual-energy X-ray absorptiometry. Cox proportional hazards models were used to estimate the hazard ratio of incident BMD decrease in subjects with or without NAFLD. Subgroup analyses were conducted according to the relevant factors. Results Across 13 354 person-years of total follow-up, decreased BMD was observed in 606 subjects, corresponding to an incidence of 45.4 cases per 1000 person-years (median follow-up duration, 2.1 years). In the model adjusted for age and sex, the hazard ratio was 0.65 (95% confidence interval, 0.51 to 0.82), and statistical significance disappeared after adjustment for body mass index (BMI) and cardiometabolic factors. In the subgroup analyses, NAFLD was associated with a lower risk of incident BMD decrease in females even after adjustment for confounders. The direction of the effect of NAFLD on the risk of BMD decrease changed depending on BMI category and body fat percentage, although the impact was statistically insignificant. Conclusions NAFLD had a significant protective effect on BMD in females. However, the effects may vary depending on BMI category or body fat percentage.
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Affiliation(s)
- Jisun Sung
- Department of Social and Preventive Medicine, Sungkyunkwan University School of Medicine, Suwon, Korea
| | - Seungho Ryu
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yun-Mi Song
- Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hae-Kwan Cheong
- Department of Social and Preventive Medicine, Sungkyunkwan University School of Medicine, Suwon, Korea
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Nikseresht M, Azarmehr N, Arya A, Alipoor B, Fadaei R, Khalvati B, Abidi H, Doustimotlagh AH. Circulating mRNA and plasma levels of osteoprotegerin and receptor activator of NF-κB ligand in nonalcoholic fatty liver disease. Biotechnol Appl Biochem 2020; 68:1243-1249. [PMID: 33010062 DOI: 10.1002/bab.2047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 09/30/2020] [Indexed: 01/13/2023]
Abstract
Pathogenesis of the beginning and progression of nonalcoholic fatty liver disease (NAFLD) has not been clarified exactly. The osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) axis seems to play an imperative function in the onset and progression of this disease. The goal of the present study was to investigate the peripheral blood mononuclear cell (PBMC) expression and plasma levels of RANKL and OPG cytokines in NAFLD patients and compare them with healthy group. Plasma levels of OPG and RANKL were determined with ELISA kits in 57 men with NAFLD and 25 healthy men as controls. Biochemical and anthropometric parameters tests were also evaluated in the study groups. RANKL and OPG mRNA contents were evaluated by quantitative RT-PCR. OPG contents were markedly decreased in NAFLD patients as compared with healthy patients [1.43 (1.05-5.45)] versus [2.94 (1.76-4.73)] ng/mL; P = 0.007). The levels of RANKL were significantly reduced in NAFLD patients [74.00 (56.26-203.52) ng/mL] than in healthy patients [119.37 (83.71-150.13) ng/mL]; (P = 0.03). Also, OPG and RANKL gene expression were significantly decreased in NAFLD patients in comparison with the control group (P < 0.05). Moreover, receiver operating characteristic curve indicated that OPG may have a good capability to discriminate between NAFLD patients and normal individuals. A positive correlation was observed between OPG and RANKL in plasma sample (r = 0.495) (P = 0.000). Decreased plasma levels and gene expression of RANKL and OPG cytokines in NAFLD patients indicate that there is a relationship between these cytokines and the pathology of NAFLD disease. Confirmation of this association as well as the mechanism and role of these cytokines in NAFLD require further studies.
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Affiliation(s)
- Mohsen Nikseresht
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Nahid Azarmehr
- Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Arash Arya
- Internal medicine Department, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Behnam Alipoor
- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Reza Fadaei
- Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Bahman Khalvati
- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Hassan Abidi
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Amir Hossein Doustimotlagh
- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.,Department of Clinical Biochemistry, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
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Zhu X, Yan H, Chang X, Xia M, Zhang L, Wang L, Sun X, Yang X, Gao X, Bian H. 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; 8:e000999. [PMID: 32759166 PMCID: PMC7409963 DOI: 10.1136/bmjdrc-2019-000999] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 04/02/2020] [Accepted: 06/22/2020] [Indexed: 12/13/2022] Open
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.
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Affiliation(s)
- Xiaopeng Zhu
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Hongmei Yan
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Xinxia Chang
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Mingfeng Xia
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Linshan Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Liu Wang
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Xiaoyang Sun
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Xinyu Yang
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Hua Bian
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
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Kumar R, Priyadarshi RN, Anand U. Non-alcoholic Fatty Liver Disease: Growing Burden, Adverse Outcomes and Associations. J Clin Transl Hepatol 2020; 8:76-86. [PMID: 32274348 PMCID: PMC7132013 DOI: 10.14218/jcth.2019.00051] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 12/03/2019] [Accepted: 12/09/2019] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a systemic disorder with a complex multifactorial pathogenesis and heterogenous clinical manifestations. NAFLD, once believed to be an innocuous condition, has now become the most common cause of chronic liver disease in many countries worldwide. NAFLD is already highly prevalent in the general population, and owing to a rising incidence of obesity and diabetes mellitus, the incidence of NAFLD and its impact on global healthcare are expected to increase in the future. A subset of patients with NAFLD develops progressive liver disease leading to cirrhosis, hepatocellular carcinoma, and liver failure. NAFLD has emerged as one of the leading causes of cirrhosis and hepatocellular carcinoma in recent years. Moreover, HCC can occur in NAFLD even in absence of cirrhosis. Compared with the general population, NAFLD increases the risk of liver-related, cardiovascular and all-cause mortality. NAFLD is bidirectionally associated with metabolic syndrome. NAFLD increases the risk and contributes to aggravation of the pathophysiology of atherosclerosis, cardiovascular diseases, diabetes mellitus, and chronic kidney disease. In addition, NAFLD is linked to colorectal polyps, polycystic ovarian syndrome, osteoporosis, obstructive sleep apnea, stroke, and various extrahepatic malignancies. Extended resection of steatotic liver is associated with increased risk of liver failure and mortality. There is an increasing trend of NAFLD-related cirrhosis requiring liver transplantation, and the recurrence of NAFLD in such patients is almost universal. This review discusses the growing burden of NAFLD, its outcomes, and adverse associations with various diseases.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | | | - Utpal Anand
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Patna, India
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Abstract
Non-alcoholic fatty liver disease (NAFLD) went beyond the competence of a gastroenterologist and acquired the character of a multidisciplinary problem. NAFLD requires the attention of many professionals. A characteristic feature of NAFLD is the variety of concomitant diseases and pathological conditions with common pathophysiological mechanisms. This review summarizes and presents the data available in the modern literature on the association of NAFLD with cardiovascular diseases, type 2 diabetes mellitus, hypothyroidism, polycystic ovary syndrome, chronic kidney disease, colorectal cancer, obstructive sleep apnea, osteoporosis, psoriasis.
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Affiliation(s)
- M. A. Livzan
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
| | - O. V. Gaus
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
| | - N. A. Nikolaev
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
| | - T. S. Krolevetz
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
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Tariq R, Axley P, Singal AK. Extra-Hepatic Manifestations of Nonalcoholic Fatty Liver Disease: A Review. J Clin Exp Hepatol 2020; 10:81-87. [PMID: 32025167 PMCID: PMC6995895 DOI: 10.1016/j.jceh.2019.07.008] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 07/17/2019] [Indexed: 02/08/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease worldwide with a strong association with metabolic syndrome. NAFLD is truly a systemic disease and is associated with a plethora of extra-hepatic manifestations or comorbidities. These are either related to secondary effects of associated obesity or from pathophysiological effects of insulin resistance in NAFLD. Three most common causes of increased morbidity and mortality associated with NAFLD are cardiovascular disease, liver disease, and cancer. In this narrative review, we will discuss comprehensively on cardiovascular disease, type 2 diabetes mellitus, and chronic kidney disease and will also highlight on malignancy especially colorectal cancer, pulmonary disorders including obstructive sleep apnea, endocrine disorders such as hypothyroidism and polycystic ovarian syndrome, dermatological disorders especially psoriasis, and hematological associations including iron overload and susceptibility to thrombosis. In addition to focusing on pathogenesis of these extrahepatic manifestations, we will highlight their clinical implications for physicians in routine clinical practice. Further, there remains an unmet need for safe and effective therapies and examining their benefits on these extra-hepatic manifestations among patients with NAFLD.
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Key Words
- CKD, chronic kidney disease
- CT, computed tomography
- CVD, cardiovascular disease
- HCC
- MetS, metabolic syndrome
- NAFL, nonalcoholic fatty liver
- NAFLD, nonalcoholic fatty liver disease
- NASH
- NASH, nonalcoholic steatohepatitis
- OSA, obstructive sleep apnea
- PCOS, polycystic ovarian syndrome
- T2DM, type 2 diabetes mellitus
- insulin resistance
- metabolic syndrome
- steatosis
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Affiliation(s)
- Raseen Tariq
- Department of Medicine, University of Rochester, Rochester, NY, USA
| | - Page Axley
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ashwani K. Singal
- Division of Gastroenterology and Hepatology, University of South Dakota Sanford School of Medicine, Transplant Hepatologist Avera University Hospital & Transplant Institute, Chief Clinical Research Affairs, Transplant Hepatology & Institute of Human Genetics Research, Sioux Falls, SD, 57105, USA,Address for correspondence: Ashwani K. Singal, MD Associate Professor of Medicine, Division of Gastroenterology and Hepatology, University of South Dakota Sanford School of Medicine, Transplant Hepatologist Avera University Hospital & Transplant Institute, Chief Clinical Research Affairs, Transplant Hepatology & Institute of Human Genetics Research, Sioux Falls, SD, 57105, USA.
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Loureiro LM, Cordeiro A, Mendes R, Luna M, Pereira S, Saboya CJ, Ramalho A. Clinic, Anthropometric And Metabolic Changes In Adults With Class III Obesity Classified As Metabolically Healthy And Metabolically Unhealthy. Diabetes Metab Syndr Obes 2019; 12:2419-2431. [PMID: 31819568 PMCID: PMC6885561 DOI: 10.2147/dmso.s210616] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Accepted: 08/30/2019] [Indexed: 12/31/2022] Open
Abstract
PURPOSE To describe clinical, biochemical and anthropometric profiles in adults with class III obesity classified as metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). PATIENTS AND METHODS This is a cross-sectional study with patients classified as MHO and MUHO according to the NCEP-ATP III. Anthropometric, biochemical and clinical variables were analyzed. RESULTS A total of 223 subjects were evaluated and 32.73% were classified as MHO and 67.26% as MUHO, respectively. The insulin resistance homeostasis model (HOMA-IR) showed elevation in the MUHO group (p=0.003) and anthropometric variables were correlated with bone markers [body index mass (BMI) vs phosphorus: r=0.31, p<0.001; BMI vs 25(OH)D: r=-0.31, p=0.041]. Visceral adiposity index was lower in MHO (p=0.001). Negative correlations between inflammatory markers and bone markers were observed in the MHO group (calcium vs C-reactive protein: -0.30, p=0.017; parathyroid hormone vs HOMA-IR: r=-0.28, p=0.017. CONCLUSION MHO individuals showed important metabolic changes, such as those observed in MUHO, despite lower prevalence and severity. Continuous monitoring of these individuals is suggested, given the transient nature of the MHO phenotype.
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Affiliation(s)
- Ligiane M Loureiro
- Postgraduate Program, Doctorate in Nutritional Sciences, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Health Sciences Institute, Faculty of Nutrition, Federal University of Pará (UFPA), Belém, Brazil
- Center for Research on Micronutrients (NPqM), Institute of Nutrition Josué de Castro of UFRJ, Rio de Janeiro, Brazil
| | - Adryana Cordeiro
- Center for Research on Micronutrients (NPqM), Institute of Nutrition Josué de Castro of UFRJ, Rio de Janeiro, Brazil
- Biomedicine Department, Biochemistry Unit, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Rodrigo Mendes
- Pontifical Catholic University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Mariana Luna
- Center for Research on Micronutrients (NPqM), Institute of Nutrition Josué de Castro of UFRJ, Rio de Janeiro, Brazil
| | - Sílvia Pereira
- Center for Research on Micronutrients (NPqM), Institute of Nutrition Josué de Castro of UFRJ, Rio de Janeiro, Brazil
- Multidisciplinary Center for Bariatric and Metabolic Surgery, Rio de Janeiro, Brazil
| | - Carlos J Saboya
- Center for Research on Micronutrients (NPqM), Institute of Nutrition Josué de Castro of UFRJ, Rio de Janeiro, Brazil
- Multidisciplinary Center for Bariatric and Metabolic Surgery, Rio de Janeiro, Brazil
| | - Andrea Ramalho
- Center for Research on Micronutrients (NPqM), Institute of Nutrition Josué de Castro of UFRJ, Rio de Janeiro, Brazil
- Department of Social and Applied Nutrition of the Institute of Nutrition, UFRJ, Rio de Janeiro, Brazil
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NAFLD and Extra-Hepatic Comorbidities: Current Evidence on a Multi-Organ Metabolic Syndrome. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16183415. [PMID: 31540048 PMCID: PMC6765902 DOI: 10.3390/ijerph16183415] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 09/06/2019] [Accepted: 09/08/2019] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and its incidence is definitely increasing. NAFLD is a metabolic disease with extensive multi-organ involvement, whose extra-hepatic manifestations include type 2 diabetes mellitus, cardiovascular disease, obstructive sleep apnea, chronic kidney disease, osteoporosis, and polycystic ovarian syndrome. Recently, further evidence has given attention to pathological correlations not strictly related to metabolic disease, also incorporating in this broad spectrum of systemic involvement hypothyroidism, psoriasis, male sexual dysfunction, periodontitis, and urolithiasis. The most common cause of mortality in NAFLD is represented by cardiovascular disease, followed by liver-related complications. Therefore, clinicians should learn to screen and initiate treatment for these extra-hepatic manifestations, in order to provide appropriate multidisciplinary assessments and rigorous surveillance. This review evaluates the current evidence regarding extra-hepatic associations of NAFLD, focusing on the pathogenic hypothesis and the clinical implications.
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Association between non-alcoholic fatty liver disease and bone turnover biomarkers in post-menopausal women with type 2 diabetes. DIABETES & METABOLISM 2019; 45:347-355. [DOI: 10.1016/j.diabet.2018.10.001] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 10/01/2018] [Accepted: 10/02/2018] [Indexed: 02/06/2023]
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Mantovani A, Gatti D, Zoppini G, Lippi G, Bonora E, Byrne CD, Nobili V, Targher G. Association Between Nonalcoholic Fatty Liver Disease and Reduced Bone Mineral Density in Children: A Meta-Analysis. Hepatology 2019; 70:812-823. [PMID: 30706504 DOI: 10.1002/hep.30538] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Accepted: 01/27/2019] [Indexed: 12/28/2022]
Abstract
Recent cross-sectional studies have examined the association between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) in children or adolescents, but these have produced conflicting results. We performed a systematic review and meta-analysis of these published studies to quantify the magnitude of the association, if any, between NAFLD and BMD. We searched publication databases from January 2000 to September 2018, using predefined keywords to identify relevant observational studies conducted in children or adolescents in whom NAFLD was diagnosed either by imaging or by histology and BMD Z score was measured by dual-energy X-ray absorptiometry. Data from selected studies were extracted, and a meta-analysis was performed using random-effects modeling. A total of eight observational cross-sectional or case-control studies enrolling 632 children and adolescents (mean age 12.8 years), 357 of whom had NAFLD, were included in the final analysis. Meta-analysis showed significant differences in whole-body or lumbar BMD Z scores between children/adolescents with and without NAFLD (n = 6 studies; pooled weighted mean difference [WMD], -0.48; 95% confidence interval [CI], -0.74 to -0.21; I2 = 55.5%), as well as between those with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and those with no-NASH (n = 4 studies; pooled WMD, -0.27; 95% CI, -0.40 to -0.13; I2 = 0%). The aforementioned WMDs in BMD Z scores were independent of common clinical risk factors, such as age, sex, race/ethnicity, and body mass index. Sensitivity analyses did not modify these findings. Funnel plot and Egger test did not reveal significant publication bias. Conclusion: This meta-analysis shows that the presence and severity of NAFLD are significantly associated with reduced whole-body BMD Z scores in children and adolescents; however, the observational design of the studies included does not allow for proving causality.
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Affiliation(s)
- Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Davide Gatti
- Section of Rheumatology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giacomo Zoppini
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Enzo Bonora
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK.,Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
| | - Valerio Nobili
- Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy.,Department of Pediatrics, University "La Sapienza", Rome, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
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45
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Ballestri S, Mantovani A, Nascimbeni F, Lugari S, Lonardo A. Extra-hepatic manifestations and complications of nonalcoholic fatty liver disease. Future Med Chem 2019; 11:2171-2192. [PMID: 31538528 DOI: 10.4155/fmc-2019-0003] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 05/07/2019] [Indexed: 12/14/2022] Open
Abstract
This review article aims to synthesize the evidence regarding nonalcoholic fatty liver disease (NAFLD) as a systemic disorder. We critically discuss the metabolic syndrome and its components; the cardiovascular and the endocrine system; chronic respiratory disorders; the musculoskeletal system; the skin; and extra-hepatic tumors. We conclude that, while some of these extra-hepatic conditions clearly predispose to the development of secondary forms of NAFLD (typically hypothyroidism-induced NAFLD), others result from pre-existent NAFLD (e.g., certain extra-hepatic tumors) and others (such as Type 2 Diabetes) have, with NAFLD, mutual and bidirectional associations. Analyzed data imply that NAFLD is not merely a hepatic disease. It is also and possibly more importantly, a systemic disorder requiring a special awareness, a multidisciplinary approach and a multidimensional vision.
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Affiliation(s)
- Stefano Ballestri
- Azienda USL di Modena - Ospedale di Pavullo - UOC di Medicina - Pavullo (Mo), Italy
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes & Metabolism, Department of Medicine, University & Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Fabio Nascimbeni
- AOU di Modena - Ospedale Civile di Baggiovara, UOC di Medicina ad indirizzo Metabolico-Nutrizionistico - Modena, Italy
| | | | - Amedeo Lonardo
- AOU di Modena - Ospedale Civile di Baggiovara, UOC di Medicina ad indirizzo Metabolico-Nutrizionistico - Modena, Italy
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46
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Mantovani A. Nonalcoholic Fatty Liver Disease and Bone Mineral Density in Children and Adolescents: Specific Considerations for Future Studies. Dig Dis Sci 2019; 64:898-900. [PMID: 30430297 DOI: 10.1007/s10620-018-5370-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 11/07/2018] [Indexed: 01/16/2023]
Affiliation(s)
- Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale A. Stefani, 1, 37126, Verona, Italy.
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Mantovani A, Dauriz M, Gatti D, Viapiana O, Zoppini G, Lippi G, Byrne CD, Bonnet F, Bonora E, Targher G. 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. Aliment Pharmacol Ther 2019; 49:375-388. [PMID: 30600540 DOI: 10.1111/apt.15087] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 10/29/2018] [Accepted: 11/16/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Several studies have explored the effect of non-alcoholic fatty liver disease (NAFLD) on bone mineral density (BMD) and risk of osteoporotic fractures in adults. However, the extent to which NAFLD adversely affects bone health remains uncertain. AIM To provide a quantitative estimation of the magnitude of the association of NAFLD with BMD or history of osteoporotic fractures in adults. METHODS We searched PubMed, Web of Science, and Scopus using predefined keywords to identify all observational studies, published up to 31 August 2018, in which NAFLD was diagnosed by imaging or histology; BMD was measured by dual energy X-ray absorptiometry; and a self-reported history of osteoporotic fractures was collected with interviewer-assisted questionnaires. Data from selected studies were extracted, and meta-analysis was performed using random-effects modelling. RESULTS Twelve cross-sectional or case-control studies with aggregate data on 30 041 adults of predominantly Asian ethnicity (30% with NAFLD) were included in the final analysis. No significant differences in BMD at different skeletal sites (whole body, lumbar spine, or femur) were observed between individuals with and without NAFLD. Conversely, NAFLD was associated with increased odds of osteoporotic fractures, especially in older Chinese men (n = 2 studies; random-effects odds ratio 2.10, 95% CI 1.36-3.25; I2 = 0%). Sensitivity analyses did not alter these findings. The funnel plot and Egger test did not reveal significant publication bias. CONCLUSIONS This meta-analysis suggests that imaging-defined or biopsy-proven NAFLD is associated with a self-reported history of osteoporotic fractures (principally in Chinese men), but not with low BMD, in middle-aged and elderly individuals.
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Affiliation(s)
- Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Marco Dauriz
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Davide Gatti
- Section of Rheumatology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Ombretta Viapiana
- Section of Rheumatology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giacomo Zoppini
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University and Azienda Ospedaliera, Universitaria Integrata of Verona, Verona, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK.,Southampton National Institute for Health Research Biomedical Research Centre, Southampton General Hospital, University Hospital Southampton, Southampton, UK
| | - Fabrice Bonnet
- Department of Endocrinology, INSERM UMR 991, University Hospital of Rennes, Rennes Cedex 9, France
| | - Enzo Bonora
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
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Mosca A, Fintini D, Scorletti E, Cappa M, Paone L, Zicari AM, Nobili V, Byrne CD. Relationship between non-alcoholic steatohepatitis, PNPLA3 I148M genotype and bone mineral density in adolescents. Liver Int 2018; 38:2301-2308. [PMID: 30176114 DOI: 10.1111/liv.13955] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 08/24/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS It is uncertain whether non-alcoholic steatohepatitis (NASH) is a risk factor for low bone mineral density (BMD). Our aim was to investigate: (a) associations between NASH and BMD values and (b) associations between PNPLA3 I148M genotypes and BMD, in children with histologically proven non-alcoholic fatty liver disease (NAFLD). METHODS BMD area (g/cm2 ) was measured using dual-energy X-ray absorptiometry (DEXA). NASH was diagnosed by a Steatosis, Activity and Fibrosis (SAF) score and FLIP algorithm. Genotyping for patatin-like phospholipase domain containing-3 (PNPLA3) I148M genotype (rs738409) (CC, CG and GG) was undertaken using the TaqMan SNP genotyping allelic discrimination method. Logistic regression was used to test associations [OR (95% CIs)] between low BMD, and both NASH and PNPLA3 I148M genotypes. RESULTS Thirty-four adolescents (mean age 13.8 ± 1.1 years) with histologically confirmed NAFLD were studied. Subjects with NASH (n = 25) had a lower BMD (means (SDs) 0.87 ± 0.06 vs 0.97 ± 0.12, P = 0.005), compared to subjects without NASH. Subjects with PNPLA3 CG+GG genotypes had a lower BMD compared with subjects with PNPLA3-CC genotype (means (SDs) 0.79 ± 0.20 vs 0.92 ± 0.10, P = 0.009). PNPLA3 CG+GG genotypes were independently associated with NASH [OR (95% CIs 1.78, 1.24, 2.99)], and low BMD was associated with both PNPLA3 CG+GG (OR 3.62 (95% CIs 1.21, 5.53), P = 0.028) and with SAF score (OR 2.76 (95% CIs 1.12, 5.41), P = 0.045). CONCLUSIONS Taken together the independent associations between: (a) low BMD and PNPLA3 CG+GG genotype; (b) low BMD and NASH; and (c) PNPLA3 CG+GG genotype and NASH, provide support for a causal relationship between NASH and low BMD.
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Affiliation(s)
- Antonella Mosca
- Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy
| | - Danilo Fintini
- Endocrinology Unit, Pediatric University Department, Bambino Gesù Children's Hospital, Research Institute, Rome, Italy
| | - Elenora Scorletti
- Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.,National Institute for Health Research Southampton Biomedical Research Centre University of Southampton, University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK
| | - Marco Cappa
- Endocrinology Unit, Pediatric University Department, Bambino Gesù Children's Hospital, Research Institute, Rome, Italy
| | - Laura Paone
- Endocrinology Unit, Pediatric University Department, Bambino Gesù Children's Hospital, Research Institute, Rome, Italy
| | - Anna M Zicari
- Department of Pediatric, University "La Sapienza", Rome, Italy
| | - Valerio Nobili
- Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy.,Department of Pediatric, University "La Sapienza", Rome, Italy
| | - Christopher D Byrne
- Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.,National Institute for Health Research Southampton Biomedical Research Centre University of Southampton, University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK
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49
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Hepatic fat content and bone mineral density in children with overweight/obesity. Pediatr Res 2018; 84:684-688. [PMID: 30120405 DOI: 10.1038/s41390-018-0129-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Revised: 06/08/2018] [Accepted: 07/11/2018] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To examine the influence of non-alcoholic fatty liver disease (NAFLD) and hepatic fat content on bone mineral density (BMD), and to investigate whether the relationship between NAFLD and BMD is independent of lifestyle factors related to BMD. METHODS Hepatic fat content (magnetic resonance imaging), BMD, lean mass index, total and abdominal fat mass (dual-energy-X-ray absorptiometry), moderate to vigorous physical activity (MVPA) (accelerometry), and calcium and vitamin D intake (two 24 h recalls) were measured in 115 children with overweight/obesity aged 10.6 ± 1.1 years old. RESULTS Children with NAFLD had lower BMD than children without NAFLD regardless of sex, puberty stage, lean mass index, fat mass, MVPA, and calcium and vitamin D intake (0.89 ± 0.01 vs. 0.93 ± 0.01 g/cm2 for NAFLD and non-NAFLD, respectively, P < 0.01). Higher hepatic fat content was significantly associated with lower BMD regardless of confounders (adjusted P < 0.05). CONCLUSIONS Findings of the current study suggest that hepatic fat accumulation is associated with decreased BMD independently of adiposity, and regardless of those lifestyle factors closely related to bone mineral accrual in children. These results may have implication in the clinical management of children with overweight/obesity given the high prevalence of pediatric NAFLD.
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50
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Filip R, Radzki RP, Bieńko M. Novel insights into the relationship between nonalcoholic fatty liver disease and osteoporosis. Clin Interv Aging 2018; 13:1879-1891. [PMID: 30323574 PMCID: PMC6174895 DOI: 10.2147/cia.s170533] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Excess fat deposition and insulin resistance are considered the main risk factors for nonalcoholic fatty liver disease (NAFLD), and therefore, not surprisingly, the global prevalence of NAFLD increases in parallel with both obesity and type 2 diabetes. Although deterioration of bone homeostasis in patients with NAFLD is commonly observed, its etiology has not been fully elucidated yet. It was shown in several studies that bone tissue seems to be independently associated with NAFLD. A mechanistic perspective puts the liver at the center of mutual interdependencies obviously involving adipose tissue and muscles and also the bone matrix and bone cells, which are relatively novel. In this review, various pathophysiological mechanisms and possible mediating molecules that may interplay between NAFLD and bone tissue are described. Chronic inflammation, vitamin D3, growth hormone, insulin-like growth factor 1, osteopontin, fetuin-A, irisin, osteocalcin, and osteoprotegerin from osteoblasts have been proposed as mediators of mutual interactions among the skeleton, fatty tissue, and liver. Although to date there are still many issues that have not been elucidated, growing evidence suggests that screening and surveillance of bone mineral density in patients with NAFLD should be considered in future strategies and guidelines for NAFLD management.
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Affiliation(s)
- Rafał Filip
- Department of Gastroenterology with IBD Unit, Clinical Hospital 2, Rzeszów, Poland,
- University of Rzeszów, Rzeszów, Poland,
| | - Radosław P Radzki
- Department of Animal Physiology, University of Life Sciences, Lublin, Poland
| | - Marek Bieńko
- Department of Animal Physiology, University of Life Sciences, Lublin, Poland
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