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Paoletta M, Moretti A, Liguori S, Gimigliano F, Iolascon G. Transient osteoporosis of the hip and fatty liver disease: Case report and pathogenic hypothesis. J Int Med Res 2025; 53:3000605251334239. [PMID: 40372122 PMCID: PMC12081969 DOI: 10.1177/03000605251334239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Accepted: 02/26/2025] [Indexed: 05/16/2025] Open
Abstract
Transient osteoporosis of the hip is a rare, temporary condition characterized by hip pain and functional limitations, which can significantly reduce the quality of life. Bone marrow edema of the proximal femur, identified through magnetic resonance imaging is the primary diagnostic feature of transient osteoporosis of the hip. While the exact cause of transient osteoporosis of the hip remains unclear, several potential pathophysiological mechanisms warrant further investigation to better understand this condition. In this case study, we present an unusual case of a patient with transient osteoporosis of the hip who was diagnosed with non-alcoholic fatty liver disease. A 42-year-old Caucasian man presented with left hip pain. After clinical and radiological evaluations, he was diagnosed with transient osteoporosis of the hip. Biochemical assessment revealed a persistent and isolated elevation of alanine aminotransferase. The patient underwent a treatment regimen involving 16 days of intramuscular neridronate along with physical therapy. At the 3- and 6-month follow-ups, he showed significant improvements in both clinical symptoms and radiological findings. In our study, we propose, for the first time, a potential association between liver disorders, specifically non-alcoholic fatty liver disease, and the onset of transient osteoporosis of the hip, exploring the possible pathophysiological mechanisms connecting these two conditions and discuss the rationale for both pharmacological and non-pharmacological treatments.
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Affiliation(s)
- Marco Paoletta
- Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Antimo Moretti
- Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Sara Liguori
- Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Francesca Gimigliano
- Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Giovanni Iolascon
- Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Naples, Italy
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2
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Rong K, Yi Ke Ran GLJ, Zhou C, Yi X. Intelligent predictive risk assessment and management of sarcopenia in chronic disease patients using machine learning and a web-based tool. Eur J Med Res 2025; 30:345. [PMID: 40301941 PMCID: PMC12039279 DOI: 10.1186/s40001-025-02606-3] [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: 03/05/2025] [Accepted: 04/16/2025] [Indexed: 05/01/2025] Open
Abstract
BACKGROUND Individuals with chronic diseases are at higher risk of sarcopenia, and precise prediction is essential for its prevention. This study aims to develop a risk scoring model using longitudinal data to predict the probability of sarcopenia in this population over next 3-5 years, thereby enabling early warning and intervention. METHODS Using data from a nationwide survey initiated in 2011, we selected patient data records from wave 1 (2011-2012) and follow-up data from wave 3 (2015-2016) as the study cohort. Retrospective data collection included demographic information, health conditions, and biochemical markers. After excluding records with missing values, a total of 2891 adults with chronic conditions were enrolled. Sarcopenia was assessed based on the Asian Working Group for Sarcopenia (AWGS) 2019 guidelines. A generalized linear mixed model (GLMM) with random effects and diverse machine learning models were utilized to explore feature contributions to sarcopenia risk. The Recursive Feature Elimination (RFE) algorithm was employed to optimize the full Multilayer Perceptron (MLP) model and develop an online application tool. RESULTS Among total population, 580 (20.1%) individuals were diagnosed with sarcopenia in wave 1 (2011-2012), and 638 (22.1%) were diagnosed in wave 3 (2015-2016), while 2165 (74.9%) individuals were not diagnosed with sarcopenia across the study period. MLP model, performed better than other three classic machine learning models, demonstrated a ROC AUC of 0.912, a PR AUC of 0.401, a sensitivity of 0.875, a specificity of 0.844, a Kappa value of 0.376, and an F1 score of 0.44. According to MLP model-based SHapley Additive exPlanations (SHAP) scoring, weight, age, BMI, height, total cholesterol, PEF, and gender were identified as the most important features of chronic disease individuals for sarcopenia. Using the RFE algorithm, we selected six key variables-weight, age, BMI, height, total cholesterol, and gender-achieving an ROC AUC of about 0.9 for the online application tool. CONCLUSION We developed an MLP machine learning model that incorporates only six easily accessible variables, enabling the prediction of sarcopenia risk in individuals with chronic diseases. Additionally, we created a practical online application tool to assist in decision-making and streamline clinical assessments.
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Affiliation(s)
- Ke Rong
- Department of Pulmonary and Critical Care Medicine, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
| | - Gu Li Jiang Yi Ke Ran
- Kuitun Hospital of Ili Kazakh Autonomous Prefecture, Kuitun, Chongqing, 833200, China
| | - Changgui Zhou
- Department of Pulmonary and Critical Care Medicine, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
| | - Xinglin Yi
- The First Hospital Affiliated with Third Military Medical University, Chongqing, China.
- Department of Respiratory Medicine, Southwest Hospital of Third Military Medical University, Chongqing, China.
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3
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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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Shirinezhad A, Eshlaghi FM, Salabat D, Azarboo A, Ardakani ZF, Esmaeili S, Hoveidaei AH, Ghaseminejad-Raeini A. Prevalent osteoporosis and fracture risk in patients with hepatic cirrhosis: a systematic review and meta-analysis. BMC Gastroenterol 2025; 25:115. [PMID: 40000980 PMCID: PMC11853567 DOI: 10.1186/s12876-025-03720-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 02/20/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Hepatic liver cirrhosis can lead to significant systemic complications, including the deterioration of bone health. The resulting bone complications can contribute to a decreased quality of life and increased healthcare burden. This study aimed to systematically review and analyze the risk of osteoporosis, fracture, and changes in bone mineral density (BMD) among patients with hepatic cirrhosis compared to non-cirrhotic healthy controls. METHODS Adhering to PRISMA guidelines, studies were sourced from MEDLINE/PubMed, Scopus, Web of Science, and Embase up to July 2024, including observational studies that assessed osteoporosis, fracture, and BMD in cirrhotic versus non-cirrhotic patients. Meta-analyses were performed by calculating odds ratios (OR) and standardized mean differences (SMD) of outcomes. Sensitivity analyses and meta-regression were also conducted to explore the robustness and sources of heterogeneity. RESULTS The analysis included 21 studies with 76,521 cirrhotic and 695,330 control patients. Cirrhotic patients demonstrated significantly higher odds of osteoporosis (OR = 1.93 [1.84 to 2.03]). Fracture was notably elevated, with cirrhotic patients showing an OR of 2.30 [1.66 to 3.18]. Reductions in BMD were observed in both the lumbar spine (SMD = -0.57[-0.79 to -0.35]) and femoral neck (SMD = -0.41 [-0.71 to -0.12]). Sensitivity analyses confirmed these findings, and meta-regression highlighted that male prevalence impacted these associations in various ways. CONCLUSIONS Patients with hepatic cirrhosis are at heightened risk for osteoporosis and fractures, underlining the need for proactive screening and preventive strategies. Integrating cirrhosis into current fracture-risk models could enhance the assessment and management of bone health in these patients.
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Affiliation(s)
| | | | - Dorsa Salabat
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Azarboo
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Sina Esmaeili
- Sina University Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Human Hoveidaei
- Sports Medicine Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Ghaseminejad-Raeini
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
- School of Medicine, Tehran University of Medical Sciences, Tehran Province, District 6, Pour Sina St, P94V+8MF, Tehran, Iran.
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Kamioka H, Saeki C, Oikawa T, Kinoshita A, Kanai T, Ueda K, Nakano M, Torisu Y, Saruta M, Tsubota A. Low geriatric nutritional risk index is associated with osteoporosis and fracture risk in patients with chronic liver disease: a cross-sectional study. BMC Gastroenterol 2024; 24:376. [PMID: 39448932 PMCID: PMC11515523 DOI: 10.1186/s12876-024-03465-8] [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: 03/27/2024] [Accepted: 10/15/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND Patients with chronic liver disease (CLD) frequently suffer from malnutrition and bone diseases, both of which heighten the risk of poor clinical outcomes. This study investigated the relationship between geriatric nutritional risk index (GNRI) and osteoporosis or fracture risk using the fracture risk assessment tool (FRAX) in patients with CLD. METHODS This cross-sectional study included 209 consecutive patients with CLD. The participants were divided into two groups: the all-risk group (GNRI ≤ 98.0) with nutrition-related risk and the no-risk group (GNRI > 98.0) without nutrition-related risk. Osteoporosis was diagnosed according to the World Health Organization criteria. The FRAX was used to estimate the 10-year probabilities of hip fracture (FRAX-HF) and major osteoporotic fracture (FRAX-MOF). RESULTS Of the 209 patients, 72 (34.4%) had osteoporosis. The all-risk group had a significantly higher prevalence of osteoporosis than the no-risk group (p < 0.001). Conversely, patients with osteoporosis had significantly lower GNRI than those without osteoporosis (p < 0.001). Multivariate analysis found lower GNRI to be a significant and independent risk factor for osteoporosis (odds ratio [OR], 0.927; p < 0.001) and high fracture risk derived from FRAX (without BMD) (OR, 0.904; p = 0.009). GNRI had a positive correlation with bone mineral density (BMD) at the lumbar spine, femoral neck, and total hip, but a negative correlation with FRAX-HF and FRAX-MOF in the FRAX with and without BMD (p < 0.001 for all). The cutoff value of GNRI for predicting osteoporosis was 104.9, with sensitivity of 0.667 and specificity of 0.657. CONCLUSIONS The GNRI was significantly associated with osteoporosis and FRAX-derived fracture risk in patients with CLD, suggesting that it could be a simple and useful indicator for the management of bone diseases.
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Affiliation(s)
- Hiroshi Kamioka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Chisato Saeki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
- Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, Shizuoka, Japan.
| | - Tsunekazu Oikawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Akiyoshi Kinoshita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Tomoya Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, Shizuoka, Japan
| | - Kaoru Ueda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Masanori Nakano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, Shizuoka, Japan
| | - Yuichi Torisu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, Shizuoka, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Akihito Tsubota
- Project Research Units, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo, Japan.
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Herrmann M, Rodriguez-Blanco G, Balasso M, Sobolewska K, Semeraro MD, Alonso N, Herrmann W. The role of bile acid metabolism in bone and muscle: from analytics to mechanisms. Crit Rev Clin Lab Sci 2024; 61:510-528. [PMID: 38488591 DOI: 10.1080/10408363.2024.2323132] [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: 12/06/2023] [Revised: 02/09/2024] [Accepted: 02/21/2024] [Indexed: 08/25/2024]
Abstract
Osteoporosis and sarcopenia are both common age-related disorders that are associated with increased morbidity and mortality. Bone and muscle are metabolically very active tissues that require large amounts of energy. Bile acids (BAs), a group of liver-derived steroid compounds, are primarily known as emulsifiers that facilitate the resorption of dietary fat and lipids. In addition, they have pleiotropic metabolic functions in lipoprotein and glucose metabolism, inflammation, and intestinal bacterial growth. Through these effects, they are related to metabolic diseases, such as diabetes, hypertriglyceridemia, atherosclerosis, and nonalcoholic steatohepatitis. BAs mediate their metabolic effects through receptor dependent and receptor-independent mechanisms. Emerging evidence suggests that BAs are also involved in bone and muscle metabolism. Under normal circumstances, BAs support bone health by shifting the delicate equilibrium of bone turnover toward bone formation. In contrast, low or excessive amounts of BAs promote bone resorption. In cholestatic liver disease, BAs accumulate in the liver, reach toxic concentrations in the circulation, and thus may contribute to bone loss and muscle wasting. In addition, the measurement of BAs is in rapid evolution with modern mass spectrometry techniques that allow for the detection of a continuously growing number of BAs. This review provides a comprehensive overview of the biochemistry, physiology and measurement of bile acids. Furthermore, it summarizes the existing literature regarding their role in bone and muscle.
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Affiliation(s)
- Markus Herrmann
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Giovanny Rodriguez-Blanco
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Marco Balasso
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Katarzyna Sobolewska
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Maria Donatella Semeraro
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Nerea Alonso
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Wolfgang Herrmann
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
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Wu JL, Luo JY, Jiang ZB. Association between antiviral treatments and fracture in elderly patients with HBV needs further evaluation. J Hepatol 2024; 81:e108-e109. [PMID: 38527526 DOI: 10.1016/j.jhep.2024.03.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 03/08/2024] [Accepted: 03/11/2024] [Indexed: 03/27/2024]
Affiliation(s)
- Jia-Lin Wu
- Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Jun-Yang Luo
- Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Zai-Bo Jiang
- Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
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Luo XY, Ying SQ, Cao Y, Jin Y, Jin F, Zheng CX, Sui BD. Liver-based inter-organ communication: A disease perspective. Life Sci 2024; 351:122824. [PMID: 38862061 DOI: 10.1016/j.lfs.2024.122824] [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: 05/10/2024] [Revised: 06/06/2024] [Accepted: 06/08/2024] [Indexed: 06/13/2024]
Abstract
Inter-organ communication through hormones, cytokines and extracellular vesicles (EVs) has emerged to contribute to the physiological states and pathological processes of the human body. Notably, the liver coordinates multiple tissues and organs to maintain homeostasis and maximize energy utilization, with the underlying mechanisms being unraveled in recent studies. Particularly, liver-derived EVs have been found to play a key role in regulating health and disease. As an endocrine organ, the liver has also been found to perform functions via the secretion of hepatokines. Investigating the multi-organ communication centered on the liver, especially in the manner of EVs and hepatokines, is of great importance to the diagnosis and treatment of liver-related diseases. This review summarizes the crosstalk between the liver and distant organs, including the brain, the bone, the adipose tissue and the intestine in noticeable situations. The discussion of these contents will add to a new dimension of organismal homeostasis and shed light on novel theranostics of pathologies.
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Affiliation(s)
- Xin-Yan Luo
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China; School of Basic Medicine, The Fourth Military Medical University, Xi'an 710032, China
| | - Si-Qi Ying
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China
| | - Yuan Cao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China; Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Yan Jin
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China
| | - Fang Jin
- Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Chen-Xi Zheng
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
| | - Bing-Dong Sui
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
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Saeki C, Saito M, Tsubota A. Association of chronic liver disease with bone diseases and muscle weakness. J Bone Miner Metab 2024; 42:399-412. [PMID: 38302761 DOI: 10.1007/s00774-023-01488-x] [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: 10/02/2023] [Accepted: 11/16/2023] [Indexed: 02/03/2024]
Abstract
The liver is a vital organ involved in nutrient metabolism, hormone regulation, immunity, cytokine production, and gut homeostasis. Impairment in liver function can result in malnutrition, chronic inflammation, decreased anabolic hormone levels, and dysbiosis. These conditions eventually cause an imbalance in osteoblast and osteoclast activities, resulting in bone loss. Osteoporosis is a frequent complication of chronic liver disease (CLD) that adversely affects quality of life and increases early mortality. Sarcopenia is another common complication of CLD characterized by progressive loss of skeletal muscle mass and function. Assessment criteria for sarcopenia specific to liver disease have been established, and sarcopenia has been reported to be associated with an increase in the risk of liver disease-related events and mortality in patients with CLD. Owing to their similar risk factors and underlying pathophysiological mechanisms, osteoporosis and sarcopenia often coexist (termed osteosarcopenia), progress in parallel, and further exacerbate the conditions mentioned above. Therefore, comprehensive management of these musculoskeletal disorders is imperative. This review summarizes the clinical implications and characteristics of osteoporosis, extending to sarcopenia and osteosarcopenia, in patients with CLD caused by different etiologies.
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Affiliation(s)
- Chisato Saeki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Mitsuru Saito
- Department of Orthopedic Surgery, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Akihito Tsubota
- Project Research Units, Research Center for Medical Science, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
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10
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Bueno MV, Munhoz L, Ortega KL, Peres MPSDM, Franco JB. Bone pattern changes in post liver transplant patients using bisphosphonates. SPECIAL CARE IN DENTISTRY 2024; 44:1273-1279. [PMID: 38481370 DOI: 10.1111/scd.12992] [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: 12/22/2023] [Revised: 02/25/2024] [Accepted: 02/28/2024] [Indexed: 07/18/2024]
Abstract
OBJECTIVE To identify radiographic findings suggestive of drug-induced osteonecrosis and evaluate radiomorphometric patterns indicative of changes in bone mineral density in individuals transplanted for liver disorders using bisphosphonates. STUDY DESIGN The study group included panoramic x-rays of liver transplant patients who are being monitored and who present a clinical status of osteoporosis and use bisphosphonates. The control group was made up of liver transplant patients who did not have osteoporosis. On panoramic radiographs, mental index (MI) and mandibular cortical index (MCI) and the presence of radiographic anomalies suggestive of osteonecrosis were evaluated. RESULTS There were significant statistical results when comparing the groups in relation to the decrease in bone mineral density (BMD) with MCI-C3 (p = 0.036), however, there were none in relation to MI (p = 0.14). There were no valid statistical results when relating MCI (p = 0.94) and MI (p = 0.66) with reduced BMD and use of bisphosphonates. CONCLUSION Liver transplant individuals using bisphosphonates present greater radiographic signs of bone sclerosis suggestive of a greater propensity to develop osteonecrosis of the jaw and an increased risk of presenting changes suggestive of reduced bone mineral density on panoramic radiographs when compared to liver transplant individuals not using bisphosphonates.
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Affiliation(s)
- Marcus Vinícius Bueno
- Department of Dentistry, Central Institute, Clinical Hospital of Medical School of the University of São Paulo, São Paulo, SP, Brazil
| | - Luciana Munhoz
- Department of Stomatology, Public Health and Forense Dentistry, School of Dentistry of University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Karem L Ortega
- Oral Medicine, Oral Surgery and Implantology, Unit (MedOralRes), Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela, Spain
- Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, SP, Brazil
| | | | - Juliana Bertoldi Franco
- Department of Dentistry, Central Institute, Clinical Hospital of Medical School of the University of São Paulo, São Paulo, SP, Brazil
- Department of Dentistry, Children and Adolescents Institute, Clinical Hospital of Medical School of the University of São Paulo, São Paulo, SP, Brazil
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Miki A, Sakuma Y, Sanada Y, Watanabe J, Onishi Y, Okada N, Horiuchi T, Omameuda T, Teratani T, Lefor AK, Kitayama J, Sata N. Changes in thoracic radio density after living donor liver transplantation. Pediatr Transplant 2024; 28:e14599. [PMID: 38713752 DOI: 10.1111/petr.14599] [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: 06/28/2022] [Revised: 06/28/2023] [Accepted: 08/17/2023] [Indexed: 05/09/2024]
Abstract
BACKGROUND The outcomes after liver transplantation have greatly improved, which has resulted in greater focus on improving non-hepatic outcomes of liver transplantation. The present study aimed to evaluate thoracic spine radio density in children and adolescents after liver transplantation. METHODS A total of 116 patients who underwent living donor liver transplantation were retrospectively analyzed. The radio density at the eleventh thoracic vertebra was measured using computed tomography scan performed preoperatively then annually for 5 years postoperatively and subsequently every 2 or 3 years. RESULTS The mean thoracic radio density of male recipients of male grafts had the lowest values during the study. The radio density of patients receiving a graft from a female donor was higher than in recipients with grafts from males. Total mean radio density decreased for first 5 years postoperatively and then increased. Changes in radio density were equally distributed in both steroid withdrawal and no steroid withdrawal groups for 5 years, after which patients with steroid withdrawal had a greater increase. Changes in radio density were equally distributed in both the steroid withdrawal and no steroid withdrawal groups up to age 20, after which patients in the steroid withdrawal group had a greater increase. CONCLUSIONS Gender differences may affect the outcome of radio density changes after transplantation. Given the moderate association between thoracic radio density and bone mineral density in skeletally mature adults and further studies are needed to validate this relationship between thoracic radio density and bone mineral density changes in pediatric liver transplantation.
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Affiliation(s)
- Atsushi Miki
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Yasunaru Sakuma
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Yukihiro Sanada
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Jun Watanabe
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Yasuharu Onishi
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Noriki Okada
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Toshio Horiuchi
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Takahiko Omameuda
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Takumi Teratani
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Alan K Lefor
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Joji Kitayama
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Naohiro Sata
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
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12
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Liu Y, Yuan M, He J, Cai L, Leng A. The Impact of Non-alcohol Fatty Liver Disease on Bone Mineral Density is Mediated by Sclerostin by Mendelian Randomization Study. Calcif Tissue Int 2024; 114:502-512. [PMID: 38555554 DOI: 10.1007/s00223-024-01204-5] [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: 05/30/2023] [Accepted: 02/19/2024] [Indexed: 04/02/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) has been found to be associated with osteoporosis (OP) in observational studies. However, the precise causal relationship between NAFLD and OP remains unclear. Here, we used Mendelian randomization (MR) to explore the causal relationship. We selected NAFLD-related single-nucleotide polymorphisms from a genome-wide meta-analysis (8434 cases and 434,770 controls) as instrumental variants. We used inverse variance weighted analysis for the primary MR analysis. Furthermore, we used similar methodologies in parallel investigations of other chronic liver diseases (CLDs). We performed sensitivity analyses to ensure the reliability of the results. We observed a causality between NAFLD and forearm bone mineral density (FABMD) (beta-estimate [β]: - 0.212; p-value: 0.034). We also found that sclerostin can act as a mediator to influence the NAFLD and FABMD pathways to form a mediated MR network (mediated proportion = 8.8%). We also identified indications of causal relationships between other CLDs and OP. However, we were unable to establish any associated mediators. Notably, our analyses did not yield any evidence of pleiotropy. Our findings have implications in the development of preventive and interventional measures aimed at managing low bone mineral density in patients with NAFLD.
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Affiliation(s)
- Yuan Liu
- Department of Gastroenterology, Xiangya Hospital, Central South University, No.88 Xiangya Road, Kaifu District, Changsha, 410000, Hunan Province, China
| | - Mengqin Yuan
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jian He
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Longjiao Cai
- Department of Gastroenterology, Xiangya Hospital, Central South University, No.88 Xiangya Road, Kaifu District, Changsha, 410000, Hunan Province, China
| | - Aimin Leng
- Department of Gastroenterology, Xiangya Hospital, Central South University, No.88 Xiangya Road, Kaifu District, Changsha, 410000, Hunan Province, China.
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Pei X, Jiang W, Li L, Zeng Q, Liu CH, Wang M, Chen E, Zhou T, Tang H, Wu D. Mendelian-randomization study revealed causal relationship between nonalcoholic fatty liver disease and osteoporosis/fractures. J Gastroenterol Hepatol 2024; 39:847-857. [PMID: 38240493 DOI: 10.1111/jgh.16448] [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: 09/26/2023] [Revised: 11/12/2023] [Accepted: 12/03/2023] [Indexed: 05/03/2024]
Abstract
BACKGROUND Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have a higher risk of osteoporosis/fractures; however, the causal relationship remains unclear. METHODS Publicly available genome-wide association studies (GWASs) were used for Mendelian randomization (MR) analysis. GWASs of NAFLD and fractures were obtained from the FinnGen Consortium. GWASs of bone mineral density (BMD) were derived from a meta-analysis. GWASs of obesity, diabetes, liver function, and serum lipid-related metrics were used to clarify whether the accompanying NAFLD symptoms contributed to fractures. Moreover, two additional GWASs of NAFLD were applied. RESULTS A causal association was not observed between NAFLD and BMD using GWASs from the FinnGen Consortium. However, a causal relationship between NAFLD and femoral neck-BMD (FN-BMD), a suggestive relationship between fibrosis and FN-BMD, and between NAFLD and osteoporosis were identified in replication GWASs. Genetically proxied body mass index (BMI), high-density lipoprotein (HDL), and hip circumference increased the likelihood of lower limb fractures. The waist-to-hip ratio decreased, whereas glycated hemoglobin (HbA1C) and homeostasis model assessment of β-cell function (HOMA-B) increased the risk of forearm fractures. Low-density lipoprotein (LDL) reduced, whereas HbA1C increased the incidence of femoral fractures. Alkaline phosphatase (ALP) raised the risk of foot fractures. However, after a multivariate MR analysis (adjusted for BMI), all the relationships became insignificant. CONCLUSIONS NAFLD caused reduced BMD, and genetically predicted HDL, LDL, HbA1C, HOMA-B, ALP, hip circumference, and waist-to-hip ratio causally increased the risk of fractures. BMI may mediate causal relationships. Larger GWASs are required to verify this finding.
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Affiliation(s)
- Xiong Pei
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Wei Jiang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lianchi Li
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Qingmin Zeng
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Chang-Hai Liu
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Ming Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Enqiang Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Taoyou Zhou
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Dongbo Wu
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
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14
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Zeng L, Li Y, Hong C, Wang J, Zhu H, Li Q, Cui H, Ma P, Li R, He J, Zhu H, Liu L, Xiao L. Association between fatty liver index and controlled attenuation parameters as markers of metabolic dysfunction-associated fatty liver disease and bone mineral density: observational and two-sample Mendelian randomization studies. Osteoporos Int 2024; 35:679-689. [PMID: 38221591 DOI: 10.1007/s00198-023-06996-0] [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: 05/16/2023] [Accepted: 12/04/2023] [Indexed: 01/16/2024]
Abstract
Previously observational studies did not draw a clear conclusion on the association between fatty liver diseases and bone mineral density (BMD). Our large-scale studies revealed that MAFLD and hepatic steatosis had no causal effect on BMD, while some metabolic factors were correlated with BMD. The findings have important implications for the relationship between fatty liver diseases and BMD, and may help direct the clinical management of MAFLD patients who experience osteoporosis and osteopenia. PURPOSE Liver and bone are active endocrine organs with several metabolic functions. However, the link between metabolic dysfunction-associated fatty liver disease (MAFLD) and bone mineral density (BMD) is contradictory. METHODS Using the UK Biobank and National Health and Nutrition Examination Survey (NHANES) dataset, we investigated the association between MAFLD, steatosis, and BMD in the observational analysis. We performed genome-wide association analysis to identify single-nucleotide polymorphisms associated with MAFLD. Large-scale two-sample Mendelian randomization (TSMR) analyses examined the potential causal relationship between MAFLD, hepatic steatosis, or major comorbid metabolic factors, and BMD. RESULTS After adjusting for demographic factors and body mass index, logistic regression analysis demonstrated a significant association between MAFLD and reduced heel BMD. However, this association disappeared after adjusting for additional metabolic factors. MAFLD was not associated with total body, femur neck, and lumbar BMD in the NHANES dataset. Magnetic resonance imaging-measured steatosis did not show significant associations with reduced total body, femur neck, and lumbar BMD in multivariate analysis. TSMR analyses indicated that MAFLD and hepatic steatosis were not associated with BMD. Among all MAFLD-related comorbid factors, overweight and type 2 diabetes showed a causal relationship with increased BMD, while waist circumference and hyperlipidemia had the opposite effect. CONCLUSION No causal effect of MAFLD and hepatic steatosis on BMD was observed in this study, while some metabolic factors were correlated with BMD. This has important implications for understanding the relationship between fatty liver disease and BMD, which may help direct the clinical management of MAFLD patients with osteoporosis.
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Affiliation(s)
- Lin Zeng
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
- Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yan Li
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Chang Hong
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jiaren Wang
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Hongbo Zhu
- Department of Medical Oncology, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan Province, China
| | - Qimei Li
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Hao Cui
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Pengcheng Ma
- Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Ruining Li
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jingzhe He
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Hong Zhu
- Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
| | - Li Liu
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
- Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
| | - Lushan Xiao
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
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15
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Jurina A, Delimar V, Giljević Z, Filipec Kanižaj T, Matković A, Vidović D, Jurjević N, Vidjak V, Duić Ž, Ćuk M, Japjec M, Dujmović T, Radeljak A, Kardum Paro MM, Vučić-Lovrenčić M, Starešinić M. Fragility spinal fractures among cirrhotic liver transplant candidates in Croatia. Injury 2024; 55:111171. [PMID: 37952477 DOI: 10.1016/j.injury.2023.111171] [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: 07/27/2023] [Revised: 08/21/2023] [Accepted: 10/28/2023] [Indexed: 11/14/2023]
Abstract
INTRODUCTION Existing data on fragility spinal fractures prevalence in liver transplant candidates are scarce and inconsistent. This may be due to other comorbidities, besides hepatic osteodystrophy (HO), that contribute to bone loss and fragility fracture prevalence in chronic liver disease (CLD). OBJECTIVES The aim of this study was to investigate the prevalence of spinal thoracic and lumbar fragility fractures among cirrhotic, non-chronic kidney disease (CKD), non-diabetic liver transplant candidates and to explore their relationship with clinical characteristics, laboratory markers and dual-energy x-ray absorptiometry (DXA) results. MATERIAL AND METHODS This cross-sectional observational study was conducted at Merkur University Hospital, Croatia, between February 2019 and May 2023. Adult patients with liver cirrhosis referred for liver transplantation were included. Patients with acute infection, CKD, diabetes mellitus, malignancies, inflammatory bone diseases and those on corticosteroid or antiresorptive therapy were excluded. Clinical, laboratory and radiological assessment was carried out and patients were accordingly allocated into non-fractured and fractured group for the purpose of statistical analysis. RESULTS A total of 90 patients were included in the study. There was 123 fractures, 87 (70.7 %) in the thoracic and 36 (29.3 %) in the lumbar region. Eighty-nine (72.4 %) fractures were grade 1, 31 (25.2 %) were grade 2 and 3 (2.4 %) were grade 3. Patients in the fractured group were significantly older (p < 0.001). No significant differences between fractured and non-fractured group according to laboratory and DXA parameters were noted. Subgroup with lumbar fractures had significantly lower bone mineral density values at L1-L4 region. Statistically significant negative correlation between bone specific alkaline phosphatase (BALP) and hip total BMD (rho = -0.414, p < 0.001) and spine total BMD (rho = -0.258, p = 0.014) values was found. CONCLUSION Present study confirmed detrimental impact of CLD and HO on bone strength. DXA measurement correlated with the presence of lumbar fragility fractures. A combination of standard X-ray imaging and DXA is needed for adequate bone evaluation in pretransplant period and BALP could be useful for detecting HO in CLD. Searching for other risk factors and implementing bone turnover markers and additional imaging techniques for bone loss evaluation in liver transplant candidates is needed.
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Affiliation(s)
- Andrija Jurina
- Division of general and sport traumatology and orthopaedics, Department of surgery, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia
| | - Valentina Delimar
- Special Hospital for Medical Rehabilitation Krapinske Toplice, Gajeva 2, 49217 Krapinske Toplice, Croatia.
| | - Zlatko Giljević
- Division of Endocrinology, Department of internal medicine, Zagreb University Hospital Centre, Kišpatićeva 12, 10000 Zagreb, Croatia; School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
| | - Tajana Filipec Kanižaj
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia; Division of Gastroenterology, Department of internal medicine, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia
| | - Andro Matković
- Clinical Department of Diagnostic and Interventional Radiology, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia
| | - Dinko Vidović
- Sestre milosrdnice University Hospital Centre, Clinic of Traumatology, Draškovićeva 19, 10000 Zagreb, Croatia; School of Dental Medicine, University of Zagreb, Gundulićeva 5, 10000 Zagreb, Croatia
| | - Nikolina Jurjević
- Clinical Department of Diagnostic and Interventional Radiology, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia
| | - Vinko Vidjak
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia; Clinical Department of Diagnostic and Interventional Radiology, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia
| | - Željko Duić
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia; Department of Gynaecology and Obstretrics, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia
| | - Mario Ćuk
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia; Department of Pediatrics, Zagreb University Hospital Centre, Kišpatićeva 12, Rebro 10000 Zagreb, Croatia
| | - Mladen Japjec
- Division of general and sport traumatology and orthopaedics, Department of surgery, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia
| | - Tomislav Dujmović
- Division of general and sport traumatology and orthopaedics, Department of surgery, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia
| | - Andrea Radeljak
- Department of Clinical Chemistry and Laboratory Medicine, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia
| | - Mirjana Marjana Kardum Paro
- Department of Clinical Chemistry and Laboratory Medicine, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia
| | - Marijana Vučić-Lovrenčić
- Department of Clinical Chemistry and Laboratory Medicine, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia
| | - Mario Starešinić
- Division of general and sport traumatology and orthopaedics, Department of surgery, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia; School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
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16
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Isaacs S, Isaacs A. Endocrinology for the Hepatologist. CURRENT HEPATOLOGY REPORTS 2024; 23:99-109. [DOI: 10.1007/s11901-024-00639-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/09/2024] [Indexed: 01/03/2025]
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17
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Liu LL, Liu ZR, Cao LJ, Wang J, Huang SM, Hu SG, Yang YZ, Li DS, Cao WW, Zeng QB, Huang S, Wu Q, Xiao JH, Liu WY, Xiao YS. Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis. J Orthop Surg Res 2024; 19:59. [PMID: 38216929 PMCID: PMC10785403 DOI: 10.1186/s13018-024-04535-z] [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: 10/20/2023] [Accepted: 01/04/2024] [Indexed: 01/14/2024] Open
Abstract
OBJECTIVE Iron accumulation is associated with osteoporosis. This study aims to explore the effect of chronic iron accumulation induced by hepcidin1 deficiency on aging osteoporosis. METHODS Iron accumulation in hepcidin1 knockout aging mice was assessed by atomic absorption spectroscopy and Perl's staining. Bone microarchitecture was observed using Micro-CT. Hepcidin, ferritin, oxidative stress, and markers of bone turnover in serum were detected by enzyme-linked immunosorbent assay. Bone formation and resorption markers were measured by real-time quantitative PCR. Cell aging was induced by D-galactose treatment. CCK-8, flow cytometry, EdU assays, and Alizarin red staining were performed to reveal the role of hepcidin1 knockout in cell model. Iron Colorimetric Assay Kit and western blot were applied to detect iron and ferritin levels in cells, respectively. RESULTS In hepcidin1-knockout mice, the ferritin and iron contents in liver and tibia were significantly increased. Iron accumulation induced by hepcidin1 knockout caused a phenotype of low bone mass and deteriorated bone microarchitecture. Osteogenic marker was decreased and osteoclast marker was increased in mice, accompanied by increased oxidative stress level. The mRNA expression levels of osteoclast differentiation markers (RANKL, Mmp9, OPG, Trap, and CTSK) were up-regulated, while bone formation markers (OCN, ALP, Runx2, SP7, and Col-1) were down-regulated in model group, compared to wild type mice. In vitro, hepcidin1 knockdown inhibited proliferation and osteogenic differentiation, while promoted apoptosis, with increased levels of iron and ferritin. CONCLUSION Iron accumulation induced by hepcidin1 deficiency aggravates the progression of aging osteoporosis via inhibiting osteogenesis and promoting osteoclast genesis.
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Affiliation(s)
- Lu-Lin Liu
- Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, No. 128, Jinling Road, Ganzhou, 341000, Jiangxi, China
- Ganzhou Key Laboratory of Osteoporosis Research, No. 23, Qingnian Road, Ganzhou, 341000, Jiangxi, China
| | - Zhong-Rui Liu
- Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, No. 128, Jinling Road, Ganzhou, 341000, Jiangxi, China
- Ganzhou Key Laboratory of Osteoporosis Research, No. 23, Qingnian Road, Ganzhou, 341000, Jiangxi, China
| | - Lu-Jun Cao
- Department of Orthopedics, The People's Hospital of Ningdu County, No. 109, Zhongshan South Road, Ningdu County, Ganzhou, 342800, Jiangxi, China
| | - Jun Wang
- Department of Orthopedics, The People's Hospital of Ningdu County, No. 109, Zhongshan South Road, Ningdu County, Ganzhou, 342800, Jiangxi, China
| | - San-Ming Huang
- Department of Orthopedics, The People's Hospital of Ningdu County, No. 109, Zhongshan South Road, Ningdu County, Ganzhou, 342800, Jiangxi, China
| | - Shui-Gen Hu
- Department of Orthopedics, The People's Hospital of Ningdu County, No. 109, Zhongshan South Road, Ningdu County, Ganzhou, 342800, Jiangxi, China
| | - Yi-Zhong Yang
- Department of Orthopedics, The People's Hospital of Ningdu County, No. 109, Zhongshan South Road, Ningdu County, Ganzhou, 342800, Jiangxi, China
| | - Dong-Sheng Li
- Department of Orthopedics, The People's Hospital of Ningdu County, No. 109, Zhongshan South Road, Ningdu County, Ganzhou, 342800, Jiangxi, China
| | - Wei-Wei Cao
- Department of Orthopedics, The People's Hospital of Ningdu County, No. 109, Zhongshan South Road, Ningdu County, Ganzhou, 342800, Jiangxi, China
| | - Qing-Bao Zeng
- Department of Orthopedics, The People's Hospital of Ningdu County, No. 109, Zhongshan South Road, Ningdu County, Ganzhou, 342800, Jiangxi, China
| | - Sheng Huang
- Department of Orthopedics, The People's Hospital of Ningdu County, No. 109, Zhongshan South Road, Ningdu County, Ganzhou, 342800, Jiangxi, China
| | - Qiong Wu
- Department of Orthopedics, The People's Hospital of Ningdu County, No. 109, Zhongshan South Road, Ningdu County, Ganzhou, 342800, Jiangxi, China
| | - Jian-Hua Xiao
- Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, No. 128, Jinling Road, Ganzhou, 341000, Jiangxi, China
- Ganzhou Key Laboratory of Osteoporosis Research, No. 23, Qingnian Road, Ganzhou, 341000, Jiangxi, China
| | - Wu-Yang Liu
- Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, No. 128, Jinling Road, Ganzhou, 341000, Jiangxi, China
- Ganzhou Key Laboratory of Osteoporosis Research, No. 23, Qingnian Road, Ganzhou, 341000, Jiangxi, China
| | - Yao-Sheng Xiao
- Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, No. 128, Jinling Road, Ganzhou, 341000, Jiangxi, China.
- Ganzhou Key Laboratory of Osteoporosis Research, No. 23, Qingnian Road, Ganzhou, 341000, Jiangxi, China.
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Sánchez-Delgado J, Profitós J, Arévalo M, Lira A, Mármol C, Miquel M, Casas M, Vergara M, Calvet X, Berlanga E, del Rio L, Valero O, Costa E, Larrosa M, Casado Burgos E. Osteoporosis and Fragility Fractures in Patients with Liver Cirrhosis: Usefulness of FRAX ® as a Screening Tool. J Clin Med 2023; 13:188. [PMID: 38202195 PMCID: PMC10780144 DOI: 10.3390/jcm13010188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 12/16/2023] [Accepted: 12/25/2023] [Indexed: 01/12/2024] Open
Abstract
PURPOSE The purpose of this study is to assess the prevalence of osteoporosis and fragility fractures in patients with liver cirrhosis (LC) and determine the associated risk factors, evaluating the usefulness of FRAX® as a screening method to identify patients at a higher risk of fracture. METHODS This was a cross-sectional study. Demographic, clinical, and analytical data were collected in a randomized sample of LC patients attending the Hepatology Department of a university hospital. We assessed the absolute risk of fracture at 10 years (FRAX®) and based on the bone mineral density (BMD), the presence of morphometric vertebral fracture with a vertebral fracture assessment (VFA), or a thoracic and lumbar X-ray and bone microarchitecture with a trabecular bone score (TBS). RESULTS Ninety-two patients were included (71% male); the mean age was 63 ± 11.3 years. The main etiology of LC was alcoholism (52.2%), and most patients were Child-Pugh A (80.4%), with a mean model for end-stage liver disease (MELD) score of 10.1 ± 3.6. Sixteen patients (17.4%) had osteoporosis, and fifty-four (58.7%) had osteopenia. Eight patients (8.7%) had suffered at least one fragility fracture. The absolute risk of a major fracture according to FRAX without the BMD was 5.7 ± 4.5%. Risk factors associated with osteoporosis were age and the female sex. BMI > 30 was a protective factor. A FRAX cut-off point for a major fracture > 6.6% had a sensitivity of 69% and a specificity of 85% for a diagnosis of osteoporosis. CONCLUSIONS The prevalence of osteoporosis and fractures in patients with LC is high, particularly in older women. FRAX® may be a useful method to identify candidates for bone densitometry. A FRAX value below 6.6% without the BMD can avoid unnecessary testing.
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Affiliation(s)
- Jordi Sánchez-Delgado
- Hepatology Unit, Digestive Disease Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (J.S.-D.); (A.L.); (M.M.); (M.C.); (M.V.); (X.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto Carlos III, 28029 Madrid, Spain
| | | | - Marta Arévalo
- Rheumatology Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (M.A.); (E.C.); (M.L.)
| | - Alba Lira
- Hepatology Unit, Digestive Disease Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (J.S.-D.); (A.L.); (M.M.); (M.C.); (M.V.); (X.C.)
| | | | - Mireia Miquel
- Hepatology Unit, Digestive Disease Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (J.S.-D.); (A.L.); (M.M.); (M.C.); (M.V.); (X.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto Carlos III, 28029 Madrid, Spain
- Department de Medicina, Universitat de Vic—Universitat Central de Catalunya (UVic-UCC), 08500 Vic, Spain
| | - Meritxell Casas
- Hepatology Unit, Digestive Disease Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (J.S.-D.); (A.L.); (M.M.); (M.C.); (M.V.); (X.C.)
| | - Mercedes Vergara
- Hepatology Unit, Digestive Disease Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (J.S.-D.); (A.L.); (M.M.); (M.C.); (M.V.); (X.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto Carlos III, 28029 Madrid, Spain
| | - Xavier Calvet
- Hepatology Unit, Digestive Disease Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (J.S.-D.); (A.L.); (M.M.); (M.C.); (M.V.); (X.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto Carlos III, 28029 Madrid, Spain
| | - Eugenio Berlanga
- Clinical Analytics Department, University Hospital Parc Taulí, 08208 Sabadell, Spain;
| | - Luís del Rio
- CETIR Ascires Centre Mèdic, 08029 Barcelona, Spain;
| | - Oliver Valero
- Department of Statistics, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;
| | - Ester Costa
- Rheumatology Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (M.A.); (E.C.); (M.L.)
| | - Marta Larrosa
- Rheumatology Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (M.A.); (E.C.); (M.L.)
| | - Enrique Casado Burgos
- Rheumatology Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (M.A.); (E.C.); (M.L.)
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19
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Hechter RC, Zhou H, Leyden WA, Yuan Q, Pak KJ, Lam JO, Alexeeff S, Lea A, Hu H, Marcus JL, Rivera AS, Adams AL, Horberg MA, Towner WJ, Lo JC, Silverberg MJ. Fracture Risk and Association With TDF Use Among People With HIV in Large Integrated Health Systems. J Acquir Immune Defic Syndr 2023; 94:341-348. [PMID: 37884055 DOI: 10.1097/qai.0000000000003274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 07/10/2023] [Indexed: 10/28/2023]
Abstract
BACKGROUND Greater decline in bone health among people with HIV (PWH) has been documented but fracture risk and the impact of specific antiretroviral therapy (ART) regimens remain unclear. SETTING Retrospective analyses of electronic health record data from 3 US integrated health care systems. METHODS Fracture incidence was compared between PWH aged 40 years or older without prior fracture and demographically matched people without HIV (PWoH), stratified by age, sex, and race/ethnicity. Multivariable Cox proportional hazards models were used to estimate fracture risk associated with HIV infection. The association of tenofovir disoproxil fumarate (TDF) use and fracture risk was evaluated in a subset of PWH initiating ART. RESULTS Incidence of fracture was higher in PWH [13.6/1000 person-years, 95% confidence interval (CI): 13.0 to 14.3, n = 24,308] compared with PWoH (9.5, 95% CI: 9.4 to 9.7, n = 247,313). Compared with PWoH, the adjusted hazard ratio (aHR) for fracture among PWH was 1.24 (95% CI: 1.18 to 1.31). The association between HIV infection and fracture risk increased with age, with the lowest aHR (1.17, 95% CI: 1.10 to 1.25) among those aged 40-49 years and the highest aHR (1.89, 95% CI: 1.30 to 2.76) among those aged 70 years or older. Among PWH initiating ART (n = 6504), TDF was not associated with significant increase in fracture risk compared with non-TDF regimens (aHR: 1.18, 95% CI: 0.89 to 1.58). CONCLUSIONS Among people aged 40 years or older, HIV infection is associated with increased risk of fractures. Bone health screening from the age of 40 years may be beneficial for PWH. Large cohort studies with longer follow-up are needed to evaluate TDF effect and the potential benefit of early screening.
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Affiliation(s)
- Rulin C Hechter
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
- Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA
| | - Hui Zhou
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
- Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA
| | - Wendy A Leyden
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Qing Yuan
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
| | - Katherine J Pak
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
| | - Jennifer O Lam
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Stacey Alexeeff
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Alexandra Lea
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Haihong Hu
- Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, MD
| | - Julia L Marcus
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA; and
| | - Adovich S Rivera
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
| | - Annette L Adams
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
| | - Michael A Horberg
- Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA
- Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, MD
| | - William J Towner
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
- Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA
| | - Joan C Lo
- Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Michael J Silverberg
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA; and
- Department of Epidemiology and Biostatistics, UCSF, San Francisco, CA
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20
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Prince DS, Nash E, Liu K. Alcohol-Associated Liver Disease: Evolving Concepts and Treatments. Drugs 2023; 83:1459-1474. [PMID: 37747685 PMCID: PMC10624727 DOI: 10.1007/s40265-023-01939-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2023] [Indexed: 09/26/2023]
Abstract
Alcohol is a prominent cause of liver disease worldwide with higher prevalence in developed nations. The spectrum of alcohol-associated liver disease (ALD) encompasses a diverse range of clinical entities, from asymptomatic isolated steatosis to decompensated cirrhosis, and in some cases, acute or chronic liver failure. Consequently, it is important for healthcare practitioners to maintain awareness and systematically screen for ALD. The optimal evaluation and management of ALD necessitates a collaborative approach, incorporating a multidisciplinary team and accounting for concurrent medical conditions. A repertoire of therapeutic interventions exists to support patients in achieving alcohol cessation and sustaining remission, with complete abstinence being the ultimate objective. This review explores the existing therapeutic options for ALD acknowledging geographical discrepancies in accessibility. Recent innovations, including the inclusion of alcohol consumption biomarkers into clinical protocols and the expansion of liver transplantation eligibility to encompass severe alcohol-associated hepatitis, are explored.
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Affiliation(s)
- David Stephen Prince
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, NSW, Australia.
- Liver Injury and Cancer Program, Centenary Institute, Sydney, NSW, Australia.
- The Ingham Institute for Applied Medical Research, Sydney, NSW, Australia.
- Faculty of Medicine and Health, The University of New South Wales, Sydney, NSW, Australia.
| | - Emily Nash
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Liver Injury and Cancer Program, Centenary Institute, Sydney, NSW, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
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21
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Espina S, Casas-Deza D, Bernal-Monterde V, Domper-Arnal MJ, García-Mateo S, Lué A. Evaluation and Management of Nutritional Consequences of Chronic Liver Diseases. Nutrients 2023; 15:3487. [PMID: 37571424 PMCID: PMC10421025 DOI: 10.3390/nu15153487] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 08/03/2023] [Accepted: 08/04/2023] [Indexed: 08/13/2023] Open
Abstract
Liver diseases are the major predisposing conditions for the development of malnutrition, sarcopenia, and frailty. Recently, the mechanism of the onset of these complications has been better established. Regardless of the etiology of the underlying liver disease, the clinical manifestations are common. The main consequences are impaired dietary intake, altered macro- and micronutrient metabolism, energy metabolism disturbances, an increase in energy expenditure, nutrient malabsorption, sarcopenia, frailty, and osteopathy. These complications have direct effects on clinical outcomes, survival, and quality of life. The nutritional status should be assessed systematically and periodically during follow-up in these patients. Maintaining and preserving an adequate nutritional status is crucial and should be a mainstay of treatment. Although general nutritional interventions have been established, special considerations are needed in specific settings such as decompensated cirrhosis, alcohol-related liver disease, and metabolic-dysfunction-associated fatty liver disease. In this review, we summarize the physiopathology and factors that impact the nutritional status of liver disease. We review how to assess malnutrition and sarcopenia and how to prevent and manage these complications in this setting.
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Affiliation(s)
- Silvia Espina
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (S.E.); (D.C.-D.); (V.B.-M.)
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, Miguel Servet University Hospital, 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; (M.J.D.-A.); (S.G.-M.)
| | - Diego Casas-Deza
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (S.E.); (D.C.-D.); (V.B.-M.)
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, Miguel Servet University Hospital, 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; (M.J.D.-A.); (S.G.-M.)
| | - Vanesa Bernal-Monterde
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (S.E.); (D.C.-D.); (V.B.-M.)
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, Miguel Servet University Hospital, 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; (M.J.D.-A.); (S.G.-M.)
| | - María José Domper-Arnal
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; (M.J.D.-A.); (S.G.-M.)
- Gastroenterology Department, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
| | - Sandra García-Mateo
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; (M.J.D.-A.); (S.G.-M.)
- Gastroenterology Department, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
| | - Alberto Lué
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; (M.J.D.-A.); (S.G.-M.)
- Gastroenterology Department, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
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22
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He S, Zhang Y, Tan C, Tan W, Yin B. Inverted U-shaped relationships between bone mineral density and VCTE-quantified degree of hepatic steatosis in adolescents: Evidence from the NHANES. PLoS One 2023; 18:e0286688. [PMID: 37294745 PMCID: PMC10256176 DOI: 10.1371/journal.pone.0286688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 05/20/2023] [Indexed: 06/11/2023] Open
Abstract
INTRODUCTION There may be inaccuracies in hepatic steatosis in past research assessing the relationship between bone metabolism and liver steatosis. The goal of the current research was to look at the associations between bone mineral density (BMD) and the hepatic steatosis and fibrosis as detected by vibration-controlled transient elastography (VCTE) in teenagers in the United States. METHODS Weighted multiple linear regression models and smoothed curve fitting were used to investigate the association between BMD and the degree of hepatic steatosis and fibrosis in adolescents. RESULTS In 829 adolescents aged 12-19 years we found a negative association between total BMD and CAP (controlled attenuation parameter) [-32.46 (-58.98, -9.05)] and a significant positive association between lumbar BMD and LSM (liver stiffness measurement) [1.35 (0.19, 2.51)]. The inverted U-shaped relationships were founded between total BMD, lumbar BMD, pelvis BMD, and CAP with inflection points of 221.22 dB/m, 219.88 dB/m, and 216.02 dB/m, respectively. CONCLUSIONS In adolescents, higher BMD is significantly associated with lower levels of hepatic steatosis and higher levels of liver stiffness.
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Affiliation(s)
- Shengmao He
- Department of Hand and Foot Surgery, The Affiliated Second Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Yun Zhang
- Department of Traumatic and Pediatric Orthopedics, The Affiliated Second Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Caixia Tan
- Department of Traumatic and Pediatric Orthopedics, The Affiliated Second Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Wenfu Tan
- Department of Traumatic and Pediatric Orthopedics, The Affiliated Second Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Bingliang Yin
- Department of Hand and Foot Surgery, The Affiliated Second Hospital, Hengyang Medical School, University of South China, Hengyang, China
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23
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Salama MM, Bayoumi EM, Sayed MM, Abdul-Rahman SA, Saleh SAB, Zaky AS, Mohamed GA. Evaluation of handgrip strength as a predictor of sarcopenia in patients with HCV-related cirrhosis. EGYPTIAN LIVER JOURNAL 2023; 13:24. [DOI: 10.1186/s43066-023-00261-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Accepted: 05/06/2023] [Indexed: 01/03/2025] Open
Abstract
Abstract
Background
Sarcopenia, characterised by a loss of muscle strength, quantity/quality, and physical performance, is associated with increased mortality and poor clinical outcomes in patients with liver cirrhosis. The use of the currently accepted methods for estimating muscle mass, such as computed tomography, dual-energy X-ray absorptiometry, and bioelectrical impedance analysis, in routine clinical practice is restricted because of limited availability, radiation exposure, time consumption, or high cost. Therefore, an alternative, simple, safe, reproducible, and financially accessible method for the routine assessment of sarcopenia is needed. Hence, we aim to assess the utility of handgrip strength (HGS) in diagnosing sarcopenia in patients with HCV-related cirrhosis compared to appendicular skeletal muscle index assessed by dual-energy X-ray absorptiometry (DEXA-ASMI). A total of 64 participants older than 18 years were consecutively recruited. The subjects were divided into the following groups: Control group included 32 healthy control subjects, and the HCV-related liver cirrhosis group included 32 patients who were subdivided equally into two subgroups (Child A and Child C) with 16 patients each. All participants were subjected to dominant hand dynamometer and DEXA scan.
Results
The prevalence of sarcopenia was significantly higher in the cirrhosis group than in the control group (7.75 ± 1.35 vs. 8.29 ± 1.25 kg/m2, P < 0.001), with increasing prevalence in the Child C class group (P < 0.001). HGS was significantly lower in the Child C group compared to other groups (P < 0.001). Regarding the differentiation of sarcopenic patients, defining HGS using a cutoff of ≤ 28.6 kg has an AUC of 0.879, sensitivity of 100%, specificity of 66.7%, PPV of 61.1%, and NPV of 100% (95% CI = 0.715 to 0.967; P < 0.0001).
Conclusion
Given the low cost, reproducibility, and safety of handgrip strength dynamometry, this is a promising method for both the diagnosis of sarcopenia as well as serial monitoring of muscle function in patients with HCV-related cirrhosis.
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24
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Bégin MJ, Ste-Marie LG, Huard G, Dorais M, Räkel A. Increased Imminent Fracture Risk in Liver Transplant Recipients Despite Bisphosphonate Therapy. Transplant Proc 2023; 55:576-585. [PMID: 37012143 DOI: 10.1016/j.transproceed.2023.02.060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 01/29/2023] [Accepted: 02/24/2023] [Indexed: 04/03/2023]
Abstract
BACKGROUND Bone loss is significant after orthotopic liver transplant (OLT) and is associated with increased fracture risk and decreased quality of life. In post-transplant fracture prevention, the cornerstone of therapeutic management is bisphosphonates. METHODS We conducted a retrospective study in a cohort of 155 OLT recipients who received a bisphosphonate prescription at hospital discharge between 2012 and 2016 to investigate post-OLT fragility fracture incidence and predictive risk factors. RESULTS Before OLT, 14 patients presented a T score < -2.5 SD, and 23 patients (14.8%) had a history of fracture. During follow-up, the cumulative incidence of fractures on bisphosphonates (99.4% risedronate/alendronate) was 9.7% at 12 months and 13.1% at 24 months. The median time to first fragility fracture was 10 months (IQR, 3-22 months) and thus within the first 2 years of follow-up. Predictive factors of fragility fractures in multivariate Cox regression analyses included age 60 years or older (hazard ratio [HR], 2.61; 95% CI, 1.14-6.01; P = .02), post-transplant diabetes mellitus (HR, 3.82; 95% CI, 1.55-9.44; P = .004), and cholestatic disease (HR, 5.93; 95% CI, 2.30-15.26; P = .0002). Additionally, the female sex was associated with a strong trend toward increased fracture risk in univariate analysis (HR, 2.27; 95% CI, 1.00-5.15; P = .05), as well as a post-transplant absolute decrease in bone mineral density at the femoral neck and total hip (P = .08). CONCLUSIONS This real-world study reports a high incidence of fractures post-OLT despite bisphosphonate therapy. Age 60 years or older, post-transplant diabetes mellitus, cholestatic disease, female sex, and femoral neck and/or total hip bone mineral density loss contribute to increased imminent fracture risk in liver transplant recipients.
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25
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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] [Download PDF] [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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26
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Park SH, Yoon SR, Nam JY, Ahn JY, Jeong SJ, Ku NS, Choi JY, Yeom JS, Kim JH. Impact of tuberculosis on the incidence of osteoporosis and osteoporotic fractures: a nationwide population-based cohort study. Public Health 2023; 216:13-20. [PMID: 36758345 DOI: 10.1016/j.puhe.2022.12.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 12/16/2022] [Accepted: 12/21/2022] [Indexed: 02/10/2023]
Abstract
OBJECTIVES Despite the high prevalence of tuberculosis (TB) and the disease burden of osteoporosis and osteoporotic fractures, there is still a lack of well-designed, large-scale studies demonstrating associations among them. We aimed to investigate the effect of TB on the incidence of osteoporosis and osteoporotic fractures. STUDY DESIGN This was a nationwide population-based cohort study. METHODS This study was conducted using the National Health Insurance Service Database of South Korea. We included patients with newly diagnosed TB aged >40 years from January 2006 to December 2017. An uninfected control for each TB patient was randomly extracted by frequency matching for sex, age, income level, residence, and registration date at a 2:1 ratio. The primary outcome was the incidence of osteoporosis and osteoporotic fractures between the two groups, adjusted for sex, age, income level, residence, comorbidities, body mass index, blood pressure, laboratory tests, alcohol drinking, and smoking. The risk factors associated with osteoporosis or osteoporotic fractures were also investigated. RESULTS A total of 164,389 patients with TB and 328,778 matched controls were included (71.9% males). The mean duration of follow-up was 7.00 ± 3.49 years. The incidence of osteoporosis in patients with TB was 6.1 cases per 1000 person-years, which was significantly higher than that in matched controls (adjusted hazard ratio [aHR] 1.349, 95% confidence interval [CI] 1.302-1.398, P < 0.001). The incidence of osteoporotic fractures was also higher in patients with TB than in controls (aHR 1.392, 95% CI 1.357-1.428, P < 0.001). Among fractures, the risk of hip fracture was the highest (aHR 1.703, 95% CI 1.612-1.798, P < 0.001). CONCLUSIONS TB independently contributes to the incidence of osteoporosis and osteoporotic fractures, particularly hip fractures.
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Affiliation(s)
- S H Park
- Chaum Life Center, CHA University, Seoul 06062, South Korea; Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang 10444, South Korea
| | - S R Yoon
- Institute of Health Insurance and Clinical Research, National Health Insurance Service Ilsan Hospital, Goyang 10444, South Korea
| | - J Y Nam
- Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang 10444, South Korea
| | - J Y Ahn
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea
| | - S J Jeong
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea
| | - N S Ku
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea
| | - J Y Choi
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea
| | - J-S Yeom
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea
| | - J H Kim
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea.
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27
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Jadzic J, Djonic D. Bone loss in chronic liver diseases: Could healthy liver be a requirement for good bone health? World J Gastroenterol 2023; 29:825-833. [PMID: 36816627 PMCID: PMC9932432 DOI: 10.3748/wjg.v29.i5.825] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 10/29/2022] [Accepted: 01/11/2023] [Indexed: 02/06/2023] Open
Abstract
Given that the liver is involved in many metabolic mechanisms, it is not surprising that chronic liver disease (CLD) could have numerous complications. Secondary osteoporosis and increased bone fragility are frequently overlooked complications in CLD patients. Previous studies implied that up to one-third of these individuals meet diagnostic criteria for osteopenia or osteoporosis. Recent publications indicated that CLD-induced bone fragility depends on the etiology, duration, and stage of liver disease. Therefore, the increased fracture risk in CLD patients puts a severe socioeconomic burden on the health system and urgently requires more effective prevention, diagnosis, and treatment measures. The pathogenesis of CLD-induced bone loss is multifactorial and still insufficiently understood, especially considering the relative impact of increased bone resorption and reduced bone formation in these individuals. It is essential to note that inconsistent findings regarding bone mineral density measurement were previously reported in these individuals. Bone mineral density is widely used as the "golden standard" in the clinical assessment of bone fragility although it is not adequate to predict individual fracture risk. Therefore, microscale bone alterations (bone microstructure, mechanical properties, and cellular indices) were analyzed in CLD individuals. These studies further support the thesis that bone strength could be compromised in CLD individuals, implying that an individualized approach to fracture risk assessment and subsequent therapy is necessary for CLD patients. However, more well-designed studies are required to solve the bone fragility puzzle in CLD patients.
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Affiliation(s)
- Jelena Jadzic
- Center of Bone Biology, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
| | - Danijela Djonic
- Center of Bone Biology, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
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Jadzic J, Djonic D. Bone loss in chronic liver diseases: Could healthy liver be a requirement for good bone health? World J Gastroenterol 2023; 29:825-833. [DOI: https:/doi.org/10.3748/wjg.v29.i5.825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/10/2024] Open
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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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Carson MD, Warner AJ, Hathaway-Schrader JD, Geiser VL, Kim J, Gerasco JE, Hill WD, Lemasters JJ, Alekseyenko AV, Wu Y, Yao H, Aguirre JI, Westwater C, Novince CM. Minocycline-induced disruption of the intestinal FXR/FGF15 axis impairs osteogenesis in mice. JCI Insight 2023; 8:160578. [PMID: 36413391 PMCID: PMC9870091 DOI: 10.1172/jci.insight.160578] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 11/16/2022] [Indexed: 11/24/2022] Open
Abstract
Antibiotic-induced shifts in the indigenous gut microbiota influence normal skeletal maturation. Current theory implies that gut microbiota actions on bone occur through a direct gut/bone signaling axis. However, our prior work supports that a gut/liver signaling axis contributes to gut microbiota effects on bone. Our purpose was to investigate the effects of minocycline, a systemic antibiotic treatment for adolescent acne, on pubertal/postpubertal skeletal maturation. Sex-matched specific pathogen-free (SPF) and germ-free (GF) C57BL/6T mice were administered a clinically relevant minocycline dose from age 6-12 weeks. Minocycline caused dysbiotic shifts in the gut bacteriome and impaired skeletal maturation in SPF mice but did not alter the skeletal phenotype in GF mice. Minocycline administration in SPF mice disrupted the intestinal farnesoid X receptor/fibroblast growth factor 15 axis, a gut/liver endocrine axis supporting systemic bile acid homeostasis. Minocycline-treated SPF mice had increased serum conjugated bile acids that were farnesoid X receptor (FXR) antagonists, suppressed osteoblast function, decreased bone mass, and impaired bone microarchitecture and fracture resistance. Stimulating osteoblasts with the serum bile acid profile from minocycline-treated SPF mice recapitulated the suppressed osteogenic phenotype found in vivo, which was mediated through attenuated FXR signaling. This work introduces bile acids as a potentially novel mediator of gut/liver signaling actions contributing to gut microbiota effects on bone.
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Affiliation(s)
- Matthew D Carson
- Department of Oral Health Sciences, College of Dental Medicine.,Department of Pediatrics, Division of Endocrinology, College of Medicine.,Department of Stomatology, Division of Periodontics, College of Dental Medicine
| | - Amy J Warner
- Department of Oral Health Sciences, College of Dental Medicine.,Department of Pediatrics, Division of Endocrinology, College of Medicine.,Department of Stomatology, Division of Periodontics, College of Dental Medicine
| | - Jessica D Hathaway-Schrader
- Department of Oral Health Sciences, College of Dental Medicine.,Department of Pediatrics, Division of Endocrinology, College of Medicine.,Department of Stomatology, Division of Periodontics, College of Dental Medicine
| | - Vincenza L Geiser
- Department of Oral Health Sciences, College of Dental Medicine.,Department of Pediatrics, Division of Endocrinology, College of Medicine.,Department of Stomatology, Division of Periodontics, College of Dental Medicine
| | - Joseph Kim
- Department of Oral Health Sciences, College of Dental Medicine.,Department of Pediatrics, Division of Endocrinology, College of Medicine.,Department of Stomatology, Division of Periodontics, College of Dental Medicine
| | - Joy E Gerasco
- Department of Oral Health Sciences, College of Dental Medicine.,Department of Drug Discovery & Biomedical Sciences, College of Pharmacy
| | - William D Hill
- Department of Pathology and Laboratory Medicine, College of Medicine
| | - John J Lemasters
- Department of Drug Discovery & Biomedical Sciences, College of Pharmacy.,Department of Biochemistry & Molecular Biology, College of Medicine
| | - Alexander V Alekseyenko
- Department of Oral Health Sciences, College of Dental Medicine.,Biomedical Informatics Center, Program for Human Microbiome Research, Department of Public Health Sciences, College of Medicine.,Department of Healthcare Leadership and Management, College of Health Professions; and
| | - Yongren Wu
- Department of Orthopedics & Physical Medicine, College of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.,Department of Bioengineering, College of Engineering, Clemson University, Clemson, South Carolina, USA
| | - Hai Yao
- Department of Oral Health Sciences, College of Dental Medicine.,Department of Bioengineering, College of Engineering, Clemson University, Clemson, South Carolina, USA
| | - J Ignacio Aguirre
- Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA
| | - Caroline Westwater
- Department of Oral Health Sciences, College of Dental Medicine.,Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Chad M Novince
- Department of Oral Health Sciences, College of Dental Medicine.,Department of Pediatrics, Division of Endocrinology, College of Medicine.,Department of Stomatology, Division of Periodontics, College of Dental Medicine
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Wang Q, Xu F, Chen J, Xie YQ, Xu SL, He WM. Serum Leukocyte Cell-Derived Chemotaxin 2 (LECT2) Level Is Associated with Osteoporosis. Lab Med 2023; 54:106-111. [PMID: 35976970 DOI: 10.1093/labmed/lmac080] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
OBJECTIVE The aim of this study was to examine serum leukocyte cell-derived chemotaxin 2 (LECT2) levels in osteoporosis subjects to confirm its association with osteoporosis. METHODS A total of 204 adult subjects were recruited. Bone mineral densities (BMD) were assessed and blood samples were collected for measurements of biomedical parameters and the bone turnover markers. Serum LECT2 levels were measured by enzyme-linked immunosorbent assay. The relationships between serum LECT2 levels and other parameters were analyzed using the Spearman correlation coefficient. RESULTS Serum LECT2 levels were significantly increased in osteoporosis subjects over controls. We found a significantly negative correlation of serum LECT2 with BMD, 25-hydroxy-vitamin D, and creatinine and a significantly positive correlation with C-terminal telopeptide of type 1 collagen and total cholesterol. CONCLUSION Serum LECT2 levels were significantly upregulated in osteoporosis subjects and correlated with the severity of bone loss. Serum LECT2 could be a potential biomarker to assess the risk of bone loss.
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Affiliation(s)
- Qiang Wang
- Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China
| | - Feng Xu
- Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China
| | - Jiong Chen
- Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Meishan Campus, Ningbo University, Ningbo, Zhejiang, China.,State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, Zhejiang, China
| | - Yan-Qing Xie
- Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China
| | - Su-Ling Xu
- Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China
| | - Wen-Ming He
- Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China
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Qiao X, Zhang K, Li X, Lv Z, Wei W, Zhou R, Yan L, Pan Y, Yang S, Sun X, Li P, Xu C, Feng Y, Tian Z. Gut microbiota and fecal metabolic signatures in rat models of disuse-induced osteoporosis. Front Cell Infect Microbiol 2022; 12:1018897. [PMID: 36590590 PMCID: PMC9798431 DOI: 10.3389/fcimb.2022.1018897] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 11/07/2022] [Indexed: 12/23/2022] Open
Abstract
Background Assessing the correlation between gut microbiota (GM) and bone homeostasis has increasingly attracted research interest. Meanwhile, GM dysbiosis has been found to be associated with abnormal bone metabolism. However, the function of GM in disuse-induced osteoporosis (DIO) remains poorly understood. In our research, we evaluated the characteristics of GM and fecal metabolomics to explore their potential correlations with DIO pathogenesis. Methods DIO rat models and controls (CON) underwent micro-CT, histological analyses, and three-point bending tests; subsequently, bone microstructures and strength were observed. ELISAs were applied for the measurement of the biochemical markers of bone turnover while GM abundance was observed using 16S rDNA sequencing. Metabolomic analyses were used to analyze alterations fecal metabolites. The potential correlations between GM, metabolites, and bone loss were then assessed. Results In the DIO group, the abundance of GM was significantly altered compared to that in the CON group. Moreover, DIO significantly altered fecal metabolites. More specifically, an abnormally active pathway associated with bile acid metabolism, as well as differential bacterial genera related to bone/tissue volume (BV/TV), were identified. Lithocholic acid, which is the main secondary bile acid produced by intestinal bacteria, was then found to have a relationship with multiple differential bacterial genera. Alterations in the intestinal flora and metabolites in feces, therefore, may be responsible for DIO-induced bone loss. Conclusions The results indicated that changes in the abundance of GM abundance and fecal metabolites were correlated with DIO-induced bone loss, which might provide new insights into the DIO pathogenesis. The detailed regulatory role of GM and metabolites in DIO-induced bone loss needs to be explored further.
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Affiliation(s)
- Xiaochen Qiao
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
- Department of Orthopedics, JinZhong Hospital Affiliated to Shanxi Medical University, Jinzhong, Shanxi, China
| | - Kun Zhang
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Xiaoyan Li
- Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China
| | - Zhi Lv
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Wenhao Wei
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Ruhao Zhou
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Lei Yan
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Yongchun Pan
- Department of Orthopedics, Third People’s Hospital of Datong City, Datong, Shanxi, China
| | - Sen Yang
- Department of Orthopedics, The Second People’s Hospital of Changzhi, Changzhi, Shanxi, China
| | - Xiaojuan Sun
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Pengcui Li
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Chaojian Xu
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Yi Feng
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
| | - Zhi Tian
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, China
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Zhu X, Chen L, Pan L, Zeng Y, Fu Q, Liu Y, Peng Y, Wang Y, You L. Risk factors of primary and recurrent fractures in postmenopausal osteoporotic Chinese patients: A retrospective analysis study. BMC Womens Health 2022; 22:465. [PMID: 36404305 PMCID: PMC9677643 DOI: 10.1186/s12905-022-02034-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Accepted: 10/13/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND As postmenopausal osteoporotic fractures can cause higher rates of disability and mortality in women; it is essential to analyze the factors associated with primary and recurrent fractures in postmenopausal osteoporosis (PMOP) patients. METHODS Retrospective analysis of 2478 PMOP patients aged ≥ 50 years who attended the Shanghai General Hospital from January 2007 to December 2016, including 1239 patients with no fractures and 1239 patients with histories of fractures (1008 in the primary fracture group and 231 in the re-fracture group). All patients' basic clinical data, serum biochemical and bone metabolic markers, bone mineral density (BMD), and other indicators were recorded uniformly. Comparing the differences between the clinical characteristics of patients with primary and recurrent fractures, as well as the differences in the clinical characteristics of patients with primary and recurrent fractures in combination with different diseases, further analyses the risk factors for primary and recurrent fractures in PMOP patients. SPSS.26 was used for statistical analysis. RESULTS Compared to the unfractured group, the fractured group was older and had lower height and bone mineral density (all P < 0.01), with the re-fractured group having lower BMD at each key site than the primary fracture group (all P < 0.01). Analysis of the combined disease subgroups showed that serum BGP levels were lower in the primary and re-fracture patients with diabetes than in the non-diabetic subgroup (P < 0.05), and serum CTX levels were lower in the re-fracture group with diabetes than in the primary fracture group with diabetes (P < 0.05). Patients with recurrent fractures with cardio-vascular diseases had lower BMD than the subgroup without cardio-vascular diseases (P < 0.05) and also had lower BMD than the group with primary fractures with cardio-vascular diseases (P < 0.05). Multiple logistic regression analysis showed that advanced age, overweight, low lumbar spine and total hip BMD were risk factors for primary and recurrent fractures; and comorbid chronic liver and kidney diseases were risk factors for primary fractures. CONCLUSION PMOP patients with advanced age, overweight, low bone mineral density, and comorbid chronic liver and kidney diseases are at greater risk of fractures and require early intervention to reduce fractures occurrence. Moreover, those who are elderly, overweight, and have low bone density should also be aware of the risk of re-fractures.
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Affiliation(s)
- Xiaonan Zhu
- grid.412478.c0000 0004 1760 4628Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080 China
| | - Lin Chen
- grid.412478.c0000 0004 1760 4628Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080 China
| | - Ling Pan
- grid.412478.c0000 0004 1760 4628Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080 China
| | - Yuexi Zeng
- grid.412478.c0000 0004 1760 4628Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080 China
| | - Qiang Fu
- grid.412478.c0000 0004 1760 4628Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080 China
| | - Yanbin Liu
- grid.412478.c0000 0004 1760 4628Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080 China
| | - Yongde Peng
- grid.412478.c0000 0004 1760 4628Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080 China
| | - Yufan Wang
- grid.412478.c0000 0004 1760 4628Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080 China
| | - Li You
- grid.412478.c0000 0004 1760 4628Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080 China
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Xie R, Zhang Y, Yan T, Huang X, Xie S, Liu C, Liu M. Relationship between nonalcoholic fatty liver disease and bone mineral density in adolescents. Medicine (Baltimore) 2022; 101:e31164. [PMID: 36253982 PMCID: PMC9575783 DOI: 10.1097/md.0000000000031164] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 09/14/2022] [Indexed: 11/26/2022] Open
Abstract
Liver metabolism is strongly linked to bone metabolism, and a significant correlation between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) in adults has been demonstrated. However, the current relationship between NAFLD and BMD in the adolescent population remains controversial. The purpose of this study was to investigate the specific relationship between NAFLD and BMD in adolescents aged 12 to 19 years in the United States. The quantitative relationship between NAFLD and total BMD was investigated using multivariate logistic regression and smoothed fitted curve curves based on multiperspective data from the National Health and Nutrition Examination Survey (NHANES). A total of 740 adolescents were included in this study after excluding unusable samples. The results showed that NAFLD was positively associated with total BMD in adolescents. The results of the subgroup analysis showed that this positive association was mainly found in boys, whites and blacks. The association was not significant in girls, Mexican Americans and other racial groups. Among US adolescents, there was a significant positive association between NAFLD and total BMD, and this relationship varied by gender and race.
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Affiliation(s)
- Ruijie Xie
- Department of Hand Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Ya Zhang
- Department of Gland Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Tao Yan
- Department of Orthopedics, Yiyang Fourth People’s Hospital, Yiyang, China
| | - Xiongjie Huang
- Department of Hand Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Songlin Xie
- Department of Hand Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Changxiong Liu
- Department of Hand Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Mingjiang Liu
- Department of Hand Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
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Majety P, Groysman A, Erlikh N, Chen ZZ, Westcott GP. Predictors of Mortality in Hypercalcemia of Advanced Chronic Liver Disease. Endocr Pract 2022; 28:1062-1068. [PMID: 35868607 DOI: 10.1016/j.eprac.2022.07.008] [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: 05/21/2022] [Revised: 07/06/2022] [Accepted: 07/14/2022] [Indexed: 11/17/2022]
Abstract
OBJECTIVE Hypercalcemia is sometimes observed in patients with cirrhosis, but very little is known about the epidemiology in patients with hypercalcemia of chronic liver disease (HCLD) or how its presence may modulate the overall mortality risk. We assessed the associations between the clinical and laboratory characteristics of patients with HCLD with 90-day mortality. METHODS A systematic search of the medical records at our institution over a 10-year period was performed to retrospectively identify subjects with HCLD during inpatient admission. Univariate and multivariable regression analyses were performed to detect the risk factors for all-cause 90-day mortality. RESULTS Thirty-eight subjects with HCLD were identified using stringent inclusion and exclusion criteria to exclude individuals with other secondary causes of hypercalcemia. A total of 35 subjects had 90-day vital status available, which revealed 40% mortality. The model for end-stage liver disease sodium score and duration of inpatient hypercalcemia were positively associated with mortality with respective odds ratios of 1.23 (95% CI, 1.06-3.23) and 1.24 (95% CI, 1.04-1.49) in a univariate regression model and 1.30 (95% CI, 1.04-1.62) and 1.33 (95% CI, 1.04-1.71) in a multivariable regression model. The admission and peak serum calcium levels were not associated with mortality. Only 6 subjects received bisphosphonates or calcitonin during their admission, limiting our ability to assess the impact of treatment on outcomes. CONCLUSION In patients admitted to the hospital with HCLD, the duration of hypercalcemia was positively associated with 90-day mortality, providing a potential interventional target to reduce mortality in this high-risk population. Studies to validate the utility of treating hypercalcemia are required.
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Affiliation(s)
- Priyanka Majety
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Anna Groysman
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Natanie Erlikh
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Zsu Zsu Chen
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Gregory P Westcott
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
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Sonoda S, Murata S, Yamaza H, Yuniartha R, Fujiyoshi J, Yoshimaru K, Matsuura T, Oda Y, Ohga S, Tajiri T, Taguchi T, Yamaza T. Targeting hepatic oxidative stress rescues bone loss in liver fibrosis. Mol Metab 2022; 66:101599. [PMID: 36113772 PMCID: PMC9515604 DOI: 10.1016/j.molmet.2022.101599] [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: 03/09/2022] [Revised: 09/01/2022] [Accepted: 09/09/2022] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE Chronic liver diseases often involve metabolic damage to the skeletal system. The underlying mechanism of bone loss in chronic liver diseases remains unclear, and appropriate therapeutic options, except for orthotopic liver transplantation, have proved insufficient for these patients. This study aimed to investigate the efficacy and mechanism of transplantation of immature hepatocyte-like cells converted from stem cells from human exfoliated deciduous teeth (SHED-Heps) in bone loss of chronic liver fibrosis. METHODS Mice that were chronically treated with CCl4 received SHED-Heps, and trabecular bone density, reactive oxygen species (ROS), and osteoclast activity were subsequently analyzed in vivo and in vitro. The effects of stanniocalcin 1 (STC1) knockdown in SHED-Heps were also evaluated in chronically CCl4 treated mice. RESULTS SHED-Hep transplantation (SHED-HepTx) improved trabecular bone loss and liver fibrosis in chronic CCl4-treated mice. SHED-HepTx reduced hepatic ROS production and interleukin 17 (Il-17) expression under chronic CCl4 damage. SHED-HepTx reduced the expression of both Il-17 and tumor necrosis factor receptor superfamily 11A (Tnfrsf11a) and ameliorated the imbalance of osteoclast and osteoblast activities in the bone marrow of CCl4-treated mice. Functional knockdown of STC1 in SHED-Heps attenuated the benefit of SHED-HepTx including anti-bone loss effect by suppressing osteoclast differentiation through TNFSF11-TNFRSF11A signaling and enhancing osteoblast differentiation in the bone marrow, as well as anti-fibrotic and anti-ROS effects in the CCl4-injured livers. CONCLUSIONS These findings suggest that targeting hepatic ROS provides a novel approach to treat bone loss resulting from chronic liver diseases.
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Affiliation(s)
- Soichiro Sonoda
- Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka, Japan
| | - Sara Murata
- Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka, Japan
| | - Haruyoshi Yamaza
- Department of Pediatric Dentistry, Kyushu University Graduate School of Dental Science, Fukuoka, Japan
| | - Ratih Yuniartha
- Department of Anatomy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Junko Fujiyoshi
- Department of Pediatrics, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Koichiro Yoshimaru
- Department of Pediatric Surgery, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Toshiharu Matsuura
- Department of Pediatric Surgery, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Shouichi Ohga
- Department of Pediatrics, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Tasturo Tajiri
- Department of Pediatric Surgery, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Tomoaki Taguchi
- Department of Pediatric Surgery, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan,Fukuoka College of Health Sciences, Fukuoka, Japan
| | - Takayoshi Yamaza
- Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka, Japan,Corresponding author. Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Fax: +81 92 642 6304.
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Liu M, Jin F, Zhang S, Li S, Zhu D, Cui Y, Cai M, Liu X, Zhang Y, Sun Y, Liu C, Wang X. Activation of farnesoid X receptor signaling by geniposidic acid promotes osteogenesis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 103:154258. [PMID: 35716540 DOI: 10.1016/j.phymed.2022.154258] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 05/26/2022] [Accepted: 06/07/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND New targets and strategies are urgently needed for the identification and development of anabolic drugs for osteoporosis. Farnesoid X receptor (FXR) is a promising novel therapeutic target for bone metabolism diseases. Although used clinically, FXR agonists have obvious side effects; therefore, the development of new FXR agonists for the treatment of osteoporosis would be welcomed. Geniposidic acid (GPA) is a bioactive compound extracted from Eucommiae cortex, which is used for treating arthritis, osteoporotic fractures, and hypertension. However, the therapeutic effects of GPA against osteoporosis remain underexplored. PURPOSE This study aims to reveal the potential osteogenic effects of FXR and to explore the effect of GPA on bone formation, osteoporosis treatment, and FXR signaling. STUDY DESIGN & METHODS The role of FXR in promoting bone formation was evaluated in Fxr knockout (Fxr-/-) mice and cell models. GPA activation of FXR was evaluated by molecular docking and luciferase reporter gene assays. Thirty female C57BL/6J mice were randomly assigned into a sham operation group (Sham) and four ovariectomized (OVX) groups (n=6 each) and were treated with vehicle or different doses of GPA (25, 50, and 100 mg/kg/day). The therapeutic effect of GPA on osteoporosis was systematically analyzed by performing bone histomorphometry and measuring serum biochemical parameters, and the molecular mechanism was also evaluated. Furthermore, the action of GPA in Fxr-/- mice was evaluated to investigate its dependency on FXR in promoting bone formation and treating osteoporosis. RESULTS We found that FXR was highly expressed in bone tissues and enriched in osteoblasts. Notably, deletion of FXR significantly reduced the bone formation rate and bone mass of the Fxr-/- mice compared with wild-type mice. Furthermore, using a high throughput drug screening strategy based on fluorescent reporter genes, we found that GPA functions as a natural agonist of FXR. We confirmed the activities of GPA on FXR activation and osteogenesis in both osteoblast differentiation models and OVX-induced osteoporosis models. We revealed that GPA strongly promotes bone formation by activating FXR/RUNX2 signaling. Moreover, the osteoporotic therapeutic effect of GPA was abolished in Fxr-/- mice. CONCLUSION This study demonstrated that FXR is a promising target for treating osteoporosis and that GPA promotes bone formation in OVX-induced osteoporosis by activating FXR signaling. These findings provide novel insight into the mechanism by which GPA promotes bone formation and more evidence for its application in the treatment of osteoporosis.
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Affiliation(s)
- Meijing Liu
- Key Laboratory of Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, China; Clinical Research Platform for Interdiscipline of Stomatology, The First Affiliated Hospital of Jinan University & Department of Stomatology, Jinan University, Guangzhou, 510632, China; School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Fujun Jin
- Key Laboratory of Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, China
| | - Shuai Zhang
- Department of Oral Implantology, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, 200072, China
| | - Shuang Li
- Key Laboratory of Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, China
| | - Danqi Zhu
- Key Laboratory of Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, China
| | - Yi Cui
- Key Laboratory of Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, China
| | - Mingxiang Cai
- Clinical Research Platform for Interdiscipline of Stomatology, The First Affiliated Hospital of Jinan University & Department of Stomatology, Jinan University, Guangzhou, 510632, China
| | - Xiangning Liu
- Clinical Research Platform for Interdiscipline of Stomatology, The First Affiliated Hospital of Jinan University & Department of Stomatology, Jinan University, Guangzhou, 510632, China
| | - Yongbiao Zhang
- Key Laboratory of Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, China
| | - Yao Sun
- Department of Oral Implantology, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, 200072, China.
| | - Changhui Liu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China..
| | - Xiaogang Wang
- Key Laboratory of Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, China; Clinical Research Platform for Interdiscipline of Stomatology, The First Affiliated Hospital of Jinan University & Department of Stomatology, Jinan University, Guangzhou, 510632, China.
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Jadzic J, Milovanovic PD, Cvetkovic D, Zivkovic V, Nikolic S, Tomanovic N, Djuric MP, Djonic D. The altered osteocytic expression of connexin 43 and sclerostin in human cadaveric donors with alcoholic liver cirrhosis: Potential treatment targets. J Anat 2022; 240:1162-1173. [PMID: 34978341 PMCID: PMC9119608 DOI: 10.1111/joa.13621] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 12/20/2021] [Accepted: 12/20/2021] [Indexed: 01/30/2023] Open
Abstract
Previous studies suggested that osteocyte lacunar network disruption could play a role in the complex pathophysiology of bone changes in aging and disease. Considering that particular research interest is lacking, we aimed to assess alcoholic liver cirrhosis (ALC)-induced changes in osteocyte lacunar network and bone marrow adiposity. Immunohistochemistry was conducted to assess changes in the micro-morphology of osteocyte lacunar network and bone marrow adiposity, and expression of connexin 43 and sclerostin in vertebral and femoral samples collected from 40 cadaveric men (age range between 44 and 70 years) divided into ALC group (n = 20) and control group (n = 20). Furthermore, the assessment of the potential association between bone changes and the severity of the hepatic disorder (given by Knodell's pathohistologic scoring) was conducted. Our data revealed fewer connexin 43-positive osteocytes per vertebral and femoral bone area (p < 0.01), suggesting defective signal transduction among osteocytes in ALC individuals. Moreover, we found an ALC-induced increase in the number of adipocytes in the vertebral bone marrow (p = 0.038). Considering significant associations between the severity of liver tissue disturbances and impaired functionality of osteocyte lacunar network (Pearson's correlation analyses, p < 0.05), we may assume that timely treatment of the liver disease may delay bone impairment. ALC induced an increase in osteocytic sclerostin expression (p < 0.001), suggesting its role in mediating low bone formation among ALC individuals. Hence, medicaments targeting low bone formation may be beneficial to attenuate the bone changes among ALC patients. However, future clinical studies are required to verify the therapeutic utility of these findings.
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Affiliation(s)
- Jelena Jadzic
- Laboratory of Bone Biology and BioanthropologyFaculty of MedicineInstitute of AnatomyUniversity of BelgradeBelgradeSerbia
| | - Petar D. Milovanovic
- Laboratory of Bone Biology and BioanthropologyFaculty of MedicineInstitute of AnatomyUniversity of BelgradeBelgradeSerbia
| | - Danica Cvetkovic
- Faculty of MedicineInstitute of Forensic MedicineUniversity of BelgradeBelgradeSerbia
| | - Vladimir Zivkovic
- Faculty of MedicineInstitute of Forensic MedicineUniversity of BelgradeBelgradeSerbia
| | - Slobodan Nikolic
- Faculty of MedicineInstitute of Forensic MedicineUniversity of BelgradeBelgradeSerbia
| | - Nada Tomanovic
- Faculty of MedicineInstitute of PathologyUniversity of BelgradeBelgradeSerbia
| | - Marija P. Djuric
- Laboratory of Bone Biology and BioanthropologyFaculty of MedicineInstitute of AnatomyUniversity of BelgradeBelgradeSerbia
| | - Danijela Djonic
- Laboratory of Bone Biology and BioanthropologyFaculty of MedicineInstitute of AnatomyUniversity of BelgradeBelgradeSerbia
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Adding liver R2* quantification to proton density fat fraction MRI of vertebral bone marrow improves the prediction of osteoporosis. Eur Radiol 2022; 32:7108-7116. [PMID: 35610386 DOI: 10.1007/s00330-022-08861-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 04/28/2022] [Accepted: 05/03/2022] [Indexed: 01/19/2023]
Abstract
OBJECTIVES To assess the predictive value of the combination of bone marrow (BM) proton density fat fraction (PDFF) and liver R2* for osteopenia and osteoporosis and the additional role of liver R2*. METHODS A total of 107 healthy women were included between June 2019 and January 2021. Each participant underwent dual-energy X-ray absorptiometry (DXA) and chemical shift-encoded 3.0-T MRI. PDFF measurements were performed for each lumbar vertebral body, and R2* measurements were performed in liver segments. Agreement among measurements was assessed by Bland-Altman analysis. Receiver operating characteristic (ROC) curves were generated to select optimised cut-offs for BM PDFF and liver R2*. Univariable and multivariable logistic regressions were performed. The C statistic and continuous net reclassification improvement (NRI) were adopted to explore the incremental predictive ability of liver R2*. RESULTS Bone mass decreased in 42 cases (39.3%) and nonbone mass decreased in 65 cases (60.7%). There were significant differences among the age groups, menopausal status groups, PDFF > 45.0% groups, and R2* > 67.7 groups. Each measurement had good reproducibility. The odds ratios (95% CIs) were 4.05 (1.22-13.43) for PDFF and 4.34 (1.41-13.35) for R2*. The C statistic (95% CI) without R2* was 0.888 (0.827-0.950), and with R2* was 0.900 (0.841-0.960). The NRI resulting from the combination of PDFF and R2* was 75.6% (p < 0.01). CONCLUSION The predictive improvement over the use of BM PDFF and other traditional risk factors demonstrates the potential of liver R2* as a biomarker for osteopenia and osteoporosis in healthy women. KEY POINTS • Liver R2* is a biomarker for the assessment of osteopenia and osteoporosis. • Liver R2* improved the ability to predict osteopenia and osteoporosis. • The intra- and interobserver measurements showed high agreement.
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Komakech R, Shim KS, Yim NH, Song JH, Yang S, Choi G, Lee J, Kim YG, Omujal F, Okello D, Agwaya MS, Kyeyune GN, Kan H, Hwang KS, Matsabisa MG, Kang Y. GC-MS and LC-TOF-MS profiles, toxicity, and macrophage-dependent in vitro anti-osteoporosis activity of Prunus africana (Hook f.) Kalkman Bark. Sci Rep 2022; 12:7044. [PMID: 35487926 PMCID: PMC9054796 DOI: 10.1038/s41598-022-10629-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 03/24/2022] [Indexed: 11/09/2022] Open
Abstract
Osteoporosis affects millions of people worldwide. As such, this study assessed the macrophage-dependent in vitro anti-osteoporosis, phytochemical profile and hepatotoxicity effects in zebrafish larvae of the stem bark extracts of P. africana. Mouse bone marrow macrophages (BMM) cells were plated in 96-well plates and treated with P. africana methanolic bark extracts at concentrations of 0, 6.25, 12.5, 25, and 50 µg/ml for 24 h. The osteoclast tartrate-resistant acid phosphatase (TRAP) activity and cell viability were measured. Lipopolysaccharides (LPS) induced Nitrite (NO) and interleukin-6 (IL-6) production inhibitory effects of P. africana bark extracts (Methanolic, 150 µg/ml) and β-sitosterol (100 µM) were conducted using RAW 264.7 cells. Additionally, inhibition of IL-1β secretion and TRAP activity were determined for chlorogenic acid, catechin, naringenin and β-sitosterol. For toxicity study, zebrafish larvae were exposed to different concentrations of 25, 50, 100, and 200 µg/ml P. africana methanolic, ethanolic and water bark extracts. Dimethyl sulfoxide (0.05%) was used as a negative control and tamoxifen (5 µM) and dexamethasone (40 µM or 80 µM) were positive controls. The methanolic P. africana extracts significantly inhibited (p < 0.001) TRAP activity at all concentrations and at 12.5 and 25 µg/ml, the extract exhibited significant (p < 0.05) BMM cell viability. NO production was significantly inhibited (all p < 0.0001) by the sample. IL-6 secretion was significantly inhibited by P. africana methanolic extract (p < 0.0001) and β-sitosterol (p < 0.0001) and further, chlorogenic acid and naringenin remarkably inhibited IL-1β production. The P. africana methanolic extract significantly inhibited RANKL-induced TRAP activity. The phytochemical study of P. africana stem bark revealed a number of chemical compounds with anti-osteoporosis activity. There was no observed hepatocyte apoptosis in the liver of zebrafish larvae. In conclusion, the stem bark of P. africana is non-toxic to the liver and its inhibition of TRAP activity makes it an important source for future anti-osteoporosis drug development.
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Affiliation(s)
- Richard Komakech
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine (KIOM), 111 Geonjae-ro, Naju-si, Jeollanam-do, 58245, Republic of Korea.,University of Science and Technology (UST), Korean Convergence Medicine Major, KIOM campus, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 34054, Republic of Korea.,Natural Chemotherapeutics Research Institute (NCRI), Ministry of Health, P.O. Box 4864, Kampala, Uganda
| | - Ki-Shuk Shim
- Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 34054, Republic of Korea
| | - Nam-Hui Yim
- Korean Medicine Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu, 41062, Republic of Korea
| | - Jun Ho Song
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine (KIOM), 111 Geonjae-ro, Naju-si, Jeollanam-do, 58245, Republic of Korea
| | - Sungyu Yang
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine (KIOM), 111 Geonjae-ro, Naju-si, Jeollanam-do, 58245, Republic of Korea
| | - Goya Choi
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine (KIOM), 111 Geonjae-ro, Naju-si, Jeollanam-do, 58245, Republic of Korea
| | - Jun Lee
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine (KIOM), 111 Geonjae-ro, Naju-si, Jeollanam-do, 58245, Republic of Korea.,University of Science and Technology (UST), Korean Convergence Medicine Major, KIOM campus, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 34054, Republic of Korea
| | - Yong-Goo Kim
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine (KIOM), 111 Geonjae-ro, Naju-si, Jeollanam-do, 58245, Republic of Korea
| | - Francis Omujal
- Natural Chemotherapeutics Research Institute (NCRI), Ministry of Health, P.O. Box 4864, Kampala, Uganda
| | - Denis Okello
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine (KIOM), 111 Geonjae-ro, Naju-si, Jeollanam-do, 58245, Republic of Korea.,University of Science and Technology (UST), Korean Convergence Medicine Major, KIOM campus, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 34054, Republic of Korea
| | - Moses Solomon Agwaya
- Natural Chemotherapeutics Research Institute (NCRI), Ministry of Health, P.O. Box 4864, Kampala, Uganda
| | - Grace Nambatya Kyeyune
- Natural Chemotherapeutics Research Institute (NCRI), Ministry of Health, P.O. Box 4864, Kampala, Uganda
| | - Hyemin Kan
- Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea
| | - Kyu-Seok Hwang
- Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea
| | - Motlalepula Gilbert Matsabisa
- IKS Research Group, Department of Pharmacology, Faculty of Health Sciences, University of the Free State, Bloemfontein, 9301, Free State, South Africa
| | - Youngmin Kang
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine (KIOM), 111 Geonjae-ro, Naju-si, Jeollanam-do, 58245, Republic of Korea. .,University of Science and Technology (UST), Korean Convergence Medicine Major, KIOM campus, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 34054, Republic of Korea.
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Wang X, Liu X, He P, Guan K, Yang Y, Lei Y, Cai J, Wang W, Wu T. The Imbalance of Mitochondrial Homeostasis of Peripheral Blood-Derived Macrophages Mediated by MAFLD May Impair the Walking Ability of Elderly Patients with Osteopenia. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:5210870. [PMID: 35368864 PMCID: PMC8970807 DOI: 10.1155/2022/5210870] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/28/2022] [Accepted: 03/04/2022] [Indexed: 12/15/2022]
Abstract
Introduction Many Asian cohort studies have shown that nonalcoholic fatty liver disease (NAFLD), now renamed as metabolic dysfunction-associated fatty liver disease (MAFLD), increases the risk of osteoporosis, yet the effect of MAFLD on elderly patients with osteopenia (OPe) has not been reported. Objective This study aimed to explore the influence of MAFLD on the function of macrophages in patients with OPe. Methods A total of 107 elderly OPe patients with or without MAFLD who visited the Huadong Hospital Affiliated to Fudan University (Shanghai, China) between January 1st, 2021, and September 30th, 2021, were evaluated for an interviewer-assisted questionnaire, as well as clinical and biological assessments. Results Comparing two groups of elderly patients with the same bone mass level, we found that the six-minute walking distance (P = 0.012) and short physical performance battery (SPPB) score (P = 0.0029) of the elderly OPe patients with MAFLD are worse than those in OPe patients without MAFLD. Our results confirmed that the mitochondrial reactive oxygen species (mtROS) in peripheral blood of OPe patients with MAFLD was significantly higher than those without. We also observed the mitochondrial metabolism level of peripheral blood-derived macrophages in the included patients and peripheral blood macrophages in patients with MAFLD with more unbalanced mitochondrial dynamics of macrophages, more weakened mitochondrial respiratory capacity, and greater mitochondrial microstructure damage, when compared with the elderly patients without MAFLD. Conclusions To conclude, our data revealed that MAFLD itself may aggravate the inflammatory state in elderly OPe people due to mitochondrial homeostasis imbalance of peripheral blood macrophages. Damaged monocyte-macrophages might trigger attenuation of the walking ability of OPe patients.
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Affiliation(s)
- Xiaojun Wang
- Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Xuanqi Liu
- Department of Respiratory and Critical Care Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Peqing He
- Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Kangwei Guan
- Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Yijing Yang
- Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Yiming Lei
- Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Jianhua Cai
- Department of General Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Wenhao Wang
- Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Tao Wu
- Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
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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: 66] [Impact Index Per Article: 22.0] [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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Jørgensen NR, Diemar SS, Christensen GL, Kimer N, Danielsen KV, Møller S. Patients With Cirrhosis Have Elevated Bone Turnover but Normal Hepatic Production of Osteoprotegerin. J Clin Endocrinol Metab 2022; 107:e980-e995. [PMID: 34718621 DOI: 10.1210/clinem/dgab788] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Indexed: 01/18/2023]
Abstract
CONTEXT Severe osteodystrophy is common in patients with liver dysfunction. Markers of bone metabolism may help in early diagnosis of osteodystrophy and in understanding underlying pathophysiological mechanisms. OBJECTIVE To elucidate changes in bone metabolism associated with cirrhosis and to determine the route of elimination for the markers. METHODS Case-control study at a public university hospital. Fifty-nine patients with cirrhosis (47 alcoholic and 12 nonalcoholic cirrhosis) and 20 controls were included. Participants underwent catheterization of the femoral artery, and the hepatic, renal, and femoral veins with collection of blood from all 4 sites. Regional arteriovenous differences in concentrations of bone metabolism markers were determined: procollagen of type I collagen propeptide (PINP), C-terminal cross-linking telopeptide of type I collagen (CTX), osteocalcin, tartrate-resistant acid phosphatase isoform 5b (TRAcP5b), osteoprotegerin (OPG), and sclerostin and correlated with degree of disease (Child-Pugh classification). RESULTS PINP concentration was higher (median: 87.9 µg/L) in patients with cirrhosis than in controls (52.6 µg/L) (P = .001), while hepatic extraction was lower (4.3% vs 14.5%) (P < .001). Both CTX and TRAcP5b were higher in patients with cirrhosis (340 ng/L and 3.20 U/L) than in controls (215 ng/L and 1.60 U/L) (P < .001 and P < .0001). Hepatic sclerostin extraction was lower in patients with cirrhosis (14.6%) than in controls (28.7%) (P < .0001). In both groups OPG showed a hepatic release rate (production) of 6%. CONCLUSION Patients with cirrhosis have increased bone resorption, but unaltered bone formation. Sclerostin is eliminated through the liver while OPG is produced in the liver. Bone markers may prove useful in evaluating bone turnover in patients with cirrhosis.
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Affiliation(s)
- Niklas Rye Jørgensen
- Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | | | - Nina Kimer
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Gastro Unit, Medical Division, Hvidovre Hospital, Hvidovre, Denmark
| | - Karen Vagner Danielsen
- Department of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, Hvidovre, Denmark
| | - Søren Møller
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, Hvidovre, Denmark
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Research Progress on the Pharmacological Action of Schisantherin A. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:6420865. [PMID: 35190748 PMCID: PMC8858060 DOI: 10.1155/2022/6420865] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 10/23/2021] [Accepted: 01/21/2022] [Indexed: 11/18/2022]
Abstract
Schisantherin A (Sch A) is a dibenzocyclooctadiene lignan monomer isolated from the fruit of Schisandra chinensis (Turcz.) Baill. (S. chinensis). At present, many studies have shown that Sch A has a wide range of pharmacological effects, including its anti-Parkinson and anti-inflammatory effects and ability to protect the liver, protect against ischemia-reperfusion (I/R) injury, suppress osteoclast formation, and improve learning and memory. Its mechanism may be related to the antioxidant, anti-inflammatory, and antiapoptotic properties of Sch A through the MAPK, NF-κB, AKT/GSK3β, and PI3K/AKT pathways. This is the first review of the recent studies on the pharmacological mechanism of Sch A.
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Tonk CH, Shoushrah SH, Babczyk P, El Khaldi-Hansen B, Schulze M, Herten M, Tobiasch E. Therapeutic Treatments for Osteoporosis-Which Combination of Pills Is the Best among the Bad? Int J Mol Sci 2022; 23:1393. [PMID: 35163315 PMCID: PMC8836178 DOI: 10.3390/ijms23031393] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/19/2022] [Accepted: 01/24/2022] [Indexed: 12/13/2022] Open
Abstract
Osteoporosis is a chronical, systemic skeletal disorder characterized by an increase in bone resorption, which leads to reduced bone density. The reduction in bone mineral density and therefore low bone mass results in an increased risk of fractures. Osteoporosis is caused by an imbalance in the normally strictly regulated bone homeostasis. This imbalance is caused by overactive bone-resorbing osteoclasts, while bone-synthesizing osteoblasts do not compensate for this. In this review, the mechanism is presented, underlined by in vitro and animal models to investigate this imbalance as well as the current status of clinical trials. Furthermore, new therapeutic strategies for osteoporosis are presented, such as anabolic treatments and catabolic treatments and treatments using biomaterials and biomolecules. Another focus is on new combination therapies with multiple drugs which are currently considered more beneficial for the treatment of osteoporosis than monotherapies. Taken together, this review starts with an overview and ends with the newest approaches for osteoporosis therapies and a future perspective not presented so far.
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Affiliation(s)
- Christian Horst Tonk
- Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig-Str. 20, 53359 Rheinbach, Germany; (C.H.T.); (S.H.S.); (P.B.); (B.E.K.-H.); (M.S.); (E.T.)
| | - Sarah Hani Shoushrah
- Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig-Str. 20, 53359 Rheinbach, Germany; (C.H.T.); (S.H.S.); (P.B.); (B.E.K.-H.); (M.S.); (E.T.)
| | - Patrick Babczyk
- Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig-Str. 20, 53359 Rheinbach, Germany; (C.H.T.); (S.H.S.); (P.B.); (B.E.K.-H.); (M.S.); (E.T.)
| | - Basma El Khaldi-Hansen
- Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig-Str. 20, 53359 Rheinbach, Germany; (C.H.T.); (S.H.S.); (P.B.); (B.E.K.-H.); (M.S.); (E.T.)
| | - Margit Schulze
- Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig-Str. 20, 53359 Rheinbach, Germany; (C.H.T.); (S.H.S.); (P.B.); (B.E.K.-H.); (M.S.); (E.T.)
| | - Monika Herten
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Edda Tobiasch
- Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig-Str. 20, 53359 Rheinbach, Germany; (C.H.T.); (S.H.S.); (P.B.); (B.E.K.-H.); (M.S.); (E.T.)
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Singh S, Taneja S, Tandon P, De A, Verma N, Premkumar M, Duseja A, Dhiman RK, Singh V. High Prevalence of Hormonal Changes and Hepatic Osteodystrophy in Frail Patients with Cirrhosis-An Observational Study. J Clin Exp Hepatol 2022; 12:800-807. [PMID: 35677501 PMCID: PMC9168697 DOI: 10.1016/j.jceh.2021.11.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 11/20/2021] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND/AIM Hormonal changes and hepatic osteodystrophy are less often studied complications of cirrhosis. This study describes the variance in hormones and osteodystrophy between Frail and Not frail patients with cirrhosis. METHODS 116 outpatients with cirrhosis were prospectively enrolled in this study. Frailty assessment was done using Liver Frailty Index (LFI). Sociodemographic assessment, anthropometry, nutritional assessment, hormone profile, and dual-energy X-ray absorptiometry scan were done in all patients. RESULTS 116 patients, predominantly males (100 (86.2%) with mean age of 50.16 years (95% CI, 48.43-51.89) were included. Malnutrition was more common in Frail group as compared to Not frail group. Subjective global assessment (SGA) class-B patients were significantly more in Frail group (37 (74%) vs 3 (4.5%), P = 0.001). The prevalence of lower parathyroid hormone (PTH) (14 (28%) vs 2 (3%)), testosterone (33 (66%) vs 15 (22.7%)), vitamin D3 (44 (88%) vs 39 (59.1%)), and cortisol (37 (74%) vs 37 (56.1) levels was higher in Frail group (P < 0.05). The number of patients diagnosed with osteodystrophy (34 (68%) vs 21 (31.8%), P = 0.001) was significantly higher in Frail group. The marker of osteoclastic activity, β-cross laps, was significantly elevated in the Frail group both in males (736 (655-818) vs 380 (329-432), P = 0.001) and (females 619 (479-758) vs 313 (83-543), P = 0.02). Bone mineral density (BMD) at lumbar spine (LS) and neck of femur (NF) had significant correlation with LFI (ρ = 0.60, P = 0.001 for LS and ρ = 0.59, P = 0.001 for NF), serum testosterone (ρ = 0.58, P = 0.001 for LS and ρ = 0.53, P = 0.001 for NF), β-cross laps (ρ = 0.38, P = 0.001for LS and ρ = 0.35, P = 0.000 for NF), vitamin D3 (ρ = 0.23, P = 0.04 for LS and ρ = 0.25, P = 0.01 for NF), PTH (ρ = 0.52, P = 0.001 for LS and ρ = 0.48. P = 0.001 for NF), and cortisol (ρ = 0.50, P = 0.001 for LS and ρ = 0.45, P = 0.001 for NF) levels. CONCLUSION This is the first study that highlights the high prevalence of hormonal changes and hepatic osteodystrophy in frail patients with cirrhosis and opens a new dimension for research and target of therapy in this field.
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Key Words
- ANOVA, analysis of variance
- BMD, bone mineral density
- BMI, body mass index
- CI, confidence interval
- CRP, C-reactive protein
- CTP, Child–Turcotte–Pugh
- DEXA, dual-energy X-ray absorptiometry
- ESR, erythrocyte sedimentation rate
- HCC, hepatocellular carcinoma
- HE, hepatic encephalopathy
- IBM, International Business Machines
- LFI, Liver Frailty Index
- MAC, mid-arm circumference
- MAMC, mid-arm muscle circumference
- MELD, model for end-stage liver disease
- MELDNa, model for end-stage liver disease with sodium
- NASH, non-alcoholic steatohepatitis
- P1-NP, procollagen type 1 N-terminal propeptide
- PTH, parathyroid Hormone
- SGA, subjective global assessment
- SPSS, Statistical Package for Social Sciences
- T3, triiodothyronine
- T4, tetraiodothyronine
- TIBC, total iron-binding capacity
- TSF, triceps skin-fold thickness
- TSH, thyroid stimulating hormone
- cirrhosis
- frailty
- hormonal changes
- osteodystrophy
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Affiliation(s)
- Surender Singh
- Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India,Address for correspondence: Dr. Sunil Taneja, Associate Professor, Department of Hepatology, PGIMER, Chandigarh, India. Tel.: +919592160444.
| | - Puneeta Tandon
- Division of Gastroenterology, University of Alberta, Edmonton, Canada
| | - Arka De
- Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Radha Krishan Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Virendra Singh
- Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
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Yang F, Xu W, Wu L, Yang L, Zhu S, Wang L, Wu W, Zhang Y, Chong Y, Peng L. NTCP Deficiency Affects the Levels of Circulating Bile Acids and Induces Osteoporosis. Front Endocrinol (Lausanne) 2022; 13:898750. [PMID: 35937832 PMCID: PMC9353038 DOI: 10.3389/fendo.2022.898750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 04/29/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The p.Ser267Phe mutation in the SLC10A1 gene can cause NTCP deficiency. However, the full clinical presentation of p.Ser267Phe homozygous individuals and its long-term consequences remain unclear. Hence, in the present study, we characterized the phenotypic characteristics of NTCP deficiency and evaluated its long-term prognosis. METHODS Ten NTCP p.Ser267Phe homozygous individuals were recruited and a comprehensive medical evaluation with a 5-year follow-up observation was performed. The phenotypic characteristics of NTCP deficiency were also demonstrated using an NTCP-global knockout mouse model. RESULTS During the 5-year follow-up observation of 10 NTCP p.Ser267Phe homozygous adults, we found that the most common phenotypic features of NTCP deficiency in adults were hypercholanemia, vitamin D deficiency, bone loss, and gallbladder abnormalities. The profile of bile acids (BAs) in the serum was significantly altered in these individuals and marked by both elevated proportion and concentration of primary and conjugated BAs. Moreover, the NTCP deficiency led to increased levels of serum BAs, decreased levels of vitamin D, and aggravated the osteoporotic phenotype induced by estrogen withdrawal in mice. CONCLUSIONS Both mice and humans with NTCP deficiency presented hypercholanemia and were more prone to vitamin D deficiency and aggravated osteoporotic phenotype. Therefore, we recommend monitoring the levels of BAs and vitamin D, bone density, and abdominal ultrasounds in individuals with NTCP deficiency.
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Affiliation(s)
- Fangji Yang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wenxiong Xu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lina Wu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Luo Yang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shu Zhu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lu Wang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wenbin Wu
- Department of Spine Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yuzhen Zhang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yutian Chong
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Key Laboratory of Liver Disease of Guangdong Province, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- *Correspondence: Liang Peng, ; Yutian Chong,
| | - Liang Peng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Key Laboratory of Liver Disease of Guangdong Province, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- *Correspondence: Liang Peng, ; Yutian Chong,
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Al-Akabi D, Kata FS. Effect of Non-alcoholic Fatty Liver Disease on Some of Bone Biomarkers in Men. Open Access Maced J Med Sci 2021. [DOI: 10.3889/oamjms.2021.6892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the common liver diseases worldwide that is not associated with alcohol consumption; it is a group of disorders caused by fat accumulation in the liver.
AIM: The research aims to assess the levels of serum sialoprotein, sclerostin, and osteocalcin in men with NAFLD.
METHODS: The current study was conducted in Basra city, Iraq in 2020, which includes 400 men with NAFLD, age ranges between (30 and 50) years, and 400 matched health men as controls, serum levels of study parameters were measured using the ELISA method.
RESULTS: The results showed a significant decrease in the levels of serum osteocalcin but a non-significant difference in sclerostin and bone sialoprotein in men with NAFLD comparing with the control group, also age and disease severity factors did not show any significant effect on study parameters in the patient’s group.
CONCLUSION: In conclusion, men with NAFLD may be prone to some disturbances in the bone health regardless of disease progression and age in Basrah city.
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Saeki C, Saito M, Kanai T, Nakano M, Oikawa T, Torisu Y, Saruta M, Tsubota A. Clinical Usefulness of FRAX Score for Predicting Sarcopenia in Patients with Chronic Liver Disease. J Clin Med 2021; 10:jcm10184080. [PMID: 34575191 PMCID: PMC8465236 DOI: 10.3390/jcm10184080] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 09/03/2021] [Accepted: 09/06/2021] [Indexed: 11/16/2022] Open
Abstract
We investigated the usefulness of the Fracture Risk Assessment tool (FRAX) for predicting sarcopenia in chronic liver disease (CLD). In this cross-sectional study, we evaluated 321 patients with CLD. The FRAX with and without bone mineral density (BMD) was employed to calculate the 10-year risks of major osteoporotic and hip fractures. The FRAX score for high fracture risk was defined as a 10-year major osteoporotic fracture probability of ≥20% or a 10-year hip fracture probability of ≥3%. The diagnosis of sarcopenia was based on the Japan Society of Hepatology criteria. According to the FRAX, with and without BMD, 134 (41.7%) and 193 (60.1%) patients had a high fracture risk, respectively. The high fracture risk group had a significantly higher frequency of sarcopenia than the non-high fracture risk group. FRAX scores of major osteoporotic and hip fractures were negatively correlated with handgrip strength and muscle mass. Using the FRAX with BMD, the cutoff scores of major osteoporotic and hip fractures for predicting sarcopenia were 8.55% (sensitivity/specificity, 0.847/0.568) and 3.35% (0.729/0.746), respectively. Using the FRAX without BMD, they were 18.5% (0.635/0.725) and 7.65% (0.729/0.758), respectively. The FRAX is a simple and convenient screening tool for predicting sarcopenia in patients with CLD.
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Affiliation(s)
- Chisato Saeki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan; (T.K.); (M.N.); (T.O.); (Y.T.); (M.S.)
- Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, 50 Takashima-cho, Fuji-shi 417-8567, Shizuoka, Japan
- Correspondence: (C.S.); (A.T.); Tel.: +81-3-3433-1111 (C.S. & A.T.)
| | - Mitsuru Saito
- Department of Orthopaedic Surgery, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan;
| | - Tomoya Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan; (T.K.); (M.N.); (T.O.); (Y.T.); (M.S.)
- Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, 50 Takashima-cho, Fuji-shi 417-8567, Shizuoka, Japan
| | - Masanori Nakano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan; (T.K.); (M.N.); (T.O.); (Y.T.); (M.S.)
- Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, 50 Takashima-cho, Fuji-shi 417-8567, Shizuoka, Japan
| | - Tsunekazu Oikawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan; (T.K.); (M.N.); (T.O.); (Y.T.); (M.S.)
| | - Yuichi Torisu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan; (T.K.); (M.N.); (T.O.); (Y.T.); (M.S.)
- Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, 50 Takashima-cho, Fuji-shi 417-8567, Shizuoka, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan; (T.K.); (M.N.); (T.O.); (Y.T.); (M.S.)
| | - Akihito Tsubota
- Core Research Facilities, Research Center for Medical Science, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan
- Correspondence: (C.S.); (A.T.); Tel.: +81-3-3433-1111 (C.S. & A.T.)
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Jadzic J, Milovanovic P, Cvetkovic D, Ivovic M, Tomanovic N, Bracanovic M, Zivkovic V, Nikolic S, Djuric M, Djonic D. Mechano-structural alteration in proximal femora of individuals with alcoholic liver disease: Implications for increased bone fragility. Bone 2021; 150:116020. [PMID: 34044170 DOI: 10.1016/j.bone.2021.116020] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 05/14/2021] [Accepted: 05/19/2021] [Indexed: 02/06/2023]
Abstract
Although increased hip fracture risk is noted in patients with alcoholic liver disease (ALD), their femoral microstructural and mechanical properties were not investigated previously. The present study aimed to analyze the associations between subregional deteriorations in femoral mechano-structural properties and clinical imaging findings to explain increased femoral fracture risk among ALD patients. This study analyzed proximal femora of 33 male cadaveric donors, divided into ALD (n = 13, 57 ± 13 years) and age-matched control group (n = 20, 54 ± 13 years). After pathohistological verification of ALD stage, DXA and HSA measurements of the proximal femora were performed, followed by micro-CT and Vickers microindentation of the superolateral neck, inferomedial neck, and intertrochanteric region. Bone mineral density and cross sectional area of the femoral neck were deteriorated in ALD donors, compared with healthy controls (p < 0.05). Significant ALD-induced degradation of trabecular and cortical microstructure and Vickers microhardness reduction were noted in the analyzed femoral regions (p < 0.05). Still, the most prominent ALD-induced mechano-structural deterioration was noted in intertrochanteric region. Additionally, more severe bone alterations were observed in individuals with an irreversible stage of ALD, alcoholic liver cirrhosis (ALC), than in those with an initial ALD stage, fatty liver disease. Observed osteodensitometric and mechano-structural changes illuminate the basis for increased femoral fracture risk in ALD patients. Additionally, our data suggest bone strength reduction that may result in increased susceptibility to intertrochanteric femoral fracture in men with ALD. Thus, femoral fracture risk assessment should be advised for all ALD patients, especially in those with ALC.
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Affiliation(s)
- Jelena Jadzic
- Laboratory for Anthropology and Skeletal biology, Institute for Anatomy, Faculty of Medicine, University of Belgrade, Dr. Subotica no. 4/2, Belgrade, Serbia
| | - Petar Milovanovic
- Laboratory for Anthropology and Skeletal biology, Institute for Anatomy, Faculty of Medicine, University of Belgrade, Dr. Subotica no. 4/2, Belgrade, Serbia
| | - Danica Cvetkovic
- Institute of Forensic Medicine, Faculty of Medicine, University of Belgrade, Deligradska no. 31a, Belgrade, Serbia
| | - Miomira Ivovic
- Institute for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Dr. Subotica no. 13, Belgrade, Serbia
| | - Nada Tomanovic
- Institute of Pathology, Faculty of Medicine, University of Belgrade, Dr. Subotica no. 1, Belgrade, Serbia
| | - Milos Bracanovic
- Clinic for Emergency Surgery, Clinical Center of Serbia, Pasterova no. 2, Belgrade, Serbia
| | - Vladimir Zivkovic
- Institute of Forensic Medicine, Faculty of Medicine, University of Belgrade, Deligradska no. 31a, Belgrade, Serbia
| | - Slobodan Nikolic
- Institute of Forensic Medicine, Faculty of Medicine, University of Belgrade, Deligradska no. 31a, Belgrade, Serbia
| | - Marija Djuric
- Laboratory for Anthropology and Skeletal biology, Institute for Anatomy, Faculty of Medicine, University of Belgrade, Dr. Subotica no. 4/2, Belgrade, Serbia
| | - Danijela Djonic
- Laboratory for Anthropology and Skeletal biology, Institute for Anatomy, Faculty of Medicine, University of Belgrade, Dr. Subotica no. 4/2, Belgrade, Serbia.
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