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Rini SS, Wibawa IDN. Evaluation and Management of Chronic Cholestatic Liver Diseases. Middle East J Dig Dis 2023; 15:148-155. [PMID: 38023462 PMCID: PMC10660321 DOI: 10.34172/mejdd.2023.336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Accepted: 05/07/2023] [Indexed: 12/01/2023] Open
Abstract
Cholestasis is defined as stagnation or a marked reduction in bile secretion and flow. Cholestatic jaundice can thus be classified as intrahepatic or extrahepatic cholestatic, depending on the level of obstruction to bile flow. It is important to recognize the complications of cholestatic in patients with chronic cholestatic liver disease. The two most common complications of cholestasis are pruritus and fatigue, with the former being the most responsive to treatment. Cholestyramine is the first-line treatment for cholestatic pruritus. Rifampicin and oral opioid antagonist naltrexone are extremely effective second-line treatments. To date, there are no specific treatments for chronic cholestatic fatigue management. Osteoporosis is a complication that can arise in chronic cholestatic conditions. It appears to be more prominent in individuals with cholestatic liver disease than in patients with other chronic liver diseases with an increased risk of fracture. The evaluation of osteoporosis in individuals with chronic cholestasis is similar to that in the general population. Antiresorptive agents such as bisphosphonates are the first-line treatment choice for osteoporosis in patients with chronic cholestasis. Other less common complications include dyslipidemia, fat-soluble vitamin deficiency, and steatorrhea. Understanding and treating these conditions can have a significant impact on the morbidity and quality of life in this group of patients. This review aimed to provide further information about the complications of chronic cholestasis and to highlight evidence-based test practices for the evaluation and effective management of these complications.
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Affiliation(s)
- Sandra Surya Rini
- Department of Internal Medicine, Bali Jimbaran Hospital, Badung, Bali, Indonesia
| | - I Dewa Nyoman Wibawa
- Department of Internal Medicine and Endoscopic Unit, BaliMed Hospital, Denpasar, Bali, Indonesia
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Ionele CM, Turcu-Stiolica A, Subtirelu MS, Ungureanu BS, Cioroianu GO, Rogoveanu I. A Systematic Review and Meta-Analysis on Metabolic Bone Disease in Patients with Primary Sclerosing Cholangitis. J Clin Med 2022; 11:3807. [PMID: 35807091 PMCID: PMC9267321 DOI: 10.3390/jcm11133807] [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] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 06/25/2022] [Accepted: 06/28/2022] [Indexed: 12/26/2022] Open
Abstract
Data about the association between primary sclerosing cholangitis (PSC) and metabolic bone disease are still unclear. PSC is a chronic cholestatic liver disease (CCLD) which affects the biliary tract, and it has a highly variable natural history. We systematically searched until 28 February 2022 MEDLINE, Cochrane Central Register of Controlled Trials, the ISI Web of Science, and SCOPUS, for studies in patients with PSC. We identified 343 references to potential studies. After screening them, we included eight studies (893 PSC patients, 398 primary biliary cirrhosis (PBC) patients, and 673 healthy controls) for the present meta-analysis. Pooled analyses found no difference in BMD-LS (Z = 0.02, p-value = 0.98) between PSC patients and healthy controls. BMD-LS was statistically lower in PBC patients than in PSC patients (Mean Difference, MD, 0.06, 95% CI 0.03 to 0.09, p-value = 0.0007). The lumbar spine T-score was higher in the PSC patients compared with PBC patients (MD 0.23, 95% CI 0.04 to 0.42, p-value = 0.02). Given the limited literature available, better designed, and larger scale primary studies will be required to confirm our conclusion.
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Affiliation(s)
- Claudiu Marinel Ionele
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (C.M.I.); (G.O.C.)
| | - Adina Turcu-Stiolica
- Department of Pharmacoeconomics, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Mihaela Simona Subtirelu
- Department of Pharmacoeconomics, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Bogdan Silviu Ungureanu
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania; (B.S.U.); (I.R.)
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - George Ovidiu Cioroianu
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (C.M.I.); (G.O.C.)
| | - Ion Rogoveanu
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania; (B.S.U.); (I.R.)
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Reshetnyak VI, Maev IV. Mechanism for development of malnutrition in primary biliary cholangitis. World J Meta-Anal 2022; 10:81-98. [DOI: 10.13105/wjma.v10.i3.81] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 04/14/2022] [Accepted: 05/23/2022] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that is associated with impaired biliary excretion processes. Along with the development of cholestasis, there is a deficient flow of bile acids into the intestinal lumen causing malnutrition (MN) that is manifested in deficiencies of both macro- and micronutrients. The mechanism for development of trophological insufficiency is multifactorial. However, the trigger of MN in PBC is impaired enterohepatic circulation of bile acids. The ingress of bile acids with a detergent effect into the general bloodstream, followed by elimination via the kidneys and skin, triggers a cascade of metabolic disturbances, which leads to the gradual development and progression of calorie MN. The latter gradually transforms into protein-calorie MN (PСM) (as marasmus) due to the insufficient entry of bile acids into the duodenum, which is accompanied by a decrease in the emulsification, hydrolysis, and absorption of fats and fat-soluble vitamins, as well as disturbance of intestinal motility and bacterial overgrowth. Fat-soluble vitamin deficiencies complement PСM with vitamin and mineral MN. The development of hepatocellular failure enhances the progression of PСM due to the impaired protein synthetic function of hepatocytes in the advanced stage of PBC, which results in deficiency of not only the somatic but also the visceral pool of proteins. A mixed PСM form of marasmus and kwashiorkor develops. Early recognition of energy, protein, micronutrient, and macronutrient deficiencies is of great importance because timely nutritional support can improve liver function and quality of life in patients with PBC. In this case, it is important to know what type (energy, protein-calorie, vitamin, and vitamin-mineral) and form (marasmus, marasmus-kwashiorkor) of MN is present in the patient and how it is associated with the stage of the disease. Therefore, it is recommended to screen all patients with PBC for MN, from the early asymptomatic stage of the disease in order to identify and avoid preventable complications, such as fatigue, malaise, performance decrement, sarcopenia, osteoporosis, and hepatic encephalopathy, which will be able to provide appropriate nutritional support for correction of the trophological status.
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Affiliation(s)
- Vasiliy Ivanovich Reshetnyak
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
| | - Igor Veniaminovich Maev
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
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Ansari Z, Shah I, Bhurwal A, Mehta H, Uppal S, Srinivasan I, Reddymasu S, Chuang KY. Decreasing Rates of Fracture-Related Hospitalization With Primary Biliary Cholangitis: Insights From the Nationwide Inpatient Sample. Cureus 2022; 14:e25001. [PMID: 35719819 PMCID: PMC9191878 DOI: 10.7759/cureus.25001] [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] [Accepted: 05/14/2022] [Indexed: 11/05/2022] Open
Abstract
Introduction Primary biliary cholangitis (PBC) is associated with an increased risk of developing fractures. Current guidelines recommend measures that can help prevent the development of fractures in these patients. The purpose of this study was to trend the rates of hospitalizations related to fractures and their burden on healthcare. Methods We performed a retrospective, cohort study of adults hospitalized in the United States with PBC between 2010 and 2014. Patients were identified using the Nationwide Inpatient Sample (NIS). Temporal analysis of PBC patients with a co-diagnosis of hip, vertebral, or wrist fractures (the study group) was performed with regards to the total number of inpatient admissions, inpatient mortality, length of stay, and total charges associated with hospitalization. Descriptive analyses were performed using the t-test for continuous data and the chi-square test for categorical data. Results During the five-year study period, there were 308,753 hospitalizations for PBC. There has been a downward trend (p=0.02) in fracture-related admissions among patients with PBC during this study period. Length of stay was higher in the PBC-fracture group (10.85 days vs 7.36 days; p<0.001). Total hospitalization charges were higher among the PBC-fracture patients when compared to the control group ($98,444 vs $72,964; p=0.004). Conclusion There has been a gradual reduction in the rate of fracture-related hospitalizations in patients with PBC. However, patients with PBC who have fractures have increased the utilization of health care resources as compared to their cohort admitted for reasons other than for a fracture.
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Sobh MM, Abdalbary M, Elnagar S, Nagy E, Elshabrawy N, Abdelsalam M, Asadipooya K, El-Husseini A. Secondary Osteoporosis and Metabolic Bone Diseases. J Clin Med 2022; 11:2382. [PMID: 35566509 PMCID: PMC9102221 DOI: 10.3390/jcm11092382] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/17/2022] [Accepted: 04/20/2022] [Indexed: 02/04/2023] Open
Abstract
Fragility fracture is a worldwide problem and a main cause of disability and impaired quality of life. It is primarily caused by osteoporosis, characterized by impaired bone quantity and or quality. Proper diagnosis of osteoporosis is essential for prevention of fragility fractures. Osteoporosis can be primary in postmenopausal women because of estrogen deficiency. Secondary forms of osteoporosis are not uncommon in both men and women. Most systemic illnesses and organ dysfunction can lead to osteoporosis. The kidney plays a crucial role in maintaining physiological bone homeostasis by controlling minerals, electrolytes, acid-base, vitamin D and parathyroid function. Chronic kidney disease with its uremic milieu disturbs this balance, leading to renal osteodystrophy. Diabetes mellitus represents the most common secondary cause of osteoporosis. Thyroid and parathyroid disorders can dysregulate the osteoblast/osteoclast functions. Gastrointestinal disorders, malnutrition and malabsorption can result in mineral and vitamin D deficiencies and bone loss. Patients with chronic liver disease have a higher risk of fracture due to hepatic osteodystrophy. Proinflammatory cytokines in infectious, autoimmune, and hematological disorders can stimulate osteoclastogenesis, leading to osteoporosis. Moreover, drug-induced osteoporosis is not uncommon. In this review, we focus on causes, pathogenesis, and management of secondary osteoporosis.
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Affiliation(s)
- Mahmoud M. Sobh
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.A.); (S.E.); (E.N.); (N.E.); (M.A.)
| | - Mohamed Abdalbary
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.A.); (S.E.); (E.N.); (N.E.); (M.A.)
- Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington, KY 40506, USA
| | - Sherouk Elnagar
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.A.); (S.E.); (E.N.); (N.E.); (M.A.)
| | - Eman Nagy
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.A.); (S.E.); (E.N.); (N.E.); (M.A.)
| | - Nehal Elshabrawy
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.A.); (S.E.); (E.N.); (N.E.); (M.A.)
| | - Mostafa Abdelsalam
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.A.); (S.E.); (E.N.); (N.E.); (M.A.)
| | - Kamyar Asadipooya
- Division of Endocrinology, University of Kentucky, Lexington, KY 40506, USA;
| | - Amr El-Husseini
- Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington, KY 40506, USA
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Pereira F, Azevedo R, Linhares M, Pinto J, Leitão C, Caldeira A, Tristan J, Pereira E, Sousa R, Banhudo A. Hepatic osteodystrophy in cirrhosis due to alcohol-related liver disease. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2020; 113:563-569. [PMID: 33267594 DOI: 10.17235/reed.2020.7301/2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
INTRODUCTION hepatic osteodystrophy, including osteoporosis, is an abnormal bone metabolism related with chronic liver diseases. Osteoporosis is associated with an increased risk of bone fractures, with a significant impact on morbidity, mortality and healthcare costs. Nevertheless, bone disorders tend to be undervalued in cirrhosis due to alcohol-related liver disease (ALD cirrhosis). This study aimed to assess the prevalence of hepatic osteodystrophy and osteoporosis in ALD cirrhosis. METHODS a prospective observational study was performed that included patients with ALD cirrhosis, between September 2017 and December 2018. Bone mineral density was determined by dual energy X-ray absorptiometry at the lumbar spine and the femoral neck. Hepatic osteodystrophy was defined as a T-score below -1 SD and osteoporosis as a T-score below -2.5 SD. RESULTS ninety-four patients were included; 24.5 % (n = 23) had prior fragility fractures and ten patients suffered new osteoporotic fractures during the study period. Hepatic osteodystrophy was diagnosed in 79.8 % (n = 75) and osteoporosis in 21.3 % (n = 20) of cases. Patients with hepatic osteodystrophy presented significantly worse Child-Turcotte-Pugh (p < 0.05) and Model for End-Stage Liver Disease (MELD-sodium) scores (p = 0.01). According to the multivariate analysis, lower body mass index (BMI) (OR = 0.787, 95 % CI: 0.688-0.901, p = 0.001) and vitamin D deficiency (OR = 6.798, 95 % CI: 1.775-26.038, p = 0.005) were significantly and independently associated with hepatic osteodystrophy. Patients with osteoporosis also had a lower BMI (p = 0.01). Female patients and those with prior fragility fractures were more likely to suffer from osteoporosis (p < 0.05). CONCLUSION our study revealed a high prevalence of hepatic osteodystrophy and osteoporosis in patients with ALD cirrhosis (particularly in those with a lower BMI) and a concerning high rate of fragility fractures. Bone mineral density should be assessed in order to allow for an early diagnosis and the implementation of preventive measures.
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Affiliation(s)
| | | | | | - João Pinto
- Gastroenterology, Amato Lusitano Hospital, Portugal
| | - Cátia Leitão
- Gastroenterology, Amato Lusitano Hospital, Portugal
| | - Ana Caldeira
- Gastroenterology, Amato Lusitano Hospital, Portugal
| | - José Tristan
- Gastroenterology, Amato Lusitano Hospital, Portugal
| | | | - Rui Sousa
- Gastroenterology, Amato Lusitano Hospital, Portugal
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Wakolbinger R, Muschitz C, Scheriau G, Bodlaj G, Kocijan R, Feichtinger X, Schanda JE, Haschka J, Resch H, Pietschmann P. Bone microarchitecture and bone turnover in hepatic cirrhosis. Osteoporos Int 2019; 30:1195-1204. [PMID: 30788527 PMCID: PMC6546655 DOI: 10.1007/s00198-019-04870-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 01/21/2019] [Indexed: 02/06/2023]
Abstract
UNLABELLED Liver cirrhosis leads to bone loss. To date, information on bone quality (three-dimensional microarchitecture) and, thus, bone strength is scarce. We observed decreased bone quality at both assessed sites, independent of disease severity. Therefore, all patients should undergo early-stage screening for osteoporosis. INTRODUCTION Recent studies found low bone mineral density in cirrhosis, but data on bone microstructure are scarce. This study assessed weight-bearing and non-weight-bearing bones in patients with cirrhosis and healthy controls. The primary objective was to evaluate trabecular and cortical microarchitecture. METHODS This was a single-center study in patients with recently diagnosed hepatic cirrhosis. Thirty-two patients and 32 controls participated in this study. After determining the type of cirrhosis, the parameters of bone microarchitecture were assessed by high-resolution peripheral quantitative computed tomography. RESULTS Both cortical and trabecular microarchitectures showed significant alterations. At the radius, trabecular bone volume fraction was 17% lower (corrected p = 0.028), and, at the tibia, differences were slightly more pronounced. Trabecular bone volume fraction was 19% lower (p = 0.024), cortical bone mineral density 7% (p = 0.007), and cortical thickness 28% (p = 0.001), while cortical porosity was 32% higher (p = 0.023), compared to controls. Areal bone mineral density was lower (lumbar spine - 13%, total hip - 11%, total body - 9%, radius - 17%, and calcaneus - 26%). There was no correlation between disease severity and microarchitecture. Areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) correlated well with parameters of cortical and trabecular microarchitecture. CONCLUSIONS Hepatic cirrhosis deteriorates both trabecular and cortical microarchitecture, regardless of disease severity. Areal bone mineral density is diminished at all sites as a sign of generalized affection. In patients with hepatic cirrhosis, regardless of its origin or disease severity, aBMD measurements are an appropriate tool for osteologic screening.
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Affiliation(s)
- R Wakolbinger
- Medical Department II-The VINFORCE Study Group, St. Vincent Hospital, Academic Teaching Hospital of the Medical University of Vienna, Stumpergasse 13, A-1060, Vienna, Austria
- Department of Physical Medicine and Rehabilitation, Danube Hospital-Social Medical Center East, Academic Teaching Hospital of the Medical University of Vienna, Langobardenstraße 122, A-1220, Vienna, Austria
| | - C Muschitz
- Medical Department II-The VINFORCE Study Group, St. Vincent Hospital, Academic Teaching Hospital of the Medical University of Vienna, Stumpergasse 13, A-1060, Vienna, Austria.
| | - G Scheriau
- Medical Department II-The VINFORCE Study Group, St. Vincent Hospital, Academic Teaching Hospital of the Medical University of Vienna, Stumpergasse 13, A-1060, Vienna, Austria
| | - G Bodlaj
- Medical Department II-The VINFORCE Study Group, St. Vincent Hospital, Academic Teaching Hospital of the Medical University of Vienna, Stumpergasse 13, A-1060, Vienna, Austria
| | - R Kocijan
- Medical Department II-The VINFORCE Study Group, St. Vincent Hospital, Academic Teaching Hospital of the Medical University of Vienna, Stumpergasse 13, A-1060, Vienna, Austria
| | - X Feichtinger
- Medical Department II-The VINFORCE Study Group, St. Vincent Hospital, Academic Teaching Hospital of the Medical University of Vienna, Stumpergasse 13, A-1060, Vienna, Austria
- AUVA Trauma Center Meidling, Kundratstraße 37, A-1120, Vienna, Austria
| | - J E Schanda
- Medical Department II-The VINFORCE Study Group, St. Vincent Hospital, Academic Teaching Hospital of the Medical University of Vienna, Stumpergasse 13, A-1060, Vienna, Austria
- AUVA Trauma Center Meidling, Kundratstraße 37, A-1120, Vienna, Austria
| | - J Haschka
- Medical Department II-The VINFORCE Study Group, St. Vincent Hospital, Academic Teaching Hospital of the Medical University of Vienna, Stumpergasse 13, A-1060, Vienna, Austria
| | - H Resch
- Medical Department II-The VINFORCE Study Group, St. Vincent Hospital, Academic Teaching Hospital of the Medical University of Vienna, Stumpergasse 13, A-1060, Vienna, Austria
| | - P Pietschmann
- Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria
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Ehnert S, Aspera-Werz RH, Ruoß M, Dooley S, Hengstler JG, Nadalin S, Relja B, Badke A, Nussler AK. Hepatic Osteodystrophy-Molecular Mechanisms Proposed to Favor Its Development. Int J Mol Sci 2019; 20:2555. [PMID: 31137669 PMCID: PMC6566554 DOI: 10.3390/ijms20102555] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 05/14/2019] [Accepted: 05/22/2019] [Indexed: 02/07/2023] Open
Abstract
Almost all patients with chronic liver diseases (CLD) show altered bone metabolism. Depending on the etiology, this manifests in a severe osteoporosis in up to 75% of the affected patients. Due to high prevalence, the generic term hepatic osteodystrophy (HOD) evolved, describing altered bone metabolism, decreased bone mineral density, and deterioration of bone structure in patients with CLD. Once developed, HOD is difficult to treat and increases the risk of fragility fractures. Existing fractures affect the quality of life and, more importantly, long-term prognosis of these patients, which presents with increased mortality. Thus, special care is required to support the healing process. However, for early diagnosis (reduce fracture risk) and development of adequate treatment strategies (support healing of existing fractures), it is essential to understand the underlying mechanisms that link disturbed liver function with this bone phenotype. In the present review, we summarize proposed molecular mechanisms favoring the development of HOD and compromising the healing of associated fractures, including alterations in vitamin D metabolism and action, disbalances in transforming growth factor beta (TGF-β) and bone morphogenetic protein (BMP) signaling with histone deacetylases (HDACs) as secondary regulators, as well as alterations in the receptor activator of nuclear factor kappa B ligand (RANKL)-osteoprotegerin (OPG) system mediated by sclerostin. Based on these mechanisms, we give an overview on the limitations of early diagnosis of HOD with established serum markers.
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Affiliation(s)
- Sabrina Ehnert
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
| | - Romina H Aspera-Werz
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
| | - Marc Ruoß
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
| | - Steven Dooley
- Department of Medicine II, Molecular Hepatology, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
| | - Jan G Hengstler
- IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, 44139 Dortmund, Germany.
| | - Silvio Nadalin
- Department of General, Visceral and Transplant Surgery, University Hospital Tuebingen, 72076 Tuebingen, Germany.
| | - Borna Relja
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590 Frankfurt, Germany.
| | - Andreas Badke
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
| | - Andreas K Nussler
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
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Liao CY, Chung CH, Chu P, Wei KY, Feng TM, Lin FH, Tsao CH, Wu CC, Chien WC. Increased risk of osteoporosis in patients with primary biliary cirrhosis. PLoS One 2018; 13:e0194418. [PMID: 29543880 PMCID: PMC5854410 DOI: 10.1371/journal.pone.0194418] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 03/04/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND We evaluated the risk of osteoporosis in patients with primary biliary cirrhosis (PBC) using a nationwide population-based dataset. METHODS In a cohort study of 986,713 individuals, we selected 2,493 PBC patients who were aged 18 years or older and had been diagnosed with PBC, based on the International Classification of Disease (ICD-9-CM) codes 571.6, during 20002010. The control cohort comprised 9,972 randomly selected, propensity matched patients (by age, gender, and index date), without PBC. Using this adjusted data, a possible association between PBC and the risk of developing osteoporosis was estimated using a Cox proportional hazard regression model. RESULTS During the follow-up period, osteoporosis was diagnosed in 150 (6.02%) patients in the PBC cohort and in 539 (5.41%) patients in the non-PBC cohort. After adjusting for covariates, osteoporosis risk was found to be 3.333 times greater in the PBC cohort than in the non-PBC cohort when measured over 6 years after PBC diagnosis. Stratification revealed that the use of ursodeoxycholic acid (UDCA) had no significance in decreasing the risk of osteoporosis when comparing the PBC cohorts with the non-PBC cohorts (P = 0.124). Additionally, osteoporosis risk was significantly higher in PBC patients with steroid use (aHR: 6.899 vs 3.333). Moreover, when comparing the PBC cohorts to the non-PBC cohorts, the non-cirrhotic patients were prone to osteoporosis at a younger age compared to those in the cirrhotic cohorts. We also found that the associated risk of fractures is only prominent for vertebral and wrist fractures in the PBC cohort compared to that in the non-PBC cohort. CONCLUSION A significant association exists between PBC and subsequent risk for osteoporosis. Therefore, PBC patients, particularly those treated with steroids, should be evaluated for subsequent risk of osteoporosis.
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Affiliation(s)
- Chen-Yi Liao
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
- Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chi-Hsiang Chung
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan
| | - Pauling Chu
- Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Kuang-yu Wei
- Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tseng-Min Feng
- Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Fu-Huang Lin
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
| | - Chang-Huei Tsao
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Department of Microbiology & Immunology, National Defense Medical Center, Taipei, Taiwan
| | - Chia-Chao Wu
- Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wu-Chien Chien
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
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Wintermeyer E, Ihle C, Ehnert S, Stöckle U, Ochs G, de Zwart P, Flesch I, Bahrs C, Nussler AK. Crucial Role of Vitamin D in the Musculoskeletal System. Nutrients 2016; 8:319. [PMID: 27258303 PMCID: PMC4924160 DOI: 10.3390/nu8060319] [Citation(s) in RCA: 139] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 05/10/2016] [Accepted: 05/11/2016] [Indexed: 12/17/2022] Open
Abstract
Vitamin D is well known to exert multiple functions in bone biology, autoimmune diseases, cell growth, inflammation or neuromuscular and other immune functions. It is a fat-soluble vitamin present in many foods. It can be endogenously produced by ultraviolet rays from sunlight when the skin is exposed to initiate vitamin D synthesis. However, since vitamin D is biologically inert when obtained from sun exposure or diet, it must first be activated in human beings before functioning. The kidney and the liver play here a crucial role by hydroxylation of vitamin D to 25-hydroxyvitamin D in the liver and to 1,25-dihydroxyvitamin D in the kidney. In the past decades, it has been proven that vitamin D deficiency is involved in many diseases. Due to vitamin D's central role in the musculoskeletal system and consequently the strong negative impact on bone health in cases of vitamin D deficiency, our aim was to underline its importance in bone physiology by summarizing recent findings on the correlation of vitamin D status and rickets, osteomalacia, osteopenia, primary and secondary osteoporosis as well as sarcopenia and musculoskeletal pain. While these diseases all positively correlate with a vitamin D deficiency, there is a great controversy regarding the appropriate vitamin D supplementation as both positive and negative effects on bone mineral density, musculoskeletal pain and incidence of falls are reported.
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Affiliation(s)
- Elke Wintermeyer
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Christoph Ihle
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Sabrina Ehnert
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Ulrich Stöckle
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Gunnar Ochs
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Peter de Zwart
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Ingo Flesch
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Christian Bahrs
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Andreas K Nussler
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
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Reshetnyak VI. Primary biliary cirrhosis: Clinical and laboratory criteria for its diagnosis. World J Gastroenterol 2015; 21:7683-7708. [PMID: 26167070 PMCID: PMC4491957 DOI: 10.3748/wjg.v21.i25.7683] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Revised: 04/07/2015] [Accepted: 06/10/2015] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic granulomatous, and destructive inflammatory lesion of small intralobular and septal bile ducts, which is likely to be caused by an autoimmune mechanism with a the presence of serum antimitochondrial antibodies and a potential tendency to progress to cirrhosis. Despite the fact that the etiology of this disease has been unknown so far, there has been a considerable body of scientific evidence that can reveal the clinical and laboratory signs of PBC and the individual components of its pathogenesis and elaborate diagnostic criteria for the disease and its symptomatic therapy. Deficiencies in autoimmune tolerance are critical factors for the initiation and perpetuation of the disease. The purpose of this review is to summarize the data available in the literature and the author's findings on clinical and laboratory criteria for the diagnosis of PBC. This review describes the major clinical manifestations of the disease and the mechanisms of its development. It presents the immunological, biochemical, and morphological signs of PBC and their significance for its diagnosis. A great deal of novel scientific evidence for the problem of PBC has been accumulated. However, the inadequate efficiency of therapy for the disease lends impetus to the quest for its etiological factors and to further investigations of its pathogenetic mechanisms and, on this basis, to searches for new methods for its early diagnosis.
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Nakchbandi IA. Osteoporosis and fractures in liver disease: Relevance, pathogenesis and therapeutic implications. World J Gastroenterol 2014; 20:9427-9438. [PMID: 25071337 PMCID: PMC4110574 DOI: 10.3748/wjg.v20.i28.9427] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Revised: 02/17/2014] [Accepted: 04/23/2014] [Indexed: 02/06/2023] Open
Abstract
It is being increasingly recognized that patients with liver disease develop bone loss that can be severe enough to lead to atraumatic fractures and thus markedly diminish life quality and expectancy. The estimated prevalence for liver-related osteoporosis is between 20-420/100000 of the general population, and fractures between 60-880/100000. It should be kept in mind that up to 40% of patients with chronic liver disease may experience a fracture. The pathogenic mediators include fibronectin, insulin like growth factor-I, and various cytokines, but decreased vitamin D and/or treatment with corticosteroids contribute to worsening bone health. Despite the advances in bone biology that have shed some light on the pathogenesis of this bone loss, treatment options remain nonspecific and tightly linked to treatments of other forms of osteoporosis. Thus, treatment should include calcium and vitamin D supplementation in all patients with chronic liver disease. Therapy with bisphosphonates should be considered, especially in patients receiving corticosteroids. This review focuses on the prevalence of this entity as well as the evidence available with regard to the pathogenesis of bone loss in liver disease, the diagnostic steps required in all patients, and the therapeutic options available.
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