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1
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Muzahim Y, Wakil A, Bassi M, Pyrsopoulos N. Treatment of Primary Biliary Cholangitis including Transplantation. Clin Liver Dis 2024; 28:103-114. [PMID: 37945152 DOI: 10.1016/j.cld.2023.07.003] [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] [Indexed: 11/12/2023]
Abstract
Ursodeoxycholic acid (UDCA) is the first-line treatment of primary biliary cholangitis (PBC). Long-term UDCA use significantly reduces progression to cirrhosis. UDCA improves liver enzymes and transplant-free survival rates. Despite the association between PBC and hyperlipidemia, treatment is indicated under specific circumstances with statins and fibrates being safe options. Osteoporosis, which is frequently seen, is usually managed based on data from postmenopausal women. Sicca syndrome is treated similarly to its standalone condition with the use of hydroxypropyl methylcellulose eye drops and anticholinergic drugs.
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Affiliation(s)
- Yasameen Muzahim
- Division of Gastroenterology and Hepatlogy, Rutgers New Jersey Medical School, 185 South Orange Avenue, MSB H Rm - 536, Newark, NJ 07101, USA
| | - Ali Wakil
- Division of Gastroenterology and Hepatlogy, Rutgers New Jersey Medical School, 185 South Orange Avenue, MSB H Rm - 536, Newark, NJ 07101, USA
| | - Mehak Bassi
- Division of Gastroenterology and Hepatoloy, Saint Peter's University Hospital, 254 Easton Avenue, New Brunswick, NJ 08901, USA
| | - Nikolaos Pyrsopoulos
- Division of Gastroenterology and Hepatlogy, Rutgers New Jersey Medical School, 185 South Orange Avenue, MSB H Rm - 536, Newark, NJ 07101, USA.
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2
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Raj H, Kamalanathan S, Sahoo J, Mohan P, Nagarajan K, Reddy SVB, Durgia H, Palui R. Effect of Zoledronic Acid in Hepatic Osteodystrophy: A Double-Blinded Placebo-Controlled Trial. Indian J Endocrinol Metab 2023; 27:552-558. [PMID: 38371182 PMCID: PMC10871003 DOI: 10.4103/ijem.ijem_233_23] [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: 06/02/2023] [Revised: 08/30/2023] [Accepted: 09/24/2023] [Indexed: 02/20/2024] Open
Abstract
PURPOSE Literature on the treatment of pre-transplant hepatic osteodystrophy (HOD) is limited. The general treatment measures and their timing are currently adopted from the literature on postmenopausal osteoporosis. Therefore, we conducted this randomized study to investigate the effect of zoledronic acid (ZA) on HOD. METHODS We randomized 36 male patients with cirrhosis (Child-Pugh class A and B) into 19 to the ZA arm and 17 to the placebo arm, respectively. Patients in the ZA arm received a single infusion of 4 mg ZA dissolved in 100 mL of normal saline at baseline, while patients in the placebo arm received a similar infusion of normal saline at baseline. The primary outcome of the study was the change in lumbar spine bone mineral density (LS-BMD) at 12 months. RESULTS Of 36 patients, 28 completed the study (15 in the ZA arm and 13 in the placebo arm). The mean increase in LS-BMD (g/cm2) in the ZA and placebo arms was 5.11% (3.50) and 0.72% (4.63) [P = 0.008], respectively. The trabecular bone score (TBS) did not improve significantly in either arm. The incidence of vertebral fractures (VFs) was similar in both arms. There was a significant decrease in plasma beta-C-terminal telopeptide (β-CTX) levels in the ZA arm compared to the placebo arm, while the change in plasma levels of procollagen 1 intact N-terminal propeptide (P1NP) was similar in both arms. Six patients (31.6%) in the ZA arm experienced adverse reactions such as fever and myalgia. CONCLUSION ZA improved LS-BMD in male patients with HOD by decreasing bone resorption. However, it may not improve trabecular microarchitecture or prevent morphometric VFs in this population.
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Affiliation(s)
- Henith Raj
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Sadishkumar Kamalanathan
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Jayaprakash Sahoo
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Pazhanivel Mohan
- Department of Medical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Krishnan Nagarajan
- Department of Radiodiagnosis, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Sagili V. B. Reddy
- Department of Vijay Diabetes, Thyroid and Endocrine Clinic, Saradambal Nagar, Puducherry, India
| | - Harsh Durgia
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Rajan Palui
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
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3
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Musio A, Perazza F, Leoni L, Stefanini B, Dajti E, Menozzi R, Petroni ML, Colecchia A, Ravaioli F. Osteosarcopenia in NAFLD/MAFLD: An Underappreciated Clinical Problem in Chronic Liver Disease. Int J Mol Sci 2023; 24:7517. [PMID: 37108675 PMCID: PMC10139188 DOI: 10.3390/ijms24087517] [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: 03/27/2023] [Revised: 04/07/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023] Open
Abstract
Chronic liver disease (CLD), including non-alcoholic fatty liver disease (NAFLD) and its advanced form, non-alcoholic steatohepatitis (NASH), affects a significant portion of the population worldwide. NAFLD is characterised by fat accumulation in the liver, while NASH is associated with inflammation and liver damage. Osteosarcopenia, which combines muscle and bone mass loss, is an emerging clinical problem in chronic liver disease that is often underappreciated. The reductions in muscle and bone mass share several common pathophysiological pathways; insulin resistance and chronic systemic inflammation are the most crucial predisposing factors and are related to the presence and gravity of NAFLD and to the worsening of the outcome of liver disease. This article explores the relationship between osteosarcopenia and NAFLD/MAFLD, focusing on the diagnosis, prevention and treatment of this condition in patients with CLD.
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Affiliation(s)
- Alessandra Musio
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
| | - Federica Perazza
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
| | - Laura Leoni
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
- Division of Metabolic Diseases and Clinical Nutrition, Department of Specialistic Medicines, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy;
| | - Bernardo Stefanini
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
| | - Elton Dajti
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
| | - Renata Menozzi
- Division of Metabolic Diseases and Clinical Nutrition, Department of Specialistic Medicines, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy;
| | - Maria Letizia Petroni
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
| | - Antonio Colecchia
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy;
| | - Federico Ravaioli
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy;
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4
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Pugliese N, Arcari I, Aghemo A, Lania AG, Lleo A, Mazziotti G. Osteosarcopenia in autoimmune cholestatic liver diseases: Causes, management, and challenges. World J Gastroenterol 2022; 28:1430-1443. [PMID: 35582674 PMCID: PMC9048470 DOI: 10.3748/wjg.v28.i14.1430] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 12/05/2021] [Accepted: 03/07/2022] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cholangitis and primary sclerosing cholangitis (PSC) are the most common cholestatic liver diseases (CLD) in adults and are both characterized by an immune pathogenesis. While primary biliary cholangitis is a model autoimmune disease, with over 90% of patients presenting very specific autoantibodies against mitochondrial antigens, PSC is considered an immune mediated disease. Osteoporosis is the most common bone disease in CLD, resulting in frequent fractures and leading to significant morbidity. Further, sarcopenia is emerging as a frequent complication of chronic liver diseases with a significant prognostic impact and severe implications on the quality of life of patients. The mechanisms underlying osteoporosis and sarcopenia in CLD are still largely unknown and the association between these clinical conditions remains to be dissected. Although timely diagnosis, prevention, and management of osteosarcopenia are crucial to limit the consequences, there are no specific guidelines for management of osteoporosis and sarcopenia in patients with CLD. International guidelines recommend screening for bone disease at the time of diagnosis of CLD. However, the optimal monitoring strategies and treatments have not been defined yet and vary among centers. We herein aim to comprehensively outline the pathogenic mechanisms and clinical implications of osteosarcopenia in CLD, and to summarize expert recommendations for appropriate diagnostic and therapeutic approaches.
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Affiliation(s)
- Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Ivan Arcari
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Andrea G Lania
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Department of Endocrinology, Diabetology and Medical Andrology Unit, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Gherardo Mazziotti
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Department of Endocrinology, Diabetology and Medical Andrology Unit, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
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5
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Ebeling PR, Nguyen HH, Aleksova J, Vincent AJ, Wong P, Milat F. Secondary Osteoporosis. Endocr Rev 2022; 43:240-313. [PMID: 34476488 DOI: 10.1210/endrev/bnab028] [Citation(s) in RCA: 150] [Impact Index Per Article: 50.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Indexed: 02/07/2023]
Abstract
Osteoporosis is a global public health problem, with fractures contributing to significant morbidity and mortality. Although postmenopausal osteoporosis is most common, up to 30% of postmenopausal women, > 50% of premenopausal women, and between 50% and 80% of men have secondary osteoporosis. Exclusion of secondary causes is important, as treatment of such patients often commences by treating the underlying condition. These are varied but often neglected, ranging from endocrine to chronic inflammatory and genetic conditions. General screening is recommended for all patients with osteoporosis, with advanced investigations reserved for premenopausal women and men aged < 50 years, for older patients in whom classical risk factors for osteoporosis are absent, and for all patients with the lowest bone mass (Z-score ≤ -2). The response of secondary osteoporosis to conventional anti-osteoporosis therapy may be inadequate if the underlying condition is unrecognized and untreated. Bone densitometry, using dual-energy x-ray absorptiometry, may underestimate fracture risk in some chronic diseases, including glucocorticoid-induced osteoporosis, type 2 diabetes, and obesity, and may overestimate fracture risk in others (eg, Turner syndrome). FRAX and trabecular bone score may provide additional information regarding fracture risk in secondary osteoporosis, but their use is limited to adults aged ≥ 40 years and ≥ 50 years, respectively. In addition, FRAX requires adjustment in some chronic conditions, such as glucocorticoid use, type 2 diabetes, and HIV. In most conditions, evidence for antiresorptive or anabolic therapy is limited to increases in bone mass. Current osteoporosis management guidelines also neglect secondary osteoporosis and these existing evidence gaps are discussed.
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Affiliation(s)
- Peter R Ebeling
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia
| | - Hanh H Nguyen
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Department of Endocrinology and Diabetes, Western Health, Victoria 3011, Australia
| | - Jasna Aleksova
- Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
| | - Amanda J Vincent
- Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Monash Centre for Health Research and Implementation, School of Public Health and Preventative Medicine, Monash University, Clayton, Victoria 3168, Australia
| | - Phillip Wong
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
| | - Frances Milat
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
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6
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Contreras-Omaña R, Velarde-Ruiz Velasco JA, Castro-Narro GE, Trujillo-Benavides O, Zamarripa-Dorsey F, Reyes-Dorantes AA, Muñoz-Espinosa L, Aiza-Haddad I, Castillo-Barradas M, Cerda-Reyes E, Cisneros-Garza LE, Flores-Calderón J, García-Jiménez ES, Higuera-de-la-Tijera MF, Lira-Pedrín MA, Marquez-Guillén E, Moctezuma-Velázquez C, Moreno-Alcántar R, Noyola-Cedillo SG, Pérez-Hernández JL, Ramos-Gómez MV, Remes-Troche JM, Rizo-Robles MT, Rodríguez-Hernández H. Approach to the patient with cholestasis and jaundice syndrome. Joint AMH, AMG, and AMEG scientific position statement. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2022; 87:80-88. [PMID: 34866042 DOI: 10.1016/j.rgmx.2021.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 04/14/2021] [Indexed: 04/21/2025]
Abstract
The term cholestasis refers to bile acid retention, whether within the hepatocyte or in the bile ducts of any caliber. Biochemically, it is defined by a level of alkaline phosphatase that is 1.67-times higher than the upper limit of normal. Cholestatic diseases can be associated with an inflammatory process of the liver that destroys hepatocytes (hepatitis), withjaundice (yellowing of the skin and mucus membranes, associated with elevated serum bilirubin levels), or with both, albeit the three concepts should not be considered synonymous. Cholestatic diseases can be classified as intrahepatic or extrahepatic, depending on their etiology. Knowing the cause of the condition is important for choosing the adequate diagnostic studies and appropriate treatment in each case. A complete medical history, together with a thorough physical examination and basic initial studies, such as liver ultrasound and liver function tests, aid the clinician in deciding which path to follow, when managing the patient with cholestasis. In a joint effort, the Asociación Mexicana de Hepatología (AMH), the Asociación Mexicana de Gastroenterología (AMG) and the Asociación Mexicana de Endoscopia Gastrointestinal (AMEG) developed the first Mexican scientific position statement on said theme.
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Affiliation(s)
- R Contreras-Omaña
- Centro de Estudio e Investigación en Enfermedades Hepáticas (CEIHE), Pachuca, Hidalgo, Mexico.
| | | | | | | | | | | | - L Muñoz-Espinosa
- Centro de Hepatología, Departamento de Medicina Interna, Hospital Universitario "Dr. José E. González", Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
| | - I Aiza-Haddad
- Clínica de Enfermedades Hepáticas, Hospital Ángeles Lomas, Mexico City, Mexico
| | - M Castillo-Barradas
- Hospital de Especialidades CMN La Raza, IMSS Hospital Ángeles Lindavista, Mexico City, Mexico
| | | | | | - J Flores-Calderón
- Servicio de Gastropediatría, UMAE Hospital de Pediatría CMN Siglo XXI IMSS, Mexico City, Mexico
| | - E S García-Jiménez
- Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara, Jalisco, Mexico
| | - M F Higuera-de-la-Tijera
- Servicio de Gastroenterología, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico
| | - M A Lira-Pedrín
- Hospital Centro Médico del Prado, Tijuana, Baja California, Mexico
| | | | | | | | - S G Noyola-Cedillo
- Centro Médico del Noreste, Clínica 25 IMSS, Monterrey, Nuevo León, Hospital Ángeles Torreón, Coahuila, Mexico
| | - J L Pérez-Hernández
- Hospital Central Sur de Alta Especialidad Petróleos Mexicanos, Mexico City, Mexico
| | - M V Ramos-Gómez
- Servicio de Gastroenterología, CMN 20 de Noviembre, ISSSTE Mexico City, Mexico
| | - J M Remes-Troche
- Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - M T Rizo-Robles
- UMAE Hospital de Especialidades CMN La Raza IMSS, Mexico City, Mexico
| | - H Rodríguez-Hernández
- Facultad de Medicina y Nutrición, Universidad Juárez del Estado de Durango, Durango, Mexico
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7
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Contreras-Omaña R, Velarde-Ruiz Velasco JA, Castro-Narro GE, Trujillo-Benavides O, Zamarripa-Dorsey F, Reyes-Dorantes AA, Muñoz-Espinosa L, Aiza-Haddad I, Castillo-Barradas M, Cerda-Reyes E, Cisneros-Garza LE, Flores-Calderón J, García-Jiménez ES, Higuera-de-la-Tijera MF, Lira-Pedrín MA, Marquez-Guillén E, Moctezuma-Velázquez C, Moreno-Alcántar R, Noyola-Cedillo SG, Pérez-Hernández JL, Ramos-Gómez MV, Remes-Troche JM, Rizo-Robles MT, Rodríguez-Hernández H. Approach to the patient with cholestasis and jaundice syndrome. Joint AMH, AMG, and AMEG scientific position statement. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2021; 87:80-88. [PMID: 34866042 DOI: 10.1016/j.rgmxen.2021.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 04/14/2021] [Indexed: 11/17/2022]
Abstract
The term cholestasis refers to bile acid retention, whether within the hepatocyte or in the bile ducts of any caliber. Biochemically, it is defined by a level of alkaline phosphatase that is 1.67-times higher than the upper limit of normal. Cholestatic diseases can be associated with an inflammatory process of the liver that destroys hepatocytes (hepatitis), withjaundice (yellowing of the skin and mucus membranes, associated with elevated serum bilirubin levels), or with both, albeit the three concepts should not be considered synonymous. Cholestatic diseases can be classified as intrahepatic or extrahepatic, depending on their etiology. Knowing the cause of the condition is important for choosing the adequate diagnostic studies and appropriate treatment in each case. A complete medical history, together with a thorough physical examination and basic initial studies, such as liver ultrasound and liver function tests, aid the clinician in deciding which path to follow, when managing the patient with cholestasis. In a joint effort, the Asociación Mexicana de Hepatología (AMH), the Asociación Mexicana de Gastroenterología (AMG) and the Asociación Mexicana de Endoscopia Gastrointestinal (AMEG) developed the first Mexican scientific position statement on said theme.
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Affiliation(s)
- R Contreras-Omaña
- Centro de Estudio e Investigación en Enfermedades Hepáticas (CEIHE), Pachuca, Hidalgo, Mexico.
| | | | | | | | | | | | - L Muñoz-Espinosa
- Centro de Hepatología, Departamento de Medicina Interna, Hospital Universitario "Dr. José E. González", Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
| | - I Aiza-Haddad
- Clínica de Enfermedades Hepáticas, Hospital Ángeles Lomas, Mexico City, Mexico
| | - M Castillo-Barradas
- Hospital de Especialidades CMN La Raza, IMSS Hospital Ángeles Lindavista, Mexico City, Mexico
| | | | | | - J Flores-Calderón
- Servicio de Gastropediatría, UMAE Hospital de Pediatría CMN Siglo XXI IMSS, Mexico City, Mexico
| | - E S García-Jiménez
- Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara, Jalisco, Mexico
| | - M F Higuera-de-la-Tijera
- Servicio de Gastroenterología, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico
| | - M A Lira-Pedrín
- Hospital Centro Médico del Prado, Tijuana, Baja California, Mexico
| | | | | | | | - S G Noyola-Cedillo
- Centro Médico del Noreste, Clínica 25 IMSS, Monterrey, Nuevo León, Hospital Ángeles Torreón, Coahuila, Mexico
| | - J L Pérez-Hernández
- Hospital Central Sur de Alta Especialidad Petróleos Mexicanos, Mexico City, Mexico
| | - M V Ramos-Gómez
- Servicio de Gastroenterología, CMN 20 de Noviembre, ISSSTE Mexico City, Mexico
| | - J M Remes-Troche
- Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - M T Rizo-Robles
- UMAE Hospital de Especialidades CMN La Raza IMSS, Mexico City, Mexico
| | - H Rodríguez-Hernández
- Facultad de Medicina y Nutrición, Universidad Juárez del Estado de Durango, Durango, Mexico
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8
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Xu XY, Ding HG, Li WG, Xu JH, Han Y, Jia JD, Wei L, Duan ZP, Ling-Hu EQ, Zhuang H. Chinese guidelines on the management of liver cirrhosis (abbreviated version). World J Gastroenterol 2020; 26:7088-7103. [PMID: 33362370 PMCID: PMC7723671 DOI: 10.3748/wjg.v26.i45.7088] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 06/03/2020] [Accepted: 11/12/2020] [Indexed: 02/06/2023] Open
Abstract
Based on reviews of the literature and experts' consensus, the Chinese Society of Hepatology developed guidelines for the diagnosis and treatment of liver cirrhosis, in order to improve clinical practice. In addition to what has been covered in previously published guidelines on the management of cirrhosis complications, these guidelines add new sections and provide updates. The guidelines emphasize the early diagnosis of the cause and assessment of complications. Comprehensive treatments including etiological treatment and complication management should be initiated immediately. In addition, regular monitoring, especially surveillance of hepatocellular carcinoma, is crucial for managing patients.
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Affiliation(s)
- Xiao-Yuan Xu
- Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
| | - Hui-Guo Ding
- Hepatology and Digestion Center, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China
| | - Wen-Gang Li
- Department of Liver Oncology, Cancer Radiation Therapy Center, Fifth Medical Center, PLA General Hospital, Beijing 100039, China
| | - Jing-Hang Xu
- Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
| | - Ying Han
- Department of Immunology and Liver Diseases, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China
| | - Ji-Dong Jia
- Hepatology Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Lai Wei
- Internal Medicine of Hepatopancreatobiliary, Beijing Tsinghua Changgung Hospital, Beijing 102218, China
| | - Zhong-Ping Duan
- Artificial Liver Center, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China
| | - En-Qiang Ling-Hu
- Department of Gastroenterology, First Medical Center, PLA General Hospital, Beijing 100853, China
| | - Hui Zhuang
- Department of Pathogenic Biology, Peking University Health Science Center, Beijing 100191, China
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9
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Danford CJ, Ezaz G, Trivedi HD, Tapper EB, Bonder A. The Pharmacologic Management of Osteoporosis in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis. J Clin Densitom 2020; 23:223-236. [PMID: 31146965 DOI: 10.1016/j.jocd.2019.05.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 05/06/2019] [Accepted: 05/07/2019] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Osteoporosis is a common complication of primary biliary cholangitis (PBC) yet evidence for effective therapy is lacking. We sought to review all randomized controlled trials evaluating pharmacotherapy against placebo or no intervention for treatment of osteoporosis in PBC. METHODOLOGY A comprehensive database search was conducted from inception through 29 March 2017. The primary outcome was incidence of fractures; secondary outcomes were change in bone mineral density (BMD) and adverse events. We assessed studies for risk of bias, graded quality of evidence, and used meta-analysis to obtain overall effect by pooling studies of the same drug class. RESULTS We identified 11 randomized controlled trials evaluating bisphosphonates (3), hormone replacement therapy (2), ursodeoxycholic acid (1), obeticholic acid (1), cyclosporin A (1), vitamin K (1), calcitriol (1), and sodium fluoride (1). No intervention significantly reduced fractures compared to control. Although significant improvement in BMD was seen in one study with alendronate, a third-generation bisphosphonate, no significant improvement was seen on pooled analysis of all bisphosphonates including first-generation bisphosphonates (standard mean difference 0.41, p = 0.68). On pooled analysis, hormone replacement therapy modestly improved lumbar BMD (standard mean difference 0.69, p = 0.02), but with significantly increased adverse events (odds ratio 8.82, p = 0.01). CONCLUSIONS There is a lack of high-quality evidence supporting the efficacy of any treatment of osteoporosis in PBC. This may be explained by lack of power in the included studies. However, our current understanding of PBC-related osteoporosis indicates that it results from decreased bone formation, which may explain the attenuated effect of traditional antiresorptive agents. Future studies should investigate newer anabolic bone agents.
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Affiliation(s)
- Christopher J Danford
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Ghideon Ezaz
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Hirsh D Trivedi
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Elliot B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Alan Bonder
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
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10
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Danford CJ, Trivedi HD, Bonder A. Bone Health in Patients With Liver Diseases. J Clin Densitom 2020; 23:212-222. [PMID: 30744928 DOI: 10.1016/j.jocd.2019.01.004] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 01/15/2019] [Accepted: 01/15/2019] [Indexed: 12/19/2022]
Abstract
Osteoporosis is the most common bone disease in chronic liver disease (CLD) resulting in frequent fractures and leading to significant morbidity in this population. In addition to patients with cirrhosis and chronic cholestasis, patients with CLD from other etiologies may be affected in the absence of cirrhosis. The mechanism of osteoporosis in CLD varies according to etiology, but in cirrhosis and cholestatic liver disease it is driven primarily by decreased bone formation, which differs from the increased bone resorption seen in postmenopausal osteoporosis. Direct toxic effects from iron and alcohol play a role in hemochromatosis and alcoholic liver disease, respectively. Chronic inflammation also has been proposed to mediate bone disease in viral hepatitis and nonalcoholic fatty liver disease. Treatment trials specific to osteoporosis in CLD are small, confined to primary biliary cholangitis and post-transplant patients, and have not consistently demonstrated a benefit in this population. As it stands, prevention of osteoporosis in CLD relies on the mitigation of risk factors such as smoking and alcohol use, treatment of underlying hypogonadism, and encouraging a healthy diet and weight-bearing exercise. The primary medical intervention for the treatment of osteoporosis in CLD remains bisphosphonates though a benefit in terms of fracture reduction has never been shown. This review outlines what is known regarding the pathogenesis of bone disease in CLD and summarizes current and emerging therapies.
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Affiliation(s)
- Christopher J Danford
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA USA
| | - Hirsh D Trivedi
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA USA
| | - Alan Bonder
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA USA.
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11
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Trivedi HD, Danford CJ, Goyes D, Bonder A. Osteoporosis in Primary Biliary Cholangitis: Prevalence, Impact and Management Challenges. Clin Exp Gastroenterol 2020; 13:17-24. [PMID: 32021374 PMCID: PMC6970242 DOI: 10.2147/ceg.s204638] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Accepted: 12/31/2019] [Indexed: 12/11/2022] Open
Abstract
Primary biliary cholangitis (PBC) is a chronic, cholestatic condition associated with symptoms that directly impact the quality of life in those afflicted with the disease. In addition to pruritus and fatigue, patients with PBC may develop metabolic bone disease from reduced bone density, such as osteopenia and osteoporosis. Osteoporosis increases the risk of fractures, as well as morbidity and mortality. The prevalence of osteoporosis in PBC is expected to increase in conjunction with the rising prevalence of PBC as a whole. Timely diagnosis, prevention and management of osteoporosis are crucial in order to optimize the quality of life. There is a paucity of data evaluating the management of osteoporosis in PBC. The optimal timing for diagnosis and monitoring is not yet established and is guided by expert opinion. National guidelines recommend screening for osteoporosis at the time of diagnosis of PBC. Monitoring strategies are based on results of initial screening and individual risk factors for bone disease. Identifying reduced bone density is imperative to institute timely preventive and treatment strategies. However, treatment remains challenging as efficacious therapies are currently lacking. The data on treatment of osteoporosis in PBC are mostly extrapolated from postmenopausal osteoporosis literature. However, this data has not directly translated to useful treatment strategies for PBC-related osteoporosis, partly because of the different pathophysiological mechanisms of the two diseases. The lack of useful preventive measures and efficacious treatment strategies remains the largest pitfall that challenges the management of patients with PBC. In this review, we comprehensively outline the epidemiology, clinical implications and challenges, as well as management strategies of PBC-related osteoporosis.
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Affiliation(s)
- Hirsh D Trivedi
- Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Christopher J Danford
- Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Daniela Goyes
- Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Alan Bonder
- Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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12
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Suri J, Patwardhan V, Bonder A. Pharmacologic management of primary sclerosing cholangitis: what's in the pipeline? Expert Rev Gastroenterol Hepatol 2019; 13:723-729. [PMID: 31257956 DOI: 10.1080/17474124.2019.1636647] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Introduction: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by biliary inflammation, fibrosis, and stricturing. Although considered progressive, its course is difficult to predict, and there is currently no definitive therapy shown to alter disease course and prevent death or the need for liver transplantation. Areas covered: There are multiple agents in the pipeline targeting various pathways hypothesized to lead to and drive this disease. Some are already used for other treatment indications, including antibiotics such as oral vancomycin, metronidazole, and minocycline. Other agents including obeticholic acid, nor-ursodeoxycholic acid, and monoclonal antibodies are also under investigation. This narrative review focuses on the most recent published clinical trials available for discussion. We attempt to summarize the data on current and future treatment options. Expert opinion: The rarity of this condition and poor understanding of its pathophysiology have created a void for safe and effective treatment options to alter mortality or transplant free survival. Nevertheless, some agents currently being tested have demonstrated therapeutic potential. We await validation and prospective data on these agents in hopes of modifying the disease course for patients in the future.
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Affiliation(s)
- Jaspreet Suri
- a Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA
| | - Vilas Patwardhan
- a Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA
| | - Alan Bonder
- a Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA
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13
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Abstract
Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune disease with a variable progressive course. PBC can cause debilitating symptoms including fatigue and pruritus and, if left untreated, is associated with a high risk of cirrhosis and related complications, liver failure, and death. Recent changes to the PBC landscape include a name change, updated guidelines for diagnosis and treatment as well as new treatment options that have recently become available. Practicing clinicians face many unanswered questions when managing PBC. To assist these healthcare providers in managing patients with PBC, the American College of Gastroenterology (ACG) Institute for Clinical Research & Education, in collaboration with the Chronic Liver Disease Foundation (CLDF), organized a panel of experts to evaluate and summarize the most current and relevant peer-reviewed literature regarding PBC. This, combined with the extensive experience and clinical expertise of this expert panel, led to the formation of this clinical guidance on the diagnosis and management of PBC.
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14
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Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology 2019; 69:394-419. [PMID: 30070375 DOI: 10.1002/hep.30145] [Citation(s) in RCA: 394] [Impact Index Per Article: 65.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 05/30/2018] [Indexed: 02/06/2023]
Affiliation(s)
- Keith D Lindor
- Arizona State University, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ
| | | | | | | | - Marlyn Mayo
- University of Texas Southwestern Medical Center, Dallas, TX
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15
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Merli M, Berzigotti A, Zelber-Sagi S, Dasarathy S, Montagnese S, Genton L, Plauth M, Parés A. EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol 2019; 70:172-193. [PMID: 30144956 PMCID: PMC6657019 DOI: 10.1016/j.jhep.2018.06.024] [Citation(s) in RCA: 650] [Impact Index Per Article: 108.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 06/28/2018] [Indexed: 12/11/2022]
Abstract
A frequent complication in liver cirrhosis is malnutrition, which is associated with the progression of liver failure, and with a higher rate of complications including infections, hepatic encephalopathy and ascites. In recent years, the rising prevalence of obesity has led to an increase in the number of cirrhosis cases related to non-alcoholic steatohepatitis. Malnutrition, obesity and sarcopenic obesity may worsen the prognosis of patients with liver cirrhosis and lower their survival. Nutritional monitoring and intervention is therefore crucial in chronic liver disease. These Clinical Practice Guidelines review the present knowledge in the field of nutrition in chronic liver disease and promote further research on this topic. Screening, assessment and principles of nutritional management are examined, with recommendations provided in specific settings such as hepatic encephalopathy, cirrhotic patients with bone disease, patients undergoing liver surgery or transplantation and critically ill cirrhotic patients.
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16
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Hirschfield GM, Dyson JK, Alexander GJM, Chapman MH, Collier J, Hübscher S, Patanwala I, Pereira SP, Thain C, Thorburn D, Tiniakos D, Walmsley M, Webster G, Jones DEJ. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut 2018; 67:1568-1594. [PMID: 29593060 PMCID: PMC6109281 DOI: 10.1136/gutjnl-2017-315259] [Citation(s) in RCA: 213] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Revised: 01/22/2018] [Accepted: 01/23/2018] [Indexed: 12/12/2022]
Abstract
Primary biliary cholangitis (formerly known as primary biliary cirrhosis, PBC) is an autoimmune liver disease in which a cycle of immune mediated biliary epithelial cell injury, cholestasis and progressive fibrosis can culminate over time in an end-stage biliary cirrhosis. Both genetic and environmental influences are presumed relevant to disease initiation. PBC is most prevalent in women and those over the age of 50, but a spectrum of disease is recognised in adult patients globally; male sex, younger age at onset (<45) and advanced disease at presentation are baseline predictors of poorer outcome. As the disease is increasingly diagnosed through the combination of cholestatic serum liver tests and the presence of antimitochondrial antibodies, most presenting patients are not cirrhotic and the term cholangitis is more accurate. Disease course is frequently accompanied by symptoms that can be burdensome for patients, and management of patients with PBC must address, in a life-long manner, both disease progression and symptom burden. Licensed therapies include ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), alongside experimental new and re-purposed agents. Disease management focuses on initiation of UDCA for all patients and risk stratification based on baseline and on-treatment factors, including in particular the response to treatment. Those intolerant of treatment with UDCA or those with high-risk disease as evidenced by UDCA treatment failure (frequently reflected in trial and clinical practice as an alkaline phosphatase >1.67 × upper limit of normal and/or elevated bilirubin) should be considered for second-line therapy, of which OCA is the only currently licensed National Institute for Health and Care Excellence recommended agent. Follow-up of patients is life-long and must address treatment of the disease and management of associated symptoms.
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Affiliation(s)
- Gideon M Hirschfield
- NIHR Birmingham Biomedical Research Centre, Birmingham, UK
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Jessica K Dyson
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
- NIHR Newcastle Biomedical Research Centre, Newcastle, United Kingdom
| | - Graeme J M Alexander
- Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK
| | - Michael H Chapman
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Jane Collier
- Translational Gastroenterology Unit, Oxford University Hospitals, University of Oxford, Oxford, UK
| | - Stefan Hübscher
- Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Imran Patanwala
- Department of Gastroenterology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
- University of Liverpool, Liverpool, UK
| | - Stephen P Pereira
- Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | | | - Douglas Thorburn
- Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK
| | - Dina Tiniakos
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | | | - George Webster
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - David E J Jones
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
- NIHR Newcastle Biomedical Research Centre, Newcastle, United Kingdom
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17
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Parvaneh M, Karimi G, Jamaluddin R, Ng MH, Zuriati I, Muhammad SI. Lactobacillus helveticus (ATCC 27558) upregulates Runx2 and Bmp2 and modulates bone mineral density in ovariectomy-induced bone loss rats. Clin Interv Aging 2018; 13:1555-1564. [PMID: 30214175 PMCID: PMC6121767 DOI: 10.2147/cia.s169223] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Purpose Osteoporosis is one of the major health concerns among the elderly population, especially in postmenopausal women. Many menopausal women over 50 years of age lose their bone density and suffer bone fractures. In addition, many mortality and morbidity cases among the elderly are related to hip fracture. This study aims to investigate the effect of Lactobacillus helveticus (L. helveticus) on bone health status among ovariectomized (OVX) bone loss-induced rats. Methods The rats were either OVX or sham OVX (sham), then were randomly assigned into three groups, G1: sham, G2: OVX and G3: OVX+L. helveticus (1 mL of 108–109 colony forming units). The supplementation was force-fed to the rats once a day for 16 weeks while control groups were force-fed with demineralized water. Results L. helveticus upregulated the expression of Runx2 and Bmp2, increased serum osteocalcin, bone volume/total volume and trabecular thickness, and decreased serum C-terminal telopeptide and total porosity percentage. It also altered bone microstructure, as a result increasing bone mineral density and bone strength. Conclusion Our results indicate that L. helveticus attenuates bone remodeling and consequently improves bone health in OVX rats by increasing bone formation along with bone resorption reduction. This study suggests a potential therapeutic effect of L. helveticus (ATCC 27558) on postmenopausal osteoporosis.
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Affiliation(s)
- Maria Parvaneh
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia, .,Discipline of Life Science, School of Dentistry, Faculty of Medicine and Health, The University of Sydney, Charles Perkin Centre, Sydney, NSW, Australia
| | - Golgis Karimi
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia, .,Department of Social and Preventive Medicine, Faculty of Medicine, Julius Centre University of Malaya (JCUM), University of Malaya, Kuala Lumpur, Malaysia
| | - Rosita Jamaluddin
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia,
| | - Min Hwei Ng
- Faculty of Medicine, Tissue Engineering Center, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Ibrahim Zuriati
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia,
| | - Sani Ismaila Muhammad
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University Sokoto, Sokoto, Nigeria
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18
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Danford CJ, Trivedi HD, Papamichael K, Tapper EB, Bonder A. Osteoporosis in primary biliary cholangitis. World J Gastroenterol 2018; 24:3513-3520. [PMID: 30131657 PMCID: PMC6102495 DOI: 10.3748/wjg.v24.i31.3513] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 07/11/2018] [Accepted: 07/21/2018] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease with multiple debilitating complications. Osteoporosis is a common complication of PBC resulting in frequent fractures and leading to significant morbidity in this population, yet evidence for effective therapy is lacking. We sought to summarize our current understanding of the pathophysiology of osteoporosis in PBC, as well as current and emerging therapies in order to guide future research directions. A complete search with a comprehensive literature review was performed with studies from PubMed, EMBASE, Web of Science, Cochrane database, and the Countway Library. Osteoporosis in PBC is driven primarily by decreased bone formation, which differs from the increased bone resorption seen in postmenopausal osteoporosis. Despite this fundamental difference, current treatment recommendations are based primarily on experience with postmenopausal osteoporosis. Trials specific to PBC-related osteoporosis are small and have not consistently demonstrated a benefit in this population. As it stands, prevention of osteoporosis in PBC relies on the mitigation of risk factors such as smoking and alcohol use, as well as encouraging a healthy diet and weight-bearing exercise. The primary medical intervention for the treatment of osteoporosis in PBC remains bisphosphonates though a benefit in terms of fracture reduction has never been shown. This review outlines what is known regarding the pathogenesis of bone disease in PBC and summarizes current and emerging therapies.
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Affiliation(s)
- Christopher J Danford
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, Unites States
| | - Hirsh D Trivedi
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, Unites States
| | - Konstantinos Papamichael
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, Unites States
| | - Elliot B Tapper
- Department of Hepatology, University of Michigan, Ann Arbor, MI 48109, Unites States
| | - Alan Bonder
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, Unites States
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Abstract
Primary biliary cholangitis is a progressive, autoimmune disease of the interlobular bile ducts, leading to secondary damage of hepatocytes that may progress to cirrhosis and liver failure. Until recently, the only approved treatment was ursodeoxycholic acid. However, 40% of patients do not have an adequate response. Obeticholic acid was approved for treatment as add-on therapy in this group of patients. Off-label use of fibrates has also been reported to be effective. Several new therapies are in development and may further add to the treatment options available to patients with primary biliary cholangitis.
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Affiliation(s)
- Kimberly A Wong
- Department of Internal Medicine, UC Davis School of Medicine, 4150 V Street, PSSB 3000, Sacramento, CA 95817, USA
| | - Runalia Bahar
- Department of Internal Medicine, UC Davis School of Medicine, 4150 V Street, PSSB 3000, Sacramento, CA 95817, USA
| | - Chung H Liu
- Division of Gastroenterology and Hepatology, UC Davis School of Medicine, 4150 V Street, PSSB 3500, Sacramento, CA 95817, USA
| | - Christopher L Bowlus
- Division of Gastroenterology and Hepatology, UC Davis School of Medicine, 4150 V Street, PSSB 3500, Sacramento, CA 95817, USA.
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20
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Parés A, Guañabens N. Primary biliary cholangitis and bone disease. Best Pract Res Clin Gastroenterol 2018; 34-35:63-70. [PMID: 30343712 DOI: 10.1016/j.bpg.2018.06.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Accepted: 06/08/2018] [Indexed: 01/31/2023]
Abstract
Osteoporosis, characterized by compromised bone strength leading to fragility fractures, is a common event in patients with primary biliary cholangitis (PBC). Osteomalacia, defined by poor bone mineralization is very uncommon. The pathogenesis of osteoporosis is not well clarified, but it mainly results from low bone formation. Few reports have revealed increased bone resorption, particularly in end-stage disease. The prevalence of osteoporosis is about 35% in the most significant studies, and it depends on the diagnostic criteria and severity of liver damage. Osteoporosis is associated with age, postmenopausal status, duration of PBC and advanced histological stage. Bone densitometry is the common method for the diagnosis of osteoporosis and should be performed in all patients with PBC. Lateral X-rays of the dorsal and lumbar spine should also be carried out to disclose vertebral fractures. There is no specific treatment but bisphosphonates, especially alendronate and ibandronate, efficiently increases bone mass and prevents bone loss. Despite these positive effects on bone mass no clear results on decreasing the fracture rate have been demonstrated, probably because the low number of patients included in the trials. The potential value of new agents requires further evaluation.
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Affiliation(s)
- Albert Parés
- Liver Unit, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
| | - Núria Guañabens
- Department of Rheumatology, Metabolic Bone Diseases Unit, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
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21
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Guañabens N, Parés A. Osteoporosis in chronic liver disease. Liver Int 2018; 38:776-785. [PMID: 29479832 DOI: 10.1111/liv.13730] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 02/19/2018] [Indexed: 12/15/2022]
Abstract
Osteoporosis is a frequent complication in patients with chronic liver disease, especially in end-stages and in chronic cholestasis, in addition to non-alcoholic fatty liver disease, haemochromatosis and alcoholism. Mechanisms underlying osteoporosis are poorly understood, but osteoporosis mainly results from low bone formation. In this setting, sclerostin, a key regulator of the Wnt/β-catenin signalling pathway which regulates bone formation, in addition to the effects of the retained substances of cholestasis such as bilirubin and bile acids on osteoblastic cells, may influence the decreased bone formation in chronic cholestasis. Similarly, the damaging effects of iron and alcohol on osteoblastic cells may partially explain bone disease in haemochromatosis and alcoholism. A role for proinflammatory cytokines has been proposed in different conditions. Increased bone resorption may occur in cholestatic women with advanced disease. Low vitamin D, poor nutrition and hypogonadism, may be contributing factors to the full picture of bone disorders in chronic liver disease.
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Affiliation(s)
- Núria Guañabens
- Metabolic Bone Diseases Unit, Department of Rheumatology, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | - Albert Parés
- Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
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22
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Zakharia K, Tabibian A, Lindor KD, Tabibian JH. Complications, symptoms, quality of life and pregnancy in cholestatic liver disease. Liver Int 2018; 38:399-411. [PMID: 28921801 DOI: 10.1111/liv.13591] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 09/12/2017] [Indexed: 12/11/2022]
Abstract
Cholestatic liver diseases (CLDs) encompass a variety of disorders of bile formation and/or flow which generally result in progressive hepatobiliary injury and ultimately end-stage liver disease. Many patients with CLD are diagnosed between the ages of 20-50 years, a particularly productive period of life professionally, biologically and in other respects; it is not surprising, thus, that CLD is often associated with impaired health-related quality of life (HRQOL) and uncertainty regarding implications for and outcomes of pregnancy. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most prominent CLDs, both having considerable morbidity and mortality and representing major indications for liver transplantation. These disorders, as a consequence of their complications (eg ascites, hepatic osteodystrophy), associated conditions (eg inflammatory bowel disease) and symptoms (eg pruritus and fatigue), can significantly impair an array of domains of HRQOL. Here we review these impactful clinical aspects of PSC and PBC as well as the topics of fertility and pregnancy.
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Affiliation(s)
- Kais Zakharia
- Internal Medicine Residency Program, Beaumont Health - Dearborn, Dearborn, MI, USA
| | - Anilga Tabibian
- Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA
| | - Keith D Lindor
- Arizona State University, Phoenix, AZ, USA
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
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Association between primary biliary cholangitis and osteoporosis: meta-analysis. Clin Rheumatol 2017; 36:2565-2571. [PMID: 28948408 DOI: 10.1007/s10067-017-3844-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2017] [Revised: 09/04/2017] [Accepted: 09/13/2017] [Indexed: 12/31/2022]
Abstract
The relationship between primary biliary cholangitis (PBC, previously termed primary biliary cirrhosis) and risks of osteoporosis remains controversial. This meta-analysis was designed to comprehensively analyze the association between PBC and osteoporosis. We conducted a systematic literature search of the PubMed, EMBASE, and Web of Science. Either fixed or random effects models were applied to assess bone mineral density (BMD), osteoporosis rates, and fractures in PBC patients and normal controls. A total of eight studies were included (including 1643 PBC patients and 10,921 controls). PBC patients had a relative risk (RR) of 2.79 (95% CI 1.26 to 6.16) for the development of osteoporosis, lower lumbar spine BMD (95% CI - 0.13 to - 0.04, P = 0.0002), hip BMD (95% CI - 0.13 to - 0.03, P = 0.002), and lumbar spine t score (95% CI - 1.69 to - 1.02, P < 0.00001) than controls. Moreover, PBC patients had an OR of 1.86 (95%CI 1.54 to 2.24, P < 0.00001) for the development of fractures. Collectively, this meta-analysis indicates that PBC patients were more likely to suffer from osteoporosis. Given the limited literature available, better designed and larger scale primary studies will be required to confirm our conclusion.
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24
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Seki A, Ikeda F, Miyatake H, Takaguchi K, Hayashi S, Osawa T, Fujioka SI, Tanaka R, Ando M, Seki H, Iwasaki Y, Yamamoto K, Okada H. Risk of secondary osteoporosis due to lobular cholestasis in non-cirrhotic primary biliary cholangitis. J Gastroenterol Hepatol 2017; 32:1611-1616. [PMID: 28114749 DOI: 10.1111/jgh.13746] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Revised: 12/28/2016] [Accepted: 01/18/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM It remains unclear whether primary biliary cholangitis (PBC) represents a risk factor for secondary osteoporosis. METHODS A case-control study was conducted to examine bone mineral density and bone turnover markers in middle-aged postmenopausal PBC patients without liver cirrhosis. We compared the incidence of low bone mineral density between propensity-score matched subgroups of PBC patients and healthy controls and investigated the mechanisms underlying unbalanced bone turnover in terms of the associations between bone turnover markers and PBC-specific histological findings. RESULT Our analysis included 128 consecutive PBC patients, all postmenopausal women aged in their 50s or 60s, without liver cirrhosis or fragility fracture at the time of PBC diagnosis. The prevalence of osteoporosis was significantly higher in the PBC group than in the control group (26% vs 10%, P = 0.015, the Fisher exact probability test). In most PBC patients (95%), the level of bone-specific alkaline phosphatase was above the normal range, indicating increased bone formation. On the other hand, the urine type I collagen-cross-linked N-telopeptide showed variable levels among our PBC patients, indicating unbalanced bone resorption. Advanced fibrosis was associated with low bone turnover. Lobular cholestasis, evaluated as aberrant keratin 7 expression in hepatocytes, showed significant negative correlations with bone formation and resorption, indicating low bone turnover. CONCLUSION Our results show that, compared with healthy controls, even non-cirrhotic PBC patients have significantly higher risk of osteoporosis. Moreover, lobular cholestasis was associated with low bone turnover, suggesting this feature of PBC may itself cause secondary osteoporosis in PBC patients.
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Affiliation(s)
- Anna Seki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Fusao Ikeda
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hirokazu Miyatake
- Department of Internal Medicine, Hiroshima City Hospital, Hiroshima, Japan
| | - Koichi Takaguchi
- Department of Internal Medicine, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Shosaku Hayashi
- Department of Internal Medicine, Ritsurin General Hospital, Takamatsu, Japan
| | - Toshiya Osawa
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Shin-Ichi Fujioka
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Ryoji Tanaka
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Masaharu Ando
- Department of Internal Medicine, Mitoyo General Hospital, Kanonji, Japan
| | - Hiroyuki Seki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Yoshiaki Iwasaki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Kazuhide Yamamoto
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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25
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Diagnosis and Management of Cirrhosis-Related Osteoporosis. BIOMED RESEARCH INTERNATIONAL 2016; 2016:1423462. [PMID: 27840821 PMCID: PMC5093239 DOI: 10.1155/2016/1423462] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/09/2016] [Accepted: 10/03/2016] [Indexed: 12/20/2022]
Abstract
Management of cirrhosis complications has greatly improved, increasing survival and quality of life of the patients. Despite that, some of these complications are still overlooked and scarcely treated, particularly those that are not related to the liver. This is the case of osteoporosis, the only cirrhosis complication that is not solved after liver transplantation, because bone loss often increases after immunosuppressant therapy. In this review, the definitions of bone conditions in cirrhotic patients are analyzed, focusing on the more common ones and on those that have the largest impact on this population. Risk factors, physiopathology, diagnosis, screening strategies, and treatment of osteoporosis in cirrhotic patients are discussed, presenting the more striking data on this issue. Therapies used for particular conditions, such as primary biliary cirrhosis and liver transplantation, are also presented.
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26
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Omori K, Yoshida K, Yokota M, Daa T, Kan M. Familial occurrence of autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis in a mother and her daughter. Clin J Gastroenterol 2016; 9:312-8. [PMID: 27503128 PMCID: PMC5035326 DOI: 10.1007/s12328-016-0676-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2016] [Accepted: 07/22/2016] [Indexed: 01/03/2023]
Abstract
We encountered two patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family. A 68-year-old woman presented at our hospital from a previous medical institution because of the diagnosis of primary biliary cholangitis. Her 49-year-old daughter was admitted with liver dysfunction 4 years later. When compared, these two related patients were found to have overlapping features of primary biliary cholangitis and autoimmune hepatitis. Their human leukocyte antigen haplotype was DRB1*04:05/DRB1*15:02. The clinical and biochemical findings of these two patients immediately improved following treatment with a combination of prednisolone and ursodeoxycholic acid, in accordance with the Japanese guidelines. It is extremely important to identify such pathological conditions as quickly as possible, particularly with the appearance of severe liver dysfunction due to liver cirrhosis, as observed in our case. The Japanese guidelines are considered to be a realistic and useful clinical policy for the swift and efficient treatment of patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis. We suggest that our two patients presented with a genetic predisposition to autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family.
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Affiliation(s)
- Kaoru Omori
- Department of Gastroenterology and Hepatology, Sato Daiichi Hospital, 77-1 Hokyoji, Usa, Oita, 879-0454, Japan.
| | - Kanako Yoshida
- Department of Gastroenterology and Hepatology, Sato Daiichi Hospital, 77-1 Hokyoji, Usa, Oita, 879-0454, Japan
| | - Masaki Yokota
- Department of Gastroenterology, Nakatsu Municipal Hospital, 173 Shimo-Ikenaga, Nakatsu, Oita, 871-8511, Japan
| | - Tsutomu Daa
- Department of Pathology, Graduate School of Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan
| | - Masahiro Kan
- Department of Gastroenterology and Hepatology, Sato Daiichi Hospital, 77-1 Hokyoji, Usa, Oita, 879-0454, Japan
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27
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Guarino M, Loperto I, Camera S, Cossiga V, Di Somma C, Colao A, Caporaso N, Morisco F. Osteoporosis across chronic liver disease. Osteoporos Int 2016; 27:1967-77. [PMID: 26846777 DOI: 10.1007/s00198-016-3512-z] [Citation(s) in RCA: 30] [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: 06/25/2015] [Accepted: 01/29/2016] [Indexed: 02/06/2023]
Abstract
Osteoporosis is a complication of chronic liver disease, with impact on morbidity, quality of life, and survival. The progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with liver disease. So, it is fundamental to make better the quality of life and to prevent complications. Metabolic bone disorders are common complications of chronic liver disease (CLD). Patients with CLD have an increased risk of bone fractures, with significant impact on morbidity, quality of life, and even on survival. Bone diseases, including osteomalacia, osteoporosis, and osteopenia, are frequently observed in many types of liver disease. The pathogenesis of damage and the mechanisms of bone loss are different in relation to the specific liver disease. The relevance of these conditions induced many authors to create a new nosographic entity known as "hepatic osteodystrophy", although this term is rarely used anymore and it is now commonly referred to as osteopenia or osteoporosis associated with chronic liver disease. This review is based on the personal experiences of the authors and upon research done of the available literature on this subject matter. The authors searched the PubMed database for publications containing the term "liver disease" in combination with "bone disease", "hepatic osteodistrophy", "osteoporosis", "osteopenia", "osteomalacia", and "fractures". They selected publications from the past 10 years but did not exclude older seminal publications, especially for colestatic liver diseases. This review of literature shows that osteoporosis crosses all CLD. It is important to underline that the progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with CLD. It is fundamental to make better the quality of life and it is mandatory to prevent complications and in particular the osteoporotic ones, especially fractures.
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Affiliation(s)
- M Guarino
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - I Loperto
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - S Camera
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - V Cossiga
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - C Di Somma
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - A Colao
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - N Caporaso
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - F Morisco
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy.
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Abstract
Primary biliary cirrhosis (PBC) is a liver-specific autoimmune disease that primarily affects women (female-to-male ratio, 10:1) between 40 and 60 years of age. Metabolic bone disease is a common complication of PBC, affecting 14% to 52% of patients, depending on the duration and severity of liver disease. The osteoporosis seen in PBC seems mainly due to low bone formation, although increased bone resorption may contribute. Treatment of osteoporosis consists primarily of antiresorptive agents. Additional large prospective, long-term studies in patients with PBC are needed to determine efficacy in improving bone density as well as reducing fracture risk.
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Affiliation(s)
- Lisa M Glass
- Gastroenterology Section, Department of Internal Medicine, VA Ann Arbor Health Care System, University of Michigan Health System, 2215 Fuller Road, Ann Arbor, MI 48105, USA
| | - Grace Li-Chun Su
- Gastroenterology Section, Specialty Care and Access, VA Ann Arbor Health Care System, University of Michigan Medical School, 2215 Fuller Road, Ann Arbor, MI 48105, USA.
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29
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Patel N, Muñoz SJ. Bone disease in cirrhosis. Clin Liver Dis (Hoboken) 2015; 6:96-99. [PMID: 31040999 PMCID: PMC6490654 DOI: 10.1002/cld.498] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2015] [Accepted: 06/12/2015] [Indexed: 02/04/2023] Open
Affiliation(s)
- Nishita Patel
- Division of Gastroenterology and Hepatology, Department of MedicineDrexel University College of MedicinePhiladelphiaPA
| | - Santiago J. Muñoz
- Division of Gastroenterology and Hepatology, Department of MedicineDrexel University College of MedicinePhiladelphiaPA
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30
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Abstract
Primary biliary cirrhosis is a chronic cholestatic liver disease characterised by destruction of small intrahepatic bile ducts, leading to fibrosis and potential cirrhosis through resulting complications. The serological hallmark of primary biliary cirrhosis is the antimitochondrial antibody, a highly disease-specific antibody identified in about 95% of patients with primary biliary cirrhosis. These patients usually have fatigue and pruritus, both of which occur independently of disease severity. The typical course of primary biliary cirrhosis has changed substantially with the introduöction of ursodeoxycholic acid (UDCA). Several randomised placebo-controlled studies have shown that UDCA improves transplant-free survival in primary biliary cirrhosis. However, about 40% of patients do not have a biochemical response to UDCA and would benefit from new therapies. Liver transplantation is a life-saving surgery with excellent outcomes for those with decompensated cirrhosis. Meanwhile, research on nuclear receptor hormones has led to the development of exciting new potential treatments. This Seminar will review the current understanding of the epidemiology, pathogenesis, and natural history of primary biliary cirrhosis, discuss management of the disease and its sequelae, and introduce research on new therapeutic options.
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Affiliation(s)
- Elizabeth J Carey
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Ahmad H Ali
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Keith D Lindor
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA; Arizona State University, College of Health Solutions, Phoenix, AZ, USA.
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31
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Mirza F, Canalis E. Management of endocrine disease: Secondary osteoporosis: pathophysiology and management. Eur J Endocrinol 2015; 173:R131-51. [PMID: 25971649 PMCID: PMC4534332 DOI: 10.1530/eje-15-0118] [Citation(s) in RCA: 202] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Accepted: 05/12/2015] [Indexed: 12/14/2022]
Abstract
Osteoporosis is a skeletal disorder characterized by decreased mass and compromised bone strength predisposing to an increased risk of fractures. Although idiopathic osteoporosis is the most common form of osteoporosis, secondary factors may contribute to the bone loss and increased fracture risk in patients presenting with fragility fractures or osteoporosis. Several medical conditions and medications significantly increase the risk for bone loss and skeletal fragility. This review focuses on some of the common causes of osteoporosis, addressing the underlying mechanisms, diagnostic approach and treatment of low bone mass in the presence of these conditions.
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Affiliation(s)
- Faryal Mirza
- Division of Endocrinology and MetabolismDepartments of MedicineOrthopaedic SurgeryUConn Musculoskeletal Institute, UConn Health, 263 Farmington Avenue, Farmington, Connecticut 06030-5456, USA
| | - Ernesto Canalis
- Division of Endocrinology and MetabolismDepartments of MedicineOrthopaedic SurgeryUConn Musculoskeletal Institute, UConn Health, 263 Farmington Avenue, Farmington, Connecticut 06030-5456, USA Division of Endocrinology and MetabolismDepartments of MedicineOrthopaedic SurgeryUConn Musculoskeletal Institute, UConn Health, 263 Farmington Avenue, Farmington, Connecticut 06030-5456, USA
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32
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Lindor KD, Kowdley KV, Harrison ME. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Am J Gastroenterol 2015; 110:646-59; quiz 660. [PMID: 25869391 DOI: 10.1038/ajg.2015.112] [Citation(s) in RCA: 330] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2014] [Accepted: 03/02/2015] [Indexed: 12/11/2022]
Abstract
Primary sclerosing cholangitis is a chronic cholestatic liver disease that can shorten life and may require liver transplantation. The cause is unknown, although it is commonly associated with colitis. There is no approved or proven therapy, although ursodeoxycholic acid is used by many on an empiric basis. Complications including portal hypertension, fat-soluble vitamin deficiency, metabolic bone diseases, and development of cancers of the bile duct or colon can occur.
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Affiliation(s)
- Keith D Lindor
- 1] College of Health Solutions, Arizona State University, Phoenix, Arizona, USA [2] Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona, USA
| | - Kris V Kowdley
- Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, Washington, USA
| | - M Edwyn Harrison
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona, USA
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33
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Marchioni Beery RM, Vaziri H, Forouhar F. Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis: a Review Featuring a Women's Health Perspective. J Clin Transl Hepatol 2014; 2:266-84. [PMID: 26357630 PMCID: PMC4521232 DOI: 10.14218/jcth.2014.00024] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2014] [Revised: 10/15/2014] [Accepted: 10/19/2014] [Indexed: 12/12/2022] Open
Abstract
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are two major types of chronic cholestatic liver disease. Each disorder has distinguishing features and variable progression, but both may ultimately result in cirrhosis and hepatic failure. The following offers a review of PBC and PSC, beginning with a general overview of disease etiology, pathogenesis, diagnosis, clinical features, natural course, and treatment. In addition to commonly associated manifestations of fatigue, pruritus, and fat-soluble vitamin deficiency, select disease-related topics pertaining to women's health are discussed including metabolic bone disease, hyperlipidemia and cardiovascular risk, and pregnancy-related issues influencing maternal disease course and birth outcomes. This comprehensive review of PBC and PSC highlights some unique clinical considerations in the care of female patients with cholestatic liver disease.
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Affiliation(s)
- Renée M. Marchioni Beery
- Division of Internal Medicine, Department of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- Correspondence to: Renée M. Marchioni Beery, DO, Division of Internal Medicine, Department of Gastroenterology and Hepatology, 263 Farmington Avenue, Farmington, CT 06030-1845, USA. Tel: +01-860-679-3158, Fax: +01-860-679-3159. E-mail:
| | - Haleh Vaziri
- Division of Internal Medicine, Department of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - Faripour Forouhar
- Department of Pathology and Lab Medicine, University of Connecticut Health Center, Farmington, CT, USA
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34
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Ali AH, Carey EJ, Lindor KD. Diagnosis and management of primary biliary cirrhosis. Expert Rev Clin Immunol 2014; 10:1667-78. [DOI: 10.1586/1744666x.2014.979792] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Osteoporosis in primary biliary cirrhosis of the liver. GASTROENTEROLOGY REVIEW 2014; 9:82-7. [PMID: 25061487 PMCID: PMC4108749 DOI: 10.5114/pg.2014.42502] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/08/2012] [Revised: 03/15/2012] [Accepted: 04/02/2012] [Indexed: 12/12/2022]
Abstract
Osteoporosis is a metabolic bone disease associated with a reduction in bone mass and deterioration of bone architecture, leading to increased fragility and subsequent low-trauma fractures in the vertebral column, hip, forearm and other bones. In literature, metabolic bone diseases such as osteoporosis and osteomalacia have been recognised as a complication of chronic liver disease, although the mechanisms of this association remain unclear. An increasing body of research data indicates a strong relationship between osteoporosis and primary biliary cirrhosis (PBC), which mainly results from early diagnosis of the disease, usually when it is still asymptomatic. The incidence of osteoporosis in PBC ranges from 20% to 44% and increases with the progression of the disease. Similarly, the incidence of bone fractures is high in this group of patients (10-20%). In this article, current knowledge on risk factors, pathogenesis, diagnosis and treatment of osteoporosis in PBC is reviewed.
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Abstract
PURPOSE OF REVIEW Primary biliary cirrhosis (PBC) was first described in the 1950s as a clinical syndrome of progressive cholestatic liver disease resulting from chronic inflammatory destruction of the intrahepatic bile ducts. In the 1980s, the autoimmune nature of the disease was appreciated with the discovery of disease-specific loss of immune tolerance to the pyruvate dehydrogenase complex and subsequent development of antimitochondrial antibodies and autoreactive T cells. Then, in the 1990s, multiple clinical trials demonstrating the efficacy of ursodiol as a treatment for PBC were published, although it has been clear that ursodiol is not a cure and only delays progression in some patients. RECENT FINDINGS The study of PBC in the 2000s has been buoyed by two basic science advances: rapid sequencing technologies that have led to genome wide association studies, and elucidation of the role of nuclear hormone receptors in the regulation of bile salt metabolism, which has led to novel therapies under study for cholestatic diseases. SUMMARY Today's clinician should be able to determine which patients with PBC are likely to progress despite treatment with ursodiol and understand the putative new bile acid and immunosuppressant treatment strategies under development, as well as be aware of the recently described genetic factors at play in the development of PBC.
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37
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Saadi M, Yu C, Othman MO. A Review of the Challenges Associated with the Diagnosis and Therapy of Primary Sclerosing Cholangitis. J Clin Transl Hepatol 2014; 2:45-52. [PMID: 26357617 PMCID: PMC4548359 DOI: 10.14218/jcth.2013.00021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 02/01/2014] [Accepted: 02/04/2014] [Indexed: 12/12/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic and progressive cholestatic liver disease that often leads to the development of cirrhosis. Complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, dominant biliary strictures, gallstones, and hepatobiliary malignancies, most commonly cholangiocarcinoma (CCA). Despite the presumed autoimmune etiology of PSC, a clear benefit from immunosuppressive agents has not yet been established, and their use is limited by their side effects. Endoscopy is required in evaluation of biliary strictures in PSC to rule out the possibility of CCA. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease. However, disease recurrence can be a source of morbidity and mortality as transplanted patients survive longer. Further studies are needed to develop an optimal therapeutic strategy for patients with PSC to decrease the incidence of complications of the disease, to decrease the need for transplantation, and to extend life expectancy.
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Affiliation(s)
- Mohammed Saadi
- Department of Medicine, Division of Gastroenterology and Hepatology, Texas Tech University Health Science Center-Paul L. Foster School of Medicine, El Paso, TX, USA
| | - Christine Yu
- Department of Medicine, Division of Gastroenterology and Hepatology, Texas Tech University Health Science Center-Paul L. Foster School of Medicine, El Paso, TX, USA
| | - Mohamed O Othman
- Department of Medicine, Division of Gastroenterology and Hepatology, Texas Tech University Health Science Center-Paul L. Foster School of Medicine, El Paso, TX, USA
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38
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Longman RS, Scherl EJ. Medical Management of Extraintestinal Manifestations of Ulcerative Colitis. MEDICAL THERAPY OF ULCERATIVE COLITIS 2014:377-391. [DOI: 10.1007/978-1-4939-1677-1_35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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39
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Abstract
The care of the patient with cholestasis hinges on identifying the etiology, treating reversible causes, and managing chronic cholestatic processes. PBC and PSC are important causes of chronic cholestasis, and are the most common causes of cholestatic liver disease. Effective therapy is available for patients with PBC, whereas none exists for patients with PSC. Awareness of the complications that may be associated with cholestasis and implementing the appropriate management are essential.
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Affiliation(s)
- Andrea A Gossard
- Cholestatic Liver Disease Study Group, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.
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40
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Angulo P. Strengthening the bones in primary biliary cirrhosis. Hepatology 2013; 58:1871-3. [PMID: 23959535 PMCID: PMC3856251 DOI: 10.1002/hep.26696] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2013] [Accepted: 08/14/2013] [Indexed: 12/29/2022]
Affiliation(s)
- Paul Angulo
- Division of Digestive Diseases & Nutrition, University of Kentucky Medical Center, 800 Rose Street, Room MN 649, Lexington, KY 40503, (859) 323-3555, (859) 257-8860 fax
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41
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Guañabens N, Monegal A, Cerdá D, Muxí Á, Gifre L, Peris P, Parés A. Randomized trial comparing monthly ibandronate and weekly alendronate for osteoporosis in patients with primary biliary cirrhosis. Hepatology 2013; 58:2070-8. [PMID: 23686738 DOI: 10.1002/hep.26466] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2013] [Accepted: 04/11/2013] [Indexed: 12/21/2022]
Abstract
UNLABELLED Osteoporosis resulting in bone fractures is a complication in patients with primary biliary cirrhosis (PBC). Once-weekly alendronate improves bone mass and is well tolerated in these patients, but there is a concern because of poor compliance. Therefore, the efficacy, adherence, and safety of monthly ibandronate (150 mg) with weekly alendronate (70 mg) were compared in a randomized, 2-year study in 42 postmenopausal women with PBC and osteoporosis. Bone mineral density (BMD) of the lumbar spine and proximal femur (by DXA), liver function, and bone markers were measured at entry and every 6 months over 2 years. Adherence to therapy was assessed by the Morisky-Green score. At enrollment, the two groups were similar with respect to age, BMD, severity of cholestasis, previous fractures, and bone markers. Thirty-three patients, 14 in the ibandronate group and 19 in the alendronate group, completed the trial. At 2 years both treatments resulted in a significant increase in BMD at the lumbar spine (from 0.875 ± 0.025 to 0.913 ± 0.026 g/cm(2), P < 0.001 with alendronate, and from 0.898 ± 0.024 to 0.949 ± 0.027 g/cm(2), P < 0.001 with ibandronate). The mean percentage change was 4.5% and 5.7%, respectively (P = not significant). BMD increased at the total hip by 2.0% and 1.2%, respectively. Changes in bone markers were similar in both groups and one patient with alendronate developed a new vertebral fracture. Adherence to therapy was higher with ibandronate (P = 0.009). Neither treatment impaired liver function or cholestasis. CONCLUSION Both regimens, weekly alendronate and monthly ibandronate, improve bone mass and are comparable in safety for osteoporosis therapy in patients with PBC, although adherence is higher with the monthly regimen. Further larger studies are needed to assess fracture prevention.
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Affiliation(s)
- Núria Guañabens
- Metabolic Bone Diseases Unit, Service of Rheumatology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Barcelona, Spain
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Mansueto P, Carroccio A, Seidita A, Di Fede G, Craxì A. Osteodystrophy in chronic liver diseases. Intern Emerg Med 2013; 8:377-88. [PMID: 22241574 DOI: 10.1007/s11739-012-0753-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2011] [Accepted: 01/04/2012] [Indexed: 12/12/2022]
Abstract
Osteoporosis and osteomalacia are, to date, among the most common metabolic diseases in the world. Lately, an association between metabolic bone diseases and chronic liver disease has been increasingly reported, inducing many authors to create a new nosographic entity known as 'hepatic osteodystrophy.' The importance of such a condition is further increased by the morbidity of these two diseases, which greatly reduce the quality of life because of frequent fractures, especially vertebral and femoral neck ones. For this reason, early identification of high-risk patients should be routinely performed by measuring bone mass density. The explanation for the association between bone diseases and chronic liver disease is still uncertain, and involves many factors: from hypogonadism to use of corticosteroid drugs, from genetic factors to interferon therapy. To date, few studies have been conducted, and all with a small number of patients to establish definitive conclusions about the possible treatment, but some evidence is beginning to emerge about the safety and efficacy of bisphosphonates.
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Affiliation(s)
- Pasquale Mansueto
- Dipartimento di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy.
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic, progressive, cholestatic liver disease characterized by multifocal strictures of intra and extrahepatic bile ducts. PSC occurs more commonly in men and is often associated with inflammatory bowel disease. At present, there is no effective medical therapy for PSC. Current management of patients with PSC is centered on endoscopic therapy of biliary strictures, management of complications of chronic cholestasis and of progressive liver disease, and close clinical monitoring for development of cholangiocarcinoma, as well as for timely referral for liver transplantation.
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Affiliation(s)
- Claudia O Zein
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue, A31, Cleveland, OH 44195, USA.
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Abstract
Cholestasis is defined as impairment of bile formation or bile flow. Care of the patient with cholestatic features is dependent on identifying the cause of the cholestasis, initiating appropriate treatment of reversible conditions, and the recognition and management of cholestasis-specific complications. Cholestasis may include extrahepatic ducts and intrahepatic bile ducts, or may be limited to one or the other. Jaundice and pruritus are the hallmarks of cholestasis clinically but biochemical evidence may, and often does, precede the clinical manifestations.
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Affiliation(s)
- Andrea A Gossard
- Cholestatic Liver Disease Study Group, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55901, USA.
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Derakhshanian H, Ghadbeigi S, Rezaian M, Bahremand A, Javanbakht MH, Golpaie A, Hosseinzadeh P, Tajik N, Dehpour AR. Quercetin improves bone strength in experimental biliary cirrhosis. Hepatol Res 2013; 43:394-400. [PMID: 22882531 DOI: 10.1111/j.1872-034x.2012.01075.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM Metabolic bone disorders and reduced bone mass are common complications in patients with biliary cirrhosis. As a result of there being no clear etiology, no specific therapy has been established yet. Previous studies have reported that quercetin, a plant-derived flavonoid, might improve bone quality. The present study was designed to investigate the effect of quercetin on bone strength of biliary cirrhotic rats. METHODS Twenty-four male Sprague-Dawley rats aged 6-7 months were randomized into three groups of eight. One group served as control (sham operated), while the other two groups underwent a complete bile duct ligation (BDL). Four weeks after the operation, serum bilirubin, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase were measured in animal blood samples to confirm the occurrence of cirrhosis in the BDL rats. Then, one of the BDL groups received placebo and the other one was injected once a day with 150 µmol/kg of quercetin for 4 weeks. At the end of the study, femora were removed and tested for bone strength and histomorphometric parameters. The serum levels of osteocalcin, C-terminal cross-linked telopeptide of type I collagen, calcium and phosphorus were determined as bone turnover markers. RESULTS Femur breaking strength was dramatically lower in the BDL group compared with control. However, receiving quercetin could reverse the deteriorating effect of cirrhosis on bone strength of BDL rats. Quercetin could noticeably elevate osteocalcin as a bone formation marker. CONCLUSION These data suggest that quercetin can significantly improve bone strength particularly due to increasing bone formation in biliary cirrhosis.
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Affiliation(s)
- Hoda Derakhshanian
- Department of Nutrition and Biochemistry, School of Public Health Department of Medicinal Chemistry, School of Pharmacy Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences Department of Histology, School of Veterinary Medicine, University of Tehran, Tehran Department of Nutrition and Biochemistry, The International Campus, Tehran University of Medical Sciences, Kish, Iran
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Carey EJ, Mayer AP, Files JA. Tired of Being Tired. J Womens Health (Larchmt) 2013; 22:289-90. [DOI: 10.1089/jwh.2012.4225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
| | - Anita P. Mayer
- Division of Women's Health –Internal Medicine, Mayo Clinic in Arizona, Phoenix, Arizona
| | - Julia A. Files
- Division of Women's Health –Internal Medicine, Mayo Clinic in Arizona, Phoenix, Arizona
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Abstract
Osteoporosis is a common skeletal complication seen in patients with chronic liver disease. Osteoporosis is usually asymptomatic and, if untreated, can result in fractures and impaired quality of life. For this review, we performed a systematic search of the PubMed database, and all recent peer-reviewed articles regarding the prevalence, pathophysiology, diagnosis, and management of osteoporosis in chronic liver disease were included. The prevalence of osteoporosis varies between 11% and 58% in patients with chronic liver disease and in transplant recipients. The etiology of osteoporosis is multifactorial and only partially understood. Various factors linked to the pathogenesis of bone loss are vitamin D, calcium, insulin growth factor-1, receptor activation of nuclear factor-κB ligand (RANKL), bilirubin, fibronectin, leptin, proinflammatory cytokines, and genetic polymorphisms. Management of osteoporosis involves early diagnosis, identifying and minimizing risk factors, general supportive care, nutrition therapy, and pharmacotherapy. Osteoporosis is diagnosed based on the bone mineral density (BMD) assessment using dual-energy X-ray absorptiometry scan. Measurement of BMD should be considered in all patients with advanced liver disease and in transplant recipients. Vitamin D and calcium supplementation is recommended for all patients with osteoporosis. Specific agents used for treatment of osteoporosis include bisphosphonates, calcitonin, hormonal therapy, and raloxifene. Bisphosphonates have become the mainstay of therapy for osteoporosis prevention and treatment. Prolonged suppression of bone remodeling resulting in atypical fractures has emerged as a significant complication with long-term use of bisphosphonates. Newer treatment agents and better fracture prevention strategies are necessary to prevent and treat osteoporosis.
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Affiliation(s)
- Anitha Yadav
- Division of Transplant Hepatology, Mayo Clinic Hospital, Phoenix, AZ 85054, USA
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Carey EJ, Lindor KD. Current pharmacotherapy for cholestatic liver disease. Expert Opin Pharmacother 2012; 13:2473-84. [PMID: 23094715 DOI: 10.1517/14656566.2012.736491] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
IMPORTANCE OF THE FIELD The cholestatic liver diseases comprise a heterogeneous group of disorders which, left untreated, usually progresses to cirrhosis and liver failure. Most are recognized before the onset of advanced fibrosis, thereby affording an opportunity for disease modifying therapy. AREAS COVERED This review will cover the current pharmacologic management of the most common causes of cholestatic liver disease in adults, including primary biliary cirrhosis, primary biliary cirrhosis-autoimmune hepatitis overlap syndrome, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, intestinal failure-associated liver disease, and immunoglobulin G4-associated cholangitis. Pharmacologic management of complications of cholestasis will also be reviewed. EXPERT OPINION Effective therapy for most cholestatic liver disease is lacking. Ursodeoxycholic acid (UDCA) slows the progression of primary biliary cirrhosis but the majority of patients do not have a full response. Even in those with a complete response, UDCA does not cure the disease. There is currently no effective medical therapy for primary sclerosing cholangitis. Symptoms and serum liver biochemistry values in intrahepatic cholestasis of pregnancy are improved with UDCA, but it is not certain if this alters the course of disease. Immunoglobulin G4-associated cholangitis is responsive to steroids but may relapse. The farnesoid X receptor agonists are a promising new class of drugs currently being tested in cholestatic liver disease.
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Affiliation(s)
- Elizabeth J Carey
- Mayo Clinic in Arizona, Division of Hepatology, Phoenix, AZ 85054, USA.
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Effect of alendronate on bone-specific alkaline phosphatase on periodontal bone loss in rats. Arch Oral Biol 2012; 57:1537-44. [PMID: 23062673 DOI: 10.1016/j.archoralbio.2012.07.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2012] [Revised: 07/11/2012] [Accepted: 07/14/2012] [Indexed: 02/01/2023]
Abstract
OBJECTIVE The study aims to evaluate the effect of alendronate (ALD) on bone-specific alkaline phosphatase (BALP) serum levels on periodontal bone loss in Wistar rats. DESIGN Periodontitis was induced by ligature around the upper second molar in 36 male Wistar rats (± 200 g). Groups of six animals received 0.9% saline (SAL) or ALD (0.01; 0.05; 0.25 mgkg(-1), s.c.), over 11 days; then they were sacrificed and their maxillae were removed to be defleshed and stained for macroscopic or histopathological analysis. Blood samples were collected for BALP, transaminases and total alkaline phosphatase (TALP) serum dosage, and haematologic study. Rats were weighed daily. RESULTS Periodontitis induction caused reduction of BALP, intense alveolar bone loss (ABL), cementum and periodontal ligament destructions and intense leucocyte infiltration seen microscopically. Systemically, periodontitis induced leucocytosis, weight loss and TALP reduction. ALD (0.25 mgkg(-1)) prevented BALP reduction (19.17 ± 1.36 Ul(-1)) when compared to SAL (13.6 ± 1.5), as well as prevented ABL, by 57.2%, when compared to SAL (4.80+0.18 mm(2)), which was corroborated by histological findings (ALD 0.25 mgkg(-1)=1.5 (1-2) and SAL=3 (2-3)) (p<0.05). ALD did not alter transaminases but reduced TALP levels (p<0.05). ALD 0.25 mgkg(-1) reduced 6th-h neutrophilia (2.50 ± 0.22cell × 10(3)mm(-3)) and 7th- (12.29 ± 0.66) and 11th-day lymphomonocytosis (15.74 ± 0.52) when compared to SAL (5.20 ± 0.28; 18.24 ± 1.05; and 23.21 ± 1.48, respectively). ALD did not alter the weight loss. CONCLUSION ALD prevented BALP reduction and ABL and reduced inflammatory infiltrate, without causing systemic alterations.
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Abstract
Bisphosphonates are pharmacological compounds that have been used for the prevention and treatment of several pathological conditions including osteoporosis, primary hyperparathyroidism, osteogenesis imperfecta, and other conditions characterized by bone fragility. Many studies have been performed to date to analyze their effects on inflammation and bone remodelling and related pathologies. The aim of this review is, starting from a background on inflammatory processes and bone remodelling, to give an update on the use of bisphosphonates, outlining the possible side effects and proposing new trends for the future. Starting from a brief introduction on inflammation and bone remodelling, we collect and analyze studies involving the use of bisphosphonates for treatment of inflammatory conditions and pathologies characterized by bone loss. Selected articles, including reviews, published between 1976 and 2011, were chosen from Pubmed/Medline on the basis of their content. Bisphosphonates exert a selective activity on inflammation and bone remodelling and related pathologies, which are characterized by an excess in bone resorption. They improve not only skeletal defects, but also general symptoms. Bisphosphonates have found clinical application preventing and treating osteoporosis, osteitis deformans (Paget's disease of bone), bone metastasis (with or without hypercalcaemia), multiple myeloma, primary hyperparathyroidism, osteogenesis imperfecta, and other conditions that feature bone fragility. Further clinical studies involving larger cohorts are needed to optimize the dosage and length of therapy for each of these agents in each clinical field in order to be able to maximize their properties concerning modulation of inflammation and bone remodelling. In the near future, although "old" bisphosphonates will reach the end of their patent life, "new" bisphosphonates will be designed to specifically target a pathological condition.
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