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Terracina S, Caronti B, Lucarelli M, Francati S, Piccioni MG, Tarani L, Ceccanti M, Caserta M, Verdone L, Venditti S, Fiore M, Ferraguti G. Alcohol Consumption and Autoimmune Diseases. Int J Mol Sci 2025; 26:845. [PMID: 39859557 PMCID: PMC11766456 DOI: 10.3390/ijms26020845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 12/31/2024] [Accepted: 01/04/2025] [Indexed: 01/27/2025] Open
Abstract
Alcohol is the second-most misused substance after tobacco. It has been identified as a causal factor in more than 200 diseases and 5.3% of all deaths and is associated with significant behavioral, social, and economic difficulties. As alcohol consumption may modulate the immune system's regulatory mechanisms to avoid attacking the body's tissues, it has been proven to play a dichotomic role in autoimmune diseases (ADs) based on the quantity of consumption. In this review, we report updated evidence on the role of alcohol in ADs, with a focus on alcohol addiction and the human biological immune system and the relationship between them, with alcohol as a risk or protective factor. Then, in this narrative review, we report the main evidence on the most studied ADs where alcohol represents a key modulator, including autoimmune thyroiditis, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, diabetes, allergic rhinitis, and primary biliary cholangitis. Alcohol at low-moderate dosages seems mostly to have a protective role in these diseases, while at higher dosages, the collateral risks surpass possible benefits. The specific mechanisms by which low-to-moderate alcohol intake relieves AD symptoms are not yet fully understood; however, emerging studies suggest that alcohol may have a systemic immunomodulatory effect, potentially altering the balance of anti-inflammatory innate and adaptive immune cells, as well as cytokines (via the NF-κB or NLRP3 pathways). It might influence the composition of the gut microbiome (increasing amounts of beneficial gut microbes) and the production of their fatty acid metabolites, such as short-chain fatty acids (SCFAs) and polyunsaturated fatty acids (PUFAs), as well as elevated concentrations of acetate, high-density lipoprotein (HDL), and nitric oxide (NO). Unfortunately, a definite acceptable daily intake (ADI) of ethanol is complicated to establish because of the many mechanisms associated with alcohol consumption such that despite the interesting content of these findings, there is a limit to their applicability and risks should be weighed in cases of alcoholic drinking recommendations. The aim of future studies should be to modulate those beneficial pathways involved in the alcohol-protective role of ADs with various strategies to avoid the risks associated with alcohol intake.
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Affiliation(s)
- Sergio Terracina
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy; (S.T.); (M.L.); (S.F.)
| | - Brunella Caronti
- Department of Human Neurosciences, Sapienza University Hospital of Rome, 00185 Rome, Italy
| | - Marco Lucarelli
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy; (S.T.); (M.L.); (S.F.)
- Pasteur Institute, Cenci Bolognetti Foundation, Sapienza University of Rome, 00161 Rome, Italy
| | - Silvia Francati
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy; (S.T.); (M.L.); (S.F.)
| | - Maria Grazia Piccioni
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00161 Rome, Italy; (M.G.P.); (L.T.)
| | - Luigi Tarani
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00161 Rome, Italy; (M.G.P.); (L.T.)
| | - Mauro Ceccanti
- SITAC, Società Italiana per il Trattamento dell’Alcolismo e le sue Complicanze, 00185 Rome, Italy;
| | - Micaela Caserta
- Institute of Molecular Biology and Pathology (IBPM-CNR), 00161 Rome, Italy; (M.C.); (L.V.)
| | - Loredana Verdone
- Institute of Molecular Biology and Pathology (IBPM-CNR), 00161 Rome, Italy; (M.C.); (L.V.)
| | - Sabrina Venditti
- Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00161 Rome, Italy;
| | - Marco Fiore
- Institute of Biochemistry and Cell Biology (IBBC-CNR), c/o Department of Sensory Organs, Sapienza University of Rome, 00161 Rome, Italy
| | - Giampiero Ferraguti
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy; (S.T.); (M.L.); (S.F.)
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2
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Kuah AH, Sattgast LH, Grant KA, Gonzales SW, Khadka R, Damrath JG, Allen MR, Burr DB, Wallace JM, Maddalozzo GF, Benton ML, Beaver LM, Branscum AJ, Turner RT, Iwaniec UT. Six months of voluntary alcohol consumption in male cynomolgus macaques reduces intracortical bone porosity without altering mineralization or mechanical properties. Bone 2024; 185:117111. [PMID: 38679220 PMCID: PMC466935 DOI: 10.1016/j.bone.2024.117111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Revised: 04/23/2024] [Accepted: 04/25/2024] [Indexed: 05/01/2024]
Abstract
Chronic heavy alcohol consumption is a risk factor for low trauma bone fracture. Using a non-human primate model of voluntary alcohol consumption, we investigated the effects of 6 months of ethanol intake on cortical bone in cynomolgus macaques (Macaca fascicularis). Young adult (6.4 ± 0.1 years old, mean ± SE) male cynomolgus macaques (n = 17) were subjected to a 4-month graded ethanol induction period, followed by voluntary self-administration of water or ethanol (4 % w/v) for 22 h/d, 7 d/wk. for 6 months. Control animals (n = 6) consumed an isocaloric maltose-dextrin solution. Tibial response was evaluated using densitometry, microcomputed tomography, histomorphometry, biomechanical testing, and Raman spectroscopy. Global bone response was evaluated using biochemical markers of bone turnover. Monkeys in the ethanol group consumed an average of 2.3 ± 0.2 g/kg/d ethanol resulting in a blood ethanol concentration of 90 ± 12 mg/dl in longitudinal samples taken 7 h after the daily session began. Ethanol consumption had no effect on tibia length, mass, density, mechanical properties, or mineralization (p > 0.642). However, compared to controls, ethanol intake resulted in a dose-dependent reduction in intracortical bone porosity (Spearman rank correlation = -0.770; p < 0.0001) and compared to baseline, a strong tendency (p = 0.058) for lower plasma CTX, a biochemical marker of global bone resorption. These findings are important because suppressed cortical bone remodeling can result in a decrease in bone quality. In conclusion, intracortical bone porosity was reduced to subnormal values 6 months following initiation of voluntary ethanol consumption but other measures of tibia architecture, mineralization, or mechanics were not altered.
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Affiliation(s)
- Amida H Kuah
- Skeletal Biology Laboratory, School of Nutrition and Public Health, Oregon State University, Corvallis, OR 97331, USA
| | - Lara H Sattgast
- Skeletal Biology Laboratory, School of Nutrition and Public Health, Oregon State University, Corvallis, OR 97331, USA
| | - Kathleen A Grant
- Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA
| | - Steven W Gonzales
- Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA
| | - Rupak Khadka
- Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA
| | - John G Damrath
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA
| | - Matthew R Allen
- Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA
| | - David B Burr
- Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA
| | - Joseph M Wallace
- Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA
| | - Gianni F Maddalozzo
- Skeletal Biology Laboratory, School of Nutrition and Public Health, Oregon State University, Corvallis, OR 97331, USA
| | | | - Laura M Beaver
- Skeletal Biology Laboratory, School of Nutrition and Public Health, Oregon State University, Corvallis, OR 97331, USA; Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
| | - Adam J Branscum
- Biostatistics Program, School of Nutrition and Public Health, Oregon State University, Corvallis, OR 97331, USA
| | - Russell T Turner
- Skeletal Biology Laboratory, School of Nutrition and Public Health, Oregon State University, Corvallis, OR 97331, USA; Center for Healthy Aging Research, Oregon State University, Corvallis, OR 97331, USA
| | - Urszula T Iwaniec
- Skeletal Biology Laboratory, School of Nutrition and Public Health, Oregon State University, Corvallis, OR 97331, USA; Center for Healthy Aging Research, Oregon State University, Corvallis, OR 97331, USA.
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Shin M, Kim DK, Jain M, Martens PJ, Turner RT, Iwaniec UT, Kruzic JJ, Gludovatz B. Impact of heavy alcohol consumption on cortical bone mechanical properties in male rhesus macaques. Bone 2024; 181:117041. [PMID: 38325648 DOI: 10.1016/j.bone.2024.117041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 01/31/2024] [Accepted: 02/02/2024] [Indexed: 02/09/2024]
Abstract
Chronic heavy alcohol consumption may influence the skeleton by suppressing intracortical bone remodeling which may impact the quality of bone and its mechanical properties. However, this aspect has not been thoroughly assessed in either humans or animal models whose cortical bone microstructure resembles the microstructure of human cortical bone. The current study is the first to investigate the effects of chronic heavy alcohol consumption on various mechanical properties of bone in a non-human primate model with intracortical remodeling. Male rhesus macaques (5.3 years old at the initiation of treatment) were induced to drink alcohol and then given the choice to voluntarily self-administer water or ethanol (4 % w/v) for approximately 14 months, followed by three abstinence phases (lasting 34, 41, and 39-46 days) with approximately 3 months of ethanol access in between. During the initial 14 months of open-access, monkeys in the alcohol group consumed an average of 2.9 ± 0.8 g/kg/d ethanol (mean ± SD) resulting in a blood ethanol concentration of 89 ± 47 mg/dl in longitudinal samples taken at 7 h after the daily sessions began. To understand the impact of alcohol consumption on material properties, various mechanical tests were conducted on the distal tibia diaphysis of 2-5 monkeys per test group, including dynamic mechanical analysis (DMA) testing, nano-indentation, microhardness testing, compression testing, and fracture resistance curve (R-curve) testing. Additionally, compositional analyses were performed using Fourier-transform infrared (FTIR) spectroscopy. Significant differences in microhardness, compressive stress-strain response, and composition were not observed with alcohol consumption, and only minor differences were detected in hardness and elastic modulus of the matrix and osteons from nanoindentation. Furthermore, the R-curves of both groups overlapped, with similar crack initiation toughness, despite a significant decrease in crack growth toughness (p = 0.032) with alcohol consumption. However, storage modulus (p = 0.029) and loss factor (p = 0.015) from DMA testing were significantly increased in the alcohol group compared to the control group, while loss modulus remained unchanged. These results indicate that heavy alcohol consumption may have only a minor influence on the material properties and the composition of cortical bone in young adult male rhesus macaques.
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Affiliation(s)
- Mihee Shin
- School of Mechanical and Manufacturing Engineering, University of New South Wales (UNSW Sydney), Sydney, NSW 2052, Australia
| | - Do Kyung Kim
- School of Mechanical and Manufacturing Engineering, University of New South Wales (UNSW Sydney), Sydney, NSW 2052, Australia; Department of Material Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea
| | - Manish Jain
- Center for Integrated Nanotechnologies, Sandia National Laboratories, Albuquerque, NM 87123, USA
| | - Penny J Martens
- Graduate School of Biomedical Engineering, University of New South Wales (UNSW Sydney), Sydney, NSW 2052, Australia
| | - Russell T Turner
- Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, 97331 Oregon, United States; Center for Healthy Aging Research, Oregon State University, Corvallis, 97331 Oregon, United States
| | - Urszula T Iwaniec
- Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, 97331 Oregon, United States; Center for Healthy Aging Research, Oregon State University, Corvallis, 97331 Oregon, United States
| | - Jamie J Kruzic
- School of Mechanical and Manufacturing Engineering, University of New South Wales (UNSW Sydney), Sydney, NSW 2052, Australia
| | - Bernd Gludovatz
- School of Mechanical and Manufacturing Engineering, University of New South Wales (UNSW Sydney), Sydney, NSW 2052, Australia.
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Lai B, Jiang H, Gao R, Zhou X. Association between alcohol intake and bone mineral density: results from the NHANES 2005-2020 and two-sample Mendelian randomization. Arch Osteoporos 2024; 19:21. [PMID: 38546895 DOI: 10.1007/s11657-024-01382-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 03/24/2024] [Indexed: 04/02/2024]
Abstract
We used the data from the NHANES cross-sectional study among 14,113 participants and indicated a positive correlation between alcohol intake frequency and bone mineral density in different body sites. Mendelian randomization was conducted, and no causal relationship is significant between these two variables. The study can provide some suggestions on the daily consumption of alcohol for osteoporosis patients. PURPOSE The effect of alcohol intake on bone mineral density (BMD) remains unclear. This study explored the association and causality between alcohol intake and BMD. METHODS Based on the 2005-2020 National Health and Nutrition Examination Survey including 14,113 participants, we conducted co-variate-adjusted multilinear regression analyses to explore the association between alcohol intake levels and spine or femur BMD. To evaluate the causal association between alcohol intake frequency and bone mineral density, the inverse variance weighted approach of two-sample Mendelian randomization (MR) was used with genetic data from the Medical Research Council Integrative Epidemiology Unit (462,346 cases) for alcohol intake frequency and the Genetic Factors for Osteoporosis Consortium (28,496 cases) for lumbar spine and femur neck BMD (32,735 cases). RESULTS Compared with non-drinkers, total femur BMDs but not total spine BMD increased with daily alcohol intake in males (β = 3.63*10-2 for mild drinkers, β = 4.21*10-2 for moderate drinkers, and β = 4.26*10-2 for heavy drinkers). By contrast, the higher total spine BMD in females was related to higher alcohol intake levels (β = 2.15*10-2 for mild drinkers, β = 2.59*10-2 for moderate drinkers, and β = 3.88*10-2 for heavy drinkers). Regarding the two-sample MR results, no causal relationship was observed between alcohol intake frequency and lumbar spine BMD (odds ratio [OR] = 1.016, P = 0.789) or femur neck BMD (OR = 1.048, P = 0.333). CONCLUSION This study suggests a positive association between alcohol intake frequency and BMD, although the causal relationship was not significant.
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Affiliation(s)
- Bowen Lai
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Heng Jiang
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Rui Gao
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Xuhui Zhou
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China.
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Suiko M, Mizukami S, Arima K, Nakashima H, Nishimura T, Tomita Y, Abe Y, Tanaka N, Honda Y, Kojima M, Okawachi T, Hasegawa M, Sou Y, Tsujimoto R, Kanagae M, Osaki M, Aoyagi K. Association between physical performance and bone mass in community-dwelling postmenopausal Japanese women: The Unzen study. PLoS One 2024; 19:e0296457. [PMID: 38165878 PMCID: PMC10760765 DOI: 10.1371/journal.pone.0296457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 12/13/2023] [Indexed: 01/04/2024] Open
Abstract
BACKGROUND Low bone mass is an independent risk factor for osteoporotic fractures. We examined the association between physical performance and bone mass using quantitative ultrasound in community-dwelling postmenopausal Japanese women. METHODS We conducted a cross-sectional study on 524 community-dwelling postmenopausal Japanese women who were not being administered osteoporosis medications. Physical performance was assessed on the basis of grip strength, chair stand time, and functional reach. The stiffness index was measured as a quantitative ultrasound parameter for heel bone mass. RESULTS Physical performance, assessed by grip strength, chair stand time, and functional reach, and the stiffness index significantly decreased with age (both p<0.001). The multiple linear regression analysis showed that grip strength (p = 0.001), chair stand time (p = 0.004), and functional reach (p = 0.048) were significantly associated with the stiffness index after adjusting for age, body mass index, smoking, drinking, and exercise. CONCLUSIONS Physical performance was significantly associated with heel bone mass in community-dwelling postmenopausal Japanese women.
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Affiliation(s)
- Masahiro Suiko
- Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Satoshi Mizukami
- Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Leading Medical Research Core Unit, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kazuhiko Arima
- Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hiroki Nakashima
- Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takayuki Nishimura
- Department of Human Science, Faculty of Design, Kyushu University, Fukuoka, Japan
| | - Yoshihito Tomita
- Department of Physical Therapy, School of Rehabilitation, Tokyo Professional University of Health Science, Tokyo, Japan
| | - Yasuyo Abe
- Department of Health and Nutrition Science, Nishikyusyu University, Kanzaki, Japan
| | - Natsumi Tanaka
- Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Yuzo Honda
- Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Michiko Kojima
- Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | | | - Maiko Hasegawa
- Medical Policy Division, Nagasaki Prefectural Government, Nagasaki, Japan
| | - Youko Sou
- Ken-Nan Health Care Office, Nagasaki, Japan
| | - Ritsu Tsujimoto
- Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Mitsuo Kanagae
- Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Department of Rehabilitation, Nishi-Isahaya Hospital, Isahaya, Japan
| | - Makoto Osaki
- Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kiyoshi Aoyagi
- Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Leading Medical Research Core Unit, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Guabello G, Zuffetti F, Ravidà A, Deflorian M, Carta G, Saleh MHA, Serroni M, Pommer B, Watzek G, Francetti L, Testori T. Avoiding implant-related complications in medically compromised patients with or without unhealthy lifestyle/Elevated oxidative stress. Periodontol 2000 2023; 92:329-349. [PMID: 37350348 DOI: 10.1111/prd.12503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 04/11/2023] [Accepted: 04/26/2023] [Indexed: 06/24/2023]
Abstract
Increased human life expectancy broadens the alternatives for missing teeth and played a role in the widespread use of dental implants and related augmentation procedures for the aging population. Though, many of these patients may have one or more diseases. These systemic conditions may directly lead to surgical complications, compromise implant/bone healing, or influence long-term peri-implant health and its response to biologic nuisances. Offering patients credible expectations regarding intra- and postoperative complications and therapeutic prognosis is an ethical and legal obligation. Clear identification of potential types of adverse effects, complications, or errors is important for decision-making processes as they may be related to different local, systemic, and technical aspects. Therefore, the present review structures the underlying biological mechanisms, clinical evidence, and clinical recommendations for the most common systemic risk factors for implant-related complications.
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Affiliation(s)
- Gregorio Guabello
- Endocrinology Unit, IRCCS Galeazzi Sant'Ambrogio Hospital, Milan, Italy
| | - Francesco Zuffetti
- Section of Implant Dentistry and Oral Rehabilitation, IRCCS Galeazzi Sant'Ambrogio Hospital, Dental Clinic, Milan, Italy
| | - Andrea Ravidà
- Department of Periodontics and Preventive Dentistry, University of Pittsburgh School of Dental Medicine, Pittsburgh, Pennsylvania, USA
| | - Matteo Deflorian
- Section of Implant Dentistry and Oral Rehabilitation, IRCCS Galeazzi Sant'Ambrogio Hospital, Dental Clinic, Milan, Italy
| | - Giorgio Carta
- Argo Academy International Research Bologna, Bologna, Italy
- Private Practice, Bologna, Italy
- Lake Como Institute, Como, Italy
| | - Muhammad H A Saleh
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
| | - Matteo Serroni
- Department of Innovative Technologies in Medicine & Dentistry, University 'G. D'Annunzio', Chieti-Pescara, Italy
| | - Bernhard Pommer
- Academy for Oral Implantology, Vienna, Austria
- Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy
| | | | - Luca Francetti
- IRCCS Galeazzi Sant'Ambrogio Hospital, Dental Clinic, Milan, Italy
- Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy
| | - Tiziano Testori
- Section of Implant Dentistry and Oral Rehabilitation, IRCCS Galeazzi Sant'Ambrogio Hospital, Dental Clinic, Milan, Italy
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
- Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy
- Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA
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Martín González C, Fernández Rodríguez CM, Abreu González P, García Rodríguez A, Alvisa Negrín JC, Cabañas Perales E, González Navarrete L, Vera Delgado VE, Ortega Toledo P, González Reimers E. Sclerostin in Excessive Drinkers: Relationships with Liver Function and Body Composition. Nutrients 2022; 14:nu14132574. [PMID: 35807755 PMCID: PMC9268012 DOI: 10.3390/nu14132574] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/16/2022] [Accepted: 06/18/2022] [Indexed: 02/01/2023] Open
Abstract
Background: Sclerostin was initially described as an inhibitor of the Wnt-β catenin bone-forming pathway, but it also exerts important effects on intermediate metabolism and body composition. Osteosarcopenia and altered body fat distribution are common findings in excessive drinkers. The role of sclerostin in these patients is uncertain. We aim to analyze the behavior of sclerostin in excessive drinkers and its relationships with body composition (fat mass, lean mass, bone mass), handgrip strength, body mass index (BMI), liver function and ethanol intake. Methods: 107 male active heavy drinkers and 26 age-matched controls were included. Serum sclerostin was determined by ELISA. Body composition analysis was performed by double X-ray absorptiometry. Handgrip strength was recorded using a dynamometer. Liver function was assessed according to Child’s classification. Results: Sclerostin was higher among Child’s C patients, keeping a relationship with deranged liver function. Obesity, defined according to BMI, and body fat were strongly related to sclerostin, being independent of serum creatinine and of liver function. The relationship of sclerostin with total hip bone mineral density was displaced by BMI. Conclusion: Deranged liver function is associated with higher sclerostin levels in alcoholics. Raised sclerostin levels are related to fat deposition and increased BMI.
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Affiliation(s)
- Candelaria Martín González
- Departamento de Medicina Interna, Universidad de La Laguna, Servicio de Medicina Interna, Hospital Universitario de Canarias, Tenerife, Canary Islands, 38320 La Laguna, Spain; (C.M.F.R.); (A.G.R.); (J.C.A.N.); (E.C.P.); (L.G.N.); (V.E.V.D.); (P.O.T.); (E.G.R.)
- Correspondence: or ; Tel.: +34-922678600
| | - Camino María Fernández Rodríguez
- Departamento de Medicina Interna, Universidad de La Laguna, Servicio de Medicina Interna, Hospital Universitario de Canarias, Tenerife, Canary Islands, 38320 La Laguna, Spain; (C.M.F.R.); (A.G.R.); (J.C.A.N.); (E.C.P.); (L.G.N.); (V.E.V.D.); (P.O.T.); (E.G.R.)
| | - Pedro Abreu González
- Departamento de Ciencias Médicas Básicas, Unidad de Fisiología, Universidad de la Laguna, Tenerife, Canary Islands, 38320 La Laguna, Spain;
| | - Alen García Rodríguez
- Departamento de Medicina Interna, Universidad de La Laguna, Servicio de Medicina Interna, Hospital Universitario de Canarias, Tenerife, Canary Islands, 38320 La Laguna, Spain; (C.M.F.R.); (A.G.R.); (J.C.A.N.); (E.C.P.); (L.G.N.); (V.E.V.D.); (P.O.T.); (E.G.R.)
| | - Julio César Alvisa Negrín
- Departamento de Medicina Interna, Universidad de La Laguna, Servicio de Medicina Interna, Hospital Universitario de Canarias, Tenerife, Canary Islands, 38320 La Laguna, Spain; (C.M.F.R.); (A.G.R.); (J.C.A.N.); (E.C.P.); (L.G.N.); (V.E.V.D.); (P.O.T.); (E.G.R.)
| | - Elisa Cabañas Perales
- Departamento de Medicina Interna, Universidad de La Laguna, Servicio de Medicina Interna, Hospital Universitario de Canarias, Tenerife, Canary Islands, 38320 La Laguna, Spain; (C.M.F.R.); (A.G.R.); (J.C.A.N.); (E.C.P.); (L.G.N.); (V.E.V.D.); (P.O.T.); (E.G.R.)
| | - Lourdes González Navarrete
- Departamento de Medicina Interna, Universidad de La Laguna, Servicio de Medicina Interna, Hospital Universitario de Canarias, Tenerife, Canary Islands, 38320 La Laguna, Spain; (C.M.F.R.); (A.G.R.); (J.C.A.N.); (E.C.P.); (L.G.N.); (V.E.V.D.); (P.O.T.); (E.G.R.)
| | - Víctor Eugenio Vera Delgado
- Departamento de Medicina Interna, Universidad de La Laguna, Servicio de Medicina Interna, Hospital Universitario de Canarias, Tenerife, Canary Islands, 38320 La Laguna, Spain; (C.M.F.R.); (A.G.R.); (J.C.A.N.); (E.C.P.); (L.G.N.); (V.E.V.D.); (P.O.T.); (E.G.R.)
| | - Paula Ortega Toledo
- Departamento de Medicina Interna, Universidad de La Laguna, Servicio de Medicina Interna, Hospital Universitario de Canarias, Tenerife, Canary Islands, 38320 La Laguna, Spain; (C.M.F.R.); (A.G.R.); (J.C.A.N.); (E.C.P.); (L.G.N.); (V.E.V.D.); (P.O.T.); (E.G.R.)
| | - Emilio González Reimers
- Departamento de Medicina Interna, Universidad de La Laguna, Servicio de Medicina Interna, Hospital Universitario de Canarias, Tenerife, Canary Islands, 38320 La Laguna, Spain; (C.M.F.R.); (A.G.R.); (J.C.A.N.); (E.C.P.); (L.G.N.); (V.E.V.D.); (P.O.T.); (E.G.R.)
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8
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Denys A, Pedersen KB, Watt J, Norman AR, Osborn ML, Chen JR, Maimone C, Littleton S, Vasiliou V, Ronis MJJ. Binge Ethanol Exposure in Mice Represses Expression of Genes Involved in Osteoblast Function and Induces Expression of Genes Involved in Osteoclast Differentiation Independently of Endogenous Catalase. Toxicol Sci 2022; 185:232-245. [PMID: 34755883 PMCID: PMC9019842 DOI: 10.1093/toxsci/kfab135] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Excessive ethanol consumption is a risk factor for osteopenia. Since a previous study showed that transgenic female mice with overexpression of catalase are partially protected from ethanol-mediated trabecular bone loss, we investigated the role of endogenous catalase in skeletal ethanol toxicity comparing catalase knockout to wild-type mice. We hypothesized that catalase depletion would exacerbate ethanol effects. The mice were tested in a newly designed binge ethanol model, in which 12-week-old mice were exposed to 4 consecutive days of gavage with ethanol at 3, 3, 4, and 4.5 g ethanol/kg body weight. Binge ethanol decreased the concentration of serum osteocalcin, a marker of bone formation. The catalase genotype did not affect the osteocalcin levels. RNA sequencing of femoral shaft RNA from males was conducted. Ethanol exposure led to significant downregulation of genes expressed in cells of the osteoblastic lineage with a role in osteoblastic function and collagen synthesis, including the genes encoding major structural bone proteins. Binge ethanol further induced a smaller set of genes with a role in osteoclastic differentiation. Catalase depletion affected genes with expression in erythroblasts and erythrocytes. There was no clear interaction between binge ethanol and the catalase genotype. In an independent experiment, we confirmed that the binge ethanol effects on gene expression were reproducible and occurred throughout the skeleton in males. In conclusion, the binge ethanol exposure, independently of endogenous catalase, reduces expression of genes involved in osteoblastic function and induces expression of genes involved in osteoclast differentiation throughout the skeleton in males.
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Affiliation(s)
- Alexandra Denys
- Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
| | - Kim B Pedersen
- Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
| | - James Watt
- Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
| | - Allison R Norman
- Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
| | - Michelle L Osborn
- Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana 70803, USA
| | - Jin-Ran Chen
- Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children’s Nutrition Center, Little Rock, Arkansas 72202, USA
| | - Cole Maimone
- Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
| | - Shana Littleton
- Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
| | - Vasilis Vasiliou
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut 06510, USA
| | - Martin J J Ronis
- Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
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9
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Dose-response effects of alcohol on biochemical markers of bone turnover in non-human primates: Effects of species, sex and age of onset of drinking. Bone Rep 2022; 16:101159. [PMID: 34977281 PMCID: PMC8683688 DOI: 10.1016/j.bonr.2021.101159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 12/02/2021] [Accepted: 12/08/2021] [Indexed: 01/11/2023] Open
Abstract
Purpose Alcohol consumption suppressed bone turnover in male non-human primates; however, it is unclear the extent to which this effect depends upon biological variables. Using archived plasma samples, we investigated whether sex, age of onset of alcohol intake, and species influence the effects of graded increases in alcohol consumption on bone turnover markers. Methods 91 male and female macaques (rhesus and cynomolgus), ranging in age from 4 years (adolescent) to 10 years (adult) were required to increase their consumption of ethanol in 30-day increments: 0 g/kg/day, followed by 0.5 g/kg/day, 1.0 g/kg/day, and, finally, 1.5 g/kg/day. Plasma osteocalcin (formation), plasma CTX (resorption) and osteocalcin to CTX ratio (turnover balance) were measured during these intervals to assess the dose-response effects of alcohol. Results We detected no relationship between dose and osteocalcin when all monkeys were combined, but there was a significant effect of sex (lower levels in females) and interactions between alcohol dose and sex (osteocalcin levels increased with dose in rhesus females). In contrast, we detected a negative linear dose-response relationship for ethanol and CTX. We did not detect a relationship between dose and osteocalcin to CTX ratio overall, but there was a significant positive relationship detected in females (no change in males). Increased age predicted lower biomarker levels for both osteocalcin and CTX. Species was a significant predictor for osteocalcin and the osteocalcin to CTX ratio in these models. Conclusion These findings indicate that age, sex, and species influence bone turnover and support the concept that factors beyond quantity of alcohol affect skeletal response to alcohol consumption.
Age, sex, and species influenced markers of bone turnover in non-human primates. Ethanol consumption resulted in a dose-dependent reduction in CTX. Ethanol consumption resulted in increased osteocalcin in rhesus females.
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10
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Pillay D, Ndou R. Intrauterine alcohol exposure delays growth and disturbs trabecular morphology in 3-week-old Sprague − Dawley rat femur. J ANAT SOC INDIA 2022. [DOI: 10.4103/jasi.jasi_183_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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11
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Gomes LA, Cardoso KMM, Reis AMS, Melo FG, Serakides R, Ocarino NM. Effect of ethanol consumption during pregnancy and lactation on bone histomorphometry and in vitro osteogenic differentiation of bone marrow mesenchymal stem cells in maternal rats. Alcohol 2021; 95:51-64. [PMID: 34284095 DOI: 10.1016/j.alcohol.2021.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 07/12/2021] [Accepted: 07/12/2021] [Indexed: 11/26/2022]
Abstract
This study aimed to evaluate the effect of maternal ethanol consumption during gestation and lactation on bone mass and osteogenic differentiation of mesenchymal stem cells of the bone marrow (BMMSCs) in rats. Thirteen adult Wistar rats were used. The rats were mated, and after confirmation of gestation, (day 0) they were distributed in two groups: the control group and the ethanol-treated group. From the ninth day of gestation, the rats of the ethanol and control groups were administered 40% alcoholic solution (4 g ethanol/kg) and distilled water, respectively, daily via gavage until the thirtieth day of lactation. The BMMSCs were extracted from the right femurs and tibiae and cultured using an osteogenic medium for 7, 14, and 21 days. The conversion of MTT to formazan crystals, alkaline phosphatase activity, and percentages of cells per field were analyzed. The number of mineralized nodules per field was examined, and quantification of the gene transcripts for osteopontin, osteocalcin, and BMP-2 was evaluated on day 21 by real-time RT-PCR. Morphometric evaluations of the percentage of trabecular bone and cortical thickness in the left femur and tibia were performed. The means were compared by the Student's t-test, and the differences were considered significant if p < 0.05. The BMMSCs of the rats that consumed ethanol during gestation and lactation, when subjected to osteogenic differentiation in vitro, demonstrated higher conversion of MTT to formazan, higher alkaline phosphatase activity, a higher percentage of cells per field, higher expression of BMP-2, and higher synthesis of mineralized nodules when compared to those of control rat cells. However, there was no significant difference in the percentage of trabecular bone or cortical thickness between both groups. Hence, the consumption of ethanol during pregnancy and lactation did not alter the trabecular and cortical bone tissues of the femur and tibia compared with that of pregnant and lactating control rats that did not consume alcohol, despite BMMSCs showing higher osteogenic differentiation under in vitro conditions.
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12
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Making Sense of the Highly Variable Effects of Alcohol on Bone. Clin Rev Bone Miner Metab 2021. [DOI: 10.1007/s12018-021-09277-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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13
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The Impact of Sedentary Lifestyle, High-fat Diet, Tobacco Smoke, and Alcohol Intake on the Hematopoietic Stem Cell Niches. Hemasphere 2021; 5:e615. [PMID: 34291194 PMCID: PMC8288907 DOI: 10.1097/hs9.0000000000000615] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 06/07/2021] [Indexed: 11/25/2022] Open
Abstract
Hematopoietic stem and progenitor cells maintain hematopoiesis throughout life by generating all major blood cell lineages through the process of self-renewal and differentiation. In adult mammals, hematopoietic stem cells (HSCs) primarily reside in the bone marrow (BM) at special microenvironments called “niches.” Niches are thought to extrinsically orchestrate the HSC fate including their quiescence and proliferation. Insight into the HSC niches mainly comes from studies in mice using surface marker identification and imaging to visualize HSC localization and association with niche cells. The advantage of mouse models is the possibility to study the 3-dimensional BM architecture and cell interactions in an intact traceable system. However, this may not be directly translational to human BM. Sedentary lifestyle, unhealthy diet, excessive alcohol intake, and smoking are all known risk factors for various diseases including hematological disorders and cancer, but how do lifestyle factors impact hematopoiesis and the associated niches? Here, we review current knowledge about the HSC niches and how unhealthy lifestyle may affect it. In addition, we summarize epidemiological data concerning the influence of lifestyle factors on hematological disorders and malignancies.
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14
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Mishra R, Das N, Varshney R, Juneja K, Sircar D, Roy P. Betel leaf extract and its major component hydroxychavicol promote osteogenesis and alleviate glucocorticoid-induced osteoporosis in rats. Food Funct 2021; 12:6603-6625. [PMID: 34105538 DOI: 10.1039/d0fo02619k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Piper betle leaves possess several ethnomedicinal properties and are immensely used in traditional medicinal practices in regions of Asian and African subcontinents. However, their effects in treating skeletal complications are least known. In this study, we evaluated cellular and molecular effects of betel leaf extract (BLE) and its major phytoconstituent, hydroxychavicol (HCV) in promoting osteogenesis in vitro and alleviating glucocorticoid induced osteoporosis (GIO) in vivo. Both BLE and HCV markedly stimulated osteoblast differentiation of C3H10T1/2 cells with increased expression of RUNX2 and osteopontin through the GSK-3β/β-catenin-signaling pathway. Also, oral administration of BLE and HCV in GIO rats resulted in restoration of bone mass and tissue microarchitecture. Thus, with our findings we conclude that BLE and HCV promote osteogenesis of C3H10T1/2 cells via the GSK-3β/β-catenin pathway and alleviate GIO in rats.
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Affiliation(s)
- Rutusmita Mishra
- Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India.
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15
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Sattgast LH, Branscum AJ, Walter NA, Newman N, Gonzales SW, Grant KA, Turner RT, Iwaniec UT. Effects of graded increases in ethanol consumption on biochemical markers of bone turnover in young adult male cynomolgus macaques. Alcohol 2021; 91:53-59. [PMID: 33358984 DOI: 10.1016/j.alcohol.2020.12.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 10/25/2020] [Accepted: 12/17/2020] [Indexed: 12/14/2022]
Abstract
Chronic heavy alcohol use is often associated with reduced bone mineral density and altered bone turnover. However, the dose response effects of ethanol on bone turnover have not been established. This study examined the effects of graded increases of ethanol consumption on biochemical markers of bone turnover in young adult male cynomolgus macaques (Macaca fascicularis). For this study, 6.6-year-old (95% CI: 6.5, 6.7) male macaques were subjected to three 30-day sessions of increased ethanol intake over a 90-day interval. During the first 30 days, the monkeys drank a predetermined volume of ethanol corresponding to 0.5 g/kg/day, followed by 1.0 g/kg/day and 1.5 g/kg/day. Osteocalcin, a marker of bone formation, and carboxyterminal cross-linking telopeptide of type 1 collagen (CTX), a marker of resorption, were measured during each 30-day session. In addition, the ratio of osteocalcin to CTX was determined as a surrogate measure of global turnover balance. Mean osteocalcin decreased by 2.6 ng/mL (1.8, 3.5) for each one-half unit (0.5 g/kg/day) increase in dose (p < 0.001). Mean CTX decreased by 0.13 ng/mL (0.06, 0.20) for each one-half unit increase in dose (p < 0.001). Furthermore, there was an inverse relationship between dose and the ratio of osteocalcin to CTX, such that the mean ratio decreased by 0.9 (0.3, 1.5) for each one-half unit increase in dose (p = 0.01). In summary, male cynomolgus macaques had decreased blood osteocalcin and CTX, and osteocalcin to CTX ratio during the 90-day interval of graded increases in ethanol consumption, indicative of reduced bone turnover and negative turnover balance, respectively. These findings suggest that over the range ingested, ethanol resulted in a linear decrease in bone turnover. Furthermore, the negative bone turnover balance observed is consistent with reported effects of chronic alcohol intake on the skeleton.
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16
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Ng JS, Chin KY. Potential mechanisms linking psychological stress to bone health. Int J Med Sci 2021; 18:604-614. [PMID: 33437195 PMCID: PMC7797546 DOI: 10.7150/ijms.50680] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 11/30/2020] [Indexed: 02/06/2023] Open
Abstract
Chronic psychological stress affects many body systems, including the skeleton, through various mechanisms. This review aims to provide an overview of the factors mediating the relationship between psychological stress and bone health. These factors can be divided into physiological and behavioural changes induced by psychological stress. The physiological factors involve endocrinological changes, such as increased glucocorticoids, prolactin, leptin and parathyroid hormone levels and reduced gonadal hormones. Low-grade inflammation and hyperactivation of the sympathetic nervous system during psychological stress are also physiological changes detrimental to bone health. The behavioural changes during mental stress, such as altered dietary pattern, cigarette smoking, alcoholism and physical inactivity, also threaten the skeletal system. Psychological stress may be partly responsible for epigenetic regulation of skeletal development. It may also mediate the relationship between socioeconomic status and bone health. However, more direct evidence is required to prove these hypotheses. In conclusion, chronic psychological stress should be recognised as a risk factor of osteoporosis and stress-coping methods should be incorporated as part of the comprehensive osteoporosis-preventing strategy.
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Affiliation(s)
- Jia-Sheng Ng
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Malaysia
| | - Kok-Yong Chin
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Malaysia
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17
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Impact of Alcohol on Bone Health, Homeostasis and Fracture repair. CURRENT PATHOBIOLOGY REPORTS 2020; 8:75-86. [PMID: 33767923 DOI: 10.1007/s40139-020-00209-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Purpose of review Alcohol use continues to rise globally. We review the current literature on the effect of alcohol on bone health, homeostasis and fracture repair to highlight what has been learned in people and animal models of alcohol consumption. Recent findings Recently, forkhead box O (FoxO) has been found to be upregulated and activated in mesenchymal stem cells (MSC) exposed to alcohol. FoxO has also been found to modulate Wnt/β-catenin signaling, which is necessary for MSC differentiation. Recent evidence suggests alcohol activates FoxO signaling, which may be dysregulating Wnt/β-catenin signaling in MSCs cultured in alcohol. Summary This review highlights the negative health effects learned from people and chronic and episodic binge alcohol consumption animal models. Studies using chronic alcohol exposure or alcohol exposure then bone fracture repair model have explored several different cellular and molecular signaling pathways important for bone homeostasis and fracture repair, and offer potential for future experiments to explore additional signaling pathways that may be dysregulated by alcohol exposure.
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18
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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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19
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Tavasolian F, Hosseini AZ, Mirzaei A, Abdollahi E, Jandaghi P, Soudi S, Naderi M, Saburi E, Momtazi-Borojeni AA, Johnston TP, Sahebkar A. Unfolded protein response-mediated modulation of mesenchymal stem cells. IUBMB Life 2020; 72:187-197. [PMID: 31444957 DOI: 10.1002/iub.2154] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 08/06/2019] [Indexed: 12/21/2022]
Abstract
The endoplasmic reticulum (ER) receives unfolded proteins predestined for the secretory pathway or to be incorporated as transmembrane proteins. The ER has to accommodate the proper folding and glycosylation of these proteins and also to properly incorporate transmembrane proteins. However, under various circumstances, the proteins shuttling through the ER can be misfolded and undergo aggregation, which causes activation of the unfolded protein response (UPR). The UPR is mediated through three primary pathways: activating transcription factor-6, inositol-requiring enzyme-1 (IRE1), and PKR-like endoplasmic reticulum kinase, which up-regulate ER folding chaperones and temporarily suppress protein translation. The UPR can be both cytoprotective and/or cytotoxic depending on the duration of UPR activation and the type of host cell. Proteostasis controls stem cell function, while stress responses affect stem cell identity and differentiation. The present review aimed to explore and discuss the effects of the UPR pathways on mesenchymal stem cells.
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Affiliation(s)
- Fataneh Tavasolian
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
- Department of Human Genetics, McGill University, Montreal, Quebec, Canada
| | - Ahmad Z Hosseini
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ali Mirzaei
- Cellular & Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Elham Abdollahi
- Halal Research Center of IRI, FDA, Tehran, Iran
- Department of Medical Immunology and Allergy, Student Research Committee, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Mater Research Institute, University of Queensland, Brisbane, Australia
| | | | - Sara Soudi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mahmood Naderi
- Cell-Based Therapies Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ehsan Saburi
- Clinical Research Development Center, Imam Hasan Hospital, North Khorasan University of Medical Sciences, Bojnurd, Iran
- Immunogenetic and Cell Culture Department, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Abbas Momtazi-Borojeni
- Halal Research Center of IRI, FDA, Tehran, Iran
- Nanotechnology Research Center, Department of Medical Biotechnology, Student Research Committee, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Thomas P Johnston
- Division of Pharmacology and Pharmaceutical Science, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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20
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Le Daré B, Lagente V, Gicquel T. Ethanol and its metabolites: update on toxicity, benefits, and focus on immunomodulatory effects. Drug Metab Rev 2019; 51:545-561. [PMID: 31646907 DOI: 10.1080/03602532.2019.1679169] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
This article summarizes recent experimental and epidemiological data on the toxic and beneficial effects of ethanol and its metabolites (acetaldehyde), and focuses on their immunomodulatory effects. The section dealing with the toxic effects of alcohol focuses on its chronic toxicity (liver disorders, carcinogenic effects, cardiovascular disorders, neuropsychic disorders, addiction and withdrawal syndrome, hematologic disorders, reprotoxicity, osteoporosis) although acute toxicity is considered. The role of oxidative metabolism of ethanol by alcohol dehydrogenase, cytochrome P450 2E1, and aldehyde dehydrogenase, as well as the impact of genetic polymorphism in its physiopathology are also highlighted. The section dealing with the beneficial effects of low to moderate alcohol consumption (on cardiovascular system, diabetes, the nervous system and sensory organs, autoimmune diseases, and rheumatology) highlights the importance of anti-inflammatory and immunomodulatory effects in these observations. This knowledge, enriched by a focus on the immunomodulatory effects of ethanol and its metabolites, in particular on the NLRP3 inflammasome pathway, might facilitate the development of treatments that can reduce ethanol's harmful effects or accentuate its beneficial effects.
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Affiliation(s)
- Brendan Le Daré
- Univ Rennes, INSERM, INRA, Institut NuMeCan (Nutrition, Metabolisms and Cancer), Rennes, France.,Pharmacy Unit, Pontchaillou University Hospital, Rennes, France.,Forensic and Toxicology Laboratory, Pontchaillou University Hospital, Rennes, France
| | - Vincent Lagente
- Univ Rennes, INSERM, INRA, Institut NuMeCan (Nutrition, Metabolisms and Cancer), Rennes, France
| | - Thomas Gicquel
- Univ Rennes, INSERM, INRA, Institut NuMeCan (Nutrition, Metabolisms and Cancer), Rennes, France.,Forensic and Toxicology Laboratory, Pontchaillou University Hospital, Rennes, France
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21
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Bilateral spontaneous simultaneous femoral neck occult fracture in a middle-aged man due to osteoporosis and vitamin D deficiency osteomalacia: A case report and literature review. Int J Surg Case Rep 2019; 60:358-362. [PMID: 31295706 PMCID: PMC6616359 DOI: 10.1016/j.ijscr.2019.06.058] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 06/25/2019] [Accepted: 06/26/2019] [Indexed: 02/07/2023] Open
Abstract
Physicians should take spontaneous femoral neck occult fracture into consideration if they report groin pain or difficulty in walking, even when findings from plain X-ray are normal. In a patient with spontaneous femoral neck occult fracture, diagnosing and treating the underlying etiology of osteoporosis and osteomalacia are essential for improving prognosis. This is the first report of a case of bilateral spontaneous simultaneous occult fracture of the femoral neck caused by osteoporosis and osteomalacia in a middle aged man. Introduction Bilateral stress fracture of the femoral neck is very rarely seen in healthy young patients who are neither athletes nor military recruits. Presentation of case The present report describes a 51-year-old male patient, not an athlete and with no previous history of disease, who developed bilateral stress fracture of the femoral neck without displacement. Discussion Simultaneous bilateral femoral neck fracture is a rare injury. In the present case, two factors predisposed to bilateral occult fracture of the femoral neck. The first was osteoporosis due to the patient’s smoking and alcohol abuse. The second was vitamin D deficiency osteomalacia associated with inadequate sun exposure. Conclusion All patients who present with spontaneous hip pain should be evaluated for osteoporosis and osteomalacia and assessed for underlying occult fracture if they report groin pain or difficulty in walking, even when findings from plain X-ray are normal, to improve prognosis in this rare and serious condition.
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22
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Ehnert S, Aspera-Werz RH, Ruoß M, Dooley S, Hengstler JG, Nadalin S, Relja B, Badke A, Nussler AK. Hepatic Osteodystrophy-Molecular Mechanisms Proposed to Favor Its Development. Int J Mol Sci 2019; 20:2555. [PMID: 31137669 PMCID: PMC6566554 DOI: 10.3390/ijms20102555] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 05/14/2019] [Accepted: 05/22/2019] [Indexed: 02/07/2023] Open
Abstract
Almost all patients with chronic liver diseases (CLD) show altered bone metabolism. Depending on the etiology, this manifests in a severe osteoporosis in up to 75% of the affected patients. Due to high prevalence, the generic term hepatic osteodystrophy (HOD) evolved, describing altered bone metabolism, decreased bone mineral density, and deterioration of bone structure in patients with CLD. Once developed, HOD is difficult to treat and increases the risk of fragility fractures. Existing fractures affect the quality of life and, more importantly, long-term prognosis of these patients, which presents with increased mortality. Thus, special care is required to support the healing process. However, for early diagnosis (reduce fracture risk) and development of adequate treatment strategies (support healing of existing fractures), it is essential to understand the underlying mechanisms that link disturbed liver function with this bone phenotype. In the present review, we summarize proposed molecular mechanisms favoring the development of HOD and compromising the healing of associated fractures, including alterations in vitamin D metabolism and action, disbalances in transforming growth factor beta (TGF-β) and bone morphogenetic protein (BMP) signaling with histone deacetylases (HDACs) as secondary regulators, as well as alterations in the receptor activator of nuclear factor kappa B ligand (RANKL)-osteoprotegerin (OPG) system mediated by sclerostin. Based on these mechanisms, we give an overview on the limitations of early diagnosis of HOD with established serum markers.
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Affiliation(s)
- Sabrina Ehnert
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
| | - Romina H Aspera-Werz
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
| | - Marc Ruoß
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
| | - Steven Dooley
- Department of Medicine II, Molecular Hepatology, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
| | - Jan G Hengstler
- IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, 44139 Dortmund, Germany.
| | - Silvio Nadalin
- Department of General, Visceral and Transplant Surgery, University Hospital Tuebingen, 72076 Tuebingen, Germany.
| | - Borna Relja
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590 Frankfurt, Germany.
| | - Andreas Badke
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
| | - Andreas K Nussler
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
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Li S, Zhang XH, Zhou GD, Wang JF. Delirium after primary percutaneous coronary intervention in aged individuals with acute ST-segment elevation myocardial infarction: A retrospective study. Exp Ther Med 2019; 17:3807-3813. [PMID: 30988767 DOI: 10.3892/etm.2019.7398] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 12/31/2018] [Indexed: 11/05/2022] Open
Abstract
The present prospective study aimed to investigate the incidence and risk factors of delirium after primary percutaneous coronary intervention (PCI) in older adults with acute ST-segment elevation myocardial infarction (STEMI). A total of 111 patients (age, ≥65 years) with acute STEMI following primary PCI were included in the present study. Neurocognitive testing was performed using the Mini-mental State Examination on the first day of hospitalization. Post-operative delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit within the first four post-operative days. A total of 32 patients (28.8%) developed delirium after primary PCI. The independent predictors of delirium were older age [odds ratio (OR)=1.192, 95% confidence interval (CI)=1.07-1.328, P=0.001], living alone (OR=4.827, 95% CI=1.315-17.725, P=0.018), history of alcohol abuse (OR=3.875, 95% CI=1.168-12.857, P=0.026), longer duration of primary PCI (OR=1.152, 95% CI=1.077-1.232, P<0.001) and post-operative pain (current pain; OR=7.663, 95% CI=1.432-41.02, P=0.017). Compared to the patients without delirium, the participants who developed delirium had longer hospital stays and a higher rate of re-admission within 30 days after discharge. The mortality within one year after discharge (one-year mortality) was similar between patients with and without delirium. In conclusion, older patients (age, ≥65 years) with acute STEMI are at a relatively high risk of delirium following primary PCI. Higher age (≥65 years), living alone, history of alcohol dependence, longer length of primary PCI (>50 min) and post-operative pain (current pain) were determined to be risk factors for delirium after primary PCI in the present cohort.
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Affiliation(s)
- Sheng Li
- Department of Cardiology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China
| | - Xiao-Hong Zhang
- Department of Cardiology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China
| | - Gen-Dong Zhou
- Department of Cardiology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China
| | - Jian-Fei Wang
- Department of Cardiology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China
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24
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Okuda T, Naruo M, Iijima O, Igarashi T, Katsuyama M, Maruyama M, Akimoto T, Ohno Y, Haseba T. The Contribution of Alcohol Dehydrogenase 3 to the Development of Alcoholic Osteoporosis in Mice. J NIPPON MED SCH 2018; 85:322-329. [DOI: 10.1272/jnms.jnms.2018_85-52] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
| | | | - Osamu Iijima
- Office for Research Administrative Support, Center for Strategic Research Initiative, Nippon Medical School
| | | | | | - Motoyo Maruyama
- Division of Laboratory Animal Science, Nippon Medical School
| | - Toshio Akimoto
- Division of Laboratory Animal Science, Nippon Medical School
| | | | - Takeshi Haseba
- Department of Legal Medicine, Nippon Medical School
- Department of Legal Medicine, Kanagawa Dental University
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25
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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: 78] [Impact Index Per Article: 11.1] [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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26
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Ulhøi MP, Meldgaard K, Steiniche T, Odgaard A, Vesterby A. Chronic Alcohol Abuse Leads to Low Bone Mass with No General Loss of Bone Structure or Bone Mechanical Strength,. J Forensic Sci 2016; 62:131-136. [PMID: 27864963 DOI: 10.1111/1556-4029.13256] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Revised: 04/26/2016] [Accepted: 05/14/2016] [Indexed: 11/27/2022]
Affiliation(s)
- Maiken Parm Ulhøi
- Department of Forensic Medicine; University of Aarhus; Palle Juul-Jensens Boulevard 99 DK-8200 Arhus N Denmark
| | - Karoline Meldgaard
- Department of Internal Medicine; Regional Hospital West Jutland; Gl. Landevej 61 DK-7400 Herning Denmark
| | - Torben Steiniche
- Institute of Pathology; Aarhus University Hospital; Noerrebrogade 44 DK-8000 Aarhus Denmark
| | - Anders Odgaard
- Department of Orthopaedics; Copenhagen University Hospital Gentofte; Kildegaardsvej 28 DK-2900 Hellerup Denmark
| | - Annie Vesterby
- Department of Forensic Medicine; University of Aarhus; Palle Juul-Jensens Boulevard 99 DK-8200 Arhus N Denmark
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27
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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: 43] [Impact Index Per Article: 4.8] [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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28
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Bone health and vitamin D status in alcoholic liver disease. Indian J Gastroenterol 2016; 35:253-9. [PMID: 27246833 DOI: 10.1007/s12664-016-0652-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 03/26/2016] [Indexed: 02/07/2023]
Abstract
Alcohol consumption is harmful to many organs and tissues, including bones, and it leads to osteoporosis. Hepatic osteodystrophy is abnormal bone metabolism that has been defined in patients with chronic liver disease (CLD), including osteopenia, osteoporosis, and osteomalacia. Decreased bone density in patients with CLD results from decreased bone formation or increased bone resorption. The prevalence of osteopenia in alcoholic liver disease (ALD) patients is between 34 % and 48 %, and the prevalence of osteoporosis is between 11 % and 36 %. Cirrhosis is also a risk factor for osteoporosis. The liver has an important role in vitamin D metabolism. Ninety percent of patients with alcoholic liver cirrhosis have vitamin D inadequacy (<80 nmol/L). The lowest serum vitamin D levels were observed in patients with Child-Pugh class C. Bone densitometry is used for the definitive diagnosis of osteoporosis in ALD. There are no specific controlled clinical studies on the treatment of osteoporosis in patients with ALD. Alcohol cessation and abstinence are principal for the prevention and treatment of osteoporosis in ALD patients, and the progression of osteopenia can be stopped in this way. Calcium and vitamin D supplementation is recommended, and associated nutritional deficiencies should also be corrected. The treatment recommendations of osteoporosis in CLD tend to be extended to ALD. Bisphosphonates have been proven to be effective in increasing bone mineral density (BMD) in chronic cholestatic disease and post-transplant patients, and they can be used in ALD patients. Randomized studies assessing the management of CLD-associated osteoporosis and the development of new drugs for osteoporosis may change the future. Here, we will discuss bone quality, vitamin D status, mechanism of bone effects, and diagnosis and treatment of osteoporosis in ALD.
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29
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Wintermeyer E, Ihle C, Ehnert S, Stöckle U, Ochs G, de Zwart P, Flesch I, Bahrs C, Nussler AK. Crucial Role of Vitamin D in the Musculoskeletal System. Nutrients 2016; 8:319. [PMID: 27258303 PMCID: PMC4924160 DOI: 10.3390/nu8060319] [Citation(s) in RCA: 139] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 05/10/2016] [Accepted: 05/11/2016] [Indexed: 12/17/2022] Open
Abstract
Vitamin D is well known to exert multiple functions in bone biology, autoimmune diseases, cell growth, inflammation or neuromuscular and other immune functions. It is a fat-soluble vitamin present in many foods. It can be endogenously produced by ultraviolet rays from sunlight when the skin is exposed to initiate vitamin D synthesis. However, since vitamin D is biologically inert when obtained from sun exposure or diet, it must first be activated in human beings before functioning. The kidney and the liver play here a crucial role by hydroxylation of vitamin D to 25-hydroxyvitamin D in the liver and to 1,25-dihydroxyvitamin D in the kidney. In the past decades, it has been proven that vitamin D deficiency is involved in many diseases. Due to vitamin D's central role in the musculoskeletal system and consequently the strong negative impact on bone health in cases of vitamin D deficiency, our aim was to underline its importance in bone physiology by summarizing recent findings on the correlation of vitamin D status and rickets, osteomalacia, osteopenia, primary and secondary osteoporosis as well as sarcopenia and musculoskeletal pain. While these diseases all positively correlate with a vitamin D deficiency, there is a great controversy regarding the appropriate vitamin D supplementation as both positive and negative effects on bone mineral density, musculoskeletal pain and incidence of falls are reported.
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Affiliation(s)
- Elke Wintermeyer
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Christoph Ihle
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Sabrina Ehnert
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Ulrich Stöckle
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Gunnar Ochs
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Peter de Zwart
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Ingo Flesch
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Christian Bahrs
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Andreas K Nussler
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
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30
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Gaddini GW, Turner RT, Grant KA, Iwaniec UT. Alcohol: A Simple Nutrient with Complex Actions on Bone in the Adult Skeleton. Alcohol Clin Exp Res 2016; 40:657-71. [PMID: 26971854 DOI: 10.1111/acer.13000] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2015] [Accepted: 01/02/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Alcohol is an important nonessential component of diet, but the overall impact of drinking on bone health, especially at moderate levels, is not well understood. Bone health is important because fractures greatly reduce quality of life and are a major cause of morbidity and mortality in the elderly. Regular alcohol consumption is most common following skeletal maturity, emphasizing the importance of understanding the skeletal consequences of drinking in adults. METHODS This review focuses on describing the complex effects of alcohol on the adult skeleton. Studies assessing the effects of alcohol on bone in adult humans as well as skeletally mature animal models published since the year 2000 are emphasized. RESULTS Light to moderate alcohol consumption is generally reported to be beneficial, resulting in higher bone mineral density (BMD) and reduced age-related bone loss, whereas heavy alcohol consumption is generally associated with decreased BMD, impaired bone quality, and increased fracture risk. Bone remodeling is the principal mechanism for maintaining a healthy skeleton in adults and dysfunction in bone remodeling can lead to bone loss and/or decreased bone quality. Light to moderate alcohol may exert beneficial effects in older individuals by slowing the rate of bone remodeling, but the impact of light to moderate alcohol on bone remodeling in younger individuals is less certain. The specific effects of alcohol on bone remodeling in heavy drinkers are even less certain because the effects are often obscured by unhealthy lifestyle choices, alcohol-associated disease, and altered endocrine signaling. CONCLUSIONS Although there have been advances in understanding the complex actions of alcohol on bone, much remains to be determined. Limited evidence implicates age, skeletal site evaluated, duration, and pattern of drinking as important variables. Few studies systematically evaluating the impact of these factors have been conducted and should be made a priority for future research. In addition, studies performed in skeletally mature animals have potential to reveal mechanistic insights into the precise actions of alcohol and associated comorbidity factors on bone remodeling.
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Affiliation(s)
- Gino W Gaddini
- Skeletal Biology Laboratory, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, Oregon
| | - Russell T Turner
- Skeletal Biology Laboratory, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, Oregon.,Center for Healthy Aging Research, Oregon State University, Corvallis, Oregon
| | - Kathleen A Grant
- Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon
| | - Urszula T Iwaniec
- Skeletal Biology Laboratory, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, Oregon.,Center for Healthy Aging Research, Oregon State University, Corvallis, Oregon
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González-Reimers E, Quintero-Platt G, Rodríguez-Rodríguez E, Martínez-Riera A, Alvisa-Negrín J, Santolaria-Fernández F. Bone changes in alcoholic liver disease. World J Hepatol 2015; 7:1258-1264. [PMID: 26019741 PMCID: PMC4438500 DOI: 10.4254/wjh.v7.i9.1258] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Revised: 01/31/2015] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
Abstract
Alcoholism has been associated with growth impairment, osteomalacia, delayed fracture healing, and aseptic necrosis (primarily necrosis of the femoral head), but the main alterations observed in the bones of alcoholic patients are osteoporosis and an increased risk of fractures. Decreased bone mass is a hallmark of osteoporosis, and it may be due either to decreased bone synthesis and/or to increased bone breakdown. Ethanol may affect both mechanisms. It is generally accepted that ethanol decreases bone synthesis, and most authors have reported decreased osteocalcin levels (a “marker” of bone synthesis), but some controversy exists regarding the effect of alcohol on bone breakdown, and, indeed, disparate results have been reported for telopeptide and other biochemical markers of bone resorption. In addition to the direct effect of ethanol, systemic alterations such as malnutrition, malabsorption, liver disease, increased levels of proinflammatory cytokines, alcoholic myopathy and neuropathy, low testosterone levels, and an increased risk of trauma, play contributory roles. The treatment of alcoholic bone disease should be aimed towards increasing bone formation and decreasing bone degradation. In this sense, vitamin D and calcium supplementation, together with biphosphonates are essential, but alcohol abstinence and nutritional improvement are equally important. In this review we study the pathogenesis of bone changes in alcoholic liver disease and discuss potential therapies.
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32
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Gaddini GW, Grant KA, Woodall A, Stull C, Maddalozzo GF, Zhang B, Turner RT, Iwaniec UT. Twelve months of voluntary heavy alcohol consumption in male rhesus macaques suppresses intracortical bone remodeling. Bone 2015; 71:227-36. [PMID: 25451322 PMCID: PMC4291183 DOI: 10.1016/j.bone.2014.10.025] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Revised: 10/19/2014] [Accepted: 10/31/2014] [Indexed: 12/25/2022]
Abstract
Chronic heavy alcohol consumption is a risk factor for cortical bone fractures in males. The increase in fracture risk may be due, in part, to reduced bone quality. Intracortical (osteonal) bone remodeling is the principle mechanism for maintaining cortical bone quality. However, it is not clear how alcohol abuse impacts intracortical bone remodeling. This study investigated the effects of long-duration heavy alcohol consumption on intracortical bone remodeling in a non-human primate model. Following a 4-month induction period, male rhesus macaques (Macaca mulatta, n=21) were allowed to voluntarily self-administer water or alcohol (4% ethanol w/v) for 22h/d, 7 d/wk for 12months. Control monkeys (n=13) received water and an isocaloric maltose-dextrin solution. Tetracycline hydrochloride was administered orally 17 and 3days prior to sacrifice for determination of active mineralization sites. Animals in the alcohol group consumed 2.7±0.2g alcohol/kg/d (mean±SE) during the 12months of self-administration, resulting in a mean daily blood alcohol concentration of 77±9mg/dl from samples taken at 7h after the start of a daily session. However, blood alcohol concentration varied widely from day to day, with peak levels exceeding 250mg/dl, modeling a binge-drinking pattern of alcohol consumption. The skeletal response to alcohol was determined by densitometry, microcomputed tomography and histomorphometry. Significant differences in tibial bone mineral content, bone mineral density, and cortical bone architecture (cross-sectional volume, cortical volume, marrow volume, cortical thickness, and polar moment of inertia) in the tibial diaphysis were not detected with treatment. However, cortical porosity was lower (1.8±0.5 % versus 0.6±0.1 %, p=0.021) and labeled osteon density was lower (0.41±0.2/mm(2)versus 0.04±0.01/mm(2), p<0.003) in alcohol-consuming monkeys compared to controls, indicating a reduced rate of intracortical bone remodeling. In concordance, plasma CTx was lower (2.5±0.3ng/ml versus 1.7±0.1ng/ml, p=0.028) in the alcohol group. These results suggest that chronic heavy alcohol consumption may negatively impact bone health, in part, by suppressing intracortical bone remodeling.
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Affiliation(s)
- Gino W Gaddini
- Skeletal Biology Laboratory, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA
| | - Kathleen A Grant
- Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA
| | - Andrew Woodall
- Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA
| | - Cara Stull
- Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA
| | - Gianni F Maddalozzo
- Skeletal Biology Laboratory, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA
| | - Bo Zhang
- Division of Biostatistics, Office of Surveillance and Biometrics, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD 20993, USA
| | - Russell T Turner
- Skeletal Biology Laboratory, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA; Center for Healthy Aging Research, Oregon State University, Corvallis, OR 97331, USA
| | - Urszula T Iwaniec
- Skeletal Biology Laboratory, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA; Center for Healthy Aging Research, Oregon State University, Corvallis, OR 97331, USA.
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Fracture risk in hepatitis C virus infected persons: results from the DANVIR cohort study. J Hepatol 2014; 61:15-21. [PMID: 24650694 DOI: 10.1016/j.jhep.2014.03.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2013] [Revised: 03/06/2014] [Accepted: 03/07/2014] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS The association between Hepatitis C virus (HCV)-infection and fracture risk is not well characterized. We compared fracture risk between HCV-seropositive (HCV-exposed) patients and the general population and between patients with cleared and chronic HCV-infection. METHODS Outcome measures were time to first fracture at any site, time to first low-energy and first non-low-energy (other) fracture in 12,013 HCV-exposed patients from the DANVIR cohort compared with a general population control cohort (n=60,065) matched by sex and age. Within DANVIR, 4500 patients with chronic HCV-infection and 2656 patients with cleared HCV-infection were studied. RESULTS Compared with population controls, HCV-exposed patients had increased overall risk of fracture [adjusted incidence rate ratio (aIRR) 2.15, 95% Confidence Interval (CI) 2.03-2.28], increased risk of low-energy fracture (aIRR 2.13, 95% CI: 1.93-2.35) and of other fracture (aIRR 2.18, 95% CI: 2.02-2.34). Compared with cleared HCV-infection, chronic HCV-infection was not associated with increased risk of fracture at any site (aIRR 1.08, 95% CI: 0.97-1.20), or other fracture (aIRR 1.04, 95% CI: 0.91-1.19). The aIRR for low-energy fracture was 1.20 (95% CI: 0.99-1.44). CONCLUSIONS HCV-exposed patients had increased risk of all fracture types. In contrast, overall risk of fracture did not differ between patients with chronic vs. cleared HCV-infection, although chronic HCV-infection might be associated with a small excess risk of low-energy fractures. Our study suggests that fracture risk in HCV-infected patients is multi-factorial and mainly determined by lifestyle-related factors associated with HCV-exposure.
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Chen CH, Ferreira JCB, Gross ER, Mochly-Rosen D. Targeting aldehyde dehydrogenase 2: new therapeutic opportunities. Physiol Rev 2014; 94:1-34. [PMID: 24382882 DOI: 10.1152/physrev.00017.2013] [Citation(s) in RCA: 469] [Impact Index Per Article: 42.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
A family of detoxifying enzymes called aldehyde dehydrogenases (ALDHs) has been a subject of recent interest, as its role in detoxifying aldehydes that accumulate through metabolism and to which we are exposed from the environment has been elucidated. Although the human genome has 19 ALDH genes, one ALDH emerges as a particularly important enzyme in a variety of human pathologies. This ALDH, ALDH2, is located in the mitochondrial matrix with much known about its role in ethanol metabolism. Less known is a new body of research to be discussed in this review, suggesting that ALDH2 dysfunction may contribute to a variety of human diseases including cardiovascular diseases, diabetes, neurodegenerative diseases, stroke, and cancer. Recent studies suggest that ALDH2 dysfunction is also associated with Fanconi anemia, pain, osteoporosis, and the process of aging. Furthermore, an ALDH2 inactivating mutation (termed ALDH2*2) is the most common single point mutation in humans, and epidemiological studies suggest a correlation between this inactivating mutation and increased propensity for common human pathologies. These data together with studies in animal models and the use of new pharmacological tools that activate ALDH2 depict a new picture related to ALDH2 as a critical health-promoting enzyme.
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35
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Donaghy ME, Mutrie N. Is exercise beneficial in the treatment and rehabilitation of the problem drinker? A critical review. PHYSICAL THERAPY REVIEWS 2013. [DOI: 10.1179/ptr.1999.4.3.153] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
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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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Kelly KN, Kelly C. Pattern and cause of fractures in patients who abuse alcohol: what should we do about it? Postgrad Med J 2013; 89:578-83. [DOI: 10.1136/postgradmedj-2013-131990] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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González-Reimers E, Martín-González C, de la Vega-Prieto MJ, Pelazas-González R, Fernández-Rodríguez C, López-Prieto J, Alvisa-Negrín J, Santolaria-Fernández F. Serum sclerostin in alcoholics: a pilot study. Alcohol Alcohol 2013; 48:278-82. [PMID: 23296214 DOI: 10.1093/alcalc/ags136] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
AIMS Sclerostin is an endogenous inhibitor of the Wnt/β-catenin pathway secreted by osteocytes, which inhibits osteoblast function, differentiation and survival. As a consequence, sclerostin tends to decrease bone mass. Alcoholics frequently present osteoporosis, mainly due to decreased bone synthesis. The behaviour of sclerostin in these patients is unknown. The aim of this work was to analyse the relationship between serum sclerostin levels and bone mineral density (BMD), ethanol consumption, nutritional status, liver function derangement and biomarkers of bone homeostasis in alcoholic patients. METHODS We included 31 alcoholic patients, of whom 11 were infected with Hepatitis C virus (HCV) and 7 age and sex-matched controls. All underwent densitometry, and serum sclerostin, osteocalcin, collagen telopeptide, parathyroid hormone (PTH), vitamin D, cortisol and testosterone were determined. RESULTS Sclerostin levels were significantly higher in patients (30.95 ± 18.91 pmol/l) than controls (t = 4.4; P < 0.001), especially in non-HCV patients; they showed an inverse correlation with osteocalcin, prothrombin activity and serum albumin, and a direct correlation with bilirubin and telopeptide, but not with BMD, nutritional status or ethanol intake. CONCLUSIONS Serum sclerostin was raised in alcoholic patients, and it correlated with decreased markers of bone synthesis and increased markers of bone breakdown. The elevation in sclerostin levels was clearly related with liver function, but not with ethanol intake, nutritional status or concomitant HCV infection.
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Affiliation(s)
- E González-Reimers
- Servicio de Medicina Interna, Hospital Universitario de Canarias, Ofra s/n, Tenerife, Canary Islands, Spain.
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Pelazas-González R, González-Reimers E, Alemán-Valls MR, Santolaria-Fernández F, López-Prieto J, González-Díaz A, Gómez-Sirvent JL, de la Vega-Prieto MJ. Bone alterations in hepatitis C virus infected patients. Eur J Intern Med 2013; 24:92-6. [PMID: 23026411 DOI: 10.1016/j.ejim.2012.09.007] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2012] [Revised: 08/20/2012] [Accepted: 09/07/2012] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS Most studies have shown that patients with chronic hepatitis C virus (HCV) infection are affected by osteoporosis. However, liver function impairment and deranged nutrition may both play a role in the bone alterations observed. In some works no osteoporosis was found, and some cases of osteosclerosis have been reported. The aim of the study is to assess bone alterations in treatment-naïve, well-nourished HCV patients, in order to discern whether or not HCV infection causes osteoporosis. METHODS Whole-body bone densitometry and assessment of T-score at lumbar spine and hip were performed to 40 patients and 40 age- and sex-matched controls, with a Lunar Prodigy Advance (General Electric, Piscataway, NJ, USA). All the patients underwent liver biopsy. Nutritional evaluation was performed by subjective nutritional assessment, body mass index (BMI), and densitometric assessment of total lean mass and total fat mass. Serum osteocalcin, osteoprotegerin, RANKL, PTH, crosslaps, vitamin D3, testosterone, IGF-1, and estradiol were determined. RESULTS Patients did not show differences in total bone mineral density (BMD) or T-score with controls. On the contrary, about a third of them showed positive T scores. Patients showed lower IGF-1, vitamin D3 and testosterone, but higher telopeptide levels, and a trend to higher osteoprotegerin levels. Multivariate analyses disclosed that age, sex, and total lean mass were the only parameters independently related with BMD. CONCLUSIONS Therefore, chronic HCV infection in well nourished patients with preserved liver function does not cause osteoporosis.
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Affiliation(s)
- Ricardo Pelazas-González
- Servicio de Medicina Interna, Hospital Universitario, Universidad de La Laguna, Tenerife, Canary Islands, Spain
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Malik P, Gasser RW, Moncayo R, Kemmler G, Wolfgang Fleischhacker W. Markers of Bone Resorption and Formation During Abstinence in Male Alcoholic Patients. Alcohol Clin Exp Res 2012; 36:2059-64. [DOI: 10.1111/j.1530-0277.2012.01834.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2011] [Accepted: 03/11/2012] [Indexed: 02/06/2023]
Affiliation(s)
- Peter Malik
- Department of Psychiatry & Psychotherapy; Medical University Innsbruck; Innsbruck; Austria
| | - Rudolf W. Gasser
- Department of Internal Medicine; Medical University Innsbruck; Innsbruck; Austria
| | - Roy Moncayo
- Department of Nuclear Medicine; Medical University Innsbruck; Innsbruck; Austria
| | - Georg Kemmler
- Department of Psychiatry & Psychotherapy; Medical University Innsbruck; Innsbruck; Austria
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Guañabens N, Parés A. Osteoporosis en la cirrosis hepática. GASTROENTEROLOGIA Y HEPATOLOGIA 2012; 35:411-20. [DOI: 10.1016/j.gastrohep.2012.01.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2012] [Accepted: 01/31/2012] [Indexed: 12/22/2022]
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Maurel DB, Boisseau N, Benhamou CL, Jaffre C. Alcohol and bone: review of dose effects and mechanisms. Osteoporos Int 2012; 23:1-16. [PMID: 21927919 DOI: 10.1007/s00198-011-1787-7] [Citation(s) in RCA: 218] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2011] [Accepted: 08/19/2011] [Indexed: 12/14/2022]
Abstract
Alcohol is widely consumed across the world. It is consumed in both social and cultural settings. Until recently, two types of alcohol consumption were recognized: heavy chronic alcohol consumption or light consumption. Today, there is a new pattern of consumption among teenagers and young adults namely: binge drinking. Heavy alcohol consumption is detrimental to many organs and tissues, including bones, and is known to induce secondary osteoporosis. Some studies, however, have reported benefits from light alcohol consumption on bone parameters. To date, little is known regarding the effects of binge drinking on bone health. Here, we review the effects of three different means of alcohol consumption: light, heavy, and binge drinking. We also review the detailed literature on the different mechanisms by which alcohol intake may decrease bone mass and strength. The effects of alcohol on bone are thought to be both direct and indirect. The decrease in bone mass and strength following alcohol consumption is mainly due to a bone remodeling imbalance, with a predominant decrease in bone formation. Recent studies, however, have reported new mechanisms by which alcohol may act on bone remodeling, including osteocyte apoptosis, oxidative stress, and Wnt signalling pathway modulation. The roles of reduced total fat mass, increased lipid content in bone marrow, and a hypoleptinemia are also discussed.
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Affiliation(s)
- D B Maurel
- Unité INSERM U658, Caractérisation du Tissu Osseux par Imagerie, Techniques et Applications, CHR Orléans, 45000 Orléans, France.
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Maurel DB, Boisseau N, Benhamou CL, Jaffré C. Cortical bone is more sensitive to alcohol dose effects than trabecular bone in the rat. Joint Bone Spine 2011; 79:492-9. [PMID: 22133445 DOI: 10.1016/j.jbspin.2011.10.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2011] [Accepted: 10/11/2011] [Indexed: 11/29/2022]
Abstract
OBJECTIVE While chronic alcohol consumption is known to decrease bone mineral content (BMC), bone mineral density (BMD), and negatively modify trabecular bone microarchitecture, the impact of alcohol on cortical microarchitecture is still unclear. The aim of this study was to investigate the effects of various doses of alcohol on bone density, trabecular and cortical parameters and bone strength in rats. METHODS Forty-eight male Wistar rats were divided into four groups: control (C), alcohol 25% v/v (A25), alcohol 30% v/v (A30) and alcohol 35% v/v (A35). Rats in the alcohol groups were fed a solution composed of ethanol and water for 17 weeks while the control group drank only water. Bone quality and quantity were evaluated through the analysis of density, trabecular and cortical bone microarchitectural parameters, osteocalcin and N-Telopeptide concentrations and a 3-point bending test. RESULTS Bone density along with trabecular and cortical thickness were lower in alcohol groups compared to C. BMD was lower in A35 vs. A30 and cortical thickness was lower in A35 vs. A25 and A30. Pore number was increased by alcohol and the porosity was greater in A35 compared to C. N-Telopeptide concentration was decreased in alcohol groups compared to control whereas no differences were observed in osteocalcin concentrations. Maximal energy to failure was lower in A25 and A35 compared to C. CONCLUSION Chronic ethanol consumption increases cortical bone damage in rats and may have detrimental effects on bone strength. These effects were dose-dependent, with greater negative effects proportionate to greater alcohol doses.
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Affiliation(s)
- Delphine B Maurel
- IPROS, Unité Inserm U658, Caractérisation du Tissu Osseux par Imagerie: Techniques et Applications, Hôpital Porte-Madeleine, 1 rue Porte-Madeleine, BP 2439, 45032 Orléans cedex 01, France.
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Steiniche T. Bone histomorphometry in the pathophysiological evaluation of primary and secondary osteoporosis and various treatment modalities. APMIS 2011. [DOI: 10.1111/j.1600-0463.1995.tb05544.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Maurel DB, Jaffre C, Rochefort GY, Aveline PC, Boisseau N, Uzbekov R, Gosset D, Pichon C, Fazzalari NL, Pallu S, Benhamou CL. Low bone accrual is associated with osteocyte apoptosis in alcohol-induced osteopenia. Bone 2011; 49:543-52. [PMID: 21689804 DOI: 10.1016/j.bone.2011.06.001] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2011] [Revised: 05/30/2011] [Accepted: 06/01/2011] [Indexed: 01/17/2023]
Abstract
INTRODUCTION Alcohol is known to decrease bone mineral density (BMD) and to induce trabecular microarchitecture deterioration. However, little is known about the effects of chronic alcohol consumption on osteocytes in situ. The aim of this study was to assess the effects of a high alcohol dose on osteocytes in an alcohol-induced osteopenia model. MATERIALS AND METHODS 24 male Wistar rats, 2-months old were separated in 2 groups: Control (C) or Alcohol (A35). The rats in the A35 group drank a beverage composed of 35% ethanol v/v mixed to water for 17 weeks. BMD was assessed by DXA, while the microarchitecture was analyzed using μCT. Bone remodeling was studied measuring serum concentration of osteocalcin, NTx and TRAP. Bone marrow adiposity, osteoblastic lineage differentiation, osteocyte morphology and apoptosis were assessed using bright field, epifluorescence, transmission electron and confocal microscopy. RESULTS BMD, trabecular thickness, TRAP and NTx concentration were significantly decreased in A35, while cortical thickness was thinner. There were 10 fold more cells stained with cleaved caspase-3, and 35% more empty lacunae in A35, these data indicating a large increase in osteocyte apoptosis in the A35 group. The number of lipid droplets in the marrow was increased in A35 (7 fold). Both the osteocyte apoptosis and the fat bone marrow content strongly correlated with femur BMD (p=0.0017, r = -0.72 and p=0.002, r = -0.70) and whole body BMD. CONCLUSION These data suggest that low BMD is associated with osteocyte apoptosis and bone marrow fat content in alcohol-induced osteopenia.
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Affiliation(s)
- D B Maurel
- Unité Inserm U658, Hôpital Porte Madeleine, Orleans, France.
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Abstract
OBJECTIVES Patients with tropical calcific pancreatitis (TCP) have multiple risk factors for developing low bone mineral density (BMD). We studied BMD and serum 25-hydroxyvitamin D (25[OH]D) in north Indian TCP patients. METHODS In a cross-sectional study, 72 TCP patients (mean age, 31 ± 10 years) and 100 controls were studied. Serum 25(OH)D was measured in all subjects; BMD was measured by dual-energy x-ray absorptiometry in 56 adult patients and 4 children and compared with a reference Indian population. RESULTS Mean BMD and BMD Z-scores at the lumbar spine and total hip were significantly lower in all age groups. The BMD Z-scores at the lumbar spine and total hip were -1.0 ± 1.0 and -1.2 ± 1.2, respectively. Low bone density (Z-score ≤ -2 at ≥ 1 sites) was present in 22 (39%) adult patients and 3 of the 4 children studied. On multivariate analysis, BMD Z-scores were positively associated with body mass index and inversely with pancreatitis. Vitamin D deficiency (25[OH]D < 50 nmol/L) was equally prevalent in patients (86%) and controls (85%). CONCLUSIONS Despite their young age, patients with TCP have significantly low BMD. Measures to improve nutrition should be instituted in all TCP patients from an early age.
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Mitchell R, McDermid J, Ma MM, Chik CL. MELD score, insulin-like growth factor 1 and cytokines on bone density in end-stage liver disease. World J Hepatol 2011; 3:157-63. [PMID: 21860675 PMCID: PMC3159496 DOI: 10.4254/wjh.v3.i6.157] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2010] [Revised: 05/20/2011] [Accepted: 05/27/2011] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the contributions of insulin-like growth factor 1 (IGF-1), cytokines and liver disease severity to bone mineral density in patients pre-transplantation. METHODS Serum IGF-1, tumor necrosis factor-α (TNFα) and interleukin 6 (IL-6) were measured and the Model for End-Stage Liver Disease (MELD) score calculated in 121 adult patients referred to a single centre for liver transplantation. Bone mineral density (BMD) of the lumbar spine and femoral neck were assessed via dual energy X-ray absorptiometry. Demographics, liver disease etiology, medication use and relevant biochemistry were recorded. RESULTS A total of 117 subjects were included, with low BMD seen in 68.6%, irrespective of disease etiology. In multivariable analysis, low body mass index (BMI), increased bone turnover and low IGF-1 were independent predictors of low spinal bone density. At the hip, BMI, IGF-1 and vitamin D status were predictive. Despite prevalent elevations of TNFα and IL-6, levels did not correlate with degree of bone loss. The MELD score failed to predict low BMD in this pre-transplant population. CONCLUSION Osteopenia/osteoporosis is common in advanced liver disease. Low serum IGF-1 is weakly predictive but serum cytokine and MELD score fail to predict the severity of bone disease.
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Affiliation(s)
- Rebecca Mitchell
- Rebecca Mitchell, Constance L Chik, Divisions of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2S2, Alberta, Canada
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Guañabens N, Parés A. Management of osteoporosis in liver disease. Clin Res Hepatol Gastroenterol 2011; 35:438-45. [PMID: 21546334 DOI: 10.1016/j.clinre.2011.03.007] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2011] [Accepted: 03/16/2011] [Indexed: 02/04/2023]
Abstract
Osteoporosis resulting in a high risk for fracture is a common complication in patients with liver disease, particularly in those with chronic cholestasis and with end-stage cirrhosis. The pathogenesis of bone loss in liver patients is poorly understood but it mainly results from low bone formation as a consequence of cholestasis or the harmful effects of alcohol or iron on osteoblasts. Increased bone resorption has also been described in cholestatic women with advanced disease. The management of bone disease in liver patients is addressed to reduce or avoid the risk factors for osteoporosis and fracture. Bisphosphonates associated with supplements of calcium and vitamin D are safe and effective for increasing bone mass in patients with chronic cholestasis and after liver transplantation, though no clear achievements in descreasing the incidence of fractures have been described, probably because of the low number of patients included in the therapeutic trials. Randomized studies assessing bisphosphonates in larger series of patients, the development of new drugs for osteoporosis and the improvement in the management of liver transplant recipients may change the future.
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Affiliation(s)
- Núria Guañabens
- Liver Unit, Department of Rheumatology, Hospital Clínic, CIBERhed, University of Barcelona, Barcelona, Spain
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González-Reimers E, Alvisa-Negrín J, Santolaria-Fernández F, Ros-Vilamajó R, Martín-González MC, Hernández-Betancor I, García-Valdecasas-Campelo E, González-Díaz A. Prognosis of osteopenia in chronic alcoholics. Alcohol 2011; 45:227-38. [PMID: 21051177 DOI: 10.1016/j.alcohol.2010.09.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2010] [Revised: 09/06/2010] [Accepted: 09/08/2010] [Indexed: 12/12/2022]
Abstract
Osteoporosis is frequent among alcoholics all by a direct effect of ethanol, malnutrition, and liver failure. Therefore, it may be related to survival. The aim of this study was to assess bone mineral density (BMD), bone mineral content, hormonal status, and to determine prognostic value of these parameters in a total of 124 alcoholics followed up for a median period of 57 months. Several bone homeostasis-related hormones were measured in patients and age- and sex-matched controls. Whole-body densitometry was performed by a Hologic QDR-2000 (Waltham, MA) densitometer; nutritional status and liver function were assessed. Sixty patients underwent a second evaluation 6 months later. Patients showed lower serum insulin-like growth factor-1 (median=58, interquartile range [IQR]=33-135 vs. 135ng/mL, IQR=116-243ng/mL, P<.001), vitamin D (25.5, IQR=18.3-36.8 vs. 79.9pg/mL, IQR=59.2-107.8pg/mL, P<.001), and osteocalcin (2.1, IQR=1.1-4.5 vs. 6.5ng/mL, IQR=4.7-8.7ng/mL, P<.001) than controls, and lower BMD values, and lower Z- and T-scores at right and left legs and arms, thoracic and lumbar spine, pelvis, and right and left ribs. By multiple regression analysis, BMD mainly depends on nutritional parameters and liver function. Kaplan-Meier curves show that subtotal BMD and BMD at both arms and pelvis were significantly related with survival. Patients who had lost total hip BMD after 6 months showed a shorter survival than those who had not, but using Cox's regression, encephalopathy, ascites, and nutritional parameters displaced BMD as prognostic factor. Therefore, osteopenia ensues in chronic alcoholic patients. It mainly depends on poor nutrition and is related to survival, although surpassed in this sense by encephalopathy, ascites, and nutritional parameters.
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Affiliation(s)
- Emilio González-Reimers
- Servicios de Medicina Interna, Hospital Universitario, Universidad de La Laguna, Ofra s/n, Tenerife, Canary Islands, Spain.
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González-Pérez JM, González-Reimers E, Durán-Castellón MDC, Santolaria-Fernández F, Galindo-Martín L, RosVilamajó R, de la Vega-Prieto MJ, Viña-Rodríguez J, Abreu-González P. Relative and combined effects of selenium, protein deficiency and ethanol on bone. J Trace Elem Med Biol 2011; 25:113-7. [PMID: 21376552 DOI: 10.1016/j.jtemb.2011.01.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2010] [Revised: 12/15/2010] [Accepted: 01/17/2011] [Indexed: 11/25/2022]
Abstract
UNLABELLED Some observations suggest that oxidative damage may affect both osteoblastic function and osteoclastic activity in alcohol-mediated bone alterations. Selenium, a potent antioxidant, is decreased in alcoholics. OBJECTIVE To analyse if the supplementation with selenium may alter bone changes observed in a murine model fed ethanol and/or a 2% protein-containing diet, following the Lieber-deCarli design. MATERIAL AND METHOD Adult male Sprague-Dawley rats were divided into 8 groups, which received the Lieber-DeCarli control diet, an isocaloric, 36% ethanol-containing diet, an isocaloric, 2% protein-containing diet; and an isocaloric diet containing 2% protein and 36% ethanol diet, and another similar four groups to which selenomethionine (1mg/kg body weight). After sacrifice (5 weeks later), trabecular bone mass was histomorphometrically assessed, bone and serum selenium were determined by flame atomic absorption spectrophotometry, and serum osteocalcin, insulin growth factor 1 (IGF-1), PTH and telopeptide, by radioimmunoanalysis. Liver glutathione peroxidase (GPX) activity was also determined. RESULTS Ethanol-fed rats showed decreased TBM, IGF-1 and osteocalcin, especially when ethanol was added to a 2%-protein diet. Selenium did not modify at all bone parameters, despite a marked increase in serum selenium and a less pronounced one in bone selenium, and an increase in liver GPX. CONCLUSION Our results do not support the existence of a beneficial effect of selenium addition on bone changes observed in this murine model treated following the Lieber-deCarli experimental design.
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