Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Bone and Mineral Metabolism

01-02-2024 | Osteoporosis | Invited Review

Association of chronic liver disease with bone diseases and muscle weakness

Authors: Chisato Saeki, Mitsuru Saito, Akihito Tsubota

Published in: Journal of Bone and Mineral Metabolism

Login to get access

Abstract

The liver is a vital organ involved in nutrient metabolism, hormone regulation, immunity, cytokine production, and gut homeostasis. Impairment in liver function can result in malnutrition, chronic inflammation, decreased anabolic hormone levels, and dysbiosis. These conditions eventually cause an imbalance in osteoblast and osteoclast activities, resulting in bone loss. Osteoporosis is a frequent complication of chronic liver disease (CLD) that adversely affects quality of life and increases early mortality. Sarcopenia is another common complication of CLD characterized by progressive loss of skeletal muscle mass and function. Assessment criteria for sarcopenia specific to liver disease have been established, and sarcopenia has been reported to be associated with an increase in the risk of liver disease-related events and mortality in patients with CLD. Owing to their similar risk factors and underlying pathophysiological mechanisms, osteoporosis and sarcopenia often coexist (termed osteosarcopenia), progress in parallel, and further exacerbate the conditions mentioned above. Therefore, comprehensive management of these musculoskeletal disorders is imperative. This review summarizes the clinical implications and characteristics of osteoporosis, extending to sarcopenia and osteosarcopenia, in patients with CLD caused by different etiologies.
Literature
1.
Nakchbandi IA, van der Merwe SW (2009) Current understanding of osteoporosis associated with liver disease. Nat Rev Gastroenterol Hepatol 6:660–670PubMedCrossRef
2.
3.
4.
5.
Yang YJ, Kim DJ (2021) An overview of the molecular mechanisms contributing to musculoskeletal disorders in chronic liver disease: osteoporosis, sarcopenia, and osteoporotic sarcopenia. Int J Mol Sci 22:2604PubMedPubMedCentralCrossRef
6.
Ehnert S, Aspera-Werz RH, Ruoß M, Dooley S, Hengstler JG, Nadalin S, Relja B, Badke A, Nussler AK (2019) Hepatic osteodystrophy-molecular mechanisms proposed to favor its development. Int J Mol Sci 20:2555PubMedPubMedCentralCrossRef
7.
Saeki C, Kanai T, Ueda K, Nakano M, Oikawa T, Torisu Y, Saruta M, Tsubota A (2023) Osteosarcopenia predicts poor survival in patients with cirrhosis: a retrospective study. BMC Gastroenterol 23:196PubMedPubMedCentralCrossRef
8.
Saeki C, Tsubota A (2021) Influencing factors and molecular pathogenesis of sarcopenia and osteosarcopenia in chronic liver disease. Life (Basel) 11:899ADSPubMed
9.
Rosenberg I (1989) Summary comments: Epidemiological and methodological problems in determining nutritional status of older persons. Am J Clin Nutr 50:1231–1233CrossRef
10.
Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinková E, Vandewoude M, Zamboni M, European Working Group on Sarcopenia in Older People (2010) Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 39:412–423PubMedPubMedCentralCrossRef
11.
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M, Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2, Sarcopenia: revised European consensus on definition and diagnosis (2019) Age Ageing 48:16–31PubMedCrossRef
12.
Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW et al (2014) Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc 15:95–101PubMedCrossRef
13.
Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY et al (2020) Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment. J Am Med Dir Assoc 21:300–307PubMedCrossRef
14.
Nishikawa H, Shiraki M, Hiramatsu A, Moriya K, Hino K, Nishiguchi S (2016) Japan Society of Hepatology guidelines for sarcopenia in liver disease (1st edition): Recommendation from the working group for creation of sarcopenia assessment criteria. Hepatol Res 46:951–963PubMedCrossRef
15.
Zeng X, Shi ZW, Yu JJ, Wang LF, Luo YY, Jin SM, Zhang LY, Tan W, Shi PM, Yu H, Zhang CQ, Xie WF (2021) Sarcopenia as a prognostic predictor of liver cirrhosis: a multicentre study in China. J Cachexia Sarcopenia Muscle 12:1948–1958PubMedPubMedCentralCrossRef
16.
Tantai X, Liu Y, Yeo YH, Praktiknjo M, Mauro E et al (2022) Effect of sarcopenia on survival in patients with cirrhosis: a meta-analysis. J Hepatol 76:588–599PubMedCrossRef
17.
Saeki C, Oikawa T, Kanai T, Nakano M, Torisu Y, Sasaki N, Abo M, Saruta M, Tsubota A (2021) Relationship between osteoporosis, sarcopenia, vertebral fracture, and osteosarcopenia in patients with primary biliary cholangitis. Eur J Gastroenterol Hepatol 33:731–737PubMedCrossRef
18.
Saeki C, Takano K, Oikawa T, Aoki Y, Kanai T, Takakura K, Nakano M, Torisu Y, Sasaki N, Abo M, Matsuura T, Tsubota A, Saruta M (2019) Comparative assessment of sarcopenia using the JSH, AWGS, and EWGSOP2 criteria and the relationship between sarcopenia, osteoporosis, and osteosarcopenia in patients with liver cirrhosis. BMC Musculoskelet Disord 20:615PubMedPubMedCentralCrossRef
19.
Bering T, Diniz KGD, Coelho MPP, Vieira DA, Soares MMS, Kakehasi AM, Correia MITD, Teixeira R, Queiroz DMM, Rocha GA, Silva LD (2018) Association between pre-sarcopenia, sarcopenia, and bone mineral density in patients with chronic hepatitis C. J Cachexia Sarcopenia Muscle 9:255–268PubMedPubMedCentralCrossRef
20.
Binkley N, Buehring B (2009) Beyond FRAX: it’s time to consider “sarco-osteopenia.” J Clin Densitom 12:413–416PubMedCrossRef
21.
Hirschfeld HP, Kinsella R, Duque G (2017) Osteosarcopenia: where bone, muscle, and fat collide. Osteoporos Int 28:2781–2790PubMedCrossRef
22.
Menon KV, Angulo P, Weston S, Dickson ER, Lindor KD (2001) Bone disease in primary biliary cirrhosis: independent indicators and rate of progression. J Hepatol 35:316–323PubMedCrossRef
23.
Guañabens N, Parés A, Ros I, Caballería L, Pons F, Vidal S, Monegal A, Peris P, Rodés J (2005) Severity of cholestasis and advanced histological stage but not menopausal status are the major risk factors for osteoporosis in primary biliary cirrhosis. J Hepatol 42:573–577PubMedCrossRef
24.
Guañabens N, Cerdá D, Monegal A, Pons F, Caballería L, Peris P, Parés A (2010) Low bone mass and severity of cholestasis affect fracture risk in patients with primary biliary cirrhosis. Gastroenterology 138:2348–2356PubMedCrossRef
25.
Seki A, Ikeda F, Miyatake H, Takaguchi K, Hayashi S, Osawa T, Fujioka SI, Tanaka R, Ando M, Seki H, Iwasaki Y, Yamamoto K, Okada H (2017) Risk of secondary osteoporosis due to lobular cholestasis in non-cirrhotic primary biliary cholangitis. J Gastroenterol Hepatol 32:1611–1616PubMedCrossRef
26.
Fan J, Wang Q, Sun L (2017) Association between primary biliary cholangitis and osteoporosis: meta-analysis. Clin Rheumatol 36:2565–2571PubMedCrossRef
27.
Tanaka A, Mori M, Matsumoto K, Ohira H, Tazuma S, Takikawa H (2019) Increase trend in the prevalence and male-to-female ratio of primary biliary cholangitis, autoimmune hepatitis, and primary sclerosing cholangitis in Japan. Hepatol Res 49:881–889PubMedCrossRef
28.
29.
Benetti A, Crosignani A, Varenna M, Giussani CS, Allocca M, Zuin M, Podda M, Battezzati PM (2008) Primary biliary cirrhosis is not an additional risk factor for bone loss in women receiving regular calcium and vitamin D supplementation: a controlled longitudinal study. J Clin Gastroenterol 42:306–311PubMedCrossRef
30.
Saeki C, Oikawa T, Ueda K, Nakano M, Torisu Y, Saruta M, Tsubota A (2022) Serum insulin-like growth factor 1 levels, fracture risk assessment tool scores and bone disorders in patients with primary biliary cholangitis. Diagnostics (Basel) 12:1957PubMedCrossRef
31.
Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ (2018) The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology 67:328–357PubMedCrossRef
32.
Kazankov K, Jørgensen SMD, Thomsen KL, Møller HJ, Vilstrup H, George J, Schuppan D, Grønbæk H (2019) The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Nat Rev Gastroenterol Hepatol 16:145–159PubMedCrossRef
33.
Vachliotis ID, Anastasilakis AD, Goulas A, Goulis DG, Polyzos SA (2022) Nonalcoholic fatty liver disease and osteoporosis: a potential association with therapeutic implications. Diabetes Obes Metab 24:1702–1720PubMedCrossRef
34.
Filip R, Radzki RP, Bieńko M (2018) Novel insights into the relationship between nonalcoholic fatty liver disease and osteoporosis. Clin Interv Aging 13:1879–1891PubMedPubMedCentralCrossRef
35.
Kim G, Kim KJ, Rhee Y, Lim SK (2017) Significant liver fibrosis assessed using liver transient elastography is independently associated with low bone mineral density in patients with non-alcoholic fatty liver disease. PLoS ONE 12:e0182202PubMedPubMedCentralCrossRef
36.
Umehara T (2018) Nonalcoholic fatty liver disease with elevated alanine aminotransferase levels is negatively associated with bone mineral density: cross-sectional study in U.S. adults. PLoS ONE 13:e0197900PubMedPubMedCentralCrossRef
37.
Ciardullo S, Muraca E, Zerbini F, Manzoni G, Perseghin G (2021) NAFLD and liver fibrosis are not associated with reduced femoral bone mineral density in the general US population. J Clin Endocrinol Metab 106:e2856–e2865PubMedCrossRef
38.
Cui R, Sheng H, Rui XF, Cheng XY, Sheng CJ, Wang JY, Qu S (2013) Low bone mineral density in Chinese adults with nonalcoholic fatty liver disease Int. J Endocrinol 2013:396545
39.
Lee SH, Yun JM, Kim SH, Seo YG, Min H, Chung E, Bae YS, Ryou IS, Cho B (2016) Association between bone mineral density and nonalcoholic fatty liver disease in Korean adults. J Endocrinol Invest 39:1329–1336PubMedCrossRef
40.
Yang HJ, Shim SG, Ma BO, Kwak JY (2016) Association of nonalcoholic fatty liver disease with bone mineral density and serum osteocalcin levels in Korean men. Eur J Gastroenterol Hepatol 28:338–344PubMedPubMedCentralCrossRef
41.
Ahn SH, Seo DH, Kim SH, Nam MS, Hong S (2018) The relationship between fatty liver index and bone mineral density in Koreans: KNHANES 2010–2011. Osteoporos Int 29:181–190PubMedCrossRef
42.
Moon SS, Lee YS, Kim SW (2012) Association of nonalcoholic fatty liver disease with low bone mass in postmenopausal women. Endocrine 42:423–429PubMedCrossRef
43.
Lee DY, Park JK, Hur KY, Um SH (2018) Association between nonalcoholic fatty liver disease and bone mineral density in postmenopausal women. Climacteric 21:498–501PubMedCrossRef
44.
Xia MF, Lin HD, Yan HM, Bian H, Chang XX, Zhang LS, He WY, Gao X (2016) The association of liver fat content and serum alanine aminotransferase with bone mineral density in middle-aged and elderly Chinese men and postmenopausal women. J Transl Med 14:11PubMedPubMedCentralCrossRef
45.
Li M, Xu Y, Xu M, Ma L, Wang T, Liu Y, Dai M, Chen Y, Lu J, Liu J, Bi Y, Ning G (2012) Association between nonalcoholic fatty liver disease (NAFLD) and osteoporotic fracture in middle-aged and elderly Chinese. J Clin Endocrinol Metab 97:2033–2038PubMedCrossRef
46.
Wang Y, Wen G, Zhou R, Zhong W, Lu S, Hu C, Chai Y (2018) Association of nonalcoholic fatty liver disease with osteoporotic fractures: a cross-sectional retrospective study of Chinese individuals. Front Endocrinol (Lausanne) 9:408PubMedCrossRef
47.
Upala S, Jaruvongvanich V, Wijarnpreecha K, Sanguankeo A (2017) Nonalcoholic fatty liver disease and osteoporosis: a systemic review and meta-analysis. J Bone Miner Metab 35:685–693PubMedCrossRef
48.
Mantovani A, Dauriz M, Gatti D, Viapiana O, Zoppini G, Lippi G, Byrne CD, Bonnet F, Bonora E, Targher G (2019) Systematic review with meta-analysis: non-alcoholic fatty liver disease is associated with a history of osteoporotic fractures but not with low bone mineral density. Aliment Pharmacol Ther 49:375–388PubMedCrossRef
49.
Pan B, Cai J, Zhao P, Liu J, Fu S, Jing G, Niu Q, Li Q (2022) Relationship between prevalence and risk of osteoporosis or osteoporotic fracture with non-alcoholic fatty liver disease: a systematic review and meta-analysis. Osteoporos Int 33:2275–2286PubMedCrossRef
50.
Zhu X, Yan H, Chang X, Xia M, Zhang L, Wang L, Sun X, Yang X, Gao X, Bian H (2020) Association between non-alcoholic fatty liver disease-associated hepatic fibrosis and bone mineral density in postmenopausal women with type 2 diabetes or impaired glucose regulation. BMJ Open Diabetes Res Care 8:e000999PubMedPubMedCentralCrossRef
51.
Barchetta I, Lubrano C, Cimini FA, Dule S, Passarella G, Dellanno A, Di Biasio A, Leonetti F, Silecchia G, Lenzi A, Cavallo MG (2023) Liver fibrosis is associated with impaired bone mineralization and microstructure in obese individuals with non-alcoholic fatty liver disease. Hepatol Int 17:357–366PubMedCrossRef
52.
Schiefke I, Fach A, Wiedmann M, Aretin AV, Schenker E, Borte G, Wiese M, Moessner J (2005) Reduced bone mineral density and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection. World J Gastroenterol 11:1843–1847PubMedPubMedCentralCrossRef
53.
Chen CH, Lin CL, Kao CH (2015) Association between chronic hepatitis B virus infection and risk of osteoporosis: a nationwide population-based study. Medicine (Baltimore) 94:e2276PubMedCrossRef
54.
Wijarnpreecha K, Thongprayoon C, Panjawatanan P, Phatharacharukul P, Ungprasert P (2017) Hepatitis C virus infection and risk of osteoporosis: a meta-analysis. Saudi J Gastroenterol 23:216–221PubMedPubMedCentralCrossRef
55.
Chen YY, Fang WH, Wang CC, Kao TW, Chang YW, Yang HF, Wu CJ, Sun YS, Chen WL (2019) Crosssectional assessment of bone mass density in adults with hepatitis B virus and hepatitis C virus infection. Sci Rep 9:5069ADSPubMedPubMedCentralCrossRef
56.
Chen CH, Lin CL, Kao CH (2015) Relation between hepatitis C virus exposure and risk of osteoporosis: a nationwide population-based study. Medicine (Baltimore) 94:e2086PubMedCrossRef
57.
Wong GL, Tse YK, Wong VW, Yip TC, Tsoi KK, Chan HL (2015) Long-term safety of oral nucleos(t)ide analogs for patients with chronic hepatitis B: A cohort study of 53,500 subjects. Hepatology 62:684–693PubMedCrossRef
58.
Wei MT, Le AK, Chang MS, Hsu H, Nguyen P, Zhang JQ, Wong C, Wong C, Cheung R, Nguyen MH (2019) Antiviral therapy and the development of osteopenia/osteoporosis among Asians with chronic hepatitis B. J Med Virol 91:1288–1294PubMedCrossRef
59.
Yang X, Yan H, Zhang X, Qin X, Guo P (2022) Comparison of renal safety and bone mineral density of tenofovir and entecavir in patients with chronic hepatitis B: a systematic review and meta-analysis. Int J Infect Dis 124:133–142PubMedCrossRef
60.
Lin JC, Hsieh TY, Wu CC, Chen PJ, Chueh TH, Chang WK, Chu HC (2012) Association between chronic hepatitis C virus infection and bone mineral density. Calcif Tissue Int 91:423–429PubMedCrossRef
61.
Lin MS, Chen PH, Wang PC, Lin HS, Huang TJ, Chang ST, Chiu WN, Chen MY (2019) Association between hepatitis C virus infection and osteoporotic fracture risk among postmenopausal women: a cross-sectional investigation in Taiwan. BMJ Open 9:e021990PubMedPubMedCentralCrossRef
62.
Wijarnpreecha K, Thongprayoon C, Panjawatanan P, Ungprasert P (2018) Hepatitis C virus infection and risk of osteoporotic fracture: a systematic review and meta-analysis. J Evid Based Med 11:20–25PubMedCrossRef
63.
64.
Lupoli R, Di Minno A, Spadarella G, Ambrosino P, Panico A, Tarantino L, Lupoli G, Lupoli G, Di Minno MN (2016) The risk of osteoporosis in patients with liver cirrhosis: a meta-analysis of literature studies. Clin Endocrinol (Oxf) 84:30–38PubMedCrossRef
65.
Liang J, Meng WD, Yang JM, Li SL, Zhong MN, Hou XX, Wang R, Long YY, Bao LX, Bao M (2018) The association between liver cirrhosis and fracture risk: a systematic review and meta-analysis. Clin Endocrinol (Oxf) 89:408–413PubMedCrossRef
66.
Chang CH, Chang CJ, Wang YC, Hu CC, Chang Y, Hsieh PH, Chen DW (2020) Increased incidence, morbidity, and mortality in cirrhotic patients with hip fractures: A nationwide population-based study. J Orthop Surg (Hong Kong) 28:2309499020918032PubMedCrossRef
67.
Hundersmarck D, Groot OQ, Schuijt HJ, Hietbrink F, Leenen LPH, Heng M (2022) Hip fractures in patients with liver cirrhosis: worsening liver function is associated with increased mortality. Clin Orthop Relat Res 480:1077–1088PubMedCrossRef
68.
Lim WH, Ng CH, Ow ZGW, Ho OTW, Tay PWL, Wong KL, Tan EXX, Tang SY, Teo CM, Muthiah MD (2021) A systematic review and meta-analysis on the incidence of osteoporosis and fractures after liver transplant. Transpl Int 34:1032–1043PubMedCrossRef
69.
Hay JE (2003) Osteoporosis in liver diseases and after liver transplantation. J Hepatol 38:856–865PubMedCrossRef
70.
Krol CG, Dekkers OM, Kroon HM, Rabelink TJ, van Hoek B, Hamdy NA (2014) Longitudinal changes in BMD and fracture risk in orthotopic liver transplant recipients not using bone-modifying treatment. J Bone Miner Res 29:1763–1769PubMedCrossRef
71.
Monegal A, Navasa M, Guañabens N, Peris P, Pons F, Martinez de Osaba MJ, Ordi J, Rimola A, Rodés J, Muñoz-Gómez J (2001) Bone disease after liver transplantation: a long-term prospective study of bone mass changes, hormonal status and histomorphometric characteristics. Osteoporos Int 12:484–492PubMedCrossRef
72.
Lai JC, Tandon P, Bernal W, Tapper EB, Ekong U, Dasarathy S, Carey EJ (2021) Malnutrition, frailty, and sarcopenia in patients with cirrhosis: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 74:1611–1644PubMedCrossRef
73.
Kim G, Kang SH, Kim MY, Baik SK (2017) Prognostic value of sarcopenia in patients with liver cirrhosis: a systematic review and meta-analysis. PLoS ONE 12:e0186990PubMedPubMedCentralCrossRef
74.
Mazeaud S, Zupo R, Couret A, Panza F, Sardone R, Castellana F (2023) Prevalence of sarcopenia in liver cirrhosis: A systematic review and meta-analysis. Clin Transl Gastroenterol 14:e00584PubMedPubMedCentralCrossRef
75.
Saeki C, Kanai T, Nakano M, Oikawa T, Torisu Y, Abo M, Saruta M, Tsubota A (2020) Relationship between osteosarcopenia and frailty in patients with chronic liver disease. J Clin Med 9:2381PubMedPubMedCentralCrossRef
76.
Singh Tejavath A, Mathur A, Nathiya D, Singh P, Raj P, Suman S, Mundada PR, Atif S, Rai RR, Tomar BS (2021) Impact of branched chain amino acid on muscle mass, muscle strength, physical performance, combined survival, and maintenance of liver function changes in laboratory and prognostic markers on sarcopenic patients with liver cirrhosis (BCAAS study): a randomized clinical trial. Front Nutr 8:715795PubMedPubMedCentralCrossRef
77.
Okubo T, Atsukawa M, Tsubota A, Yoshida Y, Arai T, Iwashita AN, Itokawa N, Kondo C, Iwakiri K (2020) Relationship between serum vitamin D level and sarcopenia in chronic liver disease. Hepatol Res 50:588–597PubMedCrossRef
78.
Saeki C, Kanai T, Nakano M, Oikawa T, Torisu Y, Saruta M, Tsubota A (2020) Low serum 25-hydroxyvitamin D levels are related to frailty and sarcopenia in patients with chronic liver disease. Nutrients 12:3810PubMedPubMedCentralCrossRef
79.
Putz-Bankuti C, Pilz S, Stojakovic T, Scharnagl H, Pieber TR, Trauner M, Obermayer-Pietsch B, Stauber RE (2012) Association of 25-hydroxyvitamin D levels with liver dysfunction and mortality in chronic liver disease. Liver Int 32:845–851PubMedCrossRef
80.
Ceglia L, Harris SS (2013) Vitamin D and its role in skeletal muscle. Calcif Tissue Int 92:151–162PubMedCrossRef
81.
Wijarnpreecha K, Werlang M, Panjawatanan P, Kroner PT, Cheungpasitporn W, Lukens FJ, Pungpapong S, Ungprasert P (2020) Association between sarcopenia and hepatic encephalopathy: a systematic review and meta-analysis. Ann Hepatol 19:245–250PubMedCrossRef
82.
Kikuchi N, Uojima H, Hidaka H, Iwasaki S, Wada N, Kubota K, Nakazawa T, Shibuya A, Fujikawa T, Kako M, Sato T, Koizumi W (2021) Prospective study for an independent predictor of prognosis in liver cirrhosis based on the new sarcopenia criteria produced by the Japan Society of Hepatology. Hepatol Res 51:968–978PubMedCrossRef
83.
Saeki C, Kanai T, Ueda K, Nakano M, Oikawa T, Torisu Y, Saruta M, Tsubota A (2023) Prognostic significance of sarcopenia and severe vitamin D deficiency in patients with cirrhosis. JGH Open 7:351–357PubMedPubMedCentralCrossRef
84.
85.
Teng Z, Zhu Y, Teng Y, Long Q, Hao Q, Yu X, Yang L, Lv Y, Liu J, Zeng Y, Lu S (2021) The analysis of osteosarcopenia as a risk factor for fractures, mortality, and falls. Osteoporos Int 32:2173–2183PubMedCrossRef
86.
Kobayashi K, Imagama S, Ando K, Machino M, Ota K, Tanaka S, Morozumi M, Kanbara S, Ito S, Ishiguro N, Hasegawa Y (2020) Epidemiology and effect on physical function of osteosarcopenia in community-dwelling elderly people in Japan. Mod Rheumatol 30:592–597PubMedCrossRef
87.
Wang YJ, Wang Y, Zhan JK, Tang ZY, He JY, Tan P, Deng HQ, Huang W, Liu YS (2015) Sarco-Osteoporosis: prevalence and association with frailty in Chinese community-dwelling older adults. Int J Endocrinol 2015:482940PubMedPubMedCentralCrossRef
88.
Park KS, Lee GY, Seo YM, Seo SH, Yoo JI (2021) Disability, Frailty and depression in the community-dwelling older adults with osteosarcopenia. BMC Geriatr 21:69PubMedPubMedCentralCrossRef
89.
Taniai T, Haruki K, Yanagaki M, Igarashi Y, Furukawa K, Onda S, Yasuda J, Matsumoto M, Tsunematsu M, Ikegami T (2023) Osteosarcopenia predicts poor prognosis for patients with intrahepatic cholangiocarcinoma after hepatic resection. Surg Today 53:82–89PubMedCrossRef
90.
Yanagaki M, Haruki K, Taniai T, Igarashi Y, Yasuda J, Furukawa K, Onda S, Shirai Y, Tsunematsu M, Ikegami T (2023) The significance of osteosarcopenia as a predictor of the long-term outcomes in hepatocellular carcinoma after hepatic resection. J Hepatobil Pancreat Sci 30:453–461CrossRef
91.
DeLuca HF (2004) Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 80:1689S-1696SPubMedCrossRef
92.
Stokes CS, Volmer DA, Grünhage F, Lammert F (2012) Vitamin D in chronic liver disease. Liver Int 33:338–352CrossRef
93.
Fernando M, Ellery SJ, Marquina C, Lim S, Naderpoor N, Mousa A (2020) Vitamin D-binding protein in pregnancy and reproductive health. Nutrients 12:1489PubMedPubMedCentralCrossRef
94.
95.
Garcia LA, King KK, Ferrini MG, Norris KC, Artaza JN (2011) 1,25 (OH)2 vitamin D3 stimulates myogenic differentiation by inhibiting cell proliferation and modulating the expression of promyogenic growth factors and myostatin in C2C12 skeletal muscle cells. Endocrinology 152:2976–2986PubMedPubMedCentralCrossRef
96.
Dankbar B, Fennen M, Brunert D, Hayer S, Frank S, Wehmeyer C, Beckmann D, Paruzel P, Bertrand J, Redlich K, Koers-Wunrau C, Stratis A, Korb-Pap A, Pap T (2015) Myostatin is a direct regulator of osteoclast differentiation and its inhibition reduces inflammatory joint destruction in mice. Nat Med 21:1085–1090PubMedCrossRef
97.
Girgis CM, Cha KM, Houweling PJ, Rao R, Mokbel N, Lin M, Clifton-Bligh RJ, Gunton JE (2015) Vitamin D receptor ablation and vitamin D deficiency result in reduced grip strength, altered muscle fibers, and increased myostatin in mice. Calcif Tissue Int 97:602–610PubMedCrossRef
98.
Atsukawa M, Tsubota A, Shimada N, Yoshizawa K, Abe H et al (2015) Influencing factors on serum 25-hydroxyvitamin D3 levels in Japanese chronic hepatitis C patients. BMC Infect Dis 15:344PubMedPubMedCentralCrossRef
99.
Arai T, Atsukawa M, Tsubota A, Koeda M, Yoshida Y, Okubo T, Nakagawa A, Itokawa N, Kondo C, Nakatsuka K, Masu T, Kato K, Shimada N, Hatori T, Emoto N, Kage M, Iwakiri K (2019) Association of vitamin D levels and vitamin D-related gene polymorphisms with liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease. Dig Liver Dis 51:1036–1042PubMedCrossRef
100.
101.
Mazziotti G, Lania AG, Canalis E (2022) Skeletal disorders associated with the growth hormone-insulin-like growth factor 1 axis. Nat Rev Endocrinol 18:353–365PubMedCrossRef
102.
Ohlsson C, Mohan S, Sjogren K, Tivesten A, Isgaard J, Isaksson O, Jansson JO, Svensson J (2009) The role of liver-derived insulin-like growth factor-I. Endocr Rev 30:494–535PubMedPubMedCentralCrossRef
103.
Kobayashi Y, Uehara S, Udagawa N, Takahashi N (2016) Regulation of bone metabolism by Wnt signals. J Biochem 159:387–392PubMedCrossRef
104.
Guerra-Menéndez L, Sádaba MC, Puche JE, Lavandera JL, de Castro LF, de Gortázar AR, Castilla-Cortázar I (2013) IGF-I increases markers of osteoblastic activity and reduces bone resorption via osteoprotegerin and RANK-ligand. J Trans Med 11:271CrossRef
105.
Sinclair M, Gow PJ, Grossmann M, Angus PW (2016) Review article: sarcopenia in cirrhosis-aetiology, implications and potential therapeutic interventions. Aliment Pharmacol Ther 43:765–777PubMedCrossRef
106.
107.
108.
109.
110.
Saeki C, Kanai T, Ueda K, Nakano M, Oikawa T, Torisu Y, Saruta M, Tsubota A (2023) Insulin-like growth factor 1 predicts decompensation and long-term prognosis in patients with compensated cirrhosis. Front Med 10:1233928CrossRef
111.
Assy N, Pruzansky Y, Gaitini D, Shen Orr Z, Hochberg Z, Baruch Y (2008) Growth hormone-stimulated IGF-1 generation in cirrhosis reflects hepatocellular dysfunction. J Hepatol 49:34–42PubMedCrossRef
112.
Nishizawa H, Iguchi G, Fukuoka H, Takahashi M, Suda K, Bando H, Matsumoto R, Yoshida K, Odake Y, Ogawa W, Takahashi Y (2016) IGF-I induces senescence of hepatic stellate cells and limits fibrosis in a p53-dependent manner. Sci Rep 6:34605ADSPubMedPubMedCentralCrossRef
113.
Zhao J, Lei H, Wang T, Xiong X (2023) Liver-bone crosstalk in non-alcoholic fatty liver disease: Clinical implications and underlying pathophysiology. Front Endocrinol 14:1161402CrossRef
114.
Tsuchida T, Friedman SL (2017) Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol 14:397–411PubMedCrossRef
115.
Kawelke N, Bentmann A, Hackl N, Hager HD, Feick P, Geursen A, Singer MV, Nakchbandi IA (2008) Isoform of fibronectin mediates bone loss in patients with primary biliary cirrhosis by suppressing bone formation. J Bone Miner Res 23:1278–1286PubMedCrossRef
116.
De La Garza RG, Morales-Garza LA, Martin-Estal I, Castilla-Cortazar I (2017) Insulin-like growth factor-1 deficiency and cirrhosis establishment. J Clin Med Res 9:233–247PubMedPubMedCentralCrossRef
117.
Castilla-Cortazar I, Garcia M, Muguerza B, Quiroga J, Perez R, Santidrian S, Prieto J (1997) Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis. Gastroenterology 113:1682–1691PubMedCrossRef
118.
119.
120.
Ono T, Hayashi M, Sasaki F, Nakashima T (2020) RANKL biology: bone metabolism, the immune system, and beyond. Inflamm Regen 40:1–16CrossRef
121.
Cenci S, Weitzmann MN, Roggia C, Namba N, Novack D, Woodring J, Pacifici R (2000) Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. J Clin Invest 106:1229–1237PubMedPubMedCentralCrossRef
122.
123.
124.
Moschen AR, Kaser A, Stadlmann S, Millonig G, Kaser S, Mühllechner P, Habior A, Graziadei I, Vogel W, Tilg H (2005) The RANKL/OPG system and bone mineral density in patients with chronic liver disease. J Hepatol 43:973–983PubMedCrossRef
125.
Kuo SJ, Chen CL, Chen SH, Ko JY (2023) Changes in serum bone metabolism markers after living donor liver transplantation (LDLT) and their association with fracture occurrences. Life (Basel) 13:1438ADSPubMed
126.
Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D (2005) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 280:19883–19887PubMedCrossRef
127.
Ellies DL, Viviano B, McCarthy J, Rey JP, Itasaki N, Saunders S, Krumlauf R (2006) Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res 21:1738–1749PubMedCrossRef
128.
129.
130.
Neong SF, Billington EO, Congly SE (2019) Sexual dysfunction and sex hormone abnormalities in patients with cirrhosis: Review of pathogenesis and management. Hepatology 69:2683–2695PubMedCrossRef
131.
Davey RA, Grossmann M (2016) Androgen receptor structure, function and biology: from bench to bedside. Clin Biochem Rev 37:3–15PubMedPubMedCentral
132.
Golds G, Houdek D, Arnason T (2017) Male hypogonadism and osteoporosis: The effects, clinical consequences, and treatment of testosterone deficiency in bone health. Int J Endocrinol 2017:4602129PubMedPubMedCentralCrossRef
133.
134.
135.
Saito M, Marumo K (2010) Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int 21:195–214PubMedCrossRef
136.
Saito M, Marumo K (2015) Effects of collagen crosslinking on bone material properties in health and disease. Calcif Tissue Int 97:242–261PubMedCrossRef
137.
Rungratanawanich W, Qu Y, Wang X, Essa MM, Song BJ (2021) Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury. Exp Mol Med 53:168–188PubMedPubMedCentralCrossRef
138.
Kida Y, Saito M, Shinohara A, Soshi S, Marumo K (2019) Non-invasive skin autofluorescence, blood and urine assays of the advanced glycation end product (AGE) pentosidine as an indirect indicator of AGE content in human bone. BMC Musculoskelet Disord 20:627PubMedPubMedCentralCrossRef
139.
Shiraki M, Kashiwabara S, Imai T, Tanaka S, Saito M (2019) The association of urinary pentosidine levels with the prevalence of osteoporotic fractures in postmenopausal women. J Bone Miner Metab 37:1067–1074PubMedCrossRef
140.
Yamamoto M, Yamaguchi T, Yamauchi M, Yano S, Sugimoto T (2008) Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab 93:1013–1019PubMedCrossRef
141.
Schwartz AV, Garnero P, Hillier TA, Sellmeyer DE, Strotmeyer ES, Feingold KR, Resnick HE, Tylavsky FA, Black DM, Cummings SR, Harris TB, Bauer DC, Health, Aging, and Body Composition Study (2009) Pentosidine and increased fracture risk in older adults with type 2 diabetes. J Clin Endocrinol Metab 94:2380–2386PubMedPubMedCentralCrossRef
142.
Neumann T, Lodes S, Kästner B, Franke S, Kiehntopf M, Lehmann T, Müller UA, Wolf G, Sämann A (2014) High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control. Osteoporos Int 25:1527–1533PubMedCrossRef
143.
Saeki C, Saito M, Kanai T, Nakano M, Oikawa T, Torisu Y, Saruta M, Tsubota A (2021) Plasma pentosidine levels are associated with prevalent fractures in patients with chronic liver disease. PLoS ONE 16:e0249728PubMedPubMedCentralCrossRef
144.
Smedsrød B, Melkko J, Araki N, Sano H, Horiuchi S (1997) Advanced glycation end products are eliminated by scavenger-receptor-mediated endocytosis in hepatic sinusoidal Kupffer and endothelial cells. Biochem J 322:567–573PubMedPubMedCentralCrossRef
145.
Zhang X, Liu J, Zhang Q, Lu A, Du Y, Ye X (2021) Elevated serum pentosidine is independently associated with the high prevalence of sarcopenia in Chinese middle-aged and elderly men with type 2 diabetes mellitus. J Diabetes Investig 12:2054–2061PubMedPubMedCentralCrossRef
146.
Moriwaki K, Matsumoto H, Tanimura C, Osaki M, Nagashima H, Hagino H (2021) Urinary pentosidine level is associated with grip strength and gait speed in community-dwelling adults: a cross-sectional study. BMC Musculoskelet Disord 22:392PubMedPubMedCentralCrossRef
147.
Machowska A, Sun J, Qureshi AR, Isoyama N, Leurs P, Anderstam B, Heimburger O, Barany P, Stenvinkel P, Lindholm B (2016) Plasma pentosidine and its association with mortality in patients with chronic kidney disease. PLoS ONE 11:e0163826PubMedPubMedCentralCrossRef
148.
Koyama Y, Takeishi Y, Arimoto T, Niizeki T, Shishido T, Takahashi H, Nozaki N, Hirono O, Tsunoda Y, Nitobe J, Watanabe T, Kubota I (2007) High serum level of pentosidine, an advanced glycation end product (AGE), is a risk factor of patients with heart failure. J Card Fail 13:199–206PubMedCrossRef
149.
Saeki C, Saito M, Tsubota A (2023) Plasma pentosidine as a useful biomarker of sarcopenia, low gait speed, and mortality in patients with cirrhosis. Front Med (Lausanne) 10:1212899PubMedCrossRef
150.
Valenti L, Varenna M, Fracanzani AL, Rossi V, Fargion S, Sinigaglia L (2009) Association between iron overload and osteoporosis in patients with hereditary hemochromatosis. Osteoporos Int 20:549–555PubMedCrossRef
151.
Ruiz-Gaspà S, Martinez-Ferrer A, Guañabens N, Dubreuil M, Peris P, Enjuanes A, De Osaba MJM, Alvarez L, Monegal A, Combalia A, Parés A (2011) Effects of bilirubin and sera from jaundiced patients on osteoblasts: Contribution to the development of osteoporosis in liver diseases. Hepatology 54:2104–2113PubMedCrossRef
152.
Ruiz-Gaspà S, Dubreuil M, Guañabens N, Combalia A, Peris P, Monegal A, Parés A (2014) Ursodeoxycholic acid decreases bilirubin-induced osteoblast apoptosis. Eur J Clin Investig 44:1206–1214CrossRef
153.
Tu Y, Yang R, Xu X, Zhou X (2021) The microbiota-gut-bone axis and bone health. J Leukoc Biol 110:525–537PubMedCrossRef
154.
Cao RR, He P, Lei SF (2021) Novel microbiota-related gene set enrichment analysis identified osteoporosis associated gut microbiota from autoimmune diseases. J Bone Miner Metab 39:984–996PubMedCrossRef
155.
156.
European Association for the Study of the Liver (2017) EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol 67:145–172CrossRef
157.
Atamaz F, Hepguler S, Karasu Z, Kilic M, Tokat Y (2006) The prevention of bone fractures after liver transplantation: experience with alendronate treatment. Transplant Proc 38:1448–1452PubMedCrossRef
158.
Shane E, Cohen A, Stein EM, McMahon DJ, Zhang C, Young P, Pandit K, Staron RB, Verna EC, Brown R, Restaino S, Mancini D (2012) Zoledronic acid versus alendronate for the prevention of bone loss after heart or liver transplantation. J Clin Endocrinol Metab 97:4481–4490PubMedPubMedCentralCrossRef
159.
Matsumoto T, Endo I (2021) RANKL as a target for the treatment of osteoporosis. J Bone Miner Metab 39:91–105PubMedCrossRef
160.
Bone HG, Wagman RB, Brandi ML, Brown JP, Chapurlat R et al (2017) 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol 5:513–523PubMedCrossRef
161.
Saeki C, Saito M, Oikawa T, Nakano M, Torisu Y, Saruta M, Tsubota A (2020) Effects of denosumab treatment in chronic liver disease patients with osteoporosis. World J Gastroenterol 26:4960–4971PubMedPubMedCentralCrossRef
162.
Brunova J, Kratochvilova S, Stepankova J (2018) Osteoporosis therapy with denosumab in organ transplant recipients. Front Endocrinol (Lausanne) 9:162PubMedCrossRef
163.
Miedany YE, Gaafary ME, Toth M, Hegazi MO, Aroussy NE, Hassan W, Almedany S, Nasr A, Bahlas S, Galal S, Egyptian Academy of Bone Health, Metabolic Bone Diseases (2021) Is there a potential dual effect of denosumab for treatment of osteoporosis and sarcopenia? Clin Rheumatol 40:4225–4232PubMedCrossRef
164.
Working Subgroup (English Version) for Clinical Practice Guidelines for Primary Biliary Cirrhosis (2014) Guidelines for the management of primary biliary cirrhosis. The Intractable Hepatobiliary Disease Study Group supported by the Ministry of Health, Labour and Welfare of Japan. Hepatol Res 44:71–90CrossRef
165.
Ida S, Kaneko R, Murata K (2018) SARC-F for screening of sarcopenia among older adults: A meta- analysis of screening test accuracy. J Am Med Dir Assoc 19:685–689PubMedCrossRef
166.
Hanai T, Hiraoka A, Shiraki M, Sugimoto R, Taniki N, Hiramatsu A, Nakamoto N, Iwasa M, Chayama K, Shimizu M (2021) Utility of the SARC-F questionnaire for sarcopenia screening in patients with chronic liver disease: a multicenter cross-sectional study in Japan. J Clin Med 10:3448PubMedPubMedCentralCrossRef
167.
Saeki C, Saito M, Kanai T, Nakano M, Oikawa T, Torisu Y, Saruta M, Tsubota A (2021) Clinical usefulness of FRAX score for predicting sarcopenia in patients with chronic liver disease. J Clin Med 10:4080PubMedPubMedCentralCrossRef
Metadata
Title
Association of chronic liver disease with bone diseases and muscle weakness
Authors
Chisato Saeki
Mitsuru Saito
Akihito Tsubota
Publication date
01-02-2024
Publisher
Springer Nature Singapore
Published in
Journal of Bone and Mineral Metabolism
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI
https://doi.org/10.1007/s00774-023-01488-x
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits