中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 42 Issue 6
Jun.  2026
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2026  >  42(6): 1253-1259

Epidemiology， mechanism， prevention， and treatment of reduced bone mineral density associated with liver cirrhosis

DOI: 10.12449/JCH260603

  • Department of Gastroenterology，Sun Yat-sen Memorial Hospital，Sun Yat-sen University，Guangzhou 510120，China

Research funding:

Guangzhou Municipal-University/Institute-Enterprise Joint Funding Project (2025A03J4203);

Guangdong Weiji Medical Development Foundation (K-20240209)

More Information
  • Corresponding author: WANG Lingyun， wanglyun@mail.sysu.edu.cn （ORCID： 0000-0002-6646-7223）
  • Received Date: 2026-02-27
  • Accepted Date: 2026-04-07
  • Published Date: 2026-06-25
    Abstract
  • Patients with liver cirrhosis often experience a reduction in bone mineral density （BMD） or even osteoporosis （OP） due to long-term chronic liver dysfunction and systemic metabolic disorders， and this condition has become one of the major complications affecting their quality of life and long-term prognosis. This article systematically reviews the epidemiological characteristics of reduced BMD associated with liver cirrhosis， summarizes the incidence of reduced BMD in liver cirrhosis patients with different etiologies， and analyzes its association with disease severity. This article further discusses the main pathophysiological mechanisms of reduced BMD induced by liver cirrhosis （including calcium/phosphorus metabolism disorders， sex hormone imbalance， chronic inflammatory response， and bone metabolism dysregulation）， reviews the clinical manifestations， fracture risk， and adverse outcomes associated with reduced BMD， and summarizes current prevention and treatment strategies for cirrhosis-related OP. This review aims to integrate recent research advances in this field and to provide a reference for future mechanistic studies and standardized clinical management.

     

    • FullText(HTML)
  • loading
    • References(56)
  • [1]
    Chinese Society of Hepatology, Chinese Medical Association. Chinese guidelines for clinical diagnosis, treatment, and management of cirrhosis(2025)[J]. Chin J Hepatol, 2025, 33( 10): 958- 976. DOI: 10.3760/cma.j.cn501113-20250728-00298.

    中华医学会肝病学分会. 肝硬化临床诊治管理指南(2025 版)[J]. 中华肝脏病杂志, 2025, 33( 10): 958- 976. DOI: 10.3760/cma.j.cn501113-20250728-00298.
    [2]
    MAN S, DENG YH, MA Y, et al. Prevalence of liver steatosis and fibrosis in the general population and various high-risk populations: A nationwide study with 5.7 million adults in China[J]. Gastroenterology, 2023, 165( 4): 1025- 1040. DOI: 10.1053/j.gastro.2023.05.053.
    [3]
    THOMSON M, SCOTT A, TROST S, et al. Low screening rates and high prevalence of osteoporosis in cirrhosis: A real-world retrospective analysis[J]. Aliment Pharmacol Ther, 2024, 59( 4): 535- 546. DOI: 10.1111/apt.17823.
    [4]
    LEBOFF MS, GREENSPAN SL, INSOGNA KL, et al. The clinician’s guide to prevention and treatment of osteoporosis[J]. Osteoporos Int, 2022, 33( 10): 2049- 2102. DOI: 10.1007/s00198-021-05900-y.
    [5]
    BILBILY A, SYME CA, ADACHI JD, et al. Opportunistic screening of low bone mineral density from standard X-rays[J]. J Am Coll Radiol, 2024, 21( 4): 633- 639. DOI: 10.1016/j.jacr.2023.07.024.
    [6]
    GROVER I, SINGH N, GUNJAN D, et al. Vitamin D status& bone health in patients with liver cirrhosis[J]. Indian J Med Res, 2023, 158( 3): 284- 291. DOI: 10.4103/ijmr.ijmr_1144_20.
    [7]
    SIQUEIRA MMLG, CASULARI LA, FREITAS WM, et al. Risk factors associated with fracture of the lumbosacral spine and its compromise in the quality of life of cirrhotics[J]. Arq Gastroenterol, 2022, 59( 1): 9- 15. DOI: 10.1590/s0004-2803.202200001-03.
    [8]
    GEORGE J, GANESH HK, ACHARYA S, et al. Bone mineral density and disorders of mineral metabolism in chronic liver disease[J]. World J Gastroenterol, 2009, 15( 28): 3516. DOI: 10.3748/wjg.15.3516.
    [9]
    GOKCAN H, KAYHAN MA, DEMIR SO, et al. Prevalence and characteristics of bone disease in cirrhotic patients[J]. Hepatol Forum, 2020, 1( 2): 48- 52. DOI: 10.14744/hf.2020.2020.0007.
    [10]
    KANG J, GOPAKUMAR H, PULI SR. Prevalence of osteoporosis in cirrhosis: A systematic review and meta-analysis[J]. Cureus, 2023, 15( 1): e33721. DOI: 10.7759/cureus.33721.
    [11]
    XIAO PL, CUI AY, HSU CJ, et al. Global, regional prevalence, and risk factors of osteoporosis according to the World Health Organization diagnostic criteria: A systematic review and meta-analysis[J]. Osteoporos Int, 2022, 33( 10): 2137- 2153. DOI: 10.1007/s00198-022-06454-3.
    [12]
    SHUKLA V, FATIMA J, SIDDIQUI Z, et al. Study of correlation of bone mineral density with severity of liver cirrhosis[J]. J Assoc Physicians India, 2023, 71( 6): 11- 12. DOI: 10.5005/japi-11001-0257.
    [13]
    MOUNACH A, OUZZIF Z, WARIAGHLI G, et al. Primary biliary cirrhosis and osteoporosis: A case-control study[J]. J Bone Miner Metab, 2008, 26( 4): 379- 384. DOI: 10.1007/s00774-007-0833-1.
    [14]
    LÓPEZ-LARRAMONA G, LUCENDO AJ, GONZÁLEZ-DELGADO L. Alcoholic liver disease and changes in bone mineral density[J]. Rev Esp Enferm Dig, 2013, 105( 10): 609- 621. DOI: 10.4321/s1130-01082013001000006.
    [15]
    LAI JC, SHOBACK DM, ZIPPERSTEIN J, et al. Bone mineral density, bone turnover, and systemic inflammation in non-cirrhotics with chronic hepatitis C[J]. Dig Dis Sci, 2015, 60( 6): 1813- 1819. DOI: 10.1007/s10620-014-3507-6.
    [16]
    BERING T, DINIZ KGD, COELHO MPP, et al. Association between pre-sarcopenia, sarcopenia, and bone mineral density in patients with chronic hepatitis C[J]. J Cachexia Sarcopenia Muscle, 2018, 9( 2): 255- 268. DOI: 10.1002/jcsm.12269.
    [17]
    ZHAI TY, CHEN Q, XU J, et al. Prevalence and trends in low bone density, osteopenia and osteoporosis in U.S. adults with non-alcoholic fatty liver disease, 2005—2014[J]. Front Endocrinol, 2022, 12: 825448. DOI: 10.3389/fendo.2021.825448.
    [18]
    WAWRZYNIAK A, BALAWENDER K. Structural and metabolic changes in bone[J]. Animals, 2022, 12( 15): 1946. DOI: 10.3390/ani12151946.
    [19]
    YASUDA H. Discovery of the RANKL/RANK/OPG system[J]. J Bone Miner Metab, 2021, 39( 1): 2- 11. DOI: 10.1007/s00774-020-01175-1.
    [20]
    TSUKASAKI M, ASANO T, MURO R, et al. OPG production matters where it happened[J]. Cell Rep, 2020, 32( 10): 108124. DOI: 10.1016/j.celrep.2020.108124.
    [21]
    ESPINA S, CASAS-DEZA D, BERNAL-MONTERDE V, et al. Evaluation and management of nutritional consequences of chronic liver diseases[J]. Nutrients, 2023, 15( 15): 3487. DOI: 10.3390/nu15153487.
    [22]
    CHAPMAN B, SINCLAIR M, GOW PJ, et al. Malnutrition in cirrhosis: More food for thought[J]. World J Hepatol, 2020, 12( 11): 883- 896. DOI: 10.4254/wjh.v12.i11.883.
    [23]
    MIROLIAEE A, NASIRI-TOOSI M, KHALILZADEH O, et al. Disturbances of parathyroid hormone-vitamin D axis in non-cholestatic chronic liver disease: A cross-sectional study[J]. Hepatol Int, 2010, 4( 3): 634- 640. DOI: 10.1007/s12072-010-9194-2.
    [24]
    XIA SZ, QIN XQ, WANG JL, et al. Advancements in the pathogenesis of hepatic osteodystrophy and the potential therapeutic of mesenchymal stromal cells[J]. Stem Cell Res Ther, 2023, 14( 1): 359. DOI: 10.1186/s13287-023-03605-z.
    [25]
    FERRARESE A, HURTADO DÍAZ de LEÓN I, TAPPER EB, et al. Sexual health and function in liver disease[J]. Hepatol Commun, 2025, 9( 4): e0691. DOI: 10.1097/hc9.0000000000000691.
    [26]
    WANG LT, CHEN LR, CHEN KH. Hormone-related and drug-induced osteoporosis: A cellular and molecular overview[J]. Int J Mol Sci, 2023, 24( 6): 5814. DOI: 10.3390/ijms24065814.
    [27]
    YANG YJ, KIM DJ. An overview of the molecular mechanisms contributing to musculoskeletal disorders in chronic liver disease: Osteoporosis, sarcopenia, and osteoporotic sarcopenia[J]. Int J Mol Sci, 2021, 22( 5): 2604. DOI: 10.3390/ijms22052604.
    [28]
    JEONG H, KIM D. Bone diseases in patients with chronic liver disease[J]. Int J Mol Sci, 2019, 20( 17): 4270. DOI: 10.3390/ijms20174270.
    [29]
    RUIZ-GASPÀ S, MARTINEZ-FERRER A, GUAÑABENS N, et al. Effects of bilirubin and sera from jaundiced patients on osteoblasts: Contribution to the development of osteoporosis in liver diseases[J]. Hepatology, 2011, 54( 6): 2104- 2113. DOI: 10.1002/hep.24605.
    [30]
    NISHIMURA N, KAJI K, KITAGAWA K, et al. Intestinal permeability is a mechanical rheostat in the pathogenesis of liver cirrhosis[J]. Int J Mol Sci, 2021, 22( 13): 6921. DOI: 10.3390/ijms22136921.
    [31]
    GUO M, HUANG YL, WU Q, et al. Chronic ethanol consumption induces osteopenia via activation of osteoblast necroptosis[J]. Oxid Med Cell Longev, 2021, 2021: 3027954. DOI: 10.1155/2021/3027954.
    [32]
    SANTOS LAA, ROMEIRO FG. Diagnosis and management of cirrhosis-related osteoporosis[J]. BioMed Res Int, 2016, 2016( 1): 1423462. DOI: 10.1155/2016/1423462.
    [33]
    ZAVATTA G, VITALE G, MORELLI MC, et al. High bone fracture risk in a large modern cohort of liver transplant recipients[J]. Intern Emerg Med, 2025, 20( 1): 139- 150. DOI: 10.1007/s11739-024-03767-5.
    [34]
    SHIRINEZHAD A, ESHLAGHI FM, SALABAT D, et al. Prevalent osteoporosis and fracture risk in patients with hepatic cirrhosis: A systematic review and meta-analysis[J]. BMC Gastroenterol, 2025, 25( 1): 115. DOI: 10.1186/s12876-025-03720-6.
    [35]
    CHEN TL, LIN CS, SHIH CC, et al. Risk and adverse outcomes of fractures in patients with liver cirrhosis: Two nationwide retrospective cohort studies[J]. BMJ Open, 2017, 7( 10): e017342. DOI: 10.1136/bmjopen-2017-017342.
    [36]
    PEARSON AG, HIND K, MACNAUGHTON LS. The impact of dietary protein supplementation on recovery from resistance exercise-induced muscle damage: A systematic review with meta-analysis[J]. Eur J Clin Nutr, 2023, 77( 8): 767- 783. DOI: 10.1038/s41430-022-01250-y.
    [37]
    ALGHAMDI A, ALMUTAIRI OA, ALQAM R ABU, et al. Evaluation of osteoporosis perception among Saudi Arabian premenopausal women: A cross-sectional survey study using the osteoporosis knowledge assessment tool(OKAT)[J]. Cureus, 2023: 15( 9): e45191. DOI: 10.7759/cureus.45191.
    [38]
    PARÉS A, GUAÑABENS N. Primary biliary cholangitis and bone disease[J]. Best Pract Res Clin Gastroenterol, 2018, 34: 63- 70. DOI: 10.1016/j.bpg.2018.06.005.
    [39]
    KIZILGUL M, OZCELIK O, DELIBASI T. Bone health and vitamin D status in alcoholic liver disease[J]. Indian J Gastroenterol, 2016, 35( 4): 253- 259. DOI: 10.1007/s12664-016-0652-1.
    [40]
    YOU H, MA X, EFE C, et al. APASL clinical practice guidance: The diagnosis and management of patients with primary biliary cholangitis[J]. Hepatol Int, 2022, 16( 1): 1- 23. DOI: 10.1007/s12072-021-10276-6.
    [41]
    ROSSOUW JE, ANDERSON GL, PRENTICE RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the women’s health initiative randomized controlled trial[J]. JAMA, 2002, 288( 3): 321- 333. DOI: 10.1001/jama.288.3.321.
    [42]
    ORMARSDÓTTIR S, MALLMIN H, NAESSÉN T, et al. An open, randomized, controlled study of transdermal hormone replacement therapy on the rate of bone loss in primary biliary cirrhosis[J]. J Intern Med, 2004, 256( 1): 63- 69. DOI: 10.1111/j.1365-2796.2004.01342.x.
    [43]
    SAEKI C, SAITO M, OIKAWA T, et al. Effects of denosumab treatment in chronic liver disease patients with osteoporosis[J]. World J Gastroenterol, 2020, 26( 33): 4960- 4971. DOI: 10.3748/wjg.v26.i33.4960.
    [44]
    PILZ S, PUTZ-BANKUTI C, GAKSCH M, et al. Effects of vitamin D supplementation on serum 25-hydroxyvitamin D concentrations in cirrhotic patients: A randomized controlled trial[J]. Nutrients, 2016, 8( 5): 278. DOI: 10.3390/nu8050278.
    [45]
    NAOT D, MUSSON DS, CORNISH J. The activity of peptides of the calcitonin family in bone[J]. Physiol Rev, 2019, 99( 1): 781- 805. DOI: 10.1152/physrev.00066.2017.
    [46]
    KAHRAMAN R, ŞAHIN A, ÖZTÜRK O, et al. Effects of long-term tenofovir and entecavir treatment on bone mineral density in patients with chronic hepatitis B[J]. Turk J Gastroenterol, 2022, 33( 1): 35- 43. DOI: 10.5152/tjg.2020.18024.
    [47]
    Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(version 2022)[J]. Chin J Clin Infect Dis, 2022, 15( 6): 401- 427. DOI: 10.3760/cma.j.issn.1674-2397.2022.06.001.

    中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2022年版)[J]. 中华临床感染病杂志, 2022, 15( 6): 401- 427. DOI: 10.3760/cma.j.issn.1674-2397.2022.06.001.
    [48]
    Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of hepatitis C(2022 version)[J]. Chin J Infect Dis, 2023, 41( 1): 29- 46. DOI: 10.3760/cma.j.cn311365-20230217-00045.

    中华医学会肝病学分会, 中华医学会感染病学分会. 丙型肝炎防治指南(2022年版)[J]. 中华传染病杂志, 2023, 41( 1): 29- 46. DOI: 10.3760/cma.j.cn311365-20230217-00045.
    [49]
    LI YM, FAN JG. Guidelines of prevention and treatment for alcoholic liver disease(2018, China)[J]. J Digest Diseases, 2019, 20( 4): 174- 180. DOI: 10.1111/1751-2980.12687.
    [50]
    Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of metabolic dysfunction-associated( non-alcoholic) fatty liver disease(Version 2024)[J]. J Prac Hepatol, 2024, 27( 4): 494- 510. DOI: 10.3760/cma.j.cn501113-20240327-00163.

    中华医学会肝病学分会. 代谢相关(非酒精性)脂肪性肝病防治指南(2024年版)[J]. 实用肝脏病杂志, 2024, 27( 4): 494- 510. DOI: 10.3760/cma.j.cn501113-20240327-00163.
    [51]
    Chinese Society of Hepatology, Chinese Medical Association. Guidelines on the diagnosis and management of autoimmune hepatitis(2021)[J]. J Clin Hepatol, 2022, 38( 1): 42- 49. DOI: 10.3760/cma.j.cn112138-20211112-00796.

    中华医学会肝病学分会. 自身免疫性肝炎诊断和治疗指南(2021)[J]. 临床肝胆病杂志, 2022, 38( 1): 42- 49. DOI: 10.3760/cma.j.cn112138-20211112-00796.
    [52]
    Chinese Society of Hepatology, Chinese Medical Association. Guidelines on the diagnosis and management of primary biliary cholangitis(2021)[J]. J Clin Hepatol, 2022, 38( 1): 35- 41. DOI: 10.3760/cma.j.cn112138-20211112-00794.

    中华医学会肝病学分会. 原发性胆汁性胆管炎的诊断和治疗指南(2021)[J]. 临床肝胆病杂志, 2022, 38( 1): 35- 41. DOI: 10.3760/cma.j.cn112138-20211112-00794.
    [53]
    ANALAY P, KARA M, FıRAT HG, et al. The relationship between antihypertensive drugs and osteoporosis in postmenopausal women: The ADiOS study[J]. J Clin Densitom, 2025, 28( 4): 101607. DOI: 10.1016/j.jocd.2025.101607.
    [54]
    LABENZ C, WÖRNS MA, ADARKWAH CC, et al. Proton pump inhibitors increase risk of bone fractures in men with cirrhosis: A population-based study[J]. Aliment Pharmacol Ther, 2020, 52( 6): 1042- 1050. DOI: 10.1111/apt.16008.
    [55]
    JOHNSTON CB, DAGAR M. Osteoporosis in older adults[J]. Med Clin N Am, 2020, 104( 5): 873- 884. DOI: 10.1016/j.mcna.2020.06.004.
    [56]
    The North American Menopause Society. Management of osteoporosis in postmenopausal women: the 2021 position statement of the North American Menopause Society[J]. Menopause, 2021, 28( 9): 973- 997. DOI: 10.1097/GME.0000000000001831.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Tables(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (55) PDF downloads(21) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return