Clinical and Experimental Hepatology
eISSN: 2449-8238
ISSN: 2392-1099
Clinical and Experimental Hepatology
Current issue Archive Manuscripts accepted About the journal Editorial board Abstracting and indexing Subscription Contact Instructions for authors Publication charge Ethical standards and procedures
Editorial System
Submit your Manuscript
SCImago Journal & Country Rank
Search
Editorial Policies
Sarajevo Declaration on Integrity and Visibility of Scholarly Publications
Share:
Send email
Share:
Review paper

Osteoporosis in primary biliary cholangitis: from cholestasis to fracture prevention

Aleksandra Andrzejuk
1
,
Magdalena Rogalska
2
,
Paweł Rogalski
3
,
Robert Flisiak
2

  1. Faculty of Medicine with the Division of Dentistry and Division of Medical Education in English, Medical University of Białystok, Poland
  2. Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Poland
  3. Department of Gastroenterology and Internal Medicine, Medical University of Białystok, Poland
Clin Exp HEPATOL 2026; 12, 1
DOI: https://doi.org/10.5114/ceh.2026.158974
Online publish date: 2026/02/12
Article file
- Osteoporosis.pdf  [0.13 MB]
Get citation
 
PlumX metrics:
 
1. Zapata M, Pagan-Torres H, Mayo MJ. Systemic complications of primary biliary cholangitis. Clin Liver Dis 2024; 28: 115-128.
2. Rogalska M, Berkan-Kawińska A, Klapaczyński J, et al. Clinical characteristics of patients with primary biliary cholangitis treated with ursodeoxycholic acid. Pol Arch Intern Med 2025; 135: 17071.
3. Chen JL, Liu Y, Bi YF, et al. Prevalence and risk factors of osteoporosis detected by dual-energy X-ray absorptiometry among Chinese patients with primary biliary cholangitis. World J Gastroenterol 2023; 29: 4580-4592.
4. Kanda T, Sasaki-Tanaka R, Kimura N, et al. Pruritus in chronic cholestatic liver diseases, especially in primary biliary cholangitis: a narrative review. Int J Mol Sci 2025; 26: 1883.
5. Zhu H, Zheng M, Li W, et al. Cholesterol-modified prognostic nutritional index as an independent prognostic biomarker in primary biliary cholangitis patients. BMC Gastroenterol 2025; 25: 421.
6. Chalifoux SL, Konyn PG, Choi G, et al. Extrahepatic manifestations of primary biliary cholangitis. Gut Liver 2017; 11: 771-780.
7. Trivedi HD, Danford CJ, Goyes D, et al. Osteoporosis in primary biliary cholangitis: prevalence, impact and management challenges. Clin Exp Gastroenterol 2020; 13: 17-24.
8. Flisiak R, Pelszynska M, Prokopowicz D, et al. High concentration of antimitochondrial antibodies predicts progressive primary biliary cirrhosis. World J Gastroenterol 2005; 11: 5706-5709.
9. Jallouli I, Doulberis M, Kountouras J. Primary biliary cholangitis: a summary of pathogenesis and therapies. Ann Gastroenterol 2025; 38: 121-132.
10. Rogalska M, Błachnio-Zabielska A, Zabielski P, et al. Acylcarnitine and free fatty acid profiles in primary biliary cholangitis: associations with fibrosis and inflammation. Nutrients 2025; 17: 1097.
11. Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology 2019; 69: 394-419.
12. Buechter M, Manka P, Bulut K, et al. Obeticholic acid improves cholestasis, liver fibrosis, and liver function in patients with primary biliary cholangitis with inadequate response to ursodeoxycholic acid. J Pers Med 2025; 15: 79.
13. European Association for the Study of the Liver EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol 2017; 67: 145-172.
14. Evans S, Hofmann A. Autoimmune biliary diseases: A review of primary biliary cholangitis, primary sclerosing cholangitis, immunoglobulin G4-related sclerosing cholangitis, and autoimmune hepatitis. Surg Clin North Am 2024; 104: 1249-1261.
15. Castiella A, Sánchez-Iturri MJ, Stampa J, et al. Identifying patients with undiagnosed primary biliary cholangitis using a clinical management process. Ann Hepatol 2025; 30: 101933.
16. Men X, Liu Y, Zhao H, et al. The treatment of primary biliary cholangitis: time for personalized medicine. Clin Rev Allergy Immunol 2025; 68: 63.
17. Mitchell NE, Chan S, Diaz DJ, et al. Evolving therapeutic landscape of primary biliary cholangitis: A review. World J Hepatol 2025; 17: 107223.
18. Amin U, McPartland A, O’Sullivan M, et al. An overview of the management of osteoporosis in the aging female population. Womens Health (Lond) 2023; 19: 17455057231176655.
19. Yong EL, Logan S. Menopausal osteoporosis: screening, prevention and treatment. Singapore Med J 2021; 62: 159-166.
20. Chou SH. Osteoporosis in men: an overlooked patient population. Curr Osteoporos Rep 2025; 23: 13.
21. Jiang S, Xu K, Chen X. Identifying modifiable factors and their causal effects on osteoporosis risk. Sci Rep 2025; 15: 19472.
22. Sermin Kilic B, Yildirim A, Atakul N. The effect of body mass index on bone density by age distribution in women. Medicine (Baltimore) 2024; 103: e40129.
23. Ishimoto AK, Shah AA. Screening and early treatment for osteoporosis: Who are we missing under age 65? Maturitas 2024; 187: 108044.
24. Abraham A, Cohen A, Shane E. Premenopausal bone health: osteoporosis in premenopausal women. Clin Obstet Gynecol 2013; 56: 722-729.
25. Porter JL, Varacallo MA. Osteoporosis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025.
26. Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. Lancet 2011; 377: 1276-1287.
27. Harris K, Zagar CA, Lawrence KV. Osteoporosis: common questions and answers. Am Fam Physician 2023; 107: 238-246.
28. Subarajan P, Arceo-Mendoza RM, Camacho PM. Postmenopausal osteoporosis: A review of latest guidelines. Endocrinol Metab Clin North Am 2024; 53: 497-512.
29. Stępień-Kłos W, Michalska-Kasiczak M, Płoszka K, et al. Assessment of fracture risk based on FRAX score and Polish guidelines in patients with newly diagnosed osteoporosis. Endokrynol Pol 2025; 76: 74-81.
30. Vandenbroucke A, Luyten FP, Flamaing J, et al. Pharmacological treatment of osteoporosis in the oldest old. Clin Interv Aging 2017; 12: 1065-1077.
31. Gambacciani M, Levancini M. Management of postmenopausal osteoporosis and the prevention of fractures. Panminerva Med 2014; 56: 115-131.
32. Nogués X, Martinez-Laguna D. Update on osteoporosis treatment. Med Clin (Barc) 2018; 150: 479-486.
33. Fan J, Wang Q, Sun L. Association between primary biliary cholangitis and osteoporosis: meta-analysis. Clin Rheumatol 2017; 36: 2565-2571.
34. Tanaka A, Ma X, Takahashi A, et al. Primary biliary cholangitis. Lancet 2024; 404: 1053-1066.
35. Selmi C, Generali E, Gershwin ME. Rheumatic manifestations in autoimmune liver disease. Rheum Dis Clin North Am 2018; 44: 65-87.
36. Liao CY, Chung CH, Chu P, et al. Increased risk of osteoporosis in patients with primary biliary cirrhosis. PLoS One 2018; 13: e0194418.
37. Jeong HM, Kim DJ. Bone diseases in patients with chronic liver disease. Int J Mol Sci 2019; 20: 4270.
38. Danford CJ, Trivedi HD, Papamichael K, et al. Osteoporosis in primary biliary cholangitis. World J Gastroenterol 2018; 24: 3513-3520.
39. Liang Y, Li J, Zhang Z, et al. Extrahepatic conditions of primary biliary cholangitis: A systematic review and meta-analysis of prevalence and risk. Clin Res Hepatol Gastroenterol 2024; 48: 102321.
40. Zhao D, Li G, Bai W, et al. Primary biliary cirrhosis and osteoporosis: a bidirectional two-sample Mendelian randomization study. Front Immunol 2023; 14: 1269069.
41. Pugliese N, Arcari I, Aghemo A, et al. Osteosarcopenia in autoimmune cholestatic liver diseases: Causes, management, and challenges. World J Gastroenterol 2022; 28: 1430-1443.
42. Lim J, Kim YJ, Kim S, et al. Increased risk of fragility fractures in patients with primary biliary cholangitis. JBMR Plus 2024; 8: ziae056.
43. Choudhary NS, Saraf N, Saigal S, et al. Long-term management of the adult liver transplantation recipients. J Clin Exp Hepatol 2021; 11: 239-253.
44. Liu W, Dai Y, Liu J, et al. Causal relationship between primary biliary cholangitis on osteoporosis: A two-sample Mendelian randomization study. Medicine (Baltimore) 2025; 104: e43164.
45. Wu Y, Qian Q, Liu Q, et al. Osteoporosis and primary biliary cholangitis: a trans-ethnic mendelian randomization analysis. Clin Rev Allergy Immunol 2024; 66: 138-148.
46. Li Y, Liu B, Li X. High C-reactive protein-to-albumin ratio levels are associated with osteoporosis in patients with primary biliary cholangitis. Front Endocrinol (Lausanne) 2024; 15: 1415488.
47. Lu Z, Li X, Qi Y, et al. Genetic evidence of the causal relationship between chronic liver diseases and musculoskeletal disorders. J Transl Med 2024; 22: 138.
48. Parés A, Guañabens N, Rodés J. Gene polymorphisms as predictors of decreased bone mineral density and osteoporosis in primary biliary cirrhosis. Eur J Gastroenterol Hepatol 2005; 17: 311-315.
49. Springer JE, Cole DE, Rubin LA, et al. Vitamin D-receptor genotypes as independent genetic predictors of decreased bone mineral density in primary biliary cirrhosis. Gastroenterology 2000; 118: 145-151.
50. Locatelli V, Bianchi VE. Effect of GH/IGF-1 on bone metabolism and osteoporsosis. Int J Endocrinol 2014; 2014: 235060.
51. Saeki C, Oikawa T, Ueda K, et al. Serum insulin-like growth factor 1 levels, facture risk assessment tool scores and bone disorders in patients with primary biliary cholangitis. Diagnostics (Basel) 2022; 12: 1957.
52. Lakatos PL, Bajnok E, Tornai I, et al. Insulin-like growth factor I gene microsatellite repeat, collagen type Ialpha1 gene Sp1 polymorphism, and bone disease in primary biliary cirrhosis. Eur J Gastroenterol Hepatol 2004; 16: 753-759.
53. Parés A, Guañabens N, Alvarez L, et al. Collagen type Ialpha1 and vitamin D receptor gene polymorphisms and bone mass in primary biliary cirrhosis. Hepatology 2001; 33: 554-560.
54. Tang R, Wei Y, Li Z, et al. A common variant in CLDN14 is associated with primary biliary cirrhosis and bone mineral density. Sci Rep 2016; 6: 19877.
55. Ruiz-Gaspà S, Guañabens N, Jurado S, et al. Bile acids and bilirubin effects on osteoblastic gene profile. Implications in the pathogenesis of osteoporosis in liver diseases. Gene 2020; 725: 144167.
56. Ruiz-Gaspà S, Guañabens N, Jurado S, et al. Bilirubin and bile acids in osteocytes and bone tissue. Potential role in the cholestatic-induced osteoporosis. Liver Int 2020; 40: 2767-2775.
57. Ruiz-Gaspà S, Dubreuil M, Guañabens N, et al. Ursodeoxycholic acid decreases bilirubin-induced osteoblast apoptosis. Eur J Clin Invest 2014; 44: 1206-1214.
58. Dubreuil M, Ruiz-Gaspà S, Guañabens N, et al. Ursodeoxycholic acid increases differentiation and mineralization and neutralizes the damaging effects of bilirubin on osteoblastic cells. Liver Int 2013; 33: 1029-1038.
59. Cao RR, He P, Lei SF. Novel microbiota-related gene set enrichment analysis identified osteoporosis associated gut microbiota from autoimmune diseases. J Bone Miner Metab 2021; 39: 984-996.
60. Liu Q, Huang B, Zhou Y, et al. Gut microbiome pattern impacts treatment response in primary biliary cholangitis. Med 2025; 6: 100504.
61. Li T, Jing W. Bibliometric analysis of research on intestinal flora and primary biliary cholangitis published between 2004 and 2024 using VOSviewer and CiteSpace visualization. Front Med (Lausanne) 2025; 12: 1565778.
62. Wang Z, Wang W, Wang Y, et al. Mapping gut microbiota and metabolite alterations in patients with postmenopausal osteoporosis in the Beijing Community of China. Eur J Med Res 2025; 30: 539.
63. Qi P, Xie R, Liu H, et al. Mechanisms of gut homeostasis regulating Th17/Treg cell balance in PMOP. Front Immunol 2024; 15: 1497311.
64. Chen Y, Xie Y, Yu X. Progress of research on the gut microbiome and its metabolite short-chain fatty acids in postmenopausal osteoporosis: a literature review. Front Med 2025; 19: 474-492.
65. Feng B, Lu J, Han Y, et al. The role of short-chain fatty acids in the regulation of osteoporosis: new perspectives from gut microbiota to bone health: A review. Medicine (Baltimore) 2024; 103: e39471.
66. Seki A, Ikeda F, Miyatake H, et al. Risk of secondary osteoporosis due to lobular cholestasis in non-cirrhotic primary biliary cholangitis. J Gastroenterol Hepatol 2017; 32: 1611-1616.
67. Guañabens N, Parés A. Liver and bone. Arch Biochem Biophys 2010; 503: 84-94.
68. Ruiz-Gaspà S, Guañabens N, Enjuanes A, et al. Lithocholic acid downregulates vitamin D effects in human osteoblasts. Eur J Clin Invest 2010; 40: 25-34.
69. Wu A, Wu NN, Xu PH, et al. Association of blood vitamin A with osteoarthritis: a nationally representative cross-sectional study. Front Nutr 2024; 11: 1459332.
70. Lerner UH. Vitamin A – discovery, metabolism, receptor signaling and effects on bone mass and fracture susceptibility. Front Endocrinol (Lausanne) 2024; 15: 1298851.
71. Skalny AV, Aschner M, Tsatsakis A, et al. Role of vitamins beyond vitamin D3 in bone health and osteoporosis (Review). Int J Mol Med 2024; 53: 9.
72. Sultana H, Komai M, Shirakawa H. The role of vitamin K in cholestatic liver disease. Nutrients 2021; 13: 2515.
73. Danford CJ, Ezaz G, Trivedi HD, et al. The pharmacologic management of osteoporosis in primary biliary cholangitis: a systematic review and meta-analysis. J Clin Densitom 2020; 23: 223-236.
74. Guanabens N, Monegal A, Cerda D, et al. Randomized trial comparing monthly ibandronate and weekly alendronate for osteoporosis in patients with primary biliary cirrhosis. Hepatology 2013; 58: 2070-2078.
75. Pereira SP, O’Donohue J, Moniz C, et al. Transdermal hormone replacement therapy improves vertebral bone density in primary biliary cirrhosis: results of a 1-year controlled trial. Aliment Pharmacol Ther 2004; 19: 563-570.
76. Boone RH, Cheung AM, Girlan LM, et al. Osteoporosis in primary biliary cirrhosis: a randomized trial of the efficacy and feasibility of estrogen/progestin. Dig Dis Sci 2006; 51: 1103-1112.
77. Muzahim Y, Wakil A, Bassi M, et al. Treatment of primary biliary cholangitis including transplantation. Clin Liver Dis 2024; 28: 103-114.
78. Anagnostis P, Florentin M, Livadas S, et al. Bone health in patients with dyslipidemias: an underestimated aspect. Int J Mol Sci 2022; 23: 1639.
79. Ghonem NS, Auclair AM, Hemme CL, et al. Fenofibrate improves liver function and reduces the toxicity of the bile acid pool in patients with primary biliary cholangitis and primary sclerosing cholangitis who are partial responders to ursodiol. Clin Pharmacol Ther 2020; 108: 1213-1223.
80. Kim YH, Jang WG, Oh SH, et al. Fenofibrate induces PPARα and BMP2 expression to stimulate osteoblast differentiation. Biochem Biophys Res Commun 2019; 520: 459-465.
81. Levy C, Manns M, Hirschfield G. New Treatment Paradigms in Primary Biliary Cholangitis. Clin Gastroenterol Hepatol. 2023; 21: 2076-2087.
82. Arase Y, Okubo T, Arai T et al. Denosumab versus zoledronic acid for osteoporosis treatment in patients with primary biliary cholangitis (the DELTA Study): A multicenter, non-inferiority randomized trial. Hepatol Commun 2025; 9: e0827.
Copyright: © Clinical and Experimental Hepatology. This is an Open Access journal, all articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0). License (http://creativecommons.org/licenses/by-nc-sa/4.0/) enables reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.
Termedia
About us Contact
Copyright notice Privacy policy Advertising policy Contact us
Quick links
Journals Books eBooks Events
© 2026 Termedia Sp. z o.o.
Developed by Termedia.