Risk of fractures and postfracture mortality in 3980 people with primary biliary cholangitis: A population-based cohort study.
bone fracture
cirrhosis
liver disease
mortality
osteoporosis
population-based register study
Journal
Journal of internal medicine
ISSN: 1365-2796
Titre abrégé: J Intern Med
Pays: England
ID NLM: 8904841
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
medline:
13
7
2023
pubmed:
25
2
2023
entrez:
24
2
2023
Statut:
ppublish
Résumé
Morbidity in primary biliary cholangitis (PBC) is multifactorial. Osteoporosis related to cholestasis is an extrahepatic complication of PBC. It is not fully established to what extent people with PBC have an increased risk for fractures, and if mortality after a fracture is increased, compared to the general population. All Swedish people with PBC diagnosed between 2001 and 2016 were identified from the National Swedish Patient Register using ICD-10 codes. Incident fractures were ascertained in the same register and compared to matched controls from the Swedish general population (1:10 for age, sex, and municipality). Cox regression was used to investigate the rates of fractures and postfracture mortality. The cumulative incidence of fractures was calculated while accounting for competing risks (death or liver transplantation). People with PBC (n = 3980) showed a higher risk of fractures at all-time points during follow-up compared to matched controls (n = 37,196), which was seen both in men and women. At 5 years of follow-up, the cumulative incidence of any fracture in people with PBC was 16.8% (95% confidence interval [CI] = 15.6-18.1), compared to 11.6% (95%CI = 11.3-12.0) in controls. The rate of osteoporotic fractures was particularly high (adjusted Hazard ratio [aHR] = 1.9; 95% = CI 1.7-2.0). The 30-day as well as the 1-year mortality after a fracture was significantly higher in people with PBC compared to controls that also experienced a fracture (aHR = 2.2; 95%CI = 1.5-3.2; aHR = 2.0; 95%CI 1.7-2.4). People with PBC have a significantly higher risk of fractures and postfracture mortality compared to matched controls from the general population.
Sections du résumé
BACKGROUND
Morbidity in primary biliary cholangitis (PBC) is multifactorial. Osteoporosis related to cholestasis is an extrahepatic complication of PBC. It is not fully established to what extent people with PBC have an increased risk for fractures, and if mortality after a fracture is increased, compared to the general population.
METHODS
All Swedish people with PBC diagnosed between 2001 and 2016 were identified from the National Swedish Patient Register using ICD-10 codes. Incident fractures were ascertained in the same register and compared to matched controls from the Swedish general population (1:10 for age, sex, and municipality). Cox regression was used to investigate the rates of fractures and postfracture mortality. The cumulative incidence of fractures was calculated while accounting for competing risks (death or liver transplantation).
RESULTS
People with PBC (n = 3980) showed a higher risk of fractures at all-time points during follow-up compared to matched controls (n = 37,196), which was seen both in men and women. At 5 years of follow-up, the cumulative incidence of any fracture in people with PBC was 16.8% (95% confidence interval [CI] = 15.6-18.1), compared to 11.6% (95%CI = 11.3-12.0) in controls. The rate of osteoporotic fractures was particularly high (adjusted Hazard ratio [aHR] = 1.9; 95% = CI 1.7-2.0). The 30-day as well as the 1-year mortality after a fracture was significantly higher in people with PBC compared to controls that also experienced a fracture (aHR = 2.2; 95%CI = 1.5-3.2; aHR = 2.0; 95%CI 1.7-2.4).
CONCLUSION
People with PBC have a significantly higher risk of fractures and postfracture mortality compared to matched controls from the general population.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
164-177Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
Références
Gidwaney NG, Pawa S, Das KM. Pathogenesis and clinical spectrum of primary sclerosing cholangitis. World J Gastroenterol. 2017;23(14):2459-69.
KV LN, Nguyen LT. The role of vitamin d in primary biliary cirrhosis: possible genetic and cell signaling mechanisms. Gastroenterol Res Pract. 2013;2013:602321.
Trivedi HD, Danford CJ, Goyes D, Bonder A. Osteoporosis in primary biliary cholangitis: prevalence, impact and management challenges. Clin Exp Gastroenterol. 2020;13:17-24.
Nakchbandi IA. Osteoporosis and fractures in liver disease: relevance, pathogenesis and therapeutic implications. World J Gastroenterol. 2014;20(28):9427-38.
Guanabens N, Pares A, Ros I, Caballería L, Pons F, Vidal S, et al. Severity of cholestasis and advanced histological stage but not menopausal status are the major risk factors for osteoporosis in primary biliary cirrhosis. J Hepatol. 2005;42(4):573-7.
Guanabens N, Cerda D, Monegal A, Pons F, Caballería L, Peris P, et al. Low bone mass and severity of cholestasis affect fracture risk in patients with primary biliary cirrhosis. Gastroenterology. 2010;138(7):2348-56.
Kempinska-Podhorodecka A, Adamowicz M, Chmielarz M, Janik MK, Milkiewicz P, Milkiewicz M. Vitamin-D receptor-gene polymorphisms affect quality of life in patients with autoimmune liver diseases. Nutrients. 2020;12(8):2244.
Agmon-Levin N, Kopilov R, Selmi C, Nussinovitch U, Sánchez-Castañón M, López-Hoyos M, et al. Vitamin D in primary biliary cirrhosis, a plausible marker of advanced disease. Immunol Res. 2015;61(1-2):141-6.
Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2021 practice guidance update from the American Association for the Study of Liver Diseases. Hepatology. 2021;75(4):1012-3.
Nevens F, Andreone P, Mazzella G, Strasser SI, Bowlus C, Invernizzi P, et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med. 2016;375(7):631-43.
Pares A, Caballeria L, Rodes J, Bruguera M, Rodrigo L, García-Plaza A, et al. Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver. J Hepatol. 2000;32(4):561-6.
Poupon RE, Bonnand AM, Chretien Y, Poupon R. Ten-year survival in ursodeoxycholic acid-treated patients with primary biliary cirrhosis. The UDCA-PBC Study Group. Hepatology. 1999;29(6):1668-71.
Levy C, Peter JA, Nelson DR, Keach J, Petz J, Cabrera R, et al. Pilot study: fenofibrate for patients with primary biliary cirrhosis and an incomplete response to ursodeoxycholic acid. Aliment Pharmacol Ther. 2011;33(2):235-42.
Liao CY, Chung CH, Chu P, Wei KY, Feng TM, Lin FH, et al. Increased risk of osteoporosis in patients with primary biliary cirrhosis. PLoS One. 2018;13(3):e0194418.
Danford CJ, Trivedi HD, Papamichael K, Tapper EB, Bonder A. Osteoporosis in primary biliary cholangitis. World J Gastroenterol. 2018;24(31):3513-20.
Kaps L, Grambihler A, Yemane B, et al. Symptom burden and treatment response in patients with primary biliary cholangitis (PBC). Dig Dis Sci. 2020;65(10):3006-13.
Hagstrom H, Shang Y, Wester A, Widman L. Cohort profile: decoding the epidemiology of liver disease in Sweden (DELIVER). Scand J Gastroenterol. 2022;57:978-83.
Simon TG, Roelstraete B, Hagstrom H, Sundstrom J, Ludvigsson JF. Non-alcoholic fatty liver disease and incident major adverse cardiovascular events: results from a nationwide histology cohort. Gut. 2021;71(9):1867-75.
Diamantopoulos AP, Rohde G, Johnsrud I, Skoie IM, Hochberg M, Haugeberg G. The epidemiology of low- and high-energy distal radius fracture in middle-aged and elderly men and women in Southern Norway. PLoS One. 2012;7(8):e43367.
Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.
Boggess VCaM. Cumulative incidence estimation in the presence of competing risks. Stata J. 2004;4(2):103-12.
Boulton-Jones JR, Fenn RM, West J, Logan RF, Ryder SD. Fracture risk of women with primary biliary cirrhosis: no increase compared with general population controls. Aliment Pharmacol Ther. 2004;20(5):551-7.
Eastell R, O'Neill TW, Hofbauer LC, Langdahl B, Reid IR, Gold DT, et al. Postmenopausal osteoporosis. Nat Rev Dis Primers. 2016;2:16069.
Solaymani-Dodaran M, Card TR, Aithal GP, West J. Fracture risk in people with primary biliary cirrhosis: a population-based cohort study. Gastroenterology. 2006;131(6):1752-7.
Liang W, Chikritzhs T. The effect of age on fracture risk: a population-based cohort study. J Aging Res. 2016;2016:5071438.
Schattenberg JM, Pares A, Kowdley KV, Heneghan MA, Caldwell S, Pratt D, et al. A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA. J Hepatol. 2021;74(6):1344-54.