{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:26:28Z","timestamp":1791246388465,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Falls and fractures are common and morbid for patients with cirrhosis. Bisphosphonates are recommended for the prevention of fractures for people with osteoporosis cirrhosis; however, data supporting effectiveness in cirrhosis are lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>We sought to emulate a clinical trial of bisphosphonates in cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used national Medicare data (2008\u20132020) to examine the 5\u2010year risk of fractures in patients who did or did not receive bisphosphonates with a new\u2010user design among people diagnosed with cirrhosis and osteoporosis. We balanced treated and untreated with inverse probability of treatment weighting, evaluated intention\u2010to\u2010treat and as\u2010treated effects, and examined both control exposures (statin use) and outcomes (decompensation) to test causal relationships.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were 253 and 20,888 new users and non\u2010users of bisphosphonates, respectively. The median age was 74\u2009years. The most common bisphosphonate used was alendronate (73.6%). Bisphosphonates significantly reduced fractures overall (27.5% vs. 33.0%, <jats:italic>p<\/jats:italic>\u2009=\u20090.0004) in the intention\u2010to\u2010treat analysis, particularly for people &lt;65\u2009years (sHR 0.56) old, men (sHR 0.64) and those with non\u2010alcohol related liver disease (sHR 0.85). Though there were fewer arm (20.7% vs. 26.4%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and femur (28.9% vs. 31.2%, <jats:italic>p<\/jats:italic>\u2009=\u20090.005), there were more spinal (25.8% vs. 19.0%), rib (40.0% vs. 32.2%) and skull (10.1% vs. 8.7%) fractures. In the as\u2010treated analysis, cumulative bisphosphonate exposure significantly reduced fractures, sHR 0.95 95% CI (0.91, 0.98). Treatment was inconsistent; bisphosphonate users spent 29.9% person\u2010years of follow\u2010up on the drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In a nationally representative cohort of elderly patients with cirrhosis, bisphosphonates reduced fractures overall. Efforts to increase uptake and drug continuation are needed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.18127","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T08:59:16Z","timestamp":1719392356000},"page":"585-592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Bisphosphonate effectiveness in patients with cirrhosis: An emulated clinical trial"],"prefix":"10.1111","volume":"60","author":[{"given":"Elliot B.","family":"Tapper","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beanna","family":"Martinez","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6641-1430","authenticated-orcid":false,"given":"Peter","family":"Jepsen","sequence":"additional","affiliation":[{"name":"Department of Hepatology &amp; Gastroenterology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine University of Aarhus  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5874-9933","authenticated-orcid":false,"given":"Neehar D.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.5997"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32049"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.04.012"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2018.01.026"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000001091"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000001166"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30489"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29756"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17823"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2016.04.014"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv254"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24616"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000386"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280215584401"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1999.10474144"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.7326\/M22-0684"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD004523.pub4"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.11005\/jbm.2017.24.1.37"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD001155.pub2"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocd.2019.05.003"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/hc9.0000000000000122"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028020970518"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000072"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000443"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.26079"}],"container-title":["Alimentary Pharmacology &amp; 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