{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T19:43:21Z","timestamp":1776973401844,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,9,25]],"date-time":"2016-09-25T00:00:00Z","timestamp":1474761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Studies have shown associations between <jats:italic>Clostridium difficile<\/jats:italic> infection (<jats:styled-content style=\"fixed-case\">CDI<\/jats:styled-content>) and non\u2010antimicrobial medications including proton pump inhibitors, osteoporosis medications, and antidepressants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Our primary objective was to evaluate oral bisphosphonates and reported <jats:styled-content style=\"fixed-case\">CDI<\/jats:styled-content> adverse drug reactions in the United States using the Food and Drug Administration Adverse Event Reporting System data (<jats:styled-content style=\"fixed-case\">FAERS<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a disproportionality analysis evaluating the proportion of reports with bisphosphonates and <jats:styled-content style=\"fixed-case\">CDI<\/jats:styled-content> compared with other adverse drug reactions in the database. A relatively increased number of reports for a given adverse drug reaction (<jats:styled-content style=\"fixed-case\">ADR<\/jats:styled-content>) is termed a \u201csignal.\u201d Four major measures of association are used to describe reports: reporting odds ratio, proportional reporting ratio, information component, and empirical Bayes geometric mean. Drugs with statistically significant safety signals were stratified by age (18\u201340, 41\u201365, and 65+ years) and gender.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Alendronate had 0.4% (103\/23,603) reports with <jats:styled-content style=\"fixed-case\">CDI<\/jats:styled-content>. There were 0.4% (16\/3672) and 0.2% (17\/7945) of reports for risedronate and ibandronate, respectively. Alendronate (Fosamax) was the only drug with a significant signal using all four calculation methods. For reports with gender available, alendronate <jats:styled-content style=\"fixed-case\">CDI ADR<\/jats:styled-content>s were more common for women (0.45% [93\/20,586]) versus men (0.25% [4\/1568]), and a signal was detected with all four methods. For reports with age available, there were limited alendronate reports for those 18\u201339 years of age, and <jats:styled-content style=\"fixed-case\">CDI<\/jats:styled-content> reports were present in 0.50% (27\/5350) of cases of 40\u201364 years and 0.49% (42\/8525) of cases aged 65 or older.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Alendronate was associated with a high number of <jats:styled-content style=\"fixed-case\">CDI ADR<\/jats:styled-content>s relative to other drugs in <jats:styled-content style=\"fixed-case\">FAERS<\/jats:styled-content>. This signal was strongest for women and those 40 years or older. This interesting finding should be interpreted with caution, and further research is warranted.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.1832","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T07:15:23Z","timestamp":1472714123000},"page":"1095-1101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Quantitative Analysis of <scp>FDA<\/scp> Adverse Event Reports with Oral Bisphosphonates and <i>Clostridium difficile<\/i>"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5056-0431","authenticated-orcid":false,"given":"Kevin W.","family":"McConeghy","sequence":"first","affiliation":[{"name":"Providence VA Medical Center Providence Rhode Island"},{"name":"Brown University School of Public Health Providence Rhode Island"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melinda M.","family":"Soriano","sequence":"additional","affiliation":[{"name":"Global Center for Scientific Affairs Merck Research Laboratories Merck &amp; Co., Inc. Kenilworth New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry H.","family":"Danziger","sequence":"additional","affiliation":[{"name":"Colleges of Pharmacy and Medicine University of Illinois at Chicago Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,9,25]]},"reference":[{"issue":"24","key":"e_1_2_7_2_1","first-page":"2369","article-title":"Burden of Clostridium difficile infection in the United States","volume":"372","author":"Lessa FC","year":"2015","journal-title":"N Eng J Med"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2014.11.004"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1198-743x.2001.00287.x"},{"issue":"121","key":"e_1_2_7_5_1","first-page":"1","article-title":"Depression, antidepressant medications, and risk of Clostridium difficile infection","volume":"11","author":"Rogers MA","year":"2013","journal-title":"BMC Med"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.23.2989"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03924.x"},{"key":"e_1_2_7_8_1","unstructured":"McConeghyKW SorianoMM DanzigerLH.Bisphosphonates a potential risk factor for Clostridium difficile infections? 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