Association Between Bisphosphonates and Hospitalized Clostridioides difficile Infection Among Frail Older Adults

Published:January 13, 2020DOI:



      Clostridioides difficile infection is a major source of morbidity and mortality among frail older adults, especially those in nursing homes (NHs). Safety reports have signaled that bisphosphonate use may be a contributing cause. We therefore evaluated the risk of C difficile hospitalization associated with oral bisphosphonate use in the NH.


      Observational, retrospective new-user cohort study.


      The cohort included US NH residents aged ≥65 years who became a long-stay resident (>100 days in the NH) between January 1, 2008 and December 31, 2009.


      We conducted a study of NH residents using linked Medicare claims and Minimum Data Set records. Residents were new users of an oral bisphosphonate 1:1 matched to new calcitonin users (“active” comparator) on propensity scores controlling for more than 100 covariates. The outcome was risk of hospitalization for C difficile infection in a Cox proportional hazards model adjusted for previous antibiotic and proton pump inhibitor use.


      Our final analytical cohort included 17,753 bisphosphonate and 5348 calcitonin users. In the matched cohort, 84/5209 (1.6%) vs 71/5209 (1.4%) C difficile–related hospitalizations occurred in bisphosphonate and calcitonin users, respectively. We observed no significant difference in the risk of hospitalization among bisphosphonate users (hazard ratio: 1.11, 95% confidence interval: 0.80-1.51). Antibiotic and proton pump inhibitor exposure before and after osteoporosis treatment was also similar between bisphosphonate and calcitonin users.

      Conclusions and Implications

      C difficile infection should not be a consideration when prescribing bisphosphonates to frail older adults given the lack of a significant association.


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