Association between Bisphosphonate use and COVID-19 related outcomes: a retrospective cohort study

Abstract

ABSTRACTBackgroundAlthough there are several efficacious vaccines against COVID-19, vaccination rates in many regions around the world remain insufficient to prevent continued high disease burden and emergence of viral variants. Repurposing of existing therapeutics that prevent or mitigate severe COVID-19 could help to address these challenges. The objective of this study was to determine whether prior use of bisphosphonates is associated with reduced incidence and/or severity of COVID-19.MethodsA retrospective cohort study utilizing payer-complete health insurance claims data from 8,239,790 patients with continuous medical and prescription insurance from 1-1-2019 to 6-30-2020 was performed. The primary exposure of interest was use of any bisphosphonate from 1-1-2019 to 2-29-2020. Outcomes of interest included: (a) testing for SARS-CoV-2 infection; (b) COVID-19 diagnosis; and (c) hospitalization with COVID-19 diagnosis between 3-1-2020 and 6-30-2020.Results7,906,603 patients for whom continuous medical and prescription insurance information was available were selected. 450,366 bisphosphonate users were identified and 1:1 propensity score-matched to bisphosphonate non-users by age, gender, insurance type, primary-care-provider visit in 2019, and comorbidity burden. Bisphosphonate users had lower odds ratios (OR) of testing for SARS-CoV-2 infection (OR=0.22; 95%CI:0.21-0.23; p<0.001), COVID-19 diagnosis (OR=0.23; 95%CI:0.22-0.24; p<0.001), and COVID-19-related hospitalization (OR=0.26; 95%CI:0.24-0.29; p<0.001). Sensitivity analyses yielded results consistent with the primary analysis. Bisphosphonate-use was also associated with decreased odds of acute bronchitis (OR=0.23; 95%CI:0.22-0.23; p<0.001) or pneumonia (OR=0.32; 95%CI:0.31-0.34; p<0.001) in 2019, suggesting that bisphosphonates may protect against respiratory infections by a variety of pathogens, including but not limited to SARS-CoV-2.ConclusionsPrior bisphosphonate-use was associated with dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations. Prospective clinical trials will be required to establish a causal role for bisphosphonate-use in COVID-19-related outcomes.