OBJECTIVES: Bisphosphonates (BPs), a class of drugs used to prevent bone loss, exert multifaceted immuno-modulatory activities. The objective of this study was to assess the association between prior BP-use and COVID-19-related outcomes.

METHODS: Closed-claims data from Komodo Health were used to identify patients with continuous medical and prescription insurance-enrollment during the study period 1/1/2019-6/30/2020 and no missing demographic information. BP-users, identified as patients with ≥1 BP-claim during the pre-observation period 1/1/2019-2/29/2020, were propensity-score-matched to BP-nonusers based on demographic and clinical characteristics. The association between BP-use and the odds ratio (OR) for SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalization during the observation period 3/1/2020-6/30/2020 were assessed using multivariable-logistic regression controlling for demographic/clinical characteristics. Sensitivity analyses performed included: restricting to females aged >50 diagnosed with osteoporosis and matching an active-control cohort of non-BP bone-medication-users to BP-users within state/insurance-type; assessing the relationship between use of other preventive-medications (statins, antihypertensives, antidiabetics, antidepressants), including impact of BP-use within users/nonusers of other preventive-medications, on COVID-19-related outcomes; and evaluating the effect of BP-use on positive-control outcomes (acute bronchitis, pneumonia) assessed 7/1/2019-12/31/2019 among BP-users 1/1/2019-6/30/2019 and their matched BP-nonuser-pair.

RESULTS: 7,906,603 patients met core eligibility criteria, of which 450,366 BP-users were identified and matched to 450,366 BP-nonusers. Compared to BP-nonusers, BP-users displayed a lower odds for SARS-CoV-2 testing (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). Consistent results were found comparing BP-users to non-BP bone-medication-users [(SARS-CoV-2 testing (OR=0.28;95%CI:0.23-0.35;p<0.001), COVID-19 diagnosis (OR=0.40;95%CI:0.32-0.49;p<0.001), COVID-19-related hospitalization (OR=0.45;95%CI:0.26-0.75;p=0.003)]. Use of other preventive-medications did not display similarly-consistent effects on COVID-19-related outcomes, though the impact of BP-use was maintained within users/nonusers of other preventive-medications. BP-use was also associated with a decreased odds of medical-services for 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.

CONCLUSIONS: Prior BP-use was associated with a reduced odds of COVID-19-related outcomes during the initial wave of the pandemic in 2020.