Common Osteoporosis Treatments May Offer Protection Against COVID-19

Investigators from the University of York and India’s Birla Institute of Technology and Science built on research conducted by Harvard Medical School to potentially provide a molecular explanation for why some osteoporosis drugs, such as alendronate (Fosamax; Merck) and zoledronate (Zometa; Novartis), can offer protection against the effects of COVID-19, the disease caused by SARS-CoV-2.^1,2

Osteoporosis drugs, through similar molecular makeup, could work as antiviral treatments for COVID-19 and prevent diagnosis or hospitalization. | Image Credit: © allvision | stock.adobe.com

In the Harvard Medical School investigation, conducted by Thompson et al, prior use of bisphosphonates (BPs) such as alendronate and zoledronate was associated with significantly reduced odds of testing for SARS-CoV-2 (OR = 0.22; 95% CI: 0.21–0.23; P < .001), being diagnosed with COVID-19 (OR = 0.23; 95% CI: 0.22–0.24; P < .001), and having COVID-19-related hospitalizations (OR = 0.26; 95% CI: 0.24–0.29; P < .001). However, study authors did not provide an explanation of the possible mechanisms behind this observation.^1,3

The current investigators sought to close the knowledge gap, due in part to the massive health burden caused by COVID-19, its associated pandemic, and the urgent need to identify new therapeutics for patients. The original Harvard investigation also notably did not systematically consider other BPs, which provided the current investigators reasoning to search more in depth for potentially effective BPs.^1,3

“Although vaccines have proved effective against Covid-19 and its variants, they are not able to prevent their transmission, and so new drugs are being sought to keep pace with the continuously mutating virus,” Seshadri Vasan, professor from University of York’s Department of Health Sciences, said in an accompanying news release.²

The investigators ran a computational drug development model that factored in molecular dynamics, pharmacokinetics, and aspects to search for potentially effective BPs that could bind to an enzyme called RNA-dependent RNA polymerase (RdRp), a key target of COVID-19 antivirals, in the entire ChEMBL database.^1,2

The database is designed to include a vast collection of molecules that may have potentially therapeutic drug-inducing effects. Identifying a molecular-level explanation for the landmark Harvard investigation and noting any other BPs that emerge as hit molecules was of utmost importance for the University of York investigators.^1,2

Across all the analyzed BPs in the database—a total of 1992 BPs—the University of York investigators identified 7 promising molecules, 2 of which closely resemble the approved drugs of minodronate (Astellas Pharma) and zoledronate. The molecule CHEMBL608526 was noted to be very similar to minodronic acid, while CHEMBL98211 was deemed to be close in its makeup to zoledronic acid. The investigators spoke highly of minodronate and its related ChEMBL molecule pertaining to COVID-19 or long COVID.¹

“Using this approach, we were able to provide a molecular explanation for osteoporosis drugs such as alendronate and zoledronate protecting against Covid-19, and predict that other molecules like minodronate, a drug used in Japan, may also be beneficial,” Vasan continued.²

The study authors discussed the importance surrounding their results, noting that the crucial gap in knowledge left unaddressed by the Harvard investigators was closed through their extensive investigation of related BPs to alendronate and zoledronate. In their conclusion, they call for further in vitro and ex vivo analyses that can better characterize their therapeutic potential in COVID-19. Human clinical trials are also necessary to determine the true effects of osteoporosis drugs in patients with COVID-19 and other coronaviruses.^1,2

REFERENCES

1. University of York. Study explains why some osteoporosis drugs may protect against COVID-19. News Release. Released January 14, 2025. Accessed January 24, 2025. https://www.eurekalert.org/news-releases/1070415

2. Muzaffar-Ur-Rehman M, Chougule KS, Chandu A, et al. In silico evaluation of bisphosphonates identifies leading candidates for SARS-CoV-2 RdRp inhibition. Journ Molecular Graphics Modelling. 2025;136:108939. doi:10.1016/j.jmgm.2024.108939

3. Thompson J, Wang Y, Dreischulte T, et al. Association between bisphosphonate use and COVID-19 related outcomes. Epidemiology and Global Health, Medicine. 2023;12:e79548. doi:10.7554/eLife.79548