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Repurposing drugs for the treatment of osteoarthritis
Wilson Kuswanto1, Matthew C Baker2
1Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, USA; Gilead Sciences Inc, Foster City, CA, USA.
Objective:
Currently, no disease-modifying therapies for osteoarthritis (OA) exist, and attempts to identify novel cellular targets have been challenging. Risk factors for OA include advanced age, obesity, and metabolic syndrome. This creates an attractive opportunity to repurpose existing drugs that are used to treat comorbidities commonly encountered in patients with OA, if those drugs possess OA disease modifying properties.
Methods:
This narrative review incorporates findings from knee or hand OA randomized clinical trials, post-hoc clinical trial analyses, prospective cohort studies, and observational data.
Results:
Drugs used for the treatment of rheumatoid arthritis (methotrexate; TNFa, IL-1, and IL-6 pathway inhibitors; hydroxychloroquine), atopic/allergic disease (anti-histamines), osteoporosis (bisphosphonates and vitamin D), type 2 diabetes (metformin and GLP-1 agonists), and cardiovascular disease (atorvastatin, fish oil, and beta blockers) were reviewed for their potential benefit in OA. This review outlines the successful attributes of repurposed drugs, the challenges in repurposing drugs, and strategies for future clinical trials to support OA drug repurposing. Potential drug candidates for OA may be identified through the use of existing datasets and via collaborations with researchers in other fields to include OA endpoints in future clinical trials.
Conclusion:
Given the association of OA with several commonly treated comorbidities, drug repurposing is an appealing approach that could provide a favorable benefit-to-risk ratio for chronic OA treatment.
Insights
Repurposing existing medications for common comorbidities offers a promising strategy for osteoarthritis (OA) treatment. This approach may provide a favorable benefit-to-risk ratio for managing OA effectively.
Area of Science:
- Rheumatology and Pharmacology
- Osteoarthritis Pathophysiology
Background:
- Osteoarthritis (OA) currently lacks disease-modifying therapies, presenting a significant unmet medical need.
- Key OA risk factors include advanced age, obesity, and metabolic syndrome, often associated with other chronic conditions.
Purpose of the Study:
- To explore the potential of repurposing existing drugs, commonly used for OA comorbidities, as disease-modifying treatments for OA.
- To identify successful attributes, challenges, and strategies for drug repurposing in OA clinical trials.
Main Methods:
- A narrative review of findings from randomized clinical trials (knee/hand OA), post-hoc analyses, prospective cohort studies, and observational data.
- Examination of drugs used for rheumatoid arthritis, allergic disease, osteoporosis, type 2 diabetes, and cardiovascular disease.
Main Results:
- Several drug classes, including methotrexate, biologics, metformin, GLP-1 agonists, bisphosphonates, and statins, were reviewed for OA potential.
- The review highlights successful drug repurposing attributes, inherent challenges, and proposes strategies for future OA clinical trials.
- Identified potential OA drug candidates through existing datasets and interdisciplinary collaborations.
Conclusions:
- Drug repurposing is an attractive strategy for OA due to its association with prevalent comorbidities.
- This approach holds the potential for a favorable benefit-to-risk profile in the chronic management of osteoarthritis.
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