The Potential of Authorised Drugs to be Repurposed for the Treatment of Osteoarthritis: A Scoping Review of Clinical Studies

BACKGROUND AND OBJECTIVES: Drug repurposing offers a low-cost and time-efficient approach to discover an effective and safe disease-modifying treatment for osteoarthritis. Although numerous studies have investigated candidate drugs for repurposing, existing narrative reviews are restricted in scope. This scoping review aims to provide an exhaustive overview of the extent and characteristics of clinical research on authorised drugs investigated for treating osteoarthritis. METHODS: Electronic database searches were performed from inception until July 2025 in MEDLINE, Embase and Cochrane. Authorised drugs approved by the US Food and Drug Administration, European Medicines Agency or Dutch Medicines Evaluation Board, investigated in clinical studies for treating osteoarthritis, were included. Dextrose and drugs indicated for pain (irrespective of aetiology) or osteoarthritis were excluded. Titles and abstracts were screened using ASReview, full texts were assessed accordingly and results were classified per drug. RESULTS: From 26,638 deduplicated records, 201 articles reporting on 220 studies were included in this review: 104 randomised controlled trials (RCTs), including 9 post-hoc analyses, 75 cohort studies, 13 case-control studies, 12 cross-sectional studies, 12 pre-post studies and 4 non-randomised CTs. In total, 52 drugs were identified, with drugs originally indicated for osteoporosis being most frequently investigated. Short-term follow-up studies (< 1 year) were mostly RCTs focussing on symptom-modifying effects, whilst long-term follow-up studies (≥ 1 year) more often used existing data and assessed both symptom- and structure-modifying effects. The most frequently used outcomes were pain (118/220) and function (74/220) for symptoms and grading systems (28/220) for structural changes. Significant effects were observed in 40% of the primary outcomes related to symptoms and structure and in 78% of outcomes related to osteoarthritis incidence or joint replacement. For GLP agonists, antihistamines, coumarins, N-acetylcysteine, sex hormones and statins, however, a mix of disease-modifying and disease-aggravating effects was found. CONCLUSIONS: Many authorised drugs have been investigated in clinical studies to be repurposed for treating osteoarthritis, with short-term studies primarily examining symptom-modifying effects, and most long-term studies also assessing structure-modifying effects. However, the broad and heterogeneous nature of clinical research in this field complicates the accurate evaluation of disease-modifying osteoarthritis drug candidates. This review, therefore, highlights the need for a more strategic research landscape on drug repurposing for osteoarthritis.