Citation

Mason D, Englund M, Watt FE. J. Orthop. Res. 2021; ePub(ePub): ePub.

Copyright

(Copyright © 2021, John Wiley and Sons)

DOI

10.1002/jor.24982

PMID

unavailable

Abstract

This overview of progress made in preventing post-traumatic osteoarthritis (PTOA) was delivered in a workshop at the Orthopaedics Research Society Annual Conference in 2019. As joint trauma is a major risk factor for OA, defining the molecular changes within the joint at the time of injury may enable the targeting of biological processestoprevent later disease. Animal models have been used to test therapeutic targets to prevent PTOA. Areview of drug treatments for PTOA in rodents and rabbits between 2016 and 2018 revealed eleven systemic interventions,fiverepeated intra-articular or topical interventions and fiveshort-term intra-articular interventions, whichreduced total OARSI scores by 30-50%, 20-70% and0-40% respectively. Standardised study design, reporting of effect size and quality metrics, alongside a 'whole joint' approach to assessing efficacywould improve translation ofpromising new drugs. A roadblock to translating preclinical discoveries has been the lack of guidelines on the design and conduct of human trials to prevent PTOA.An international workshop addressing this in 2016 considered inclusion criteria and study design, andadvocated the use ofexperimental medicine studies to triage candidate treatments andthe development ofearly biological and imaging biomarkers.Human trials for prevention of PTOA have testedanakinraafter anterior cruciate ligament rupture and dexamethasone after radiocarpal injury. PTOA offers a unique opportunity for defining early mechanisms of OA to target therapeutically. Progress in trial design andhigh quality preclinical research, and allegiance with patients, regulatory bodies and the pharmaceutical industry, will advance this field. This article is protected by copyright. All rights reserved.

Language: en

Keywords

Pathophysiology; Treatment; Clinical; Disease Process; Knee; Therapeutics