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Prevention of posttraumatic osteoarthritis at the time of injury: Where are we now, and where are we going?

Mason, Deborah, Englund, Martin and Watt, Fiona E. 2021. Prevention of posttraumatic osteoarthritis at the time of injury: Where are we now, and where are we going? Journal of Orthopaedic Research 10.1002/jor.24982

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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 processes to prevent later disease. Animal models have been used to test therapeutic targets to prevent PTOA. A review of drug treatments for PTOA in rodents and rabbits between 2016 and 2018 revealed 11 systemic interventions, 5 repeated intra‐articular or topical interventions, and 5 short‐term intra‐articular interventions, which reduced total Osteoarthritis Research Society International scores by 30%–50%, 20%–70%, and 0%–40%, respectively. Standardized study design, reporting of effect size, and quality metrics, alongside a “whole joint” approach to assessing efficacy, would improve the translation of promising 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, and advocated the use of experimental medicine studies to triage candidate treatments and the development of early biological and imaging biomarkers. Human trials for the prevention of PTOA have tested anakinra after 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 and high‐quality preclinical research, and allegiance with patients, regulatory bodies, and the pharmaceutical industry, will advance this field.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Biosciences
Additional Information: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Publisher: Wiley
ISSN: 0736-0266
Funders: Arthritis Research UK
Date of First Compliant Deposit: 8 March 2021
Date of Acceptance: 11 January 2021
Last Modified: 19 Mar 2021 09:43
URI: http://orca.cf.ac.uk/id/eprint/139379

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