Updates in Osteoarthritis: Research Provides Insights into Molecular Pathogenesis of OA

ACR Convergence 2021—The session Updates in OA: Distinguishing OA Subtypes & Illuminating Future Therapies at ACR Convergence 2021 featured two presenters. Carla R. Scanzello, MD, PhD, associate professor, Division of Rheumatology, University of Pennsylvania Perelman School of Medicine and rheumatology section chief, Corporal Michael J. Crescenz VA Medical Center, both in Philadelphia, gave a talk titled Understand the Diagnostic Landscape of Osteoarthritis & Defining OA Phenotypes.

Dr. Scanzello was followed by Tonia Vincent, MD, PhD, FRCP, professor of musculoskeletal biology at the Kennedy Institute of Rheumatology, University of Oxford, United Kingdom, whose talk was called OA: New Horizons for Therapy.

Phenotypes & Endotypes

Dr. Carla Scanzello

Dr. Scanzello began with noting that consideration of both phenotypes and endotypes is important for the design of clinical trials and for therapeutic development for osteoarthritis (OA).

She reviewed some of the clinical heterogeneity that has led to efforts to define phenotypes of OA. For example, joint involvement can be a single joint or multiple joints. Symptoms can manifest early or late, and progression can happen slowly or rapidly. Bone pathology seen on radiography can be described as atrophic, hypertrophic or erosive.

As researchers try to find associations between these variable phenotypes of OA and prognosis, Gullo et al. found that patients with multi-joint OA had a poorer perception of their health and poorer physical function.¹ Others have identified characteristics of knee OA patients with more rapid progression of both pathology and pain.^2.3   

Dr. Scanzello also presented research on erosive hand OA to further examine phenotypes. Erosive hand OA is associated with more clinical inflammation, and genetic associations and biomarkers for erosive hand OA may differ from those for non-erosive hand OA. A study from Vanhaverbeke et al. found that erosive changes and clinical swelling were predictive of radiographic progression of hand OA over 10 years, suggesting that this is a more aggressive form of hand OA, Dr. Scanzello said.⁴

Limitations in OA Research

Dr. Scanzello also shared some of the challenges associated with conducting OA research.

Established criteria used to include patients in OA clinical trials have important limitations, Dr. Scanzello noted. For example, most studies require a grade of 2 on the Kellgren-Lawrence radiographic scale to be included in clinical studies.⁵ However, recent studies show that those with a grade of 1 also have progression of disease. “The tools that we use to include people in trials are limited in the ability to detect early OA, when patients may be more amenable to treatment,” she said.