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

Another challenge with early (pre-radiographic) OA is identifying it in the clinic. Along with joint line tenderness on physical exam, symptoms, such as episodic pain, crepitus and a feeling of the joint “giving way,” are already common early in disease. The person with early OA may have physical function limitations, but they typically are associated with leisure activities. In the clinic, health providers will want to be sure to rule out inflammatory arthritis, bursitis and tendinitis in these patients.

When deciding whether OA is a continuum of a disease or one with distinct phenotypes and subsets, Dr. Scanzello believes it is a little of both. More research is needed to examine the interplay of risk factors that can influence prognosis, as patients often develop more risk factors over the course of their disease, she said.

Another important question is how the clinical variables might reflect underlying disease mechanisms. This requires investigating endotypes—subtypes defined by distinct causes or biological mechanisms—that are reflected in many animal models of OA, and close collaboration between those working with these models and those working with human patients. “Defining these mechanisms and understanding the timelines (of pathology and pain) are leading us to a better understanding of when to target and how,” Dr. Scanzello said.

Examining New Targets for OA Therapy

Dr. Tonia Vincent

By tapping both translational and clinical research, rheumatologists are more likely to find real targets to treat OA, said Dr. Vincent in the second part of the session.

The past 20 years have provided huge insights into the molecular pathogenesis of OA. Some of these have arisen from genome-wide studies, she said.

“In that time, we’ve discovered that it is unhelpful to make assumptions about OA. We shouldn’t assume it’s like the arthritides we’ve dealt with before,” Dr. Vincent noted.

“Although research can provide insights into OA, it is also essential to check that the biology in the preclinical models is really relevant to the patient,” Dr. Vincent advised. Rheumatologists should also consider the debate over whether OA has distinct endotypes or whether it’s a single disease.

Dr. Vincent presented work to support two major mechanically driven processes that impact the pathogenesis of OA, with one side induced by compressive load that releases a number of growth factors from the tissue, and another activated by shear stress or friction of the joint surface, which drives mechanoflammation and activates inflammatory genes.^6,7 The former pathway, which is strongly supported by genome-wide association studies, drives joint protection in patients with OA, Dr. Vincent said.