THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Better understanding of osteoarthritis biology will lead to improved treatment options

Richard F. Loeser, Jr., MD
Richard F. Loeser, Jr., MD

This year’s Rheumatology Research Foundation Lectureship to Honor Herbert Kaplan, MD on Monday morning will look at the evolution of osteoarthritis (OA) from an inevitable result of aging and injury to a chronic condition that can be managed effectively for many patients.

“We have developed a much more complete understanding of the biology of osteoarthritis, including the recognition that there is an important role for inflammation,” said Richard F. Loeser Jr., MD, Director of the Thurston Arthritis Research Center and the Herman and Louise Smith Distinguished Professor of Medicine at the University of North Carolina. “There are clearly a number of different inflammatory factors that are promoting degradation of joint tissues in OA. And we are developing new targets for therapy.”

Dr. Loeser will explore the latest findings in the biology and pathogenesis of osteoarthritis during Osteoarthritis: Past, Present and Future from 9:00 – 10:00 am in Room B312-B314, Building B of the Georgia World Congress Center.

Osteoarthritis (OA) is the most common — and most confounding — form of arthritis. It is clearly an inflammatory disease involving the entire joint, bone, cartilage, and synovial tissues, and not a disease of wear and tear that primarily affects the cartilage. Macrophages appear to be key mediators of inflammation in OA, not the T-cells so commonly seen in rheumatoid arthritis.

There are even advances in treatment. Clinicians increasingly focus on the importance of exercise and weight loss that may help to maintain and even improve joint mobility rather than a progression of nonsteroidal anti-inflammatory analgesics that do little or nothing to affect disease progression.

Effective management of OA still lies in the future, Dr. Loeser cautioned. There are still no treatments proven to slow progression of OA, no confirmed pathways leading to clinical OA and no clear cause of the disease. What has become clear is that OA is not a single condition.

“OA is a heterogeneous group of conditions, and there are likely people with different subtypes of OA that will need to be treated differently,” he said. “You might develop OA after you have had joint injuries such as an ACL tear and that may be quite a different pathway to OA than somebody who is obese and developed OA at a relatively young age or someone who develops OA as part of the aging process.”

Multiple inflammatory pathways appear to play different roles in different subsets of OA, Dr. Loeser continued. And while macrophages appear to be a common mediator, researchers have yet to uncover one or more driving factors that play the kind of key role that TNF-alpha plays in rheumatoid arthritis.

One of the more promising lines of research focuses on the role of cell senescence. As cells age, they become senescent and produce inflammatory factors that can affect neighboring cells and tissues. In mouse models of OA, pharmacotherapy that targets and kills senescent cells in the joints can slow OA progression.

Another potential approach is to reverse senescence and restore aging cells to more normal function. The search for antiaging compounds continues, so far without success. For now, Dr. Loeser said, removing senescent cells so the remaining cells can continue to function normally seems a more promising approach.

Identifying OA in the early stages is another potentially useful approach.

Dr. Loeser said that not everyone who sees a doctor for joint pain is going to develop severe disease. A challenge is addressing the lack of biomarkers and imaging techniques that can accurately identify individuals likely to progress to severe disease.

“We are making progress in being able to identify progressors who will need more intensive treatment, just like we are making progress in identifying new treatment targets for OA. It’s just a matter of hitting the right ones,” he said.