Gluck Lecturer Will Discuss the Impactful History of Discovery in Osteoimmunology Research

Osteoimmunology, an interdisciplinary field that explores the roles of shared molecules and interactions between the immune system and the skeleton, is a relatively new field of research that has contributed to seminal advances in the understanding and the development of novel treatments for numerous rheumatic diseases.

Mary Beth Humphrey, MD, PhD, Professor of Medicine and the Associate Dean for Research at the University of Oklahoma College of Medicine and Health Sciences Center, will discuss some of the key discoveries in osteoimmunology research over the past two decades and current questions that are driving the field today when she delivers this year’s Gluck Memorial Lecture, Osteoimmunology: The Little Niche with Big Impact, on Monday, Nov. 18, from 10:30–11:30 a.m. ET in Room 144ABC of the Walter E. Washington Convention Center. The session will be available on demand within 48 hours for registered ACR Convergence 2024 participants.

“As a rheumatology fellow in the early 2000s, I was starting to study osteoclasts, the cells that resorb and break down old bone so that osteoblasts can make new bone,” Dr. Humphrey said. “At that time, the paradigm was that an osteoclast, even though it came from an immune cell, had lost all of its immune capabilities, that it didn’t have any immune receptors anymore and didn’t function in any way or respond to the immune system.”

It was also around this time that researchers discovered what is now known as receptor activator of NF-κB ligand (RANKL) and its role as the master cytokine that drives osteoclastogenesis.

“That discovery led to the first real evidence that there was something important in the immune system that actually could regulate bone remodeling,” Dr. Humphrey said. “That really launched the field of osteoimmunology, and I began exploring the signals that were important in osteoclastogenesis, which ultimately led to my further studies in osteoporosis and osteoarthritis.”

Since that time, the field of osteoimmunology has continued to become more robust and continues to provide important contributions to understanding the pathophysiology of rheumatoid arthritis (RA), psoriatic arthritis, and other rheumatic diseases.

“We understand now, for example, how bone cells within the bone marrow are critical for maintaining the hematopoietic stem cells that you need for your entire life to maintain your immune system and make red blood cells,” Dr. Humphrey said.

Additionally, research continues to increase understanding of the immune dysregulation that occurs at menopause and how it not only contributes to accelerated heart disease in women but also drives postmenopausal osteoporosis.

“Diseases we once thought were just endocrine diseases, we now understand are significantly impacted by the interaction of the immune system with bone cells,” she said. “That has led to the development of many of the biologic agents — the anti-TNFs (tumor necrosis factors), anti-IL-6 (anti-interleukin-6), and anti-IL-1 (anti-interleukin-1), for example — that we are able to use today because we understand these interactions.”

Several of the key questions driving osteoimmunology research today regard furthering the understanding of the crosstalk that happens between osteoblasts, osteoclasts, and osteocytes, and how that impacts interaction with cytokines and immune cells.

“Additionally, ongoing research continues to increase our understanding of IL-17 (interleukin 17) and the pathogenic T helper 17 (TH17) cells, which are very bad for the bones,” Dr. Humphrey said. “By understanding all the different ways that we can get to those cells, we may find alternatives to simply blocking the IL-17 and ultimately be able to block the production of those cells and protect the bones in erosive diseases like RA and psoriasis.”

Other important areas of burgeoning research she identified include the role of the microbiome and microbiota in bone health and how the microenvironment can impact the metabolism of both bone cells and immune cells and how that affects their interaction.

“As the field of osteoimmunology continues to grow, I think it’s important for people to understand that many of the breakthroughs we’ve made, and many of the life-changing treatments we have today, are because people thought specifically to look at the interaction of bone cells with the immune system,” Dr. Humphrey said. “That idea has led us to significant new pathways where we can target diseases once they’ve started and, hopefully, will one day lead us to ways we can prevent disease before it becomes full-fledged.”