Largest osteoarthritis genetic study uncovers pathways to new therapies and repurposed drugs

The research, which analyzed data from nearly 2 million people in diverse populations worldwide, was recently published in Nature. It represents an extensive genetic exploration of osteoarthritis, a condition affecting over 600 million people globally.

Conducted by an international team led by Helmholtz Munich in collaboration with Rush University Medical Center and 125 top academic institutions worldwide, this initiative is the largest genetic investigation into osteoarthritis conducted and the largest musculoskeletal study.

The study uncovered 962 genetic variants associated with the disease and spotlighted 69 key genes whose protein products are already targeted by 473 approved drugs -- many of which could be redirected to manage osteoarthritis more effectively. This discovery leads to a fast-track to personalized medicine and innovative clinical trials.

"This study takes a leap forward in offering tailored therapies for osteoarthritis patients, many of whom have long awaited disease-modifying options," said Dino Samartzis, DSc, co-author, professor and director of the international spine research and innovation initiative of the Department of Orthopedic Surgery at Rush.

"This research is a beacon of hope. By leveraging human genetics, we can now reimagine much more effectively as to how we treat this widespread condition."

Osteoarthritis results from the gradual breakdown of cartilage in the joints.

It differs from rheumatoid arthritis, an autoimmune disorder, and is a leading cause of pain, reduced mobility and disability -- projected to affect 1 billion people by 2050. It costs the United States nearly $486 billion annually and up to €817 billion in Europe.

"As orthopedic specialists, we see firsthand how osteoarthritis affects quality of life," said Brian Cole, MD, professor of orthopedics at Rush. "This study takes us closer to developing targeted biologics that not only alleviate symptoms but also slow disease progression and, ideally, restore joint health."

"With 10% of our genetic targets already linked to existing drugs, we're poised to accelerate the development of transformative treatments for osteoarthritis," said Eleftheria Zeggini, BSc, co-author and director of the Institute of Translational Genomics at Helmholtz Munich and professor of translational genomics at the Technical University of Munich. "This is precision medicine at work -- offering new hope to millions."

Traditionally, osteoarthritis has been managed with pain relievers and mobility aids, but no disease-modifying therapies exist to date. This study not only redefines our genetic understanding of the disease but also provides a path toward repurposing safe, approved drugs, potentially slashing the time and cost to bring effective treatments to market.

The team stresses the need for more genetically diverse studies and functional genomics data from global populations to further refine their findings. By integrating genetics with tissue-level molecular insights, the pathway to new, effective and personalized treatments for osteoarthritis becomes increasingly attainable.

"This is one of the finest examples of impactful team science," Samartzis said. "Researchers and clinicians from across the globe united with a singular goal -- to change the trajectory of osteoarthritis care for generations to come."