Osteoarthritis: Gene Study Finds New Drug Targets and Treatment Options

Researchers explore new strategies to treat progressive osteoarthritis.

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Current treatments for osteoarthritis—the top cause of disability around the world—relieve symptoms, but they don’t delay or reverse progression because they can’t address the underlying causes.

A recent German meta-analysis published in Nature may offer data to help improve the lives of people with osteoarthritis. Researchers identified 700 genes that could be involved in the etiology, or underlying causes, of the disease. Because these causes vary from person to person, this discovery could potentially lead to personalized treatments that target the biological factors contributing to the condition.

Findings from Genetic Testing

The causes of osteoarthritis involve an interplay between genetic and environmental factors, the study authors stated. To identify causes that might lead to more effective treatments, researchers examined the genetic makeup of more than 1.9 million people.

They found 962 gene variants associated with osteoarthritis. Among these, they were able to identify those variants specifically associated with different types of the condition—for instance, 151 were associated with hip arthritis and 146 were associated with knee arthritis. Of the 962 variants, 700 were designated as effector genes, meaning they are very likely causal for osteoarthritis.

Approximately 10 percent of the effector genes express a protein that approved medications already target. These approved medications come from a variety of drug classes, including treatments for:

• Heart attacks
• Recurrent inflammation of a vein from blood clots
• Dupuytren’s contracture (permanently bent fingers)
• Abnormal growths
• Connective tissue conditions
• Anemia
• Immune system and inflammatory disorders

According to the researchers, if these medications are repurposed for osteoarthritis treatment, tailoring the drug to a person’s specific gene variants could improve outcomes.

“With 10 percent of our genetic targets already linked to approved drugs, we are now one step closer to accelerating the development of effective treatments for osteoarthritis,” study leader Eleftheria Zeggini, director of the Institute of Translational Genomics at Helmholtz Munich and professor of translational genomics at the Technical University of Munich, said in a statement.

Additionally, the authors found eight key metabolic pathways that play a role in osteoarthritis—factors that may underlie abnormal physiological changes leading to the condition.

“Our discovery suggests that targeted interventions regulating one or more of these eight processes could play another significant role in slowing or even halting disease progression,” co-first author Konstantinos Hatzikotoulas said in the statement.

Because current drug treatments don’t address the root cause of osteoarthritis, their benefits remain limited.

Repurpose Drugs

The study helps connect the dots between what we see in the clinic and what may be happening deep in the body, Dr. Bill Kapp, a board-certified orthopedic surgeon, told The Epoch Times in an email.

“Osteoarthritis often feels like a wear-and-tear problem, but it is more layered than that,” he said. “Finding hundreds of genes tied to it shows how much biology is driving joint changes long before symptoms show up.”

Kapp, whose work focuses on how genomics may reshape treatment strategies for age-related conditions such as osteoarthritis, said he is encouraged that 10 percent of the osteoarthritis-linked genes have targets that drugs already in use can address. That opens the door to using existing treatments in new ways, he said.

These new options mean that we may not have to wait decades to test ideas in the real world. This research offers a path to do more than just treat symptoms—it gives doctors a shot at slowing or even stopping joint damage earlier, Kapp said. “For people who are aging but still active, that could be life-changing. If we can match genetic patterns with therapies that are already out there, we may get to better treatment faster. That’s a shift in how we think about joint health.”

Lifestyle Changes

Dr. Jacob Teitelbaum, a board-certified internist and leading expert in pain management, described the study as fascinating and potentially powerful.

“Sadly, it loses much of its power because it is looking at the research exclusively through a pharmaceutical lens,” he told The Epoch Times. “The study largely ignores research on effective, safe, and low-cost natural options, predominantly focusing on expensive pharmaceuticals.”

This shortcoming doesn’t make the research unhelpful, he said. Rather, it highlights the need for proper assessments of cost, safety risk, and benefits when evaluating treatment prospects. Despite its limitations, the study offers clues about how to help prevent and treat arthritis, he said.

According to Teitelbaum, many of the medications suggested for repurposing simply poison physiological systems, causing side effects that can be worse than the disease—especially when the systems affected are widespread in the body.

Just as the German meta-analysis suggested personalizing treatment to gene variants, it also suggested tailoring interventions to one of eight metabolic pathways. Two of these are circadian rhythms (the body’s sleep-wake cycle) and microglial activation, a form of brain inflammation that intensifies chronic pain. It’s not surprising that these two areas are involved, as they both reflect dysfunction of a key brain control center called the hypothalamus, Teitelbaum said.

“To address the circadian rhythms and glial cell activation pathways, the authors recommend NSAIDs [nonsteroidal anti-inflammatory drugs], standard arthritis medications,” he said, explaining that NSAIDs work by blocking the cyclooxygenase (COX) enzyme system, which plays a key role in inflammation. While this can reduce inflammation, COX is critically important for protecting the stomach lining from ulcers and protecting arteries leading to the heart and brain from blockages.

Meta-analyses of more than 400,000 people have shown that NSAIDs increase the risk of heart attack and stroke by 35 percent, Teitelbaum said. Other research indicates that gastrointestinal side effects, such as bleeding ulcers, cause at least 16,500 deaths per year among arthritis patients.

Instead of treating circadian rhythm disruptions via NSAIDs, Teitelbaum said that the pathway could be managed more safely and inexpensively by improving sleep through good hygiene practices, herbal blends, or sustained-release melatonin. He noted that none of these approaches are mentioned in the study.

“Likewise, rather than stopping microglial activation with NSAIDs, research has shown that natural options can be very helpful for pain,” he said, adding that many studies support the use of palmitoylethanolamide (PEA), a fat-derived compound, to relieve microglial-activated pain, including pain from arthritis. In his practice, he prefers a highly absorbable form called PEA Healthy Inflammation Response.

Limitations of Current Drug Treatment

Current osteoarthritis drug treatments offer only temporary relief or modest reductions in pain and inflammation, according to the study authors. Meanwhile, the disease worsens over time. While some patients are minimally affected, others experience severe disability, including walking difficulty, joint malalignment, increased risks of falls, and decreased range of motion.

When nonsurgical treatments fail to control pain in advanced osteoarthritis, joint replacement surgery becomes necessary. However, total joint replacements have a limited lifespan and eventually require revision surgery, which has a much higher risk of failure.