Methotrexate Toxicity, Dosage, and Osteoarthritis: What You Should Know About Methotrexate for OA

Recent advances in OA treatment are pointing to methotrexate; is methotrexate toxicity, efficacy something that we should be talking about? This article answers all your questions about this well know inflammatory athirtis drug that is now being explored as a possible treatmen for the more common wear-and-tear arthritis. 

Osteoarthritis (OA) remains one of the most common causes of pain and disability worldwide, particularly affecting aging populations and those with physically demanding lifestyles. While traditionally viewed as a degenerative joint disease driven by wear and tear, new studies are challenging long-held assumptions about osteoarthritis, particularly when it comes to treatment.

Traditionally viewed as a mechanical “wear and tear” condition, osteoarthritis is now increasingly linked to low-grade inflammation in the joints. This shift in understanding has opened the door to treatments that were once reserved for inflammatory autoimmune diseases—most notably, methotrexate.

Methotrexate (MTX), commonly prescribed for autoimmune conditions like rheumatoid arthritis and psoriasis, is now under consideration for osteoarthritis management.

Recent findings from the University of Leeds and other research bodies suggest that methotrexate may have a place in osteoarthritis treatment, especially in patients with persistent pain and signs of inflammation. But while the results are promising, the discussion around methotrexate toxicity—especially in long-term or off-label use—needs to be part of the conversation.

"The results of the clinical trial show methotrexate, a medication already used for autoimmune conditions, to be effective in relieving both the pain and stiffness caused by knee osteoarthritis which affects 5.4 million people in the UK, and 364 million globally [...]Our study demonstrates that a drug already commonly used for rheumatoid arthritis, methotrexate, might help the pain of osteoarthritis, and also gives us a clue about which subset of patients, those with elevated blood inflammation levels, might get benefit from this therapy."

Below, we break down what patients should understand before considering methotrexate as part of an osteoarthritis management plan.

Low Dose Methotrexate Side Effects

In osteoarthritis research, the doses used have been on the lower end—typically around 20 mg taken weekly.

At this level, most side effects tend to be manageable, but they’re not negligible. Common issues include fatigue, nausea, and gastrointestinal discomfort. In some cases, patients may experience headaches, dizziness, or thinning hair.

Because methotrexate suppresses parts of the immune system, even low doses require monitoring. Routine blood tests are often used to track liver enzymes, white blood cell counts, and kidney function to catch early signs of toxicity.

Drinking on Methotrexate

Alcohol consumption is a key concern for anyone taking methotrexate. Both alcohol and methotrexate are metabolized in the liver, which means combining them can increase the risk of liver damage—especially over time.

That said, occasional or moderate alcohol use may be acceptable for some patients, depending on their individual health profile. This is something that should be discussed honestly with a physician, and regular liver function tests should be part of ongoing care if methotrexate is being used long-term.

Methotrexate and Mouth Sores

Mouth ulcers and sores are a well-documented side effect of methotrexate. These are often caused by folate deficiency, as methotrexate interferes with folic acid metabolism. Supplementing with folic acid is standard protocol and can help reduce this particular side effect.

If mouth sores develop or worsen while on methotrexate, it’s important to notify a healthcare provider. This could indicate either an intolerance to the drug or early signs of toxicity.

Signs of Methotrexate Toxicity

Most people on low-dose methotrexate tolerate it well—but toxicity can occur. Symptoms that should prompt immediate medical attention include:

• Shortness of breath
• Unusual bruising or bleeding
• Severe fatigue or muscle weakness
• Yellowing of the skin or eyes (jaundice)
• Persistent nausea or vomiting

These symptoms could signal liver damage, bone marrow suppression, or other serious complications. Regular monitoring makes it possible to detect issues early, which is why lab work is not just precautionary—it’s necessary.

Why It’s Gaining Attention for Osteoarthritis

While methotrexate isn’t approved specifically for osteoarthritis, results from small but promising studies are giving this treatment option more traction. One study published found that a weekly dose of methotrexate helped reduce pain and stiffness in people with hand osteoarthritis over six months. Another from the Annals of the Rheumatic Diseases highlighted its clinical benefit and acceptable safety profile in patients with inflammatory features.

This research suggests methotrexate may be especially helpful in a subset of OA patients with symptoms that aren’t explained by joint damage alone—those whose pain and swelling point to inflammation.

Beyond Medication: Practical Tools for Managing Osteoarthritis Daily

For those living with osteoarthritis, daily comfort often comes down to small but consistent interventions. Supportive devices and lifestyle modifications can dramatically improve quality of life, particularly when tailored to the affected joints.

One effective strategy is the use of compression supports and braces designed to reduce swelling, provide stability, and improve joint alignment during movement. The Dr. Arthritis range of supports offers practical, medically-designed solutions for those dealing with OA in the knees, hands, wrists, or ankles. For example, their Copper-Infused Knee Brace provides lightweight compression ideal for individuals with mild to moderate knee OA, while the Doctor-Developed Arthritis Gloves can help reduce stiffness and swelling in the hands during both daytime activities and nighttime rest.

Ergonomic aids such as jar openers, wide-handled utensils, and orthopedic cushions may also reduce strain on vulnerable joints. Additionally, maintaining a consistent movement routine—whether through guided physical therapy, yoga, or low-impact exercise like swimming—can help preserve joint function and prevent stiffness.

In some cases, combining pharmacological treatment such as methotrexate with targeted physical support can create a more comprehensive care plan. Pain management is rarely solved by one intervention alone. Instead, a blend of medical, physical, and supportive tools often yields the best outcomes.

For those seeking to manage their osteoarthritis proactively, consultation with a rheumatologist or orthopedic specialist remains the first step. From there, integrating trusted support products like those from Dr. Arthritis into a daily care regimen can offer meaningful relief and restore a sense of control in day-to-day life.