Smoking Can Be Hazardous to Your Joints
According to a 2022 article in The New York Times, cigarettes are cool again, at least among some Gen Zers. That could eventually lead to arthritis.
Rheumatoid arthritis (RA) and certain types of osteoarthritis (OA) have a genetic component, but genes alone aren’t enough to cause either disease. Most people who have so-called “susceptibility genes” never get arthritis, while others who don’t have them develop joint pain and stiffness. Even with a genetic predisposition, something in the environment, such as an injury, infection, trauma or lifestyle factor is needed to trigger symptoms. Of several known environmental triggers, smoking is among the most well studied.
The role of smoking in autoimmune and inflammatory forms of arthritis as well as dozens of other diseases isn’t in doubt. Twenty years ago, researchers reported that the risk of RA was twice as high in male smokers and 1.3 times higher in female smokers compared to people who didn’t smoke. Other research found that the risk increased with the length of time and number of cigarettes smoked – about 26% higher risk for people who smoked one to 10 pack years (the number of cigarettes smoked per day times the number of years smoked) and 94% higher risk for those who smoked more than 20 pack years). Cigarettes can also lead to RA developing in people who don’t have a genetic susceptibility. Plus, unlike lung cancer and heart disease risk, the increased likelihood of RA persists after smoking stops.
Anti-citrullinated protein autoantibodies (ACPAs) are a strong biomarker for RA and often show up in blood tests years before symptoms do. Studies have shown mixed results when it comes to ACPA-positive and ACPA-negative smokers, with some research showing a higher risk in ACPA-positive people. There are also conflicting opinions about whether exposure to secondhand smoke in childhood increases RA risk. This is in contrast to the latest research on lung cancer, which shows significantly greater odds of lung cancer developing in nonsmokers with genetic risk factors who were exposed to secondhand smoke before birth or in childhood.
Smoking and Arthritis
Smoking causes whole-body inflammation, one of the main triggers for arthritis. The more cigarettes and the longer you smoke, the greater the inflammation. Here’s why:
- Immune system. Cigarette smoke contains thousands of toxins and cancer-causing chemicals. The immune system sees them as a threat and marshals defenses against them, leading to an explosion of faulty T cells, inflammatory proteins such as tumor necrosis factor (TNF) and a whole army of interleukins. All are the targets of various arthritis drugs, including abatacept (Orencia) TNF blockers like adalimumab (Humira) and interleukin (IL) blockers like tocilizumab (Actemra).
- Free radicals. Cigarette smoke is loaded with free radicals – unstable atoms the body produces as a byproduct of normal metabolism and exposure to toxins. Free radicals are serial daters, always looking to hook up with other atoms. In their brief, swipe-left swipe-right search, they damage cells and accelerate inflammation. That inflammation generates more free radicals in a never-ending loop.
- Autoantibodies. Citrullination occurs when arginine, an amino acid in protein, is converted to another amino acid called citrulline. Inflamed tissues have higher levels of these proteins, and smoking can lead to even more. In genetically susceptible people, citrullinated proteins may cause chronic inflammation and an autoimmune response, both hallmarks of RA.
- Gum disease. Smoking is a leading cause of gum disease, which can lead to a number of health problems, including arthritis. Researchers have found oral bacteria in the synovial fluid (the viscous fluid between joints) of patients with RA as well as those with osteoarthritis. It seems likely the bacteria escape from the mouth through damaged gum tissue, enter the bloodstream and travel to sites throughout the body.
- Extra-articular symptoms. Smoking is associated with inflammatory symptoms in other parts of the body, such as the heart, lungs and eyes, and may set the stage for more severe disease outside the joints.
Smoking Affects Arthritis Treatment
Methotrexate, the mainstay drug for RA, is effective for only about half of the people who use it. Many studies have shown that smoking is one reason for a poor response to methotrexate, and that is dose-dependent. People who smoke fewer than 10 cigarettes a day are more likely to respond to methotrexate treatment than those who smoke more. Smoking also limits response to other arthritis drugs, including rituximab (Rituxan) and anti-TNF biologics.
There are several theories as to why smoking negatively affects arthritis treatment. One is that it alters ABC transporters – proteins that move drugs and other toxic substances out of cells. Another is that it changes the gut microbiome so that medications are less available to the body.
Smoking and OA: Problem Solved?
The path from smoking to osteoarthritis hasn’t been straight. Older studies, dating from the late 1990s to mid-2000s, not only found no connection between cigarettes and OA, but also that smoking actually reduced the risk. Over the years, studies have battled back and forth, including a large 2019 Dutch study that found no connection between current smoking and OA.
But a 2022 Mendelian randomization study of hundreds of thousands of patients in the United Kingdom Biobank as well as the results of published research did find a connection between osteoarthritis, smoking, obesity and lower education levels. Mendelian randomization studies avoid some of the problems inherent in public health research by looking for links between health outcomes and genetic differences that stand in for factors like smoking and drinking. Still, this is probably not the last word on this topic.
Smoking exacts a toll on every part of the body – heart, lungs, kidneys, liver and eyes as well as joints. Quitting isn’t easy – some people make as many as 30 attempts before they succeed – but there are many things that can help beyond patches, gum and medications, including acupuncture, hypnosis and cognitive behavioral therapy. Some insurance through the Affordable Care Act may cover the cost of treatments to quit but be sure to check with your carrier. A tobacco cessation counselor – covered under Medicare – may also help.
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