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Gum Disease &amo; Arthritis

Treat Gum Disease to Relieve RA Pain and Stiffness

A thorough dental cleaning can control symptoms.
| By Brenda Goodman

One of the best weapons against the swollen, painful joints that characterize rheumatoid arthritis (RA) may just be the dentist’s chair.

Researchers at Case Western Reserve University in Cleveland, OH, split 40 people with severe RA into two groups: One was given a “deep” nonsurgical dental cleaning, in which bacteria are scraped from the root surface and from under the gum line and tartar is removed from the teeth. The other group got instructions from a dentist about how to keep their teeth clean at home.

Within six weeks, the group that had the professional cleaning had significantly less pain and morning stiffness and fewer swollen and painful joints than the group that cleaned their teeth at home. Even more impressive, researchers found that the deep cleaning actually decreased levels of tumor necrosis factor-alpha, an inflammatory protein in the blood that triggers inflammation. 

“If you get rid of inflammation and infection in the mouth, you subdue it in the joints,” says Nabil Bissada, chair of the Department of Periodontics, who led the study.

If you have RA, but don’t have deep pockets under the gum line, Bissada says a regular professional cleaning should suffice.

Dr. Bissada joined forces with Ali Askari MD, chair of the rheumatology department at the University Hospitals of Cleveland, to study the relationship between periodontal disease and RA.

This time the researchers split 40 people – all with both severe RA and moderate to severe periodontal disease – into four groups. Two groups received biologic drugs that block the production of tumor necrosis factor-alpha (TNF-alpha). The other two groups did not receive these drugs.

Researchers provided standard, nonsurgical periodontal treatment to one set of participants from both the drug and non-drug groups during the study. The other sets received treatment after the study ended.

RA symptoms improved for all patients receiving the periodontal treatment, whether they were on the anti-TNF-alpha drug or not. Those who did receive TNF inhibitors showed a greater improvement in symptoms.

Rheumatoid Arthritis and Gum Disease

Research suggests that taking care of your teeth may be a good way to take care of your joints.
| By Mary Anne Dunkin

Losing teeth can do more than affect the ability to enjoy a fresh, crunchy apple or flash a healthy smile. New research suggests that tooth loss – a marker for periodontal (gum) disease – may predict rheumatoid arthritis and its severity.  The more teeth lost, the greater the risk of RA, one study found.

In the study of 636 patients with early arthritis, presented at the 2012 European Congress of Rheumatology in Berlin, 24.2 percent had 10 or fewer teeth, 16.1 percent had 11 to 20, 36.3 percent had 21 to 27 teeth, and 23.3 percent had 28 or more teeth. (A full set of adult teeth, including wisdom teeth, numbers 32.)

At six months’ follow-up, 52 percent had a good response to treatment, 32 percent had a moderate response and 16 had no response. The worst prognosis was for those with the fewest teeth. People with 10 or fewer teeth had more severe arthritis – evidenced by a significantly greater erythrocyte sedimentation rate, higher tender and swollen joint counts, and a higher Disease Activity Score – than those with more than 10 teeth. 

In a separate study presented at the same meeting, Italian researchers reported that tooth loss was associated with joint symptoms in a group of 366 first-degree relatives of people with RA, which put them at increased risk of RA themselves.

Participants with one or more swollen joints had an average of 26 teeth, compared with an average of 29 teeth for those with no swollen joints. The fewer the teeth participants had the greater their risk for joint inflammation, the researchers found. Patients with fewer than 20 teeth had eight times the risk of having at least one swollen joint compared to those with all 32 original teeth.

The Mouth-Joint Connection

The two studies are just the latest in a growing body of research linking periodontal disease and rheumatoid arthritis. In a study of 6,616 men and women who underwent four medical exams between 1987 and 1998 and an assessment for periodontal disease between 1996 and 1998, those who had moderate to severe periodontitis had more than twice the risk of RA compared to those with mild or no periodontitis, says study author Jerry A. Molitor, MD, PhD, associate professor in the rheumatic and autoimmune disease division of the department of medicine at the University of Minnesota, Minneapolis.

Such research grew from earlier observations that people with rheumatoid arthritis tended to have more periodontal disease and people with periodontal disease tended to have more rheumatoid arthritis.

Doctors assumed that periodontal disease was a result of RA itself (stiff, painful hands made oral hygiene difficult) or the medications to treat it (drugs that suppressed the immune system inhibited the body’s ability to fight harmful bacteria in the mouth), says Dr. Molitor. Furthermore, Sjögren’s syndrome with RA diminished production of the mouth’s protective saliva, leaving it vulnerable to disease. 

“There is clearly a relationship between periodontal disease and RA,” says  Dr. Molitor. Yet research in recent years suggests the connection is much more complicated than those earlier assumptions, he says. 

In a 2008 study examining the connection between RA and oral health, German researchers examined the oral hygiene status – by means of a comprehensive oral examination – in 57 patients with RA and 52 healthy controls. While the study found that patients with RA were nearly eight times as likely to have periodontal disease as the healthy controls, the researchers found that oral hygiene alone did not explain the increased risk.

A separate study out of India, which was published this year in the Annals of the Rheumatic Diseases, found twice as many cases of periodontal disease in 91 patients with RA compared to 93 patients without RA. Because none of the people with arthritis had taken disease-modifying antirheumatic drugs (DMARDs), the drugs’ suppression of the immune system could not be blamed for the disparity.

While research hasn’t proven a cause and effect, increasingly it is showing that periodontal disease in people with RA doesn’t always come after RA – in some cases it precedes it, says Dr. Molitor.

A Common Pathway

Researchers studying the RA-periodontal disease connection have found likenesses in the joint and oral tissues, as well as in the inflammatory processes that affect them.

“If you look at the tissues of the mouth in periodontitis and the tissues of the joint in RA, there are a number of similarities – including the types of cells that are infiltrating tissues of the mouth in periodontitis and the tissue of the joint,” says Clifton O. Bingham III, MD, associate professor of medicine and director of the Johns Hopkins Arthritis Center at Johns Hopkins University in Baltimore. He also notes that the levels of proinflammatory proteins like tumor necrosis factor, interleukin-1 and interleukin-6 are also similar in RA and periodontitis. 

Research has also shown a genetic link between the two. In a study published in  Journal of Periodontology, scientists in Israel found HLA-DR4 – a genetic type that occurs with high frequency in people with rheumatoid arthritis – in 8 out of 10 patients with rapidly progressive periodontitis, compared to just a little over a third of a healthy control group.       

Such findings led doctors to believe that there may in fact be a relationship between the two driven by an underlying disease process, says Dr. Bingham.

A potential advance in the understanding of that disease process came around a decade ago when scientists began to understand that one of the early markers of RA is the development of antibodies to citrullinated peptides.

Citrullination is when a protein undergoes a molecular change in structure, says Dr. Bingham. In RA, that change results in the immune system seeing the protein as a foreign body and mounting an attack against it by creating anti-cyclic cirtrullinated (anti-CCP) antibodies. (The presence of these antibodies is associated with more severe RA.) One of the oral bacteria involved in periodontitis has been found to induce citrullination.

Dr. Molitor’s study, which was presented at the 2009 scientific meeting of the American College of Rheumatology, found that people with periodontitis who tested positive for anti-CCP antibodies were more likely to have moderate to severe periodontitis and be a smoker, a risk factor for both RA and periodontal disease. These findings suggest that bacteria in the mouth could actually be a cause of RA or that existing periodontal disease could be triggering rheumatoid arthritis.

In people with a genetic susceptibility to RA, citrullination of particular proteins will cause an immune response against those proteins. “So everybody has citrullination,” says Dr. Bingham. “If you are unlucky enough to have citrullination occurring in the wrong place or against the wrong protein, your body will make an immune response against it and that can be one of the early markers events in the development of RA.”

Sharing Treatment

If oral bacteria are involved in the development or progression of RA, or inflammation in the mouth somehow fuels inflammation in the joints, one might reason that clearing up the periodontal disease would also help prevent or treat RA. 

At least one small study suggests that may be the case. In a study of 40 people with both RA and periodontal disease, researchers at Case Western University School of Dental Medicine and University found that those who received nonsurgical treatments for their gum disease reported significantly more improvement in their RA symptoms than those who received treatment for RA only.

Dr. Bingham says more research is needed to better determine whether treating periodontal disease improves or and if efforts to prevent periodontal disease might also help prevent RA.  In the meantime, he says, there is reason for people with RA and their doctors to pay particular attention to oral health.

“My bottom line is that we find such a high prevalence of periodontal disease in patients with rheumatoid arthritis and given that there is this highly plausible biological connection between these two disease processes, we need to pay attention to the oral cavity in patients with RA and refer people for dental and periodontal evaluation and treatment,”  says Dr. Bingham.

If you have RA, the message is to take care of your teeth.  Schedule regular dental exams, eat healthfully, brush and floss and, if you have trouble taking care of your teeth due to stiff, painful hands or jaws, speak to your dentist or occupational therapist about ways to make dental care easier, including the use of special assistive devices.

It’s also important to work with your doctor to get your arthritis under control. Doing so could potentially save both your joints and your teeth.

Mouth and Other Bacteria May Trigger RA

Studies increasingly highlight the role of microbes in rheumatoid arthritis and other inflammatory diseases.
| By Linda Rath

A century ago, it was widely believed that gum infections were the source of many inflammatory diseases, including appendicitis and rheumatoid arthritis (RA). The treatment for so-called oral sepsis was total tooth extraction – which rarely improved symptoms and was unpopular with patients – and by the 1930s, the oral sepsis theory had largely been discredited.

Now, however, the link between RA and oral bacteria is attracting serious attention, bolstered by research on the complex interactions between the immune system and microbes in the mouth, lungs and digestive tract.

Collectively referred to as the microbiota, the trillions of bacteria that live on and in the human body are generally beneficial and protective – aiding digestion and guarding against pathogens and inflammation. But it is becoming increasingly clear that in certain circumstances, these bugs may lead to the development of RA and other autoinflammatory disorders.

"We used to think that the bacteria [in our bodies] were benign partners, helping us out while we provide them with food and other nutrients. But when we alter the relative composition of [bacterial communities], can that trigger an immune response targeting the body's own tissues? At least in animal models, the answer seems to be 'yes,'" says Jose Scher, MD, director of the Microbiome Center for Rheumatology and Autoimmunity at New York University Langone Medical Center Hospital for Joint Diseases in New York City.

The answer also seems to be yes in some human studies. In the last few years, a great deal of research, aided by DNA sequencing techniques, has shown an association between the germs that cause periodontal disease and RA.

As early as 2009, researchers from Case Western Reserve University in Cleveland reported in the Journal of Periodontology that patients with severe RA had less joint pain and swelling and better overall health when they received treatment for gum disease in addition to arthritis medications. The researchers also noted that bone erosion and tissue destruction in both diseases are caused by similar inflammatory processes.

A 2010 epidemiological study, also in the Journal of Periodontology, found that RA patients were twice as likely to have gum disease compared to others (without RA) and their periodontal disease was more severe. Other studies have found an even higher incidence of gum disease in people with RA.

In a 2013 study, researchers at Massachusetts General Hospital in Boston showed that patients newly diagnosed with RA were far more likely to have antibodies to Porphyromonas gingivalis, a bacterium that causes gum disease, than healthy controls or people with other autoimmune disorders.

Patients who had the antibodies were more likely to be rheumatoid factor positive (a sign of more-aggressive disease), and to have more inflammation and greater dysfunction than RA patients who didn't. After a year of treatment, the P. gingivalis patients continued to have worse disease and were 50 percent less likely to be in remission. The results appeared online in Arthritis Research & Therapy.

So what is going on here? Sheila Arvikar, MD, a rheumatologist at Massachusetts General Hospital and lead author of the study, explains that P. gingivalis contains a unique enzyme that alters proteins – in a process called citrullination – so the body perceives them as a threat. This can lead to the production of antibodies against the proteins in the joint lining, causing inflammation and eventually RA. The autoantibodies are strong disease markers and can be detected in the blood years before symptoms appear.

Recently, researchers from the University of Louisville School of Dentistry in Kentucky and the European Union's Gums and Joints project reported that P. gingivalis may lead to earlier onset, faster progression and significantly increased bone and cartilage destruction in RA patients.

The lungs, too?

Meanwhile, Kevin Deane, MD, an assistant professor at the University of Colorado School of Medicine in Aurora, suggests that bacteria in the lungs might trigger RA in some people.

According to a pilot study published in the October 2013 issue of Arthritis and Rheumatism, Dr. Deane and colleagues found that people considered at high risk of RA had elevated RA-related autoantibodies in their sputum, but not in their blood, suggesting that the lungs may also be a source of an immune response that triggers RA.

Dr. Deane notes that immune cells and proteins "move around in the body," which may cause different people to have different sites of RA-related autoimmunity – "some in the gums, others the lungs and still others the gut mucosa" where changes in bacteria are associated with RA.

Future RA prevention and treatment

Evidence about the role of bacteria in diseases like RA has sparked intense speculation about future treatments. Stephen Paget, physician-in-chief emeritus of rheumatology at Hospital for Special Surgery in New York City and an expert in autoimmune diseases, has suggested that therapies for autoimmune disease may need to focus on enhancing immunity, via our bacterial communities, rather than suppressing it. Other experts argue for restoring healthy gut communities with probiotics or fecal therapy. And still others think treating gum infections might cure a variety of systemic diseases. What is almost universally acknowledged is that more research – probably a lot more – is still needed.

Dr. Scher is especially cautious. "Rheumatoid arthritis is very complex and multifactorial. Maybe it will be possible to identify some metabolites produced by bacteria that we can target that have an effect on arthritis, but we are at such a preliminary stage," he says. "What we are learning is that there is something happening between the mucosal surfaces in the mouth, lung and gut and the inflammatory response. We have seen in animal models that there is a clear connection. But how that translates into human disease needs more investigation."