Arthritis & Obesity

In some cases, obesity raises the risk of getting a certain type of arthritis; in all cases, obesity makes arthritis worse. One in 5 Americans has been diagnosed with arthritis, but according to the Centers for Disease Control and Prevention (CDC), that number jumps to more than 1 in 3 among obese people – and 2 out of 3 Americans are either overweight or obese.

How Fat Affects Arthritis

Being overweight can make arthritis, gout, lupus, fibromyalgia and other joint diseases and conditions worse
| By Andrea Kane

If you were to ask people to name a health problem related to obesity, odds are good they’d say “heart disease” or “diabetes.” And they’d be right; those two chronic diseases have a very strong relationship to excess weight. They are the safe bets.

But if you like long odds, put your money on arthritis. It’s not as commonly known, but obesity in some cases raises the risk of getting a certain type of arthritis; in all cases, obesity makes arthritis worse. One in 5 Americans has been diagnosed with arthritis, but according to the Centers for Disease Control and Prevention (CDC), that number jumps to more than 1 in 3 among obese people – and 2 out of 3 Americans are either overweight or obese.

Here’s a look at what fat does to arthritis, as well as some tips to put you on the road to losing weight.

Fat and Osteoarthritis

Osteoarthritis, OA, is the most common type of arthritis, affecting approximately 27 million Americans. It is characterized by the breakdown of cartilage – the flexible but tough connective tissue that covers the ends of bones at joints. Age, injury, heredity and lifestyle factors all affect the risk of OA.

Why Obesity Matters

OA has a logical link to obesity: The more weight that’s on a joint, the more stressed the joint becomes, and the more likely it will wear down and be damaged.

“Weight plays an important role in joint stress, so when people are very overweight, it puts stress on their joints, especially their weight-bearing joints, like the knees and the hips,” says Eric Matteson, MD, chair of the rheumatology division at the Mayo Clinic in Rochester, Minn.

Every pound of excess weight exerts about 4 pounds of extra pressure on the knees. So a person who is 10 pounds overweight has 40 pounds of extra pressure on his knees; if a person is 100 pounds overweight, that is 400 pounds of extra pressure on his knees. “So if you think about all the steps you take in a day, you can see why it would lead to premature damage in weight-bearing joints,” says Dr. Matteson.

That’s why people who are overweight are at greater risk of developing arthritis in the first place. And once a person has arthritis, “the additional weight causes even more problems on already damaged joints,” says Dr. Matteson.

But it’s not just the extra weight on joints that’s causing damage. The fat itself is active tissue that creates and releases chemicals, many of which promote inflammation.

“These chemicals can influence the development of OA,” explains Jeffrey N. Katz, MD, a professor of medicine and orthopaedic surgery at Harvard Medical School and Brigham and Women’s Hospital in Boston.

This effect can be seen in the numerous studies that have linked extra weight to hand OA. “Obviously, you don’t walk on your hands, so there may be something that is produced by fat cells in the body that causes the joint to break down more rapidly than it might otherwise,” says David Felson, MD, a professor of medicine and epidemiology at Boston University School of Medicine.

For both reasons – excess joint stress and inflammatory chemicals – fat should be kept in check among all people, especially those who already have OA.

Fat and Rheumatoid Arthritis

Rheumatoid arthritis, RA, affecting 1.5 million Americans, is an autoimmune disease in which the body’s immune system attacks its own joint tissue. This creates inflammation throughout the body, and can lead to joint erosion and pain.

Why Obesity Matters

The inflammatory chemicals from fat that may play a role in OA are also culprits in RA. Some of these chemicals, called cytokines, can impact different body systems, including musculoskeletal and cardiovascular systems. Many types of cytokines are released by fat tissue, and researchers are working to identify them and understand the specific effects of each kind.

One important group is called adipokines, and most types of adipokines promote inflammation – “not a good thing in RA,” says Jon Giles, MD, an assistant professor of medicine in the division of rheumatology at Columbia University College of Physicians and Surgeons, in New York City.

Other cytokines released by fat include tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). Both are overactive in RA and cause inflammation. You may be familiar with the biologic drugs that suppress them, including etanercept, brand name Enbrel, and infliximab, brand name Remicade, which target TNF-alpha, and anakinra, brand name Kineret, which targets IL-1.

One type of adipokine, called adiponectin, is good for the heart, because it has an anti-inflammatory effect on blood vessels – but it causes inflammation in joints. When people gain weight, they make less adiponectin, which may be one reason overweight RA patients can have less joint damage than those who are not overweight. But don’t think that means being overweight has a protective effect, says Dr. Matteson of the Mayo Clinic. “In fact, you are still at risk for your arthritis to advance more rapidly in your weight-bearing joints simply because of the biomechanical forces that come into play.”

And people with RA – including those who have a body mass index (BMI) in the normal range – have yet another reason to watch their diet and exercise. “The disease process changes body composition in an unfavorable way; it favors having more fat and less muscle,” says Dr. Giles, who has conducted many studies on the effects of body composition and inflammatory arthritis.

In addition, researchers have found the excess fat is often located around the abdomen (known as visceral fat), which is a risk factor for heart disease and insulin resistance.

“RA patients have a 50 percent higher cardiovascular mortality risk than the general population, so controlling cardiovascular risk factors is a priority in RA patients. You don’t want to have fat that increases your risk of heart disease,” says Dr. Giles.

Fat and Gout

Gout is a form of inflammatory arthritis that occurs when an excess of uric acid in the body leads to the formation of uric acid crystals in the joints, triggering painful attacks. These are most common in the big toe, but also occur elsewhere.

Why Obesity Matters

Obesity is closely linked to gout; as the country’s obesity rate has gone up, so has its rate of gout. According to studies, about 70 percent of people with gout are overweight and 14 percent are obese. Being obese puts a person at a higher risk of developing gout in the first place – and of getting gout 11 years earlier on average than someone of normal weight.

“In the highest [weight] group versus the lowest group, it could be a tenfold or higher risk of developing gout,” says gout expert Hyon Choi, MD, a professor of medicine at Boston University School of Medicine. Dr. Choi has authored pivotal population-based studies examining the link between gout and obesity.

So what is going on? Uric acid is formed when the body breaks down purines – a compound found in human tissue and in most foods, and concentrated in certain meats, seafood and beer. Some people’s bodies produce too much uric acid; other people’s kidneys can’t eliminate it quickly enough.

It’s worse for obese people. “When people are obese, their kidneys can’t excrete efficiently. The prime suspect is insulin,” Dr. Choi says. “When people are big, [their insulin] doesn’t work as well, so they produce more. Insulin inhibits uric acid excretion in the kidneys.”

The good news is that small changes can make a big difference. “Lifestyle matters a lot in gout, like it does for diabetes, so you can control gout if you really stick to good lifestyle [choices]. You can prevent it to large degree. You have a lot more control than in RA,” he says.

Studies have shown that losing even a small amount of weight can lower uric acid levels, and losing more weight has a bigger effect on reducing uric acid. “Losing weight drags down uric acid levels. If you get rid of the root cause, your risk will drop,” says Dr. Choi.

Fat and Psoriatic Arthritis

Psoriatic arthritis (PsA) is a type of inflammatory arthritis that affects up to 30 percent of people with psoriasis, an autoimmune condition that causes scaly and inflamed skin. Psoriasis usually precedes psoriatic arthritis.

Why Obesity Matters

According to studies, obesity is a risk factor for psoriasis and is associated with more severe disease. People with psoriasis are more likely than people without it to have a higher BMI and higher levels of the obesity-related hormone leptin. One of the first studies to look at the link between psoriasis and the development of PsA found that psoriasis patients who are obese at age 18 had triple the risk of developing PsA than those with a normal BMI – and they developed PsA earlier in life.

“It is a double whammy; first they get psoriasis, then they get psoriatic arthritis,” says Dafna Gladman, MD, professor of medicine at the University of Toronto and co-author of many studies on psoriatic arthritis.

The exact mechanism, however, is unknown. “There are a lot of metabolic things going on [in obesity] – adiponectin, leptin, pro-inflammatory cytokines that are increased. We don’t know if it is just the fat, or if it is what the fat is associated with,” says Dr. Gladman.

What is certain is that being overweight or obese plays a role in PsA. “Because you carry around more weight, especially in the lower extremities and back, there are additional forces at play,” says Dr. Gladman. “Also, when you are overweight, it’s difficult to figure out the dose of medication you might need. [Dosing of] Remicade is weight-related, but other drugs don’t have that, so obese patients may be undertreated because we don’t know the precise dose we should be using.”

Fat and Lupus

Systemic lupus erythematosus is a chronic, inflammatory autoimmune disease in which the body’s immune system mistakenly attacks its own tissues and organs.

Why Obesity Matters

Several studies have found that the rates of obesity are higher in people with lupus than in the general population. Obesity in patients with lupus is associated with high levels of disability and possibly cognitive impairment.

“What we found is that there is a higher rate of obesity among women with lupus than there is in general population, and there is a big effect of obesity on functioning,” says Patricia Katz, PhD, professor of medicine and health policy at the University of California, San Francisco.

In one of her numerous lupus studies, obese lupus patients performed significantly worse than those who were not obese in three areas of functioning: work, basic physical functions (such as climbing stairs or bending over) and daily activities (including self care and social activities).

“Not only did obese women do worse at first look, but they had greater decline in functioning,” says Katz.

In another study, obese and/or inactive women with lupus had a higher rate of cognitive impairment – although it didn’t show that one condition caused the other.

As in OA and RA, the cytokines that fat releases create inflammation in different parts of the body. “Fat tissue is not inert,” Katz says, echoing other researchers.

But it’s hard to know if obesity is a cause or an effect of health risks associated with lupus, she says. For example, people with lupus have a higher risk of heart disease. “If you are fat, maybe you release more inflammatory cytokines, which affects cardiovascular risk.”

In addition, even though obesity is categorized as a BMI of 30 or more, Katz’s studies have found that patients with lupus who have a BMI of 27 have the same cardiovascular risk factors and disability as heavier lupus patients. “Really, if you want to set a criterion for obesity in lupus using BMI, you need to move the number lower, to 26.8,” she explains.

And, as with other forms of arthritis, there’s the issue of body mechanics. “If you are obese, the loading on your joints will make the pain worse,” she says.

Fibromyalgia

Fibromyalgia is a chronic pain disorder that affects 3 to 6 percent of Americans, mostly women. Symptoms are widespread muscle pain and “tender points,” and can include fatigue, sleep problems, depression, bladder and bowel irritability and cognitive difficulties.

Why Obesity Matters

Eighty percent of people with fibromyalgia are overweight or obese, compared with 67 percent in the general population. Numerous studies have shown that heavier fibromyalgia patients have worse symptoms and a lower quality of life than those of normal weight. Additionally, being overweight, especially if you are inactive, puts you at greater risk of developing fibromyalgia, according to a large Norwegian study.

Both fibromyalgia and obesity are characterized by the malfunctioning of the HPA axis – a communication system between glands that helps regulate the immune system, digestion, mood, hormones and other functions. Understanding the HPA axis issue could lead to better treatments for both conditions, says Akiko Okifuji, PhD, a psychologist at the Pain Research and Management Center and professor at the University of Utah, in Salt Lake City.

Each condition poses “a potential barrier to treat the other,” says Okifuji. “In order to help people attain reduction in symptoms and weight, we have to target both.”

Osteoarthritis and Obesity

More than just overloading joints, obesity can lead to fat cells taking aim at joints.
| By Jeanne Erdmann

Fat does more than hang around inconvenient places and make it tough to pull on your favorite pair of jeans. Excess body fat can destroy joints in ways that have come to surprise researchers.

“We know that obesity is the number-one preventable risk factor for osteoarthritis but it hasn’t been studied much because everyone dismissed it as overloading joints,” says Farish Guilak PhD, a professor of orthopedic surgery at Duke University Medical Center at Durham, N.C.

He and others began to wonder whether obesity alone told the whole story of joint destruction. Some athletic endeavors put greater biomechanical forces on knees than obesity. And, people who are obese are more likely to have osteoarthritis (OA) in their wrists, fingers and hands. Our hands sometimes bear loads (think of carrying a heavy flower pot) but not our body weight (we don’t walk on our hands).

For folks so overweight as to be deemed obese (defined as twenty pounds heavier than your upper weight range), those excess pounds of fat carry hidden dangers that researchers like Guilak are just beginning to understand.

Fat, or adipose tissue in medical lingo, is home to millions upon millions of busy adipocytes, or fat cells. A flurry of research over the past few years is starting to explain how adipocytes work against the body to destroy joints by misguided responses to high levels of glucose and exposure to cytokines (immune proteins). In reaction to such exposure, adipocytes churn out high levels of their own immune proteins called adipokines.

Year after year of obesity fuels a steady barrage of friendly fire that in turn generates low-level chronic inflammation. Not an inflamed immune system, like an infection but a soft drum-beat of immune proteins that over time can damage tissues such as joints,  “that’s insidious because it’s continuous,” says Robert Mooney, PhD, professor of pathology and laboratory medicine at the University of Rochester in New York.

Mooney recently redirected his research efforts from diabetes and obesity in the liver to the effects of obesity and diabetes on musculoskeletal disease. His experience researching metabolic disturbances in diabetes told him that adipocytes could also be a bad influence on joints.

To study the link between a disrupted metabolic system and osteoarthritis, Mooney turned to a trusted mouse model of diabetic mice. In work recently published in Arthritis Research and Therapy, Mooney’s team studied whether a high-fat diet in diabetic mice would damage joints.

One group of mice ate a high-fat diet and then had surgery that mimics knee injuries in people and is designed to quickly bring on osteoarthritis. The second group of mice ate regular mouse chow until they had the surgery, and then ate the high-fat diet after surgery. At monthly intervals, the team examined bone and cartilage tissues in the knee joints for markers that would reveal signs of osteoarthritis.

The mice fed the high-fat diet before and after surgery ended up with a body weight considered obese; mice fed the high-fat diet after surgery gained more weight than controls but were not obese.

Mice in both groups ended up with abnormal changes to their metabolism and early signs of OA. As it turns out, obesity alone wasn’t enough to damage joints; even mice that weighed less had changes in their joint tissue that showed the progression to OA. In all mice, such metabolic disturbances occurred long before mice gained a lot of weight.

 “These results argue that all you need is metabolic changes. You don’t need gross weight gain to have changes in the progression of osteoarthritis,” says Mooney. 

Next Mooney’s team will try and decipher the molecular pathways that lead from metabolic disturbances to joint damage. Mooney will also use his expertise in diabetes to see whether insulin resistance – a condition in which the tissues don’t respond to insulin well and thus can’t lower blood sugar – plays a role in damaging joints. These efforts may bring to light a potential therapy; perhaps correcting diabetes and correct insulin resistance will slow down progression to OA, says Mooney.

The link between obesity and OA is actually very complicated. Adipocytes secrete many adipokines, one of which includes leptin, which regulates metabolism and body weight. Researchers need to figure out whether leptin and its protein cousins can damage cartilage directly or whether they recruit other cells for their dirty work. When, Guilak and his team at Duke studied the full range of adipokines that fat cells produce, they discovered that many are exactly the same immune proteins that OA researchers have been studying for years, “and no one had put them together to say all of the stuff in your joints may be coming from the fat,” says Guilak.

Guilak and his team set out to different ways that fat can be dangerous. In one set of experiments the researchers wondered whether exercise could reduce inflammation from a high fat-diet.

In work that was published recently in Arthritis & Rheumatism, the team fed mice a diet that was 60 percent fats, aiming to accelerate OA and hasten obesity. (An average healthy diet should include 13 percent fat but a typical, western diet comprises about 25 percent fat intake).  Would exercise have any impact at all if mice ate a lard-rich diet that contained 60 percent fat?

As it happens, mice love to run, so the team gave some of the mice on the high-fat diet access to a running wheel; the other mice on the high fat diet didn’t run at all. All of the mice ended up obese, even mice that ran the equivalent of two miles each night. But tests on the mice that were allowed exercise showed that exercise alone slowed down the immune proteins that lead to inflammation, and reduced the severity of OA.

Guilaks’ team is now studying whether different types of fat can lead to inflammation and joint damage. In the meantime, he says that obese people can protect their joints even if they don’t lose weight. “Diet is how you are going to lose weight,” says Guilak.  “Running two miles a day for a mouse was not enough to overcome an awful diet, which is true for people too. It’s very hard to overcome the balance if you are eating that much more.”

If all of this advice to eat a low fat diet and exercise seems all too familiar, think about this, reminds Guilak: Once osteoarthritis takes hold and the bones and joints are on the path to end stage joint disease, but total joint replacement may be the only option.

How Fat Affects Rheumatoid Arthritis

Excess body weight increases inflammation and may affect drug effectiveness in RA.
| By Emily Delzell

About two-thirds of people with rheumatoid arthritis (RA) are overweight or obese, the same proportion as in the general US population. In people with RA, however, excess body fat creates special complications in addition to its well-known role in increasing risks of heart disease, stroke and other conditions.

Fat Increases Inflammation

Fat is chemically active, constantly releasing proteins that cause inflammation, which then turns up the “volume” of RA itself.

Fat cells, or adipocytes, release proteins called cytokines that, in excess, cause constant, low-grade inflammation throughout the body. “Fat, or adipose, tissue is a source of many of the same inflammatory cytokines that are produced by inflamed joint tissue in people with inflammatory arthritis,” says Jon T. Giles, MD, MPH, assistant professor of medicine at Columbia University in New York City.

The more pounds you add, the more of these proteins circulate in the body, which also seems to lead to more severe RA, says Dr. Shoenfeld, author of a 2014 Autoimmunity Reviews analysis that looked at 329 studies of obesity in autoimmune diseases.

“Fat is not a passive bystander in RA and other autoimmune diseases,” explains immunologist Yehuda Shoenfeld, MD, director of the Zabludowicz Center for Autoimmune Diseases in Tel Aviv, Israel. “When you have an excess of fat cells, it produces higher levels of inflammatory proteins that aggravate the inflammation that is already within joints.”

Shoenfeld and his co-authors detailed data showing that people with RA who are obese have more active disease, more pain and worse overall health. Inflammation-causing cytokines, which include tumor necrosis factor-alpha (TNF-alpha), interleukin-1 and interleukin-6, are already overactive in RA.

Fat May Reduce Benefit of RA Drugs

But biologics, as well as some traditional disease-modifying antirheumatic drugs (DMARDs), work less well in obese individuals with RA than in people of a healthy weight. A 2013 study, published in Arthritis Care & Research, found overweight and obese patients are as much as 50 percent less likely to have a positive outcome after 12 months of therapy with biologics that block TNF-alpha than healthy-weight patients.

“This poor response is particularly true with infliximab [Remicade],” says Eric Toussirot, MD, PhD, professor of rheumatology at the Clinical Investigation Center for Biotherapy at the University Hospital of Besançon in France. “Conversely, weight loss is related to a better clinical response.”

How fat undercuts the activity of RA drugs isn’t yet understood. “It could be that fat cells are able to produce many inflammatory proteins that can contribute and sustain the inflammatory process,” says Dr. Toussirot. “A less-studied theory is that the fat cells may fix to monoclonal antibodies such as infliximab or adalimumab [Humira] and render them non-functional.”

Fat and Joint Damage

Extra fat mass adds stress to joints, particularly weight-bearing joints, says Eric Matteson, MD, chair of the rheumatology division at the Mayo Clinic, in Rochester, Minn. Every 10 pounds of excess weight, for example, puts 40 pounds of extra pressure on knees. “If you think about all the steps you take in a day, you can see why it would lead to damage,” he says. The inflammation due to RA can cause joint erosion, and this effect can be compounded by excess body weight.

But one confusing finding about fat in RA is that several studies have found that obese people with the condition have less joint damage on x-rays than thinner people with RA, says Dr. Giles. “This may due to the action of adiponectin, an inflammatory protein produced by fat cells, that is actually found in higher levels in leaner people with RA,” he says. “Adiponectin may be harmful for inflamed joints and, as its levels tend to go down with obesity, people with more fat seem to gain a protective effect, but no studies have yet shown that weight loss is associated with more damage.”

These findings do not mean that being obese or overweight will prevent joint damage from RA. “In fact,” says Dr. Matteson, “you are still at risk for your arthritis to advance more rapidly in your weight-bearing joints simply because of the biomechanical forces that come into play.”

Getting to a healthy weight can be a challenge but finding fun ways to be physically active and learning about the arthritis diet can put you on a path to success.