Beyond the Scale: Obesity’s Hidden Ties to Rheumatology

No surprise to most, there’s a number of diseases associated with being affected by obesity. They’re out there as easily as a Google search can show, sleep apnea (where you inadvertently “hold your breath” overnight), high blood pressure, diabetes mellitus, etc. One that’s a bit less talked about but affects us more day-to-day than most the others is osteoarthritis, i.e. the wear and tear of our joints with age, a common primary care and rheumatologic (eventually orthopedic) problem.

The hole goes deeper than osteoarthritis; it has its fingers in a number of different rheumatic diseases, some mechanical issues like osteoarthritis and others autoimmune. Let’s dive in a bit.

We look at the dangers of being affected by obesity two ways: we can call it “fat mass disease” and “sick adipose”. Fat mass disease is talking about the direct force, the weight the excess fat around and carried by our tissues is imposing. Think specifically here for example osteoarthritis, i.e. the way that we describe the wear/tear of our joints as we age. Fat mass is a key driver for osteoarthritis here as in the excess weight we might be carrying has to be carried on our knees, our hips, our feet, and underneath the surface it’s what our bones are supporting, the cartilage our bones rest on, all this kept in place by supporting structures like ligaments and muscles. Another example would be the excess weight on our chests that leads our airway to collapse overnight while we sleep, thus causing obstructive sleep apnea. Sick adipose is the way obesity can hurt us, and it’s really a descriptive term: this is how the adipose (fat) tissue makes us sick but more in a metabolic, systemic sense such as insulin resistance (promoting diabetes!), fatty liver disease (excess calories that causes liver damage), and, maybe most importantly to us out there dealing with inflammatory diseases, inflammation. Between the direct force and the metabolic changes adipose tissue encourages, we can end up with some harmful consequences to our joints.

Fat Mass and Beyond: Focus on Osteoarthritic Pain

As I mentioned, it’s the direct forces (“fat mass” using the language above) in play on joints that seem the most obvious to us when we’re talking osteoarthritis. If we have more weight to carry, we have more force our joints have to support – this is especially true in our lower body joints than upper body, i.e. our low backs, hips, knees, and feet/ankles support everything above them whereas our arms, torsos, and necks get off fairly lightly in comparison. To that point, we know that dropping our body weight by 10% can drop the force applied to each knee, with each step, by about 40%. Forty percent! Everyone with more advanced knee arthritis knows how much taking each step can hurt, now imagine cutting that by 40%? Think of compounding interest in one’s bank account… what does a 40% drop in force applied to each step we take amount to in terms of personal comfort and pain after a year? What about two years? Ten years? We’ve advocated this as rheumatologists for decades – this simple fact (but much harder solution) that going after the excess weight with osteoarthritis should be in the conversation anyone suffering from osteoarthritis is having with their doctor. If your doctor hasn’t brought it up, ask them!

So force aside, it doesn’t stop there – osteoarthritis isn’t all about direct mechanical force. There are more factors in play that we honestly don’t have the full picture of yet. Reyes in 2016 made an important observation: those affected by obesity not only were more likely to develop knee and hip osteoarthritis (2x and 4x!), but were almost twice as likely to develop symptomatic hand arthritis. It’s not an obvious link at all, in other words the hands aren’t supporting the body or having to carry any extra weight, so, what’s happening to these?

Confusing the picture more, our imaging tools don’t tell us the whole picture about osteoarthritis, a fact some of you might have noticed. The images don’t tell us how much an arthritic joint should hurt, for example an X-ray of a joint from a person in a moderate amount of pain can look 100% normal, look like it was the aftermath of a high-speed car crash, or anywhere between – you’ll see it happen to both extremes in different individuals practically everyday of a busy clinic. Said the other way, you’ll often see two joints from two different individuals with identical-looking X-rays but the symptoms felt by Person A can be a full night and day difference from Person B.

The answer here, as in how can obesity promote hand arthritis symptoms and why might the symptoms of one person with mild knee arthritis feel so different to another with the same “mild” appearance on X-ray, is probably more about inflammation and other microscopic forces at work at the joints and in the brain… and there’s at least more than a few of these forces. One example, Frommel found circulating free fatty acids (FFAs), these being a form of fuel for our cells that travel the body (but end up in much higher concentration when we’re affected by a metabolic disease like obesity), stimulate the bone cells that line our joints and ends up producing an inflammatory signature much like the one we might see in rheumatoid arthritis, a fairly destructive inflammatory cousin of osteoarthritis. Shift gears to a different part of our body: in obesity, we see this disproportionately high level of a specific immune cell circulating (M1 macrophages, if you’re interested). These cells produce a signal called CCL2, ultimately the same signal molecule our joints use to tell our brains when an arthritic joint should hurt. So, obesity can actually actively promote bony changes in joints far, far away from where the weight’s being carried and then indirectly might be responsible for why we’re more symptomatic, more in pain, in the same joints.

Obesity really hits us in the arthritis standpoint in a couple ways here.

So if this concept applies to osteoarthritis, i.e. obesity can promote changes in inflammation and cause us symptoms, does it apply to inflammatory diseases, like say, rheumatoid arthritis?

Inflammatory Cytokines: The Bridge Between Obesity and Rheumatism

These inflammatory signals that travel the body and interact with other cells we call cytokines. Cytokines come from everywhere: our white blood cells, our liver, bone marrow, and, maybe no surprise at this point, our adipose/fat cells. We suspect adipose cells release a few specific inflammatory cytokines (some of these might be familiar to those of you with rheumatoid arthritis, especially if on biologic therapy): interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFa). Those with obesity and higher weights meaning they have more adipose tissue? We see more IL-1, IL-6, and TNFa. The story is the same with our M1 macrophage friends that might worsen our symptoms in osteoarthritis: these cells too promote more IL-1, IL-6, and TNFa release and we tend to see much more of these cells in our tissue with obesity than without.

What does this mean specifically for rheumatoid arthritis sufferers and their symptoms? I’d stop short of saying there’s causation, as in we can’t say for sure obesity directly worsens our RA symptoms, but there’s a very suspect association there at minimum. A nice piece some ten years ago now by Ajeganova in 2012 looked at a large group and found just that: those affected by obesity ultimately had higher levels of measured inflammation (our C-reactive protein, sedimentation rates), more active rheumatoid disease, and ultimately a lower likelihood of being in remission. We end up with worse symptoms in general, and cytokines from adipose and macrophages are probably only part of that picture we’re still piecing together.

In Summary…

Obesity really can have its fingers in a host of different issues. In terms of joint disease and rheumatic/autoimmune disease we have some clear connections with still quite a few unanswered questions (i.e. what other means are these connected? what’s the purpose of the adipose cells making so many inflammatory signals?). We know being affected by obesity promotes mechanical stress and accelerates a joint’s wear/tear (i.e. through “fat mass”) and we know there’s at least a couple pathways where adipose cells can cause joint issues far away from where they sit in our bodies (i.e. “sick adipose”). We see some common themes between obesity’s low-grade, chronic type of inflammation and the type of inflammation strongly associated with rheumatoid arthritis and likely others. The end of the day: obesity is just one factor, one piece of the puzzle here when we’re talking about rheumatic and other joint diseases, but it’s one that we can’t afford to ignore. If you have any joint issues or autoimmune/rheumatic disease and weight isn’t being addressed by your primary physician or rheumatologist, ask them!

Ajeganova, S., Andersson, M.L., Hafström, I. and (2013), Association of obesity with worse disease severity in rheumatoid arthritis as well as with comorbidities: A long-term followup from disease onset. Arthritis Care Res, 65: 78-87.

Reyes C, Leyland KM, Peat G, Cooper C, Arden NK, Prieto-Alhambra D. Association Between Overweight and Obesity and Risk of Clinically Diagnosed Knee, Hip, and Hand Osteoarthritis: A Population-Based Cohort Study. Arthritis Rheumatol. 2016;68(8):1869-1875. doi:10.1002/art.39707

Vincent TL. Peripheral pain mechanisms in osteoarthritis. Pain. 2020;161 Suppl 1(1):S138-S146. doi:10.1097/j.pain.0000000000001923