Arthritis – What we now know

Arthritis is an age-old problem, and often a problem of old age, but chronic joint pain and reduced mobility need not be inevitable in our later years. In fact, research from recent years has shown us that arthritis, one of the most common health issues affecting Canadians, may be largely preventable using simple diet and lifestyle interventions. What’s more, your body clock may have a significant role in the development and severity of osteoarthritis!

Let’s take a look at some of the most interesting arthritis research from the last little while.

Is arthritis more common than we think?

Estimates of the prevalence of arthritis in the United States, and elsewhere, might be significantly underestimated, according to a study published in the journal Arthritis & Rheumatology.[1] This is because the surveys currently used to assess arthritis prevalence rely on patients reporting a diagnosis of the condition.

The authors of this latest study suggest that it may be better to look at how patients respond to questions about symptoms associated with arthritis and the duration of such symptoms. Using this strategy to analyze data from the 2015 National Health Interview Survey (NHIS), led the researchers to conclude that the actual number of people suffering from arthritis could be 68% higher than current national estimates. That would amount to 91.2 million adults in the USA, or around 36.8% of the population. This included a staggering 31.6% of adults under the age of 65.

According to the Arthritis Society of Canada, osteoarthritis affects one in six people, or nearly five million Canadians, and those numbers are increasing. An estimated one in four Canadians will have osteoarthritis by 2035, with a new diagnosis every 60 seconds.[2]

Lifestyle, diet, and arthritis

Regular exercise and a good diet might help prevent osteoarthritis, according to a new report in Nature Reviews Rheumatology.[3] The report looked at the link between metabolism and osteoarthritis and found that a poor diet and sedentary lifestyle could trigger genetic reprogramming in the cells found in the joints. This reprogramming altered cellular energy production, leading to excessive glucose synthesis. Unused glucose was then transformed into lactic acid, which increases inflammation in cartilage.

Instead of being a disease of “wear and tear”, the authors of this study suggest that osteoarthritis may be better understood as a metabolic disease. This means that rather than relying on painkillers to manage the condition, the better option could be to use diet and exercise to support a healthier metabolism.

Adding to this discussion of diet and arthritis, another review recently found that a person’s risk of developing rheumatoid arthritis (RA), the most common autoimmune condition affecting the joints, increased if they ate a typical Western-style diet high in red meat, processed meat, refined grains, fried food, high-fat dairy, and sweets. In contrast, a diet consisting mostly of plant-based foods, with some fish and poultry, was associated with a lower risk of RA.

Indeed, individuals whose diets closely matched the Dietary Guidelines for Americans had a 33% reduced risk of developing RA compared to those whose diets were not similar to the guidelines.

Exercise and arthritis

In other news, research suggests that just 45 minutes of moderate activity each week is beneficial for maintaining functional independence in older adults with arthritis.[4] According to a new study, seniors often find the recommended 150 minutes of exercise a week daunting, which can cause them to become less active overall. Thankfully, though, exercising for even a third of that time is still beneficial, and may help prevent premature death and serious illness in older adults.

In this latest study, carried out by the Northwestern University Feinberg School of Medicine, participants who got a minimum of 45 minutes of moderate activity each week were 80% more likely to experience improvements or to sustain high function over two years compared to those moving less. Moderate activity can include brisk walking and can be done in short bursts of just a few minutes.

Current health guidelines recommend 150 minutes in bursts of at least 10 minutes, so as to support cardiovascular health. The current study focused just on the participants’ functional independence, however, and found that sessions didn’t need to last 10 minutes to be beneficial.

The weather and arthritis

Does the weather cause aches and pains in your joints? Possibly! But not in the way you might think.

New research based on Google searches about joint pain found that the common view that arthritis symptoms are exacerbated by cold, wet weather seems to be contrary to fact. Instead, the data suggests that more people ask Google about knee and hip pain when the weather is warmer and drier[5]. What’s going on? Well, the scientists behind this study believe that this can be explained by the idea that nicer weather means people spend more time being physically active outdoors, which could lead them to overdo things and suffer from joint pain afterwards.

The most searches asking about knee pain occurred when the temperature peaked at 23 °C). For hip pain, peak search occurred at 28 °C). Searches for both decreased when rainy weather occurred, and the pattern was consistent across the United States. The researchers used stomach pain as a control search parameter and found a different correlation (higher numbers of searches when temperatures were low or high, compared to mild temperatures).

The body clock and arthritis

What does your body clock have to do with arthritis? A lot, it seems.

A biologist at the University of Manchester, UK, recently found that chondrocytes (cartilage cells) have their own internal body clock which controls thousands of genes which tell the cells when to be active and when to rest and repair[6]. As we age, these cellular clocks don’t function so well, meaning that our joint cells aren’t as good at knowing when to repair themselves after wear and tear.

One particular protein, BMAL1, controls the body clock, but the expression of this protein by cartilage cells decreased when the severity of osteoarthritis increased. The same thing happened with age, suggesting a link between the risk of osteoarthritis and the aging process in general.

This research also suggests that things that disrupt the wider body clock, i.e., our circadian rhythm, could also increase our risk of osteoarthritis. Such things would include jet lag and shift work. To counteract this increased risk, it could help to establish patterns that help the body clock stay on track, such as eating, exercising, and sleeping at set times of the day.

The body clock, inflammation, and arthritis medications

The body clock may also have an influence on the effectiveness of medications for osteoarthritis, at least according to researchers at the University of Manchester, UK[7]. In a study published in The FASEB Journal, researchers describe how the body clock regulates inflammation by producing a protein called cryptochrome at night. This protein actively represses inflammatory pathways in limbs affected by osteoarthritis and is produced by cells in the joints called fibroblast-like synoviocytes which have a 24-hour rhythm.

The authors of this study used drugs to activate the cells’ production of the cryptochrome protein and found that this helped protect against inflammation. Again, this suggests that supporting your body’s natural circadian rhythm may be beneficial in managing osteoarthritis, with researchers also suggesting that this discovery may have ramifications for the best time of day to administer drug therapies.

Testing for arthritis

A new blood test for osteoarthritis could be available soon, according to researchers at the University of Warwick, UK. Typically, osteoarthritis is hard to diagnose in its very early stages, meaning that irreversible damage may occur before treatment commences. It can also be hard to distinguish osteoarthritis from other joint conditions in early stages, further delaying treatment.

This new test is based on research showing that specific biomarkers for blood joint proteins damaged by the processes of oxidation, nitration and glycation[8]. These damaged proteins leak into the blood from joints and allow clinicians to classify the type of joint condition present, if any. Additional research is helping pave the way for the development of a simple blood test to detect early-stage osteoarthritis, allowing treatment to begin earlier for more effective prevention and management.[9]

Two new biomarkers have also been identified that appear to not only be useful in diagnosing spine osteoarthritis, but also seem to directly contribute to the joint degeneration seen in the condition.[10]

These biomarkers, microRNA-181a-5p and microRNA-4454, are involved in increased inflammation and cartilage destruction and were identified by researchers at the University of Toronto. By assessing levels of these two microRNAs, clinicians can determine the degree of possible cartilage destruction and the stage of a person’s osteoarthritis. The biomarkers promote the death of cartilage cells and deplete collagen. New treatments that block the activity of these microRNAs may be developed on the basis of this discovery.

Ones to watch

Scientists have been busy investigating another molecule for its potential in the treatment of osteoarthritis. This molecule, which bears the rather lengthy name of “Regulator of Cartilage Growth and Differentiation,” or RCGD 423 for short, appears to enhance cartilage regeneration and decrease inflammation[11]. It does this by altering the activity of various receptors in cartilage cells that influence degenerative and reparative processes.

Applying RCGD 423 to cartilage cells in the lab helped increase cell proliferation and reduce cell death. Researchers also damaged rats’ knee cartilage and then injected the tissue with RCGD 423. Those injected with the molecule healed better from the induced injuries.

Researchers are also looking into whether algae might hold some promise as a future treatment for osteoarthritis. Brown algae contains a substance called polysaccharide alginate which is similar to a type of molecule in human cartilage. After adding sulfate to the alginate, the researchers applied it to cartilage cells. They found that the substance significantly reduced oxidative stress and that this alginate sulfate also downregulated the expression of genes that trigger inflammatory activity in the joints.[12]

References:

  1. Jafarzadeh SR, Felson DT. Updated estimates suggest a much higher prevalence of arthritis in US adults than previous ones. Arthritis & Rheumatology. 2018 Feb; 70(2):185-192.
  2. Arthritis Society of Canada. Accessed October 2018. Available: https://www.arthritis.ca/about-arthritis/arthritis-types-(a-z)/types/osteoarthritis.
  3. Mobasheri A, Rayman MP, Gualillo O, et al. The role of metabolism in the pathogenesis of osteoarthritis. Nature Reviews Rheumatology. 2017; 13(5):302.
  4. Dunlop DD, Song J, Lee J, et al. Physical activity minimum threshold predicting improved function in adults with lower limb symptoms. Arthritis Care & Research. 2017 Apr; 69(4):475-483.
  5. Telfer S, Obradovich N. Local weather is associated with rates of online searches for musculoskeletal pain symptoms. PLOS ONE. 2017; 12(8):e0181266.
  6. Dudek M, Gossan N, Yang N, et al. The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity. Journal of Clinical Investigation. 2016 Jan; 126(1):365-76.
  7. Hand LE, Hopwood TW, Dickson SH, et al. The circadian clock regulates inflammatory arthritis. The FASEB Journal. 2016 Nov; 30(11):3759-3770.
  8. Ahmed U, Anwar A, Savage RS, et al. Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease. Arthritis Research & Therapy. 2016; 18(1):250.
  9. Li J, Lan CN, Kong Y, et al. Identification and Analysis of Blood Gene Expression Signature for Osteoarthritis With Advanced Feature Selection Methods. Front Genet. 2018 Aug 30; 9:246.
  10. Nakamura A, Rampersaud YR, Sharma A, et al. Identification of microRNA-181a-5p and microRNA-4454 as mediators of facet cartilage degeneration. JCI Insight. 2016 Aug 4; 1(12):e86820.
  11. Shkhyan R, Van Handel B, Bogdanov J, et al. Drug-induced modulation of gp130 signalling prevents articular cartilage degeneration and promotes repair. Annals of the Rheumatic Diseases. 2018 May; 77(5):760-769.
  12. Kerschenmeyer A, Arlov Ø, Malheiro V, et al. Antioxidant and immune-modulatory properties of sulfated alginate derivatives on human chondrocytes and macrophages. Biomater Sci. 2017; (9):1756.