Why osteoarthritis is a whole-person disease rather than just a joint disease
In the previous blog, we talked about the evolving understanding of osteoarthritis, the most common cause of chronic joint pain, as a disease of the whole person rather than just a local ailment of the joint. We discussed the current limitations of conventional medicine in the treatment of this disease and highlighted the importance of an integrative and functional medicine approach to treating osteoarthritis. We pointed out that, in fact, the New England Journal of Medicine and many medical societies emphasize non-pharmacologic therapy over pharmacologic therapy in osteoarthritis (1, 2).
In this blog, part of a multi-blog series, we will discuss in more depth what is happening at the whole-person level in osteoarthritis.
What is happening at the joint level in osteoarthritis?
To understand why osteoarthritis is not just a joint disease, let’s first briefly discuss what is happening at the joint level. Traditionally, osteoarthritis was thought of as an inevitable part of aging, a result of gradual wear and tear on the joints.
When a person has osteoarthritis, what is happening at the level of the joint is that there is destruction and loss of the joint cartilage, which is the smooth, translucent tissue that covers the ends of bones and acts as a shock absorber. In addition, there is inflammation in the thin membrane that lines the inside of the joint (called synovium) and produces lubricating fluid. With ongoing inflammation and irritation, the lining becomes stiff and scarred, making it less flexible (3).
The bone directly underneath the cartilage (called subchondral bone) also becomes hardened and undergoes abnormal changes, which can lead to bone spurs, changing how the joint moves, increasing stress on the cartilage, and worsening the damage on the cartilage. These abnormal processes are interconnected and create an inflammatory environment in the joint, further promoting cartilage damage and inflammation of the synovium (3). Damage to the menisci (shock-absorbing pads) and ligaments also change how the joint moves and promote inflammation. Ultimately, joint tissue is broken down faster than it can be repaired, until the joint fails structurally.
Osteoarthritis is a whole-person disease rather than just a joint disease
Clinical research findings have come to suggest that the traditional concept of “wear and tear” on the joints may be too simplistic an explanation of why osteoarthritis happens. For example, a study that included more than 5,000 people with no evidence of knee osteoarthritis or rheumatoid arthritis at the beginning of the study found that, over 5 to 12 years of follow-up, recreational physical activity (such as sports and walking/cycling activities, traditionally thought to contribute to “wear and tear” on the joints) was not associated with new-onset painful knee osteoarthritis. More hours spent per week engaged in physical activity was also not correlated with knee osteoarthritis in this study (4). These results suggest that joint wear and tear alone would not explain why a person gets osteoarthritis.
There are people who do not have knee pain or structural joint damage with age, indicating that aging and osteoarthritis can be two separate events that don’t always go hand-in-hand. Obesity increases the odds of getting osteoarthritis but does not guarantee it. Knee injury is a risk factor for developing knee osteoarthritis in the future (5), but why do some people with a history of knee injury develop osteoarthritis while others do not? The answer is still not clear, but what we do know is that factors related to the whole body, such as obesity, increase the odds of osteoarthritis after a joint injury (6). These observations support the big picture that systemic factors affecting the whole person, combined with local factors affecting the joint, ultimately result in the manifestation of osteoarthritis in a person.
The best-known whole-person factors that influence the chance of getting osteoarthritis include age, genetics, sex, obesity, inflammation affecting the whole body, and disruption of the gut microbiome (7). Research evidence is coming together to show that osteoarthritis develops and progresses as a result of several things working together: what’s happening inside the joint itself, how the immune system responds, and whole-person factors such as aging and obesity (6).
Genetic factors are strongly associated with osteoarthritis, especially for the hip, hand, and spine. Genes involved in bone development could be a major factor, while genes involved in immune response and inflammation, muscle function, nerve function/development, and fat production could also play a role in osteoarthritis (7).
Some experts believe that even knee osteoarthritis that develops after knee injury—a phenomenon that typically only involves the local, affected knee—could potentially be linked to a person’s genetics or whole-person factors. That would explain why some people go on to get knee osteoarthritis while others do not, even after having experienced the same type and severity of knee injury (6).
Women account for 60% of people with osteoarthritis. Hormonal influences, among other reasons, have been suggested as a potential explanation for the higher prevalence in women, but no research studies have provided conclusive evidence that they explain this association (8).
The role of obesity and inflammation in osteoarthritis
Obesity or overweight increases the risk of osteoarthritis. The metabolic dysfunction and low-grade whole-body inflammation associated with obesity could explain its contribution to osteoarthritis, but experts agree that the exact underlying causal mechanism is not clear (7).
The longest-standing explanation for how obesity may increase the risk of osteoarthritis is that the weight-bearing joints experience abnormal physical stress. Intuitively, one may think that the abnormal stress causes wear and tear. However, research shows that such abnormal stress actually causes joint damage by triggering the cells inside the cartilage (called chondrocytes) to produce destructive proteins that break down the cartilage (9).
Beyond such mechanical factors, though, obesity increases the risk of osteoarthritis not only in weight-bearing joints but also in non-weight-bearing joints, such as in the hands. This observation points to the fact that there must be other whole-person factors, other than abnormal physical stress on the joints, that increase the risk of osteoarthritis. This would also help to explain why not all people with overweight and obesity develop knee or hip osteoarthritis.
Research evidence indicates that inflammatory factors produced by body fat (adipose tissue) and released into the bloodstream play an important role in the process of developing osteoarthritis. These blood factors promote chronic low-grade inflammation in the person. One of these factors is called leptin, a hormone produced by body fat, which seems to be especially important in initiating osteoarthritis. It is so important, in fact, that in laboratory experiments, obese mice that lack leptin do not develop knee osteoarthritis with age (9). This and other fat-produced inflammatory factors in the blood enter the fluid inside the joint space and activate destructive enzymes that break down cartilage and other joint tissues.
Interestingly, experiments in mice fed high-fat diets showed that the type of dietary fat (for example, saturated fat, omega-6 fatty acids, or omega-3 fatty acids) influences the development of osteoarthritis. A small amount of omega-3 fatty acids in the diet was enough to mitigate the development of osteoarthritis in these mice and decrease levels of the harmful factor, leptin, that was mentioned above (10). In addition, omega-3 fatty acids improved wound healing, while saturated fats or omega-6 fatty acids worsened osteoarthritis severity.
In a human study looking at osteoarthritis of the hand, people with overweight and obesity have more severe pain not only in the weight-bearing joints (the knees and hips) but also in their hands. This increased pain in the hands was found to be driven in part by leptin, which circulates throughout the whole body (6).
Leptin is a hormone that tells the body, “I am full.” In mice experiments, leptin alone is enough to cause osteoarthritis even when the mice lacked fat tissue (6). This observation suggests that body weight and fat tissue by themselves do not fully explain the association between obesity and osteoarthritis, and that substances such as leptin are important players. However, how exactly leptin causes osteoarthritis is still unknown.
It should be pointed out that osteoarthritis is also common in people without overweight or obesity, and in this situation, whole-person factors other than weight itself are at play, including those we have already discussed so far. In people without obesity, the lifetime risk of being diagnosed with knee osteoarthritis is 11%, compared with 20% in people with obesity (11). Women have higher leptin levels than men at any given body weight, and this may also explain why osteoarthritis is more common in women (12).
In people without overweight or obesity, leptin can still be elevated. First, leptin levels rise in line with fat percentage in the body, not body weight (13). So a person with low muscle mass but more fat (from inactivity, for example) (14) could still have normal weight and elevated leptin. Leptin is also higher in women because they have a higher percentage of body fat. In addition, higher leptin levels are associated with insulin resistance, a metabolic disturbance that underlies type 2 diabetes. (We discussed the potential root causes of insulin resistance in a previous blog.) In a study of young Japanese women, insulin resistance was associated with higher leptin production per unit of body fat (15). In other words, the body fat in people with insulin resistance could churn out more leptin even if there is not necessarily more body fat. Finally, in experimental studies, stress hormones (glucocorticoids) stimulate fat tissue to produce and release leptin (16). However, whether psychological stress in the real world is associated with higher leptin levels is less clear.
Because leptin and other inflammatory factors may play roles in the development of osteoarthritis and the pain associated with it, mitigating the overall inflammatory environment is a prudent approach. Leptin, for instance, can be lowered through weight loss, reversal of insulin resistance, and exercise training (17)—all of these choices have metabolic and cardiovascular benefits as well. For the treatment of osteoarthritis, such whole-person factors are a reason why an integrative and functional medicine approach that addresses whole-person health is a more fundamental way to achieve healing.
In my clinical experience, whole-person treatment strategies that include anti-inflammatory dietary interventions, when implemented as part of a comprehensive integrative / functional medicine treatment plan, can make a significant difference in the lives of people with osteoarthritis, even when they have lived with the disease for years—especially when combined with acupuncture in longstanding or difficult cases.
In order to supply research evidence on the effect of anti-inflammatory diets on osteoarthritis outcomes and potentially influence the standard of osteoarthritis care more broadly, clinical researchers in Australia are recruiting participants for a high-quality randomized controlled trial that will investigate the effects of an anti-inflammatory diet, compared with a standard care low-fat diet, on knee pain, function, and quality of life in people with knee osteoarthritis (18).
In future blogs, we will continue to explore why osteoarthritis is a whole-person disease rather than just a joint disease, so that this knowledge can empower patients to take control of their health and realize that there is a more effective way to heal from osteoarthritis than a superficial, temporary-fix approach that overlooks issues of a more fundamental level.
References
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