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Rheumatology and Obesity

Obesity is associated with multiple rheumatological conditions including but not limited to osteoarthritis (OA), lower back pain and gout. There are a number of risk factors for OA, some of which are non-modifiable such as age, sex and family history. One of the most important modifiable risk factors, particularly for knee OA, is having overweight or obesity
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SPEAKER 1: This lecture will outline some of the research looking at the effects of weight loss on outcomes in the osteoarthritis. If we start the effects of weight loss on biomechanics, one of the first randomised controlled trials was the 18-month ADAPT trial led by Dr. Steve Messier in the USA. The trial included four groups– a lifestyle control group, an exercise only group, a diet only group, and a combined diet plus exercise group– with both diet groups aiming to achieve a 5% loss of body weight. The weight loss intervention included three phases. Phase one, the intensive weight loss phase, involves a restricted diet, including meal replacements, and extensive health behaviour change support.
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Phase two was a transition from the calorie restricted diet to a healthy diet with reduction in the amount of behaviour change support provided. And phase three was the maintenance phase to work towards maintaining the weight loss. The exercise comprised strengthening and aerobic exercise performed three times per week.
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The results of this study found that the diet groups lost around 5% of their body weight. In a subsample of 142, and using three-dimensional gait analysis, they found that each kilogramme of weight loss resulted in a reduction of 41 newtons of compressive force at the knee. That is, for each unit of weight loss, there is a four-fold reduction in the load exerted on the knee per step during daily activities. Accumulated over thousands of steps per day a reduction of this magnitude could be clinically meaningful.
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The IDEA trial was a subsequent trial performed by this same group, and it was a pivotal trial for the field published in the prestigious Journal of the American Medical Association. It also ran for 18 months and compared three groups– an intensive diet group, an exercise group, and a combined diet plus exercise group. In this study the aim was to achieve a larger amount of weight loss with the diet than in their previous ADAPT trial aiming this time for more than a 10% reduction in body weight. The intensive diet involved two meal replacements per day, with an energy intake deficit of 800 to 1,000 calories per day, around 4,000 kilojoules. The programme also included weekly or biweekly nutrition and behavioural sessions.
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The exercise intervention was one hour, three days per week for 18 months. And importantly the diet and exercise interventionists were trained in behaviour change techniques.
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The study had a number of outcome measures, including knee forces during walking, pain, function, quality of life, and other patient measures, levels of interleukin 6 and imaging markers.
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Both diet groups lost substantial amounts of weight 8.9% in the diet group and 11.4% in the combined diet plus exercise group– while there was minimal weight loss as expected in the exercise group, only 1.8%.
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The results for the biomechanical outcomes showed that both diet groups had significantly greater reductions in compressive knee forces than the exercise group.
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For the outcome of interleukin 6, which acts as a pro-inflammatory cytokine, both diet groups had greater reductions in IL-6 than the exercise group. This likely relates to the reduction in weight and fat mass given that we know that adipose tissue is an important source of such cytokines.
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For patient-reported outcomes, diet and exercise led to greater improvement in both knee pain and function than exercise alone.
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Here are the results for pain measured by the WOMAC scale plotted for the three groups. And you can see that at six months all three groups showed improvement, but by 18 months the diet plus size group showed significantly greater improvements in pain compared to the exercise alone and the diet alone groups.
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If we now look at the results of a systematic review by Dr. Michelle Hall at the University of Melbourne, she examined the effects of dietary-induced weight loss either alone or in combination with exercise in people with knee osteoarthritis who are overweight or have obesity. In this review they found 16 publications from nine clinical trials addressing this issue.
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Here is a forest plot pulling the results of different trials, examining the effect of diet only treatments for the outcome of pain. For those who aren’t familiar with forest plots, they show the size of the effect as summarised by the diamond. If the diamond crosses the vertical zero line, that means that there is no effect of the intervention– in this case, diet only. You can say that the results, overall, as indicated by the red diamond, showed no effect for diet only interventions on knee pain as compared to control. And this was the case for the trials that were less than 12 months in duration, as well as for those that were 12 months or more in duration.
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The next forest plot shows the results for diet only interventions on the outcome of physical function. Here you can see that the red diamond does not cross the vertical zero line, and in fact, favours diet interventions over control for improving physical function. The average size of the effect of the diet only interventions is minus 0.3, which would be considered a moderate effect. You can also see that the benefit seems to be mostly in those trials that are less than 12 months’ duration, whereas the trials that were 12 months or longer did not show significant effects.
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This time, these graphs summarise the results for trials looking at a combined diet plus exercise intervention. For pain, you can see that, overall, there’s a significant moderate effect of diet plus exercise compared to control for improving pain. But this effect seems to be driven by the findings of the single trial of less than 12 months’ duration, whereas the two trials of 12 months or longer duration did not show significant benefits for pain. The same findings apply here for physical function as the outcome in this graph. Again, we can see a significant benefit overall of diet plus exercise. But this is mostly due to the benefits seen in the trials of less than 12 months’ duration.
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So the results of this systematic review show that diet plus exercise has greater benefits for pain and function than diet alone. It aligns with clinical guideline recommendations from organisations around the world that emphasise exercise for all patients with knee osteoarthritis. And additionally, weight loss for those who are overweight or obese.
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So the question then is, how much weight loss should we be recommending for our patients, in order for them to obtain clinically meaningful effects for their knee? And this is important, because it will determine the intensity of the weight loss programme that might be most suitable.
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An Australian study investigated whether there was a dose response effect of weight loss on symptomatic outcomes. They evaluated over 1,300 individuals with knee osteoarthritis– who were overweight or had obesity, who were enrolled in the 18-week osteoarthritis Healthy Weight for Life weight loss programme. This graph shows the improvement in osteoarthritis symptoms using the knee injury and osteoarthritis outcome score, or the KOOS, over the 18 weeks with all of the participants pulled together.
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They then divided the participants into categories based on the percentage of body weight they lost over the 18 weeks. You can see that there is a pattern indicating a dose response relationship, whereby greater improvements in symptoms were seen in participants with the greatest amount of weight loss. What they also found from their data set was that a body weight loss of at least 7.7% was needed in order to achieve a clinically relevant improvement in physical function.
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These results were supported by Messier and colleagues using data from their IDEA clinical trial of weight loss, which was conducted over a longer time frame of 18 months. As you can see from the graphs, they also found relationships between the amount of weight loss and clinical improvements, including in interleukin 6, in pain, and in physical function. And this relationship seemed particularly pronounced when comparing the effects in those who lost small amounts, less than 5% of body weight, compared with those who lost large amounts, such as greater than 20% of their body weight.
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And they also found that individuals losing greater than 20% body weight had 25% less pain and better function than those losing greater than 10% body weight. But it must be remembered that a 20% loss of body weight is a very large amount, and it takes an enormous commitment from the person over an extended period. So it’s important to let patients know that even modest weight loss can be beneficial.
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We’ve had a look at the effects of weight loss on knee osteoarthritis symptoms, but what about the effects of weight loss on knee joint structure, which has relevance for disease progression? This was investigated in a systematic review by Daugaard, published in 2020. They found a limited number of studies, and only two randomised controlled trials that included structural outcomes. A range of pathologies were evaluated, but they found inconsistent evidence of the effects, meaning that we currently cannot be sure what effect weight loss has on knee joint structures, particularly over the longer term.
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So we now know that weight loss, particularly when combined with exercise is beneficial for knee osteoarthritis, but as will be discussed in the next module, we also know that keeping the weight off is very difficult. And this is because biological factors work against achieving and maintaining significant weight loss. The body act as though it is in starvation mode, and attempts, at all costs, to defend higher body weights. This leads to increased feelings of hunger, suppressed satiety, and slowed metabolic rate. There have been some interesting studies from a group in Denmark investigating weight loss maintenance in people with knee osteoarthritis and obesity following an intensive weight loss programme.
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In this clinical trial, 192 people with knee osteoarthritis and obesity underwent an intensive weight loss programme for 16 weeks, where the average weight loss was 12.8 kilogrammes. For the following one year weight maintenance phase, they were randomly allocated into one of three groups. One group received continuous support from the dietitian, another group undertook a specialised knee exercise programme, and a third group received no attention. Then at the end of that year a number of outcomes were measured, in terms of pain, MRI imaging of knee joints structures, body composition, and cardiovascular risk factors.
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The results showed that the group receiving continuous dietetic support gained the least amount of weight, 1.1 kilogrammes, compared to the other two groups. The outcomes showed that all three groups had improved knee pain with no difference between the groups. For body composition, there was no detrimental effects on bone in any groups, and this is important, as a reduction in bone density can be a concern with extensive weight loss programmes. Imaging findings showed no difference in cartilage loss, synovitis, or effusion between the groups. And all three groups had maintained the improvements in cardiovascular risk factors seen following the initial weight loss.
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The investigators were then interested in looking at weight maintenance over an even longer time period and comparing different strategies. So at the end of their study, participants were then randomised, again, into one of two groups. One group received intermittent dietary treatment involving a low-energy diet for five weeks every four months for the next three years. And the other group received regular dietary treatment where they had daily meal replacements for one to two meals for three years, as well. They found that both groups showed minimal gains in weight over the three years, with no difference between the two different weight management strategies.
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And while the numbers were small, they also found no difference in the rate of knee joint replacement over the three years between the two groups. These results do show that it is possible to maintain weight loss over a long period, and that the commonly held assumption that weight regain is inevitable is not necessarily the case. However, I think you can recognise that this did require considerable commitment by participants to longer term dietary modification.
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So what lessons do we have from the weight loss literature in knee osteoarthritis? Well, we know that they all used very low calorie dietary interventions, generally, including meal replacements. And these were effective in achieving weight loss. For the very low calorie dietary interventions to be successful there has to be a transition to healthy eating, with support from health professionals.
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And the effects of these dietary interventions was greatest when accompanied by an exercise programme. Another common factor was, they all had extensive behaviour change support provided through groups or one-to-one, and this is imperative to help patients change their behaviours.
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And all of them had lengthy intervention periods. And so we need to be able to motivate patients and help them to adhere to programmes over a long frame. So in summary, the key points for this lecture are– that weight loss has biomechanical effects and reduces absolute knee load during walking, dietary weight loss alone may have moderate benefits for function, but not for pain, and the clinical effects are greater when diet is combined with exercise, patients should aim to lose at least 5% of their body weight for symptomatic benefits, but greater weight loss will have greater benefits, there is no consistent evidence for the effects of weight loss on joint structures, and weight maintenance is possible over the longer term and is associated with maintenance of symptom and health benefits.
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The references used throughout this presentation are shown on this slide and the slide following. [AUDIO OUT]

Obesity is associated with multiple rheumatological conditions including but not limited to osteoarthritis (OA), lower back pain and gout.

Osteoarthritis

Osteoarthritis is:

  • Complex disorder of synovial joints, which can affect all joint tissues
  • Clinical syndrome of joint pain, functional limitation and impaired quality of life
  • Chronic disease with varying symptom severity and disease course

There are a number of risk factors for OA, some of which are non-modifiable such as age, sex and family history. One of the most important modifiable risk factors, particularly for knee OA, is having overweight or obesity 35, 36. In addition to increasing the risk of OA disease onset, overweight and obesity adversely affect outcomes for people with OA at every stage of the disease by aggravating pain and disability, accelerating OA progression37, increasing the likelihood of requiring joint replacement surgery38 and adversely impacting outcomes following joint surgery39.

Being overweight or having obesity increases risk of: 1) Developing osteoarthritis 2) More severe symptoms 3) Greater disease progression 4) Having a joint replacement 5) Worse outcomes following joint replacement

  • Compared to a healthy weight, overweight increases the risk of developing knee OA 2.5 times while obesity increases the risk 4.6 times40
  • Obesity in earlier life may also be a contributing factor. Body mass index measured from as young as 11 years in females and 20 years in males was related to the risk of developing knee OA in mid-life41. Weight gain and persistent excess weight from early adulthood increased the risk of later hip and knee total joint replacement for OA42.

How Obesity Contributes to the Disease State

Altered biomechanics, impaired muscle function and reduced cyclic loading through lack of physical activity in people who have overweight or obesity are thought to contribute to OA structural joint damage. Evidence shows that obesity alters gait and joint biomechanics.

At self-selected speed, and compared with normal-weight individuals, those with obesity exhibit:43

  • Slower walking speed
  • Shorter stride length (shorter steps)
  • Greater step widths (wider steps)
  • Lower step frequency
  • Longer stance phase
  • Longer double support phase
  • Higher absolute ground reaction forces
  • Higher absolute joint moments

The gait changes and altered biomechanics can negatively affect the load bearing regions of the articular cartilage contributing to disease.

Muscles also play a role in absorbing limb loading and providing dynamic joint stability. Muscle strength, particularly of the quadriceps muscle, is also a major determinant of physical function. Muscle weakness is common in people with OA and those with obesity can have lower strength relative to their body mass than those with a healthy weight. In addition, excess adipose tissue infiltration of muscle in individuals who have obesity can impair muscle function, which again may contribute to the severity of symptoms experienced.

Reduced physical activity levels – Cyclic physiologic loading of the limbs, as occurs with a physically active lifestyle and exercise can reduce inflammation systemically as well as locally in adipose tissue and cartilage. People with OA who have overweight or obesity often have lower levels of physical activity. Thus a reduction in regular daily joint loading may increase the susceptibility of joint tissues to inflammatory stress44.

Excess adipokines and leptin secreted in the obese state are thought to have catabolic effects on joint tissues including cartilage; there is a relationship between leptin levels and pain, radiographic severity of knee OA and knee cartilage loss. Excess adipokines are also produced locally in the infrapatellar fat pad which is closely associated to the knee joint. In addition, there is evidence that abnormal, altered or injurious mechanical stress of the joint can increase the expression of pro-inflammatory factors by joint cells and contribute to the catabolic processes that occur in joint tissues in OA45.

Benefits of Weight Loss

All international guidelines for the management of OA recommend weight loss for patients who have overweight or obesity as part of a conservative management plan. Evidence suggests that effective lifestyle interventions should include dietary change (typically a very low calorie diet using meal replacements to lose weight followed by healthy eating to maintain weight), behaviour change support and an exercise plan including strengthening exercise and aerobic activity.

Evidence shows that weight loss can lead to:

  • Reductions in knee compressive force and peak knee load during walking46
  • Improvements in pain and function, (more so with a diet and exercise than a diet alone intervention)47
  • Reduction in levels of pro-inflammatory markers47

Clinical guidelines generally recommend weight loss of at least 5% body weight in order to improve symptoms in knee OA. However, greater amounts of weight loss appear to have greater benefits with >10% body weight loss giving moderate to large symptomatic effects 48 with a dose-response relationship demonstrated48.

For those interested in the benefits of weight loss for osteoarthritis symptoms, please watch the 15 minute video above produced by the University of Melbourne providing an in-depth evidence-based overview of the effects of weight loss in osteoarthritis.

Lower back pain

Mechanism by which obesity contributes to the disease state

Lower back pain is one of the leading causes of disability worldwide. Obesity is associated with lower back pain, with the link thought be partially biomechanical, with increased abdominal mass causing the pelvis and lower back to slant forward causing chronic back pain. Evidence also suggests that chronic systemic inflammation can contribute to back pain associated with obesity49.

Benefits of weight loss

Evidence shows that non-surgical weight loss attempts which resulted in reduced BMI were associated with clinically important improvements in function, and short-term improvements in pain50. Surgical weight loss in patients with chronic lower back pain has also been demonstrated to significantly improve the degree of functional disability of those with morbid obesity51 as well as being associated with a moderate improvement in pain52.

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EduWeight: Weight Management for Adult Patients with Chronic Disease

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