In this blog for our Evidence for Everyday Health Choices series, Sarah Chapman looks at new Cochrane evidence on two treatments for hip and knee osteoarthritis: paracetamol and exercise.

This week two things have prompted me to blog about osteoarthritis, a very common condition in the UK, where almost one in five people aged 50 and older have disabling knee or hip pain. The first is a newly updated Cochrane Review on the effects of paracetamol for people with osteoarthritis of the hip or knee. Might there be new evidence to move forward the debate about whether it is actually helpful or safe? Secondly, the Best of the Cochrane Library: 2018 in review has just been published and shows that the fifth most accessed Cochrane Review published last year is one that addresses another area of uncertainty for this populationThe group of people being studied. Populations may be defined by any characteristics e.g. where they live, age group, certain diseases. – the effects of exercise, often recommended to help reduce pain and increase joint function, on aspects of mental wellbeing as well as physical health and the complex relationship between them.

Taking a fresh look at paracetamol

If you go to your doctor with osteoarthritis pain, it is likely that the first thing they will suggest you try is paracetamol. Pain researcher and Cochrane authorSomebody responsible for preparing and, in the case of Cochrane Reviews, keeping up-to-date a systematic review. The term ‘reviewer’ is also sometimes used to refer to an external peer reviewer, or referee. Andrew Moore comments in his blog on paracetamol that this decades old drug, the go-to medicine for many pain conditions, “doesn’t effectively relieve pain but has demonstrable rare but serious adverse events”. Recalling this, I was intrigued to see what this review would find. It includes ten studies with 3541 people with hip or knee osteoarthritis, who were randomly allocated to take paracetamol or placeboAn intervention that appears to be the same as that which is being assessed but does not have the active component. For example, a placebo could be a tablet made of sugar, compared with a tablet containing a medicine..

The review has high-certaintyThe certainty (or quality) of evidence is the extent to which we can be confident that what the research tells us about a particular treatment effect is likely to be accurate. Concerns about factors such as bias can reduce the certainty of the evidence. Evidence may be of high certainty; moderate certainty; low certainty or very-low certainty.  Cochrane has adopted the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) for assessing certainty (or quality) of evidence. Find out more here: https://training.cochrane.org/grade-approach evidence confirming that paracetamol has “minimal, probably clinically unimportant benefits in the immediate and short term for people with hip or knee osteoarthritis”. There was no evidence of a difference in the effect on pain and function according to dose (3.0g/day or less versus 3.9g/day or more).

Whilst there is also high-certaintyThe certainty (or quality) of evidence is the extent to which we can be confident that what the research tells us about a particular treatment effect is likely to be accurate. Concerns about factors such as bias can reduce the certainty of the evidence. Evidence may be of high certainty; moderate certainty; low certainty or very-low certainty.  Cochrane has adopted the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) for assessing certainty (or quality) of evidence. Find out more here: https://training.cochrane.org/grade-approach evidence that paracetamol does not increase the riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of adverse events (harms) overall, the review authors are less certain whether paracetamol increases the riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of serious adverse events or withdrawals from the studies due to adverse events. Paracetamol probably increases the rateThe speed or frequency of occurrence of an event, usually expressed with respect to time. For instance, a mortality rate might be the number of deaths per year, per 100,000 people. of abnormal liver function tests but this may not be clinically importantClinical significance is the practical importance of an effect (e.g. a reduction in symptoms); whether it has a real genuine, palpable, noticeable effect on daily life. It is not the same as statistical significance. For instance, showing that a drug lowered the heart rate by an average of 1 beat per minute would not be clinically significant, as it is unlikely to be a big enough effect to be important to patients and healthcare providers.. None of the studies looked at long term toxicityThe degree to which a medicine is poisonous. How much of a medicine can be taken before it has a toxic effect. or quality of life.

With clinical guidelines recommending paracetamol as the first painkiller to try for the pain of hip or knee osteoarthritis, the review authors say their results call for these recommendations to be reconsidered.*

Exercise: benefits and beliefs

It’s really good to see the approach taken to this review on exercise interventions for people with hip and/or knee osteoarthritis, which sought to understand people’s beliefs about exercise in managing their osteoarthritis and their experiences of it, as well as its physical effects.

Firstly, let’s look at the evidence from the 21 studies (with 2372 people), from high income countries across the world, on the effects of exercise on pain and/or movement as well as on people’s mental wellbeing and their social interactions. There was a lot of variation in the types of exercise programmes, how often exercise was done and for how long. Exercise was were compared to a range of things including being on a waiting list and having home visits.

The most common types of exercise were walking and or/cycling for aerobic exercise and strength training through exercises such as knee extensions and step-ups.  Only one studyAn investigation of a healthcare problem. There are different types of studies used to answer research questions, for example randomised controlled trials or observational studies. looked at water-based exercise, but another Cochrane Review has shown that exercises done in water probably have small benefits for people with hip or knee osteoarthritis in terms of their pain, disability and quality of life.

Probable benefits and some uncertainties

They found that exercise probably slightly improves physical function, pain and depression. It may also improve people’s confidence in what they can do and their social interaction, but probably has no effect on anxiety. Regrettably, we don’t know whether there were any harms associated with the exercise programmes as none of the studies reported on this. We also don’t know whether changes happened quickly or gradually and whether improvements lasted.

The review authors comment:

“These benefits may arise indirectly from a reduction in pain and improvement in function, or directly as a result of attending a rehabilitation programme that developed positive attitudes toward living with OA [osteoarthritis], support from clinicians and sharing experiences with people who have similar problems.”

A need for advice and reassurance

Evidence from a further 12 studies looking at people’s beliefs and experiences relating to exercise and their osteoarthritis can help us understand more about this. As we might expect, pain dominated the lives of people with osteoarthritis interviewed in these studies because it affected most aspects of everyday life. Physical factors such as pain and stiffness but also people’s perceptions of their physical fitness restricted the amount and type of exercise they did, and fear of exercise causing them harm was another limiting factor. These studies highlighted that people with osteoarthritis want better information and advice about the benefits of exercise and whether it is safe for them. The review authors explain:

“People are confused about the cause of their pain, and bewildered by its variability and randomness. Without adequate information and advice from healthcare professionals, people do not know what they should and should not do, and, as a consequence, avoid activity for fear of causing harm… Providing reassurance and clear advice about the value of exercise in controlling symptoms, and opportunities to participate in exercise programmes that people regard as enjoyable and relevant, may encourage greater exercise participation, which brings a range of health benefits to a large populationThe group of people being studied. Populations may be defined by any characteristics e.g. where they live, age group, certain diseases. of people.”

Communication is key

I found myself nodding reading this summary of what people with osteoarthritis want. The need for information and reassurance stands out and surely these are two pillars of good healthcare in so many contexts. I am reminded of my own experiences when I had a frozen shoulder – I didn’t know whether, how, or how much to exercise it. I wanted to know how to help myself but not cause damage. The leaflet I was given by the GP covered a wide range of ‘shoulder problems’ and I didn’t feel confident that the exercise advice in it applied to me. It felt very different when I saw a physio and had one-to-one advice and instructions about exercises tailored for me. I thought too of my daughter, who was discharged from hospital after surgery with a tick in the box on the discharge summary indicating ‘no mobility problems’ (hobbling and nursing a large wound, she didn’t agree!) and no advice about how or why she should exercise.

The exercise review has more rich detail about people’s attitudes to exercise for managing their osteoarthritis and I’d urge those interested to head to the discussion section of the review to read more. Between them, these two reviews offer plenty of food for thought. When we think about exercise as a treatmentSomething done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes., we perhaps need to think more holistically and imaginatively – trying to put ourselves in that person’s (running!) shoes; and about paracetamol – this evidence suggests we need to think twice.

*Footnote: The current NICE guideline on osteoarthritis is being updated (expected publication date August 2021) and in their latest review of the existing guideline they acknowledge that: “evidence identified in surveillance suggests that paracetamol may not have a clinically importantClinical significance is the practical importance of an effect (e.g. a reduction in symptoms); whether it has a real genuine, palpable, noticeable effect on daily life. It is not the same as statistical significance. For instance, showing that a drug lowered the heart rate by an average of 1 beat per minute would not be clinically significant, as it is unlikely to be a big enough effect to be important to patients and healthcare providers. effect on pain in people with osteoarthritis”. NICE plans to update the guideline, including a full review of oral analgesics. Once the update begins, people can check its progress on the guideline’s in-development page. 

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References (pdf)

Sarah Chapman has nothing to disclose.