Knee arthritis is not good, is exercise useful in the end? This uniquely designed experiment is of concern

▎ WuXi AppTec content team editor

Knee arthritis is very common, and in addition to pain, patients face problems such as joint stiffness, decreased joint stability, reduced range of motion, muscle atrophy, and decreased muscle strength, which can lead to a decline in the quality of daily life.

Whether to exercise for knee arthritis is the doubt of many patients. A recently published randomized trial with a unique design suggested that the exercise effect was consistent with intra-articular saline injections, in other words, the placebo effect. The study attracted attention after publication. So, can exercise improve knee arthritis?

Image credit: 123RF

Guidelines recommend, but the evidence is limited

In fact, the potential beneficial effects of exercise on improving osteoarthritis in non-pharmacological therapies have received increasing attention. The benefits of exercise include joint-specific effects such as reduced joint pain, increased muscle strength, increased range of motion and flexibility, and exercise can also help improve overall physical and mental health.

Since the 1990s, guidelines have proposed the treatment of knee arthritis and hip arthritis through exercise. Exercise is highly recommended in the latest recommendations of the American Academy of Rheumatology (ACR), and in the Guidelines of the International Association for the Study of Osteoarthritis (OARSI), exercise is also considered a core treatment.

However, whether there is enough evidence to support the effectiveness of the campaign has indeed been controversial. On the one hand, blinding exercise interventions is extremely difficult; on the other hand, exercise and patient education programs are often a complex set of interventions rather than a single tool. This makes clinical trial design and implementation challenging and lacks adequate placebo-controlled studies.

Discoveries of new trials

The study was an open-label randomized controlled equivalent trial that included a placebo intervention, led by academics at the University Hospital of Copenhagen in Denmark. The study recruited ≥ 50-year-old patients with symptomatic and imaging-confirmed knee arthritis in Denmark. A total of 206 patients (average 68.4 years, 54% male) were randomly grouped 1:1 into an education and exercise program (8 weeks, including two 1.5-hour educational sessions + 12 1-hour exercise sessions) or intra-articular saline injections (4 in total).

This is a very special contrast design. In studies of osteoarthritis, the placebo effect is usually evident. In this study, to address the placebo effect of exercise, the researchers used saline injections as a control comparison. Previous studies have shown that intra-articular saline injections can cause a considerable placebo response if used properly, and are also inactive substances commonly used in control in clinical trials of knee arthritis.

Screenshot from Annals of the Rheumatic Diseases

There were 102 people in the practical education and sports group, with an average participation rate of 79.3% in the course, and 104 people in the saline injection group, who received an average of 3.4 injections (injection rate of 84.9%).

The primary outcome measure was an improvement in the KOOS (Knee Injury and Osteoarthritis Outcome Score) pain score (worst 0, best 100) from the start of the study to week 9. The results showed no statistical difference between the two groups on this indicator.

The KOOS pain score ± 8 scored as a pre-specified margin of equivalent.

The mean change in least squares between the two sets of scores was 10 points vs 7.3 points (difference of 2.7 points, 95% CI: -0.6 to 6.0); the equivalence test p= 0.0008.

On key secondary outcome measures, the overall assessment of disease effects by patients in the education and exercise groups improved significantly better, but there was no difference in KOOS function and quality of life score improvements between the two groups. Adverse events and serious adverse events were also similar in both groups.

Therefore, the research team concluded that in patients with knee arthritis, the symptom and functional improvement effects of an 8-week education and exercise program were equivalent to the effects of 4 intra-articular saline injections in 8 weeks.

Read carefully, more questions to be answered

However, the contemporaneous editorials give a more cautious interpretation. For example, the study still has limitations, such as the intervention was not blinded; the measure of outcome measures was subjective, and the muscle strength test results were less biased but not conducted in this trial. Moreover, intra-articular injections also have a strong placebo effect compared to oral medications, especially when repeated injections are given for a short period of time. If the placebo effect differs between the two groups, it is impossible to estimate the true effect of the treatment, which makes the results of this trial difficult to interpret.

The editorial also mentions that regulatory agencies such as THE NIHR (Uk.K. Health Care Institute) have published a corresponding research framework for challenges that are complex and difficult to accurately assess through trials. What's more, overall, there is still plenty of convincing evidence to support the use of exercise therapy to treat osteoarthritis, especially the knee and hip joints.

Comparing trials of two different therapies can further increase our understanding of the relative efficacy of different treatment regimens. Two years earlier, the New England Journal of Medicine (NEJM) published a randomized trial comparing physical therapy with intra-articular glucocorticoid injections, which provided important evidence to support the effectiveness of education and exercise therapy and its role as a core treatment. The trial was conducted in 156 patients, and patients with knee arthritis who received physiotherapy improved pain and dysfunction after 1 year of treatment compared to glucocorticoid injections.

Of course, in the future, we need randomized clinical trials or real-world studies to answer more important questions, such as which (combined) education or exercise method is most effective? What is the most effective and safest approach in a particular subpopulation, such as patients with comorbidities? What is the minimum amount of activity required to produce beneficial results? How to maintain results in the long term? It is expected that these issues will be better supported by evidence in the future.