Guideline for the management of knee and hip osteoarthritis

Recommendations

Intra-articular injections

Guideline for the management of knee and hip osteoarthritis
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Pharmacological interventions

Intra-articular injections


 

Corticosteroid injection - Knee (OA) and/or hip

Recommendation

It may be appropriate to offer an intra-articular corticosteroid injection for some people with knee and/or hip osteoarthritis for short-term pain relief. Clinicians need to be cautious of the potential harms of repeated use.

Strength of recommendation

Conditional for recommendation

Quality of evidence

Very low

What is it?

Corticosteroids are medications that mimic the effects of the hormone cortisol, which is produced naturally by the adrenal glands. Cortisol helps to lower the levels of prostaglandins and downplays the interaction between certain white blood cells involved in the immune response. Corticosteroid injections are frequently used for the short-term symptom relief of a flare of joint symptoms or when a rapid reduction in symptoms is required.

Rationale

The studies upon which the recommendation is based were at serious risk of bias and generally small in size. The overall quality of the evidence was judged to be low to very low (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). Beneficial effects on knee pain and function were demonstrated at up to six weeks. These findings were not present when follow-up was extended to three months.

For hip pain, the clinical benefits were demonstrated for up to 12 weeks; however, there is lack of long-term data. In addition, considering the complexity of the hip joint, image guidance would be required, which would further add to the costs.
The working group considered intra-articular corticosteroid injections can be used as an adjunct to core treatment for short-term reduction of moderate-to-severe pain in people with knee or hip OA.

Harms

Serious and total adverse events were not significantly increased, compared with placebo. However, there are concerns of more rapid cartilage loss with repeated injections with no benefit in long-term symptom outcomes at two years, so these injections should be used judiciously.118

Viscosupplementation injection - Knee/hip

Recommendation

We suggest not offering viscosupplementation injection for people with knee hip OA.

 

Strength of recommendation

Conditional against recommendation

Quality of evidence

Low

Recommendation

We do not recommend offering viscosupplementation injection for people with hip OA.

Strength of recommendation

Strong against recommendation

Quality of evidence

Low

What is it?

Hyaluronate is a naturally occurring component of cartilage and synovial fluid, and responsible for the rheologic properties of synovial fluid, enabling it to act as a lubricant or shock absorber. In OA, synovial hyaluronate is depolymerised and cleared at higher rates than normal. The therapeutic goal of intraarticular hyaluronate administration is to provide and maintain intraarticular lubrication. This in turn increases the viscoelastic properties of synovial fluid, and is sometimes termed ‘viscosupplementation’. It has also been reported that hyaluronate exerts anti-inflammatory, analgesic and possibly chondroprotective effects on the articular cartilage and joint synovium.119

Rationale

The major analyses upon which the recommendation is based were considered to be at serious risk of bias, but the large number of studies analysed involved, in total, a large number of participants. For knee pain, function and adverse events, the overall quality of the evidence was judged to be moderate. Despite some inconsistency on the conclusions among the analyses, a positive effect, albeit small and not clinically relevant, was demonstrated for pain and function.

The recommendation for hip OA is based on three small randomised controlled trials (RCTs), which were judged to not be at serious risk of bias (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). The overall quality of evidence was judged to low. No effect on pain nor function was demonstrated, and the risk of total and serious adverse events and local reactions was greater in the viscosupplementation group. In addition, for a hip injection, image guidance would be required, further adding to complexity and cost. However, the increased risk of total and serious adverse events concerned the working group, and when cost and the complexity of the intervention were taken into account, a conditional against recommendation was agreed upon.

Harms

Minor side effects include pain at the injection site (1–33%), local joint pain and swelling (<1–30%), and local skin reactions (3–21%). Pseudoseptic reactions (1–3%), which are characterised by inflammation and swelling of the joint that are not caused by infection, can be severe and may require further medical treatment. These reactions usually occur after sensitisation with the second or third injection of a series, or with a repeat treatment course. True joint infections have also been reported, but these appear to be rare.120

Platelet-rich plasma (PRP) injection – Knee and/or hip

Recommendation

We are unable to recommend either for or against the use of PRP injection for people with knee and/or hip OA.

Strength of recommendation

Conditional (neutral) recommendation

Quality of evidence

Very low

What is it?

PRP is an autologous concentration of a high number of platelets in a small volume of plasma, and it is prepared by centrifugation of blood. Platelets contain significant amounts of cytokines and growth factors, which are capable of stimulating cellular growth, vascularisation, proliferation, tissue regeneration and collagen synthesis.

Rationale

The studies upon which the recommendation is based were at serious risk of bias and inconsistency, and were generally small in size (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). The overall quality of the evidence was judged to be very low. Beneficial effects on both knee pain and Western Ontario and McMaster Universities (WOMAC) function were demonstrated at six months. With the concern of potential reporting bias and low-quality data, the beneficial effects are likely to be overinflated. In addition, there is no consensus on eligible participant selection, number and frequency of injections, preparation technique, or appropriate platelet concentration,121 leading to large variations in the design of PRP trials.

No RCT was conducted in hip OA. However, during working group discussions, it was suggested that the mechanism of action should be no different in hip OA. Therefore, the findings might be transferrable to hip OA, but with a particular caution in terms of the complexity of the hip joint.

The cost of PRP treatment is high, and additional equipment might be required for the preparation and administration.

Harms

Most common treatment-related adverse events were local swelling and transient regional pain. PRP did not increase the risk of adverse events, compared with hyaluronic acid and saline according to other systematic reviews.122

Stem cell therapy – Knee and/or hip

Recommendation

We do not recommend offering stem cell therapy  for people with knee and/or hip OA.

Strength of recommendation

Strong against recommendation

Quality of evidence

Very low

What is it?

Stem cells are cells that have the ability to divide and develop into many different types of cell in the body, and can be categorised as pluripotent and multipotent. Mesenchymal stem cells (MSCs) are a common form of multipotent cells that may offer an alternative to cartilage repair techniques that is not hampered by availability and donor site morbidity. MSCs can be isolated from adipose tissue, bone marrow, synovial tissue and other sources.

Rationale

The two studies upon which the recommendation is based were at very serious risk of bias and were small in size. The overall quality of the evidence was judged to be low to very low. Beneficial effects on pain and function were demonstrated at up to six months. The between-group differences reported for pain and function appeared to be remarkably good (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). As they deviate significantly from those of other successful interventions, replication is required in high quality, large RCTs before a more favourable recommendation can be considered.

Consistent with a recent position statement from the Australian College of Sports and Exercise Physicians, stem cell administration should be part of a rigorously designed study and the priority for individual health and welfare.123

Harms

No serious adverse events were reported in those trials. There are two groups reporting minor adverse events, including mild pain and effusion after the injections, which persisted for no more than seven days.124,125

Dextrose prolotherapy – Knee and/or hip

Recommendation

We suggest not offering dextrose prolotherapy for people with knee and/or hip OA.

Strength of recommendation

Conditional against recommendation

Quality of evidence

Low

What is it?

Hypertonic dextrose injection, also termed as prolotherapy, is an injection-based treatment used for a variety of painful chronic musculoskeletal pain conditions. The core practice principle of prolotherapy is injection of relatively small volumes (0.5–6 ml) of an irritant solution, usually hypertonic dextrose, at painful ligament and tendon attachments, and in adjacent joint spaces. The hypothesised mechanisms for pain relief include stimulation of local healing, reduction of joint instability through the strengthening of stretched or torn ligaments and stimulation of cellular proliferation.

Rationale

The recommendation is based on the evidence of only one small RCT of low quality. The risk of bias in this study was not determined to be serious. No clinically significant effects were found for pain at 24 and 52 weeks follow-up. In terms of function, no clinically significant effects were found for pain at 24 weeks, but a marginally significant effect was recorded at  52 weeks (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). Furthermore, high-quality RCTs with low risk of bias and specifically for hip OA are required.
As prolotherapy is relatively cheap and accessible, it is likely to be injudiciously used. The working group agreed on a ‘Conditional against recommendation’.

Harms

The study reported self-limited bruises after dextrose (n = 3) and saline (n = 5) injections. This was an expected side effect and deemed to be of minimal clinical relevance because of its transient nature. No serious adverse events were reported; however, this may be because the study sample size is not large enough to detect uncommon adverse events.126

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