The growing prevalence of knee osteoarthritis could bring more patients into doctors’ offices, asking for pain relief. One clinical treatment option is intra-articular injections, but guidelines differ on what to recommend. How should physicians educate patients on the procedure?
Dr. Ivan Wong, an orthopedic surgeon in Halifax and president of the Arthroscopy Association of Canada (AAC) and Dr. Lauren King, a rheumatologist at St. Michael’s Hospital in Toronto, provided advice on knee injections for osteoarthritis.
Corticosteroid injections should not be repeated on a regular basis. Corticosteroid injections are the most common and best studied injections available for knee osteoarthritis. In the 2019 AAC position statement on intra-articular injections for knee osteoarthritis, they are said to provide “short-term, moderate pain relief and restoration of function” in patients with early knee osteoarthritis. The American College of Rheumatology (ACR) strongly recommends them for patients with knee osteoarthritis.
The beneficial effects peak around two weeks following an injection and usually lasts up to three months. Adverse events are often minor and include swelling and joint tenderness.
While the injection is localized, the corticosteroid could still affect blood sugar levels in patients with diabetes. “Generally, we recommend that the person watch their blood sugar in the days following their injection,” Dr. King said. Patients can adjust their insulin dose as needed.
The cost of corticosteroid injections makes them accessible to most patients, at around $25 an injection.
While the injections may bring pain relief, they shouldn’t be overused.
“Our biggest concern is there is more documentation now showing that corticosteroids can actually damage cartilage,” Dr. Wong said. “Repeat injections can actually accelerate arthritis.”
The concern comes in part from a randomized clinical trial comparing regular intra-articular injections of 40 mg triamcinolone and saline on knee pain and the progression of cartilage loss. When injections were given every three months for two years, the patients given triamcinolone injections had significantly more cartilage volume loss than those who had saline injections. There was no significant difference in knee pain as measured by the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. The trial results were published in JAMA in 2017.
“It’s still not clear if that’s a clinical significant difference,” Dr. King said. The ACR guidelines point out that the change in cartilage thickness in the JAMA study was not associated with more pain or decreased functioning, so it is uncertain if it’s clinically meaningful. However, due to the concern about harm and efficacy with repeated corticosteroid knee injections, “We wouldn’t repeat them on a regular basis,” Dr. King said.
Patients should not receive more than four injections a year, according to a patient education article from the Arthritis Society Canada.
Consider hyaluronic acid injections after trying other treatments. There is some controversy around intra-articular hyaluronic acid injections, also called viscosupplementation. These injections provide lubrication to the joint, which may improve function and reduce pain. The effect often lasts longer than corticosteroid injections. The injections have been approved by Health Canada since 1992, but the evidence supporting their use is conflicting enough that guidelines differ in their recommendations.
The American Association of Orthopedic Surgeons guidelines and ACR guidelines do not recommend the routine use of hyaluronic acid injections as a treatment of osteoarthritis of the knee, where the AAC position statement and Osteoarthritis Research Society International (OARSI) guidelines recommend they be considered for patients with mild to moderate knee osteoarthritis.
The difference, Dr. Wong explained, is due to the varying quality of synthetic hyaluronic acid preparations. A 2017 Canadian review found that hyaluronic acid injections significantly improved pain, function and stiffness in patients with mild to moderate knee osteoarthritis, and higher molecular weight preparations were more likely to provide a clinically important therapeutic effect than low molecular weight preparations. The paper was published in Therapeutic Advances in Musculoskeletal Diseases. Other studies showed highly cross-linked hyaluronic acid also provided greater benefit than non-cross linked hyaluronic acid.
“There are enough studies out there that show this is the right thing to do,” Dr. Wong said.
A more recent Canadian review of clinical trials, published in BMJ in July 2022, found that while hyaluronic acid injections were, “significantly associated with a small reduction in pain intensity compared to placebo,” the effects were not clinically significant. There was also a higher incidence of serious adverse effects with hyaluronic acid injections compared to placebo.
The evidence itself is hard to pin down. In their BMJ paper, Tiago Pereira, Dr. Peter Jüni, Bruno da Costa and colleagues note that more than a dozen unpublished industry-sponsored trials haven’t made it into systematic reviews, meaning some data are being left out in the analysis. The dramatic increase in the number of trials since 2009 have also “outpaced the field’s capacity to find, appraise, and distill the evidence,” they wrote.
The discrepancy in the guidelines mean that it is up to physicians to decide if hyaluronic acid injections are appropriate for their patients or not, Dr. King said. In the Arthritis Society patient education article, Dr. King suggests these injections may come after a physician and patient have explored other treatment options, including physical activity, weight management and corticosteroid injections.
The cost for hyaluronic acid injections ranges from $50 to $600 per injection, depending on the product and the clinic offering the procedure.
View PRP injections with caution.
Platelet-rich plasma (PRP) injections use the patient’s own blood. Whole blood centrifugation separates out the red blood cells and when the remaining PRP is injected into the knee, the platelets release proteins, cytokines and growth factors that regulate inflammation. The composition of PRP preparations can be affected by many factors, from the time of day the blood was drawn to what preparation system was used. These differences make it hard to measure how effective PRP injections are on treating knee osteoarthritis.
People are talking about PRP injections, but “the data to date has really mitigated my enthusiasm,” Dr. King said. “The quality of studies have been overwhelmingly poor.”
The AAC position statement notes that studies suggest PRP injections can give some relief from pain and improve functional outcomes in patients with mild to moderate knee osteoarthritis, but the strength of the evidence is low. The AAC does not recommend for or against the use of PRP injections. The American College of Rheumatology guidelines recommend against using PRP treatment in patients with knee osteoarthritis. The guidelines note that the lack of standardization of the preparations use make it difficult to identify what is being injected. Health Canada even published a warning about autologous cell therapies in 2019.
One randomized clinical trial comparing PRP intra-articular injections to saline in patients with mild to moderate knee osteoarthritis found no difference in pain scores or cartilage volume between the two groups. The trial was published in JAMA in 2021.
“At this point it is really challenging to make a recommendation for it,” Dr. King said.
When researchers do pinpoint the best method of preparing PRP, it may provide benefit to some patients, Dr. Wong said. “The higher quality PRP will likely show improved outcome."
Educate on the role of knee injections in osteoarthritis management.
Dr. King said that physicians and patients should consider the role knee injections play in the wider context of osteoarthritis management. Over the past decade, there’s been a change in what is considered first-line treatment for osteoarthritis, with a shift away from pharmacological treatments to non-pharmacological interventions, “because that’s where we have the best evidence for improvements in pain and physical function for the long-term,” she said. This includes weight management, physical activity and physiotherapy.
Corticosteroid injections could be used as an adjunct treatment, such as when a patient needs to get over an exacerbation in order to pursue an exercise program that will bring longerterm benefit, Dr. King said.
Patients need to know the evidence surrounding intra-articular injections so they understand how injections could fit into an osteoarthritis treatment plan. “If a patient comes in and asks for an injection, it’s a great opportunity to discuss other treatments,” Dr. King said.
Prepare your patients for injections.
Patients should know what reactions to expect following an injection and when to seek help. The Arthritis Society Canada recommends resting the joint for a 24 to 48 hours following a corticosteroid injection and 48 hours after a hyaluronic acid injection. Any discomfort in the joint can often be treated with a cold pack or acetaminophen or an NSAID.
Again, patients with diabetes should monitor their blood sugar for a few days following corticosteroid injections. The procedure itself doesn’t take long. While ultrasound-guided injections are recommended for hyaluronic acid, the ACR states in their guidelines that ultrasound guidance is not necessary for corticosteroid intra-articular injections into the knee.
It’s a good idea to followup with patients to see if the injections are beneficial, Dr. King said. If a patient experiences only a few days of relief, it may not be a worthwhile treatment, but a month or more of improvement in symptoms suggests it may have merit for that patient, she said.