Evaluation of the Benefit of Corticosteroid Injection Before Exercise Therapy in Patient with Osteoarthritis of the Knee

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. "Evaluation of the benefit of corticosteroid injection before exercise therapy in patients with osteoarthritis of the knee: a randomized clinical trial.". '. . :.

Clinical Question

In patients with osteoarthritis of the knee, does a corticosteroid injection before exercise compared to placebo improve patient response to exercise therapy?

Bottom Line

No additional benefit results from adding an intra-articular injection of 40mg of corticosteroid before exercise in patients with painful osteoarthritis (OA) of the knee.

Major Points

The highly recommended non-pharmacologic treatment for knee osteoarthritis is exercising, while the highly recommended pharmacologic treatment is intra-articular corticosteroid injection. At this time, only single treatments have been investigated. The question of whether a combination of exercise and corticosteroid treatment will provide greater efficacy and synergistic clinical benefit has not yet been assessed. This trial was a randomized, blinded, placebo-controlled clinical trial of 100 participants who had OA of the knee. The participants were randomly assigned to an intra-articular corticosteroid group (n=50 or 45) or a placebo group (n=50 or 44). The placebo group received an injection of isotonic saline and lidocaine while the intervention group received an injection of methylprednisolone acetate and lidocaine. Two weeks after the injection all participants started an exercise program. At week 14 participants were assessed for a change in the pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire (range 0-100 where higher scores indicate greater improvement). A follow-up was done at week 26 to further assess changes to find no significant secondary outcomes. Although decent improvements were observed throughout the trial, no evidence suggested any benefit of the corticosteroid treatment compared to the placebo. Limitations to the study existed as the dose for the corticosteroid used in the trial was at the lower end of the recommended dosage provided for osteoarthritis in the knee, as well as the addition of Lidocaine to the injections for possible pain relief in both intervention and placebo groups. More evidence and testing is needed to provide evidence to suggest superiority. Therefore, the results suggest the use of corticosteroids prior to starting exercise does not provide any additional synergistic benefit.


1. American College of Rheumatology (ACR) Pharmacologic Recommendations in OA of the Knee (2012, adapted): Patients with knee OA should can use intra-articular corticosteroid injections and should participate in exercises.

2. European League Against Rheumatism (EULAR) Recommendations for Nonpharmacologic Management of Knee OA (2013): Strengthening exercises in knee OA shows that both specific quadriceps strengthening exercises or strength training for the lower limb reduce pain effectively and improve physical function

3. Osteoarthritis Research Society International (OARSI) Guidelines for the Non-Surgical Management of Knee OA (2014): Intra-articular corticosteroid treatment is one recommended option for knee only OA with or without co-morbidities.

4.OARSI Recommendations for the Management of Hip and Knee Osteoarthritis: Part III (2010, updated): Intra-articular (IA) corticosteroids treatment may need to be repeated at frequent intervals to maintain efficacy; IA steroid injections had no significant effect on physical function


•Randomized, blinded, placebo-controlled clinical trial


oPlacebo Injection (n=50); Corticosteroid Injection (n=50)

•Setting: Outpatient OA clinic at Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark.

•Enrollment: October 1, 2012 - April 2, 2014

•Follow-Up: 14 weeks and 26 weeks

•Analysis: Intent-to-treat

•Primary Outcome: Mean KOOS Pain subscale score


Inclusion Criteria

•Age ≥40 years

•Radiographic confirmation of a clinical diagnosis of tibiofemoral OA

•Clinical signs of localized knee inflammation, knee pain during walking (score of >4 on a scale of 0-10points)

•Body mass index of 35 or less (calculated by weight in kilograms divided by height in meters squared)

Exclusion Criteria

•Corticosteroid injections or participation in exercise therapy within the past 3 years

•Current or recent (within 4 weeks) use of oral corticosteroids

•Inflammatory arthritis

•History of arthroplasty of the knee

•Conditions precluding participation in exercise

•Contraindications to corticosteroid injections

•Regional pain syndromes (eg, fibromyalgia)

•Spinal nerve root compression syndromes

Baseline Characteristics

• No clinically relevant differences between corticosteroid and placebo groups.


•Patients were randomized to either intra-articular corticosteroid group or placebo group: 1.Corticosteroid group: Received a 1-mL intra-articular injection of methylprednisolone acetate (Depo-Medrol) (40mg) dissolved in 4mL of Lidocaine Hydrochloride (10mg/mL). 2.Placebo group: Received a 1-mL injection of isotonic saline mixed with 4mL of Lidocaine Hydrochloride (10mg/mL).

•Injections from both groups were performed by a specialist in musculoskeletal sonography under ultrasonographic guidance to ensure correct bolus deposition in the joint cavity using a 25-gauge (38-mm) needle with a 10-mL syringe. The participants were informed that symptomatic exacerbation may occur during the next 2 days.

•In two weeks from the injection, the participants started an exercise program:

oThe program was functionalized and individualized and was monitored by a physiotherapist 3 times a week for 12 weeks.

oThe exercise program complies with the minimal recommendations for improvements for osteoarthritis in the knee.

oThe program was performed in groups and attendance was recorded.

•Outcomes were measured at baseline, at the 2- and 14- week visits, and at the 26-week follow-up visit using the KOOS questionnaire and sub-scales.


All comparisons are intra-articular injection vs placebo.

Primary Outcomes

• Mean KOOS Pain subscale score at 14 weeks: 13.6 vs 14.8 (95% CI -3.8-6.2; P=0.64) • Not statistically significant • Scores range from 0 to 100, with higher scores indicating better outcomes.

Secondary Outcomes

• No significant differences in KOOS subscale scores at 14 weeks, functional weight-bearing pain test at 14 weeks, muscle strength, blood sample analysis, or MRI analysis among groups.

Subgroup Analysis

All subgroup outcomes confirm the primary analyses. • Mean KOOS Pain subscale score at 14 weeks: 14.8 vs 15.0 (95% CI -6.0-6.4; P=0.95) • Subgroup was created after the trial to look at the same outcomes as the original trial

Adverse Events

•After Week 2 (start of exercise): 0 vs. 2 events

•After Week 14 (stop exercise): 1 vs. 1 event

•Details about adverse events not provided



•Amount of attention given to participants and the participant’s expectation concerning the upcoming exercise program may have overshadowed the effect of corticosteroid treatment

•The dose of corticosteroid used was in the lower range of the recommended dosage for knee joints

•Addition of lidocaine to the injection may have been a limitation


•Limited sample size (only 100 participants)

•No description of the adverse events seen during the trial


Funding from the Danish Council for Independent Research, Medical Science and by the Oak Foundation, Association of Danish Physiotherapists, Lundbeck Foundation and Capital Region of Denmark. All authors are independent of the funding sources. Authors with conflicts of interest disclosed.