Category: Rheumatology

Intra-Articular Treatments for Knee Osteoarthritis: A Review

Intra-articular treatments provide an attractive alternative to prescription therapies in patients with osteoarthritis of the knees. This condition is fairly common, affecting more than 1 in every 10 U.S. adult at or over the age of 60 years old1. Current treatment options are designed to solely relieve pain and do not reverse the disease progression. As a result, studies have shown that more than half of patients with Knee OA will eventually meet the criteria for total knee replacement.

Read on as Attune Health founder and rheumatologist Swamy Venuturupalli, MD and physician assistant Bryant Uy dissect this condition, the efficacy of intra-articular medications, and the future of osteoarthritis treatments.


As osteoarthritis of the knees is a progressive condition, the disease can be divided into five stages:

  • Stage 0: Classified as a normal “healthy” knee
  • Stage 1: The patient is exhibiting very minor bone spur growth. Usually at this stage, there is no pain or discomfort.
  • Stage 2: Considered the “mild stage,” patients with Stage 2 Knee OA have greater bone spur growth, but cartilage is still at a healthy size, meaning their bones are not scraping each other.
  • Stage 3: This stage is considered “moderate stage.” Patients typically show cartilage with obvious damage and will experience pain and/or discomfort when walking.
  • Stage 4: This is considered “severe” osteoarthritis. People suffering from this stage experience a great deal of pain when walk or rotate the joint.


Common medications prescribed for patients with osteoarthritis of the knees are painkillers such as acetaminophen (Tylenol), narcotics, and non-steroidal anti-inflammatory medicines (aspirin, ibuprofen, naproxen, etc). These medications can appear in both oral and topical forms (i.e. Diclofenac gel)  However, there currently is no cure for this condition; these interventions are typically given with the intention of pain relief rather than reversing the progress of the condition.

Intra-articular agents provide an attractive option for knee OA patients due to the possibility of fewer damaging effects, ability to target the cartilage, and increased efficiency of delivery. In spite of this, further research must be done to figure out the extent to which improvement can be attributed to the drug rather than just the patient’s mind (the placebo effect).

A typical intra-articular agent administered by clinicians is a hyaluronic acid (brand names include Euflexxa, Genvisc, Monovisc, Orthovisc, Synvisc, and Hylagan), which has been shown to be effective in clinical practice and has a patient satisfaction rate of nearly 70%. Another intra-articular intervention is a corticosteroid injection, which is commonly used by clinicians as another method of reducing pain.3 Corticosteroid injections typically provide short-term relief, but in the last year a new long acting form of corticosteroids called Zilretta has just become available.  

Recently, intra-articular Hyaluronic acid injections have been somewhat controversial: the American Orthopedic association recommended against them being used in routine practice, as the data has not shown significant enough improvement. However, this recommendation has been challenged by other authorities. In our own clinic we continue to offer these interventions to our patients as an alternative to steroid injections and also due to lack of good medication options. In our experience, if these injections are targeted to diseased areas using ultrasound guidance, they might be more effective than blind injections. This approach hasn’t been studied extensively.


The field is growing by leaps and bounds, with numerous biotech companies conducting clinical trials of various products that delay the progression of osteoarthritis and perhaps even change the quality of the cartilage. “In 2019, I expect numerous additional clinical trials to be completed and look forward to data that might emerge. The hope is that we can finally bring relief to our numerous patients suffering from this common and debilitating condition,” says Dr. Venuturupalli.

If you are interested in participating in a clinical trial of an intra-articular medication for knee osteoarthritis please contact our research division at [email protected].


1  “Osteoarthritis News, Latest Articles | OA Research Findings.” Rheumatology Advisor,

2  Altman RD, Bedi A, Karlsson J, Sancheti P, Schemitsch E. Product differences in intra-articular hyaluronic acids for osteoarthritis of the knee. Am J Sports Med. 2016;44(8):2158-2165.

3 Jones IA, Togashi R, Wilson ML, Heckmann N, Vangsness CT.  Intra-articular treatment options for knee osteoarthritis. Nat Rev Rheumatol. 2019;15(2):77-90.