Treatment of Knee Osteoarthritis

By | April 14, 2016

Osteoarthritis is defined as a type of joint disease that results from breakdown of joint cartilage and underlying bone(1). Osteoarthritis of the knee is usually associated with pain, stiffness, swelling and decreased mobility and is the result of degeneration of the articular cartilage around the joint.

The usual care for knee osteoarthritis;(2)

  1. Medications such as Tylenol and NSAIDS (Ibuprofen, Diclofenac, Naproxen)
  2. Physical Therapy and Occupational Therapy
  3. Braces or shoe inserts
  4. Education on how to manage your symptoms
  5. Corticosteroid injections or Hylauronic acid injections
  6. Joint Replacement

Corticosteroid injections are one of the most common standard treatments you are likely to receive from a physician when more conservative treatments such as exercise, physical therapy and NSAIDs are not providing the relief you seek. Two recent studies in 2015 and 2016 evaluated the addition of corticosteroid injections to exercise for knee osteoarthritis and compared it to placebo injections of saline. Both studies concluded that there were no benefits to corticosteroid injections at any point during follow up for knee osteoarthritis over placebo.(3)(4)

Regenerative injection therapies on the other hand have demonstrated clinically meaningful benefits for knee osteoarthritis.


Patients between the ages of 40-75 years old with moderate knee osteoarthritis, received 3 injections spaced ten days apart of either 12.5% dextrose or 15 gamma ozone. Both groups showed about a 60% reduction in pain scores as well as a 45% improvement in function scores using the popular WOMAC questionnaire at 3 months follow up.(5) Two other studies evaluating more long term outcomes of 6-12 months also found benefits for intra-articular prolotherapy in reducing pain and improving disability scores.(6)(7)

But how did prolotherapy compare to placebo? In a study comparing 3-5 intra-articular prolotherapy injections using 12.5% dextrose with placebo injections, prolotherapy resulted in clinically meaningful sustained improvement of pain, function, and stiffness scores for knee osteoarthritis compared with blinded saline injections at 1 year follow up.(8)

In elderly women, average age 71 years old with severe knee osteoarthritis, a series of 4-6 monthly intra-articular injections of 12.5% dextrose showed that in 35% of biopsies there was cartilage growth compared to pre-treatment and an increase in disability scores by about 13 points. (0-100) (9)

Ozone Injections

Intra-articular ozone injections for knee osteoarthritis have been shown to have short term benefits of about 3 months in pain and function in the research literature(5). The only long term study evaluating ozone for knee osteoarthritis showed that four ozone injections using 30 gamma all performed in the same week were clinically effective at 1 month follow-up, but started to lose their effectiveness after about 3 months and by 6 months the clinical effect of ozone had disappeared.(10) It is unclear if further treatments would have provided a more long term benefit, but ozone should be done monthly for the most effective outcomes, otherwise the effectiveness may start to disappear.

Hylauronic Acid

We recommend against the use of hylauronic acid because it has been shown in a 2012 systematic review to be associated with a small and clinically irrelevant benefit and an increased risk for serious adverse events.(11)

Platelet Rich Plasma

PRP has been studied quite a bit in the treatment of knee osteoarthritis. A recent 2016 Cochrane Review (considered the highest level of evidence) found that PRP resulted in significant clinical improvements up to 12 months post injection for both pain and function in knee osteoarthritis compared to hylauronic acid.(12) A separate recent 2016 systematic review compared PRP to hylauronic acid for a period of 12 months post injection and also concluded that PRP was more effective for reducing knee disability scores, and the difference between the two treatments were statistically significant.(13) Finally, a recent 2016 study comparing PRP to ozone and hylauronic acid found that at the end of the 12th months, PRP was determined to be both statistically and clinically superior to the other two therapies.(10) PRP has the benefit of only requiring 1-2 treatments and having the effects last long term, unlike most other treatments.

PRP has also been shown to be more effective than placebo for knee osteoarthritis, which is always the most widely asked question. In an FDA-sanctioned high quality double blind placebo controlled trial, PRP was compared to saline injections. Patients received 3 weekly injections and were followed up for 1 year. Patients in the PRP group had improved their disability scores by 78% compared to pre-treatment levels at 3 months follow-up and maintained this improvement for 1 year. The placebo group had showed a 32% improvement at 2 months, which fell to 7% at 1 year.(14). PRP provided safe and quantifiable benefits for pain relief and functional improvement with regard to knee osteoarthritis that were sustainable. No adverse events were reported for PRP administration.

Does PRP regenerate cartilage as well?
According to an April 2016 study(15)

PRP modulates the repair and regeneration of damaged articular cartilage in the joints and delays the degeneration of cartilage by stimulation of mesenchymal stem cell migration, proliferation, and differentiation into articular chondrocytes. In addition to the symptomatic relief, PRP is a biological response modifier of inflammatory nuclear factor-κB signaling pathway and PRP reduces the pain by decreasing inflammation and angiogenesis of the synovial membrane where pain receptors are localized, and . PRP has the therapeutic potential not only to promote tissue regeneration, but also to contribute to articular cartilage lubrication by decreasing the friction coefficient and minimizing wear.

Because PRP has been shown to have long term effects lasting at least 12-24 months and has been shown to promote tissue regeneration and cartilage lubriaction, we recommend PRP for knee osteoarthritis if it fits the patient's budget, with prolotherapy being a backup option.


  1. Atlas of Osteoarthritis. Springer. 2015. p. 21. ISBN 9781910315163.
  2. Mayo Clinic. Osteoarthritis: Treatment and Drugs (Oct 2014). Accessed at
  3. Henriksen M. "Evaluation of the benefit of corticosteroid injection before exercise therapy in patients with osteoarthritis of the knee: a randomized clinical trial." in Jama Intern Med 175, Issue 6 (June 2015), pp 923-30. Accessed at
  4. Soriano-Maldonado A, "Intra-Articular Corticosteroids in Addition to Exercise for Reducing Pain Sensitivity in Knee Osteoarthritis: Exploratory Outcome from a Randomized Controlled Trial." in PLoS One 11, Issue 2 (Feb 2016), e0149168. Accessed at
  5. Hashemi M. "The Effects of Prolotherapy With Hypertonic Dextrose Versus Prolozone (Intraarticular Ozone) in Patients With Knee Osteoarthritis" in Anesth Pain Med 5, Issue 5, (Oct 2015), e27585. Accessed at
  6. Rabago D, "Hypertonic dextrose injection (prolotherapy) for knee osteoarthritis: Long term outcomes." in Complement Ther Med 23 Issue 3 (June 2015), pp 388-95. Accessed at
  7. Eslamian F, "Therapeutic effects of prolotherapy with intra-articular dextrose injection in patients with moderate knee osteoarthritis: a single-arm study with 6 months follow up." in Ther Adv Musculoskelet Dis 7 Issue 2 (April 2015) pp 35-44. Accessed at
  8. Rabago D. "Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial." in Ann Fam Med 11, Issue 3 (May 2013), pp 229-37. Accessed at
  9. Topol GA, "The Chondrogenic Effect of Intra-articular Hypertonic-dextrose (prolotherapy) in Severe Knee Osteoarthritis." in PM&R, 2016 Apr 4, pii: S1934-1482(16)30054-5. doi: 10.1016/j.pmrj.2016.03.008. Accessed at
  10. Duymus TM. "Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options." in Knee Surg Sports Traumatol Arthrosc (April 2016). Accessed at
  11. Anne WS, "Viscosupplementation for Osteoarthritis of the Knee: A Systematic Review and Meta-analysis" in Ann Intern Med 157, Issue 3 (August 2012) pp 180-191. Accessed at
  12. Meheux CJ, "Efficacy of Intra-articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Systematic Review." in Arthroscopy 32, Issue 3 (March 2016) pp 495-505. Accessed at
  13. Sadabad HN. "Efficacy of Platelet-Rich Plasma versus Hyaluronic Acid for treatment of Knee Osteoarthritis: A systematic review and meta-analysis" in Electron Physician 8, Issue 3 (March 2016) pp 2115-22. Accessed at
  14. Smith PA. "Intra-articular Autologous Conditioned Plasma Injections Provide Safe and Efficacious Treatment for Knee Osteoarthritis: An FDA-Sanctioned, Randomized, Double-blind, Placebo-controlled Clinical Trial" in Am J Sports Med 44, Issue 4 (April 2016) pp 884-91. Accessed at
  15. Sakata R. "Platelet-Rich Plasma Modulates Actions on Articular Cartilage Lubrication and Regeneration" in Tissue Eng Part B Rev, April 2016, ePub ahead of print. Accessed at