Do Hyaluronic Acid Injections Work for Knee Osteoarthritis?

The results of hyaluronic acid injections for knee osteoarthritis vary with each patient. Some people experience complete relief from knee osteoarthritis symptoms, while others receive partial relief or no relief.¹Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl):S28-33.^,2Rutjes AW, Jüni P, Da costa BR, Trelle S, Nüesch E, Reichenbach S. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med. 2012;157(3):180-91.

Research Regarding Hyaluronic Acid Injections for Knee Osteoarthritis

Several clinical studies have investigated the effectiveness of hyaluronic acid injections in treating knee osteoarthritis.

A few findings from these studies include:

• Pain relief is not immediate, and usually begins around the fourth week after the initial injection.³Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015;16:321. Published 2015 Oct 26. doi:10.1186/s12891-015-0775-z^,4Cooper C, Rannou F, Richette P, et al. Use of Intraarticular Hyaluronic Acid in the Management of Knee Osteoarthritis in Clinical Practice. Arthritis Care Res (Hoboken). 2017;69(9):1287-1296.^,5Trojian TH, Concoff AL, Joy SM, Hatzenbuehler JR, Saulsberry WJ, Coleman CI. AMSSM Scientific Statement Concerning Viscosupplementation Injections for Knee Osteoarthritis. Clinical Journal of Sport Medicine. 2016;26(1):1-11. doi:10.1097/jsm.0000000000000274
• Duration of relief periods may vary from 2 months up to 6 months.¹Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl):S28-33.^,3Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015;16:321. Published 2015 Oct 26. doi:10.1186/s12891-015-0775-z^,4Cooper C, Rannou F, Richette P, et al. Use of Intraarticular Hyaluronic Acid in the Management of Knee Osteoarthritis in Clinical Practice. Arthritis Care Res (Hoboken). 2017;69(9):1287-1296.^,5Trojian TH, Concoff AL, Joy SM, Hatzenbuehler JR, Saulsberry WJ, Coleman CI. AMSSM Scientific Statement Concerning Viscosupplementation Injections for Knee Osteoarthritis. Clinical Journal of Sport Medicine. 2016;26(1):1-11. doi:10.1097/jsm.0000000000000274^,6Chen YP, Wang SM, Wu Y, et al. Worsen depression after viscosupplementation treatment for geriatric people with knee osteoarthritis?. Int J Clin Health Psychol. 2018;19(1):31-40. The most effective period is usually between weeks 5 and 13.¹Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl):S28-33.^,7Hunter DJ. Viscosupplementation for Osteoarthritis of the Knee. Jarcho JA, ed. New England Journal of Medicine. 2015;372(11):1040-1047. doi:10.1056/nejmct1215534
• Multiple injections regimes may be more effective than a single injection in some people.⁸Altman R, Hackel J, Niazi F, Shaw P, Nicholls M. Efficacy and safety of repeated courses of hyaluronic acid injections for knee osteoarthritis: A systematic review. Seminars in Arthritis and Rheumatism. 2018;48(2):168-175. doi:10.1016/j.semarthrit.2018.01.009^,9Concoff A, Sancheti P, Niazi F, Shaw P, Rosen J. The efficacy of multiple versus single hyaluronic acid injections: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2017;18(1):542. Published 2017 Dec 21. doi:10.1186/s12891-017-1897-2
• Additional injections may provide longer relief up to 3 years in some patients who show initial improvement with this treatment. This long period of pain relief may help postpone total knee replacement surgery in some cases.¹Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl):S28-33.

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Not all studies conducted to test the effectiveness of hyaluronic acid injections in treating knee osteoarthritis have reported positive results. For this reason, some doctors may not recommend this treatment.²Rutjes AW, Jüni P, Da costa BR, Trelle S, Nüesch E, Reichenbach S. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med. 2012;157(3):180-91. Research also shows that these injections may not work in overweight people due to the narrowing of joint space in the knee.¹⁰Eymard F, Conrozier T, Chevalier X OP0135 Predictive Factors of Failure of Viscosupplementation in Patients with Knee Osteoarthritis. Results of A Post-Hoc Analysis of A Double Blind, Controlled Non Inferiority Trial Annals of the Rheumatic Diseases 2016;75:107.

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How Hyaluronic Acid Injections Work in the Osteoarthritic Knee

Research suggests that hyaluronic acid injections may work in several ways to reduce knee osteoarthritis symptoms.¹Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl):S28-33.^,3Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015;16:321. Published 2015 Oct 26. doi:10.1186/s12891-015-0775-z For example, hyaluronic acid injections may reduce inflammation and friction; and the slow the degeneration of cartilage and bone.

Effects on knee pain and inflammation
Hyaluronic acid injections may reduce knee osteoarthritic symptoms by one or more of its following properties:

• Lubrication. In some people, the viscosity of hyaluronic acid may provide better lubrication and shock absorption in the knee joint. These effects may reduce friction within the joint, thereby reducing pain and stiffness, and preventing the loss of cartilage and bone.¹Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl):S28-33.^,3Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015;16:321. Published 2015 Oct 26. doi:10.1186/s12891-015-0775-z
• Anti-inflammatory effects. Research shows hyaluronic acid injections may provide anti-inflammatory effects such as reduced pain, inflammation, and/or swelling in the knee.¹Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl):S28-33.^,3Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015;16:321. Published 2015 Oct 26. doi:10.1186/s12891-015-0775-z
• Pain-relieving effects. In some people, hyaluronic acid molecules form a boundary around nerve endings, preventing pain signals from being sent to the brain. These molecules also bind to other cells in the knee that signal pain. Through these mechanisms, knee pain may be decreased.¹Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl):S28-33.^,3Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015;16:321. Published 2015 Oct 26. doi:10.1186/s12891-015-0775-z

The viscosity of hyaluronic acid may also have positive effects on the cartilage, bone, and other surrounding tissues in the knee.

Effects on knee cartilage and bone
In general, hyaluronic acid that is injected in the knee stays in the joint for only a few days. However, the results may last for months. Proponents believe this extended pain relief suggests hyaluronic acid injections may actually modify the osteoarthritic disease process—and not just suppress the symptoms.¹Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl):S28-33.^,3Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015;16:321. Published 2015 Oct 26. doi:10.1186/s12891-015-0775-z

Specifically, in some people, hyaluronic acid knee injections may act by:

• Aiding the growth and protection of cartilage by stimulating an increase in the growth of cartilage-producing cells, called chondrocytes. These injections also protect existing chondrocytes, thereby increasing the overall cartilage formation.¹Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl):S28-33.^,3Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015;16:321. Published 2015 Oct 26. doi:10.1186/s12891-015-0775-z
• Strengthening existing cartilage by producing important proteins (proteoglycans) and carbohydrates (glycosaminoglycans).³Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015;16:321. Published 2015 Oct 26. doi:10.1186/s12891-015-0775-z
• Strengthening existing bone by altering the density and thickness of the knee’s subchondral bone (bone that lies immediately below the cartilage). The changes in bone structure may help reduce stresses on the cartilage when the knee bears weight.³Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015;16:321. Published 2015 Oct 26. doi:10.1186/s12891-015-0775-z
• Stimulating the body to produce its own hyaluronic acid, in turn restoring the quantity of hyaluronic acid in the knee and providing long-term effects.¹Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl):S28-33.^,3Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015;16:321. Published 2015 Oct 26. doi:10.1186/s12891-015-0775-z

These effects may help prevent the progression of osteoarthritis.

Hyaluronic Acid Injections: Approved Use and Brand Names

The US Food and Drug Administration (FDA) has approved the use of hyaluronic acid injections for knee osteoarthritis. The FDA also states that this injection must be used after other treatments such as physical therapy and the use of pain-relieving medications have been tried and failed.⁷Hunter DJ. Viscosupplementation for Osteoarthritis of the Knee. Jarcho JA, ed. New England Journal of Medicine. 2015;372(11):1040-1047. doi:10.1056/nejmct1215534 Off-label use of hyaluronic acid injections may be considered by some doctors in treating osteoarthritis of the ankle, shoulder, and thumb joints.

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Depending on the pharmaceutical brand, there can be one (Synvisc One), three (Euflexxa, Synvisc), four (Orthovisc), or five (Hyalgan) injections of hyaluronic acid for knee osteoarthritis. For brands using more than one injection, each shot is given once a week (for 3 to 5 weeks).⁷Hunter DJ. Viscosupplementation for Osteoarthritis of the Knee. Jarcho JA, ed. New England Journal of Medicine. 2015;372(11):1040-1047. doi:10.1056/nejmct1215534 Generic formulations are also available.