Little or no pain or discomfort²

First symptoms may occur
when joint in use²

Frequent pain and stiffness when
walking, running, and bending²

Great pain, stiffness, and reduced
range of motion when walking²

Healthy

Stage 1

Stage 2

Stage 3

Stage 4

High molecular weight linear HA binds
to CD44 receptors PROMOTING activation of
ANTI-INFLAMMATORY cytokine production.^3,4

Low molecular weight linear HA binds
suboptimally to CD44 receptors PROMOTING
PRO-INFLAMMATORY cytokine production.^3,4

Legend

Not all HA injections are the same

All HA injections provide lubrication and shock
absorption, but only certain HAs may slow down OA
of the knee and preserve knee function.^7,10

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Hyaluronic Acid
(HA) Injection

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Hyaluronic Acid
(HA) Injection

Repeat injections with
high molecular weight HA
may help enhance the way
the synovial fluids' high
molecular weight HA moves
throughout the knee. This
can improve the joint's ability
to make its own HA.^7-9

HA injections can have two
important elements:

In clinical trials, HAs with high molecular
weight made a clinically significant
difference in pain relief when compared
to HAs with low molecular weight.^1,4,6

high molecular weight

LINEAR Structure

In a healthy knee, natural fluid has a linear
structure and high molecular weight. Linear
high molecular weight HA most closely
resembles the HA naturally found in the knee.⁴

Choosing the right HA
provides both

Joint lubrication
Increased shock absorption

physical benefits

cellular benefits

Reduces pain by coating nerve endings^1,6
Reduces inflammation^1,6
Protects cartilage, decreases wear and tear^1,6
Helps your body create more of your own naturally made HA³

Click here to
learn more about a
hyaluronic acid
(HA) injection

For healthcare
providers

For
patients

Stages of OA

Why Molecular
Weight Matters

Injections to
Treat OA

References

Click here to
learn more about a
hyaluronic acid
(HA) injection

For healthcare
providers

For
patients

References: 1. Altman 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. doi:10.1186/s12891-015-0775-z 2. Healthline. Stages of osteoarthritis of the knee. Updated March 12, 2021. Accessed September 16, 2022. https://www.healthline.com/health/osteoarthritis-stages-of-oa-of-the-knee 3. Yang C, Cao M, Liu H, et al. The high and low molecular weight forms of hyaluronan have distinct effects on CD44 clustering. J Biol Chem. 2012;287(51):43094-43107. 4. Nicholls M, et al. A comparison between rheological properties of intra-articular hyaluronic acid preparations and reported human synovial fluid.Adv Ther. 2018;35:523-530. 5. Silvers HJ. Viscosupplementation during rehabilitation. Sports Phys Ther. 2014;6(5):422-426 6. Altman R, Bedi A, Manjoo A, Niazi F, Shaw P, Mease P. Anti-inflammatory effects of intra-articular hyaluronic acid: a systematic review. Cartilage. 2019;10(1):43-52. doi:10.1177/1947603517749919 7. Smith MM, Ghosh P. The synthesis of hyaluronic acid by human synovial fibroblasts is influenced by the nature of the hyaluronate in the extracellular environment. Rheumatol Int. 1987;7(3):113-122. 8. Concoff 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 Dec 21;18(1):542. doi: 10.1186/s12891-017-1897-2 9. Lokhnauth J, Driscoll KE, Bendele A, Niazi F, Liang A, Larsen CC. Viscosupplementation may preserve tibial cartilage and collagen in osteoarthritis: findings from a preclinical model of osteoarthritis. J Exp Orthop. 2020 May 31;7(1):39. doi: 10.1186/s40634-020-00256-4 10. Band PA, Heeter J, Wisniewski HG, et al. Hyaluronan molecular weight distribution is associated with the risk of knee osteoarthritis progression. Osteoarthritis Cartilage. 2015 January; 23(1):70-76.