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Am J Sports Med. 2016 Aug;44(8):2158-65. doi: 10.1177/0363546515609599. Epub 2015 Nov 17.

Product Differences in Intra-articular Hyaluronic Acids for Osteoarthritis of the Knee.

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Division of Rheumatology and Immunology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA
Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Department of Orthopedics, Sahlgrenska Academy, Sahlgrenska University Hospital, Gothenburg, Sweden.
Sancheti Institute for Orthopaedics and Rehabilitation, Pune, Maharashtra, India.
Department of Orthopaedic Surgery, University of Toronto, Toronto, Ontario, Canada.



Knee osteoarthritis (OA) is a common and often disabling joint disorder among adults that may result in impaired activity and daily function. A variety of treatment options are currently available and prescribed for knee OA depending on the severity of the disorder and physician preference. Intra-articular hyaluronic acid (IA-HA) injection is a treatment for knee OA that reportedly provides numerous biochemical and biological benefits, including shock absorption, chondroprotection, and anti-inflammatory effects within the knee. Clarity is needed as to whether the available IA-HA products should be considered for therapy as a group or whether there are significant differences in the products that need to be considered in treatment of OA of the knee.


To determine whether there are differences in efficacy and safety with respect to intrinsic properties of available IA-HA injections for knee OA.




A comprehensive literature search of the Medline, EMBASE, and PubMed databases was conducted for all existing randomized trials of IA-HA. The primary outcome measure analyzed was the mean pain score at the reported follow-up nearest to 26 weeks after injection. Pooled efficacy and safety results were recorded for subgroupings of HA product characteristics.


A total of 68 studies were included for analysis. Products with an average molecular weight ≥3000 kDa provided favorable efficacy results when compared with products of an average molecular weight <3000 kDa. Products with a molecular weight ≥3000 kDa demonstrated significantly fewer discontinuations due to treatment-related adverse events than did ≤1500 kDa counterparts, while trial discontinuation rates were similar between biological fermentation-derived HA products and avian-derived HA. The results did not demonstrate a significant difference in the occurrence of effusion across molecular weight subgroups. Additionally, biological fermentation-derived HA had a significantly smaller incidence of effusion than did avian-derived HA. Biological fermentation-derived HA demonstrated fewer acute flare-ups at the injection site than did avian-derived HA products, while high-molecular-weight products demonstrated the highest rate of injection site flare-up.


Despite similarities, IA-HA products should not be treated as a group, as there are differences in IA-HA products that influence both efficacy and safety. In the available literature, IA-HA products with a molecular weight ≥3000 kDa and those derived from biological fermentation relate to superior efficacy and safety-factors that may influence selection an IA-HA product for OA of the knee.


hyaluronic acid; knee; osteoarthritis; viscosupplementation

[Indexed for MEDLINE]

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