Evidence map›Paper›PMID 26503103›Full record

SynthesisBMC musculoskeletal disorders2015

The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review.

R D Altman, A Manjoo, A Fierlinger, F Niazi, M Nicholls

2 registry-linked trialsOpen access · goldAbstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMC musculoskeletal disorders, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 222 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
222citing papers in PubMed, 12 pooled it
20.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03421054 nacompletednot on this mapstarted 2018, after this paper: background citation

Pilot, Open Non-controled Trial to Assess the Feasibility of Implementing Objective Parameters as Primary Endpoints in a Clinical Trial With Patients Affected by Knee Osteoarthritis

TypeinterventionalSponsorRiver Pharma S.r.l.Ran2018 to 2018Enrolled8ConditionsKnee OsteoarthritisArmspatients assuming nutraceutical containing HA
NCT03612986 nacompletednot on this mapstarted 2018, after this paper: background citation

Double Blind, Placebo Controlled Trial to Evaluate the Effects of a Nutraceutical Containing High-Molecular-Weight Hyaluronic Acid (HA) and Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) in Patients Affected by Knee Osteoarthritis

TypeinterventionalSponsorRiver Pharma S.r.l.Ran2018 to 2019Enrolled72ConditionsKnee OsteoarthritisArmsSYALOX® 300 Plus, Placebo
3 · Its place in the literature

Who cites it

222 citing papers in PubMed, 12 syntheses or guidelines pooled it, 472 citations in OpenAlex.

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  4. Intra-articular hyaluronic acid injections for hip osteoarthritis: a level I systematic review.European journal of orthopaedic surgery & traumatology : orthopedie traumatologie · 2025
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  8. Intra-articular injections of ozone versus hyaluronic acid for knee osteoarthritis: a level I meta-analysis.European journal of orthopaedic surgery & traumatology : orthopedie traumatologie · 2024
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162 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

R D AltmanDivision of Rheumatology and Immunology, David Geffen School of Medicine, University of California at Los Angeles, 1000 Veterans Ave, 90024, Los Angeles, CA, USA. journals@royaltman.com.
A ManjooDivision of Orthopaedics, McMaster University, Hamilton, ON, Canada. amanjoo@gmail.com.
A FierlingerFerring Pharmaceuticals Inc., Parsippany, NJ, USA. anke.fierlinger@ferring.com.
F NiaziFerring Pharmaceuticals Inc., Parsippany, NJ, USA. faizan.niazi@ferring.com.
M NichollsKentucky Orthopaedic and Hand Surgeons, A division of Ortho Kentucky, Lexington, KY, USA. matn@mindspring.com.
Ferring Pharmaceuticals (United States) · USMcMaster University · CAUniversity of California, Los Angeles · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundKnee osteoarthritis (OA) is one of the leading causes of disability within the adult population. Current treatment options for OA of the knee include intra-articular (IA) hyaluronic acid (HA), a molecule found intrinsically within the knee joint that provides viscoelastic properties to the synovial fluid. A variety of mechanisms in which HA is thought to combat knee OA are reported in the current basic literature.

methodsWe conducted a comprehensive literature search to identify currently available primary non-clinical basic science articles focussing on the mechanism of action of IA-HA treatment. Included articles were assessed and categorized based on the mechanism of action described within them. The key findings and conclusions from each included article were obtained and analyzed in aggregate with studies of the same categorical assignment.

resultsChondroprotection was the most frequent mechanism reported within the included articles, followed by proteoglycan and glycosaminoglycan synthesis, anti-inflammatory, mechanical, subchondral, and analgesic actions. HA-cluster of differentiation 44 (CD44) receptor binding was the most frequently reported biological cause of the mechanisms presented. High molecular weight HA was seen to be superior to lower molecular weight HA products. HA derived through a biological fermentation process is also described as having favorable safety outcomes over avian-derived HA products.

conclusionsThe non-clinical basic science literature provides evidence for numerous mechanisms in which HA acts on joint structures and function. These actions provide support for the purported clinical benefit of IA-HA in OA of the knee. Future research should not only focus on the pain relief provided by IA-HA treatment, but the disease modification properties that this treatment modality possesses as well.

Indexed as

AnalgesicsAnti-Inflammatory AgentsBone and BonesChondrocytesGlycosaminoglycansHumansHyaluronic AcidOsteoarthritis, KneeProteoglycansViscosupplementsAnalgesicsAnti-Inflammatory AgentsGlycosaminoglycansHyaluronic AcidProteoglycansViscosupplements

Identifiers

PMID26503103
PMCPMC4621876
OpenAlexW1831989259

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.