High molecular weight Intraarticular hyaluronic acid for the treatment of knee osteoarthritis: a network meta-analysis
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(2020) 21:702
RESEARCH ARTICLE
Open Access
High molecular weight Intraarticular hyaluronic acid for the treatment of knee osteoarthritis: a network meta-analysis Charles D. Hummer1*, Felix Angst2, Wilson Ngai3, Craig Whittington3,4, Sophie S. Yoon4, Lionel Duarte4, Colleen Manitt5 and Emil Schemitsch6
Abstract Background: The 2013 American Academy of Orthopaedic Surgeons (AAOS) guidelines made strong recommendations against intraarticular hyaluronic acid (IAHA) for patients with knee osteoarthritis (OA), as evidence supporting improvements in pain did not meet the minimal clinically important improvement (MCII) threshold. However, there may be important distinctions based on IAHA molecular weight (MW). Hence our objective was to evaluate the efficacy of IAHAs in knee OA based on molecular weight. Methods: Randomized controlled trials were searched within MEDLINE, Embase, and CENTRAL and selected based on AAOS criteria. A pain measure hierarchy and longest follow-up were used to select one effect size from each trial. Mean differences between interventions were converted to standardized mean differences (SMDs) and incorporated into a random-effects Bayesian network meta-analysis. High MW (HMW) was defined as ≥6000 kDa, and low MW (LMW) as < 750 kDa. Results: HMW IAHA was associated with a statistically significant and possibly clinically significant improvement in pain (SMD − 0.57 (95% credible interval [Crl]: − 1.04, − 0.11), exceeding the − 0.50 MCII threshold. LMW IAHA had a lesser, nonsignificant improvement (− 0.23, 95% Crl: − 0.67, 0.20). Back-transforming SMDs to the WOMAC pain scale indicated a 14.65 (95% CI: 13.93, 15.62) point improvement over IA placebo, substantially better than the 8.3 AAOS MCII threshold. Conclusions: Unlike LMW IAHA, HMW IAHA exceeded the MCII threshold for pain relief, suggesting that improvements can be subjectively perceived by the treated patient. Amalgamation of LMW and HMW may have blurred the benefits of IAHA in the past, leading to negative recommendations. Differentiation according to MW offers refined insight for treatment with IAHA. Keywords: Hyaluronic acid, Knee osteoarthritis, Molecular weight, Meta-analysis
Background A common approach for managing osteoarthritis (OA) is by attenuating inflammation and pain in affected joints [1]. Some theorized mechanisms for the therapeutic effect of viscosupplementation through intraarticular hyaluronic * Correspondence: [email protected] 1 Premier Orthopaedics and Sports Medicine, 300 Evergreen Drive, Suite 200, Glen Mills, PA 19342, USA Full list of author information is available at the end of the article
acids (IAHAs) include possible anti-inflammatory properties and chondroprotection by mitigating proteoglycan loss in cartilage and apoptosis of chondrocytes [2, 3]. IAHA treatment has also been shown to stimulate endogenous production of additional HA by human synoviocytes suggesting IAHA may restore viscoelastic properties to the synovial fluid in patients with OA [2]. IAHAs possess a wide range of possible molecul
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