High molecular weight Intraarticular hyaluronic acid for the treatment of knee osteoarthritis: a network meta-analysis

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, non-significant 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.

Delay to TKA and Costs Associated with Knee Osteoarthritis Care Using Intra-Articular Hyaluronic Acid: Analysis of an Administrative Database

“…From a value-perspective, the potential cost savings seen when IA-HA is utilized should be taken into consideration along with the efficacy and safety evidence for this treatment. 11,12,22,23 The results of this study, coupled with the efficacy and safety data, suggest that IA-HA is a safe and effective treatment that may provide substantial TKA delay and cost benefits, particularly among those patients who may eventually progress to TKA. Conversely, the lack of use or availability of IA-HA may actually increase KOA-related costs of care in patients with KOA.…”

Cells and material-based strategies for regenerative endodontics

“…It has been well-recorded for some time that molecular weight and size of assembled hyaluronic acid-based gels impacts its biological response, although most applications employ higher molecular weight species [ [129] , [130] , [131] , [134] , [135] , [136] , [137] , [138] , [139] , [140] , [141] ]. In the dental niche, low (the result of enzymatic cleavage) and high molecular weight hyaluronic acid can differentially affect adjacent cells and tissue [ 142 ].…”

Intra-articular hyaluronic acid injections and oral collagen supplementation for knee OA: A case report of an elite female soccer player

“…The HA used for this treatment was a high molecular weight hyaluronic acid 30mg/2ml each. High molecular weight hyaluronic acids derived from biological fermentation were found to be superior in efficacy and safety if compared to low molecular weight hyaluronic acids (Altman et al, 2016;Hummer et al, 2020).…”