Hyaluronic Acid in the Treatment of Knee Osteoarthritis

Colen, Sascha; Bekerom, Michel P.J. van den; Mulier, Michiel; Haverkamp, Daniël

doi:10.1007/bf03261884

Cited by 120 publications

(49 citation statements)

References 76 publications

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“…Three RCTs [22, 29, 34] and 13 observational studies (reported in 16 articles [35–50]) reported on TKR, but evidence on delay or avoidance of TKR was insufficient to draw conclusions. Two large, good quality systematic reviews with meta-analyses for pain outcomes showed a significant and clinically important effect among adults of all ages [8, 51]. …”

Section: Resultsmentioning

confidence: 99%

Hyaluronic acid injection therapy for osteoarthritis of the knee: concordant efficacy and conflicting serious adverse events in two systematic reviews

et al. 2016

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BackgroundThe prevalence of knee osteoarthritis (OA)/degenerative joint disease (DJD) is increasing in the USA. Systematic reviews of treatment efficacy and adverse events (AEs) of hyaluronic acid (HA) injections report conflicting evidence about the balance of benefits and harms. We review evidence on efficacy and AEs of intraarticular viscosupplementation with HA in older individuals with knee osteoarthritis and account for differences in these conclusions from another systematic review.MethodsWe searched PubMed and eight other databases and gray literature sources from 1990 to December 12, 2014. Double-blind placebo-controlled randomized controlled trials (RCTs) reporting functional outcomes or quality-of-life; RCTs and observational studies on delay/avoidance of arthroplasty; RCTs, case reports, and large cohort studies and case series assessing safety; and systematic reviews reporting on knee pain were considered for inclusion.A standardized, pre-defined protocol was applied by two independent reviewers to screen titles and abstracts, review full text, and extract details on study design, interventions, outcomes, and quality. We compared our results with those of a prior systematic review and found them to be discrepant; our analysis of why this discrepancy occurred is the focus of this manuscript.ResultsEighteen RCTs reported functional outcomes: pooled analysis of ten placebo-controlled, blinded trials showed a standardized mean difference of −0.23 (95 % confidence interval (CI) −0.45 to −0.01) favoring HA at 6 months. Studies reported few serious adverse events (SAEs) and no significant differences in non-serious adverse events (NSAEs) (relative risk (RR) [95 % CI] 1.03 [0.93–1.15] or SAEs (RR [95 % CI] 1.39 [0.78–2.47]). A recent prior systematic review reported similar functional outcomes, but significant SAE risk. Differences in SAE inclusion and synthesis accounted for the disparate conclusions.ConclusionsTrials show a small but significant effect of HA on function on which recent systematic reviews agree, but lack of AE synthesis standardization leads to opposite conclusions about the balance of benefits and harms. A limitation of the re-analysis of the prior systematic review is that it required imputation of missing data.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0363-9) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Hyaluronic acid injection therapy for osteoarthritis of the knee: concordant efficacy and conflicting serious adverse events in two systematic reviews

et al. 2016

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“…In a previous study involving 57 patients following knee arthroscopy, the same group demonstrated equal efficacy in pain relief whether saline alone or saline with 2mg morphine were IA injected into the knee [7]. In a systematic review and meta-analysis of 74 randomized clinical trials for the treatment of OAK with hyaluronic acid, it was concluded that saline has a “large placebo effect” of approximately 30% pain reduction [8]. Other meta-analyses of randomized controlled trials have demonstrated that the administration of IA saline significantly improves short-term (≤ 3 months) and long-term (6-12 months) knee pain, improves function, and decreases stiffness [9, 10].…”

Section: Analgesic Effects Of Salinementioning

confidence: 99%

Use of Saline as a Placebo in Intra-articular Injections in Osteoarthritis: Potential Contributions to Nociceptive Pain Relief

Bar‐Or¹,

Rael²,

Brody³

2017

TORJ

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Background:Osteoarthritis of the knee (OAK) is a severe debilitating condition characterized by joint pain, stiffness, and resultant limited mobility. In recent years, intra-articular (IA) injections have been used to relieve symptoms and have succeeded to varying degrees either with sodium hyaluronate preparations or with a biologic.Objective:The objective of this review is to evaluate multiple studies that demonstrate some relief from the symptoms of OAK in the saline arm of various clinical trials.Method:A thorough literature search (PubMed) was performed assessing the pain efficacy of various compounds compared to saline injections in clinical trials. A total of 73 studies were identified in the literature search including a total of 5,816 patients. These clinical trials all involved the IA injection of a viscosupplement (hyaluronate, platelet rich plasma (PRP), etc.) or a biologic (the low molecular weight fraction (< 5kDa) of human serum albumin (LMWF-5A)). For all of these studies, the control arm was injection of sterile physiological saline that approximates the salt concentration and total solute concentration of blood and most tissues.Results:Based on our review of the current literature, the tested compounds performed with mixed results when compared to saline injections. Moreover, OAK is a variable disease, with severity measured on the Kellgren and Lawrence (KL) scale where various hyaluronate preparations have a therapeutic effect mostly on KL 2-3 patients while a biologic works best on KL 3-4 patients.Conclusion:Since the effect of saline injection is always greater than no treatment, the evaluations of these treatments can be confounded in clinical trials. Therefore, the question of whether there are known therapeutic effects of saline injections might explain these results.

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“…HA is a hydrophilic dipolysaccharide with a very high molecular weight (200kDa~325kDa in this study). HA has been used for a wide variety of medical applications including osteoarthritis [15], embryo implantation [16], and cutaneous wound healing [17, 18]. In dermatology and cosmetic practice, HA has been employed to help the skin to regain elasticity, turgor and moisture [19].…”

Section: Introductionmentioning

confidence: 99%

Topical delivery of hyaluronic acid into skin using SPACE-peptide carriers

Chen

Gupta

Anselmo

et al. 2014

Journal of Controlled Release

102

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Topical penetration of macromolecules into skin is limited by their low permeability. Here, we report the use of a skin penetrating peptide, SPACE peptide, to enhance topical delivery of a macromolecule, hyaluronic acid (HA, MW: 200–325 kDa). The peptide was conjugated to phospholipids and used to prepare an ethosomal carrier system (~110 nm diameter), encapsulating HA. The SPACE-ethosomal system (SES) enhanced HA penetration into porcine skin in vitro by 7.8+/−1.1-fold compared to PBS. The system also enhanced penetration of HA in human skin in vitro, penetrating deep into the epidermis and dermis in skin of both species. In vivo experiments performed using SKH1 hairless mice also confirmed increased dermal penetration of HA using the delivery system; a 5-fold enhancement in penetration was found compared to PBS control. Concentrations of HA in skin were about 1000-fold higher than those in blood; confirming the localized nature of HA delivery into skin. The SPACE-ethosomal delivery system provides a formulation for topical delivery of macromolecules that are otherwise difficult to deliver into skin.

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Hyaluronic Acid in the Treatment of Knee Osteoarthritis

Cited by 120 publications

References 76 publications

Hyaluronic acid injection therapy for osteoarthritis of the knee: concordant efficacy and conflicting serious adverse events in two systematic reviews

Hyaluronic acid injection therapy for osteoarthritis of the knee: concordant efficacy and conflicting serious adverse events in two systematic reviews

Use of Saline as a Placebo in Intra-articular Injections in Osteoarthritis: Potential Contributions to Nociceptive Pain Relief

Topical delivery of hyaluronic acid into skin using SPACE-peptide carriers

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