Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials

We conducted a systematic review and meta-analysis of randomized saline-controlled trials to determine the safety and efficacy of US-approved intra-articular hyaluronic acid (IAHA) injections for symptomatic knee osteoarthritis. A total of 29 studies representing 4,866 unique subjects (IAHA: 2,673, saline: 2,193) were included. IAHA injection resulted in very large treatment effects between 4 and 26 weeks for knee pain and function compared to pre-injection values, with standardized mean difference (SMD) values ranging from 1.07–1.37 (all P < 0.001). Compared to saline controls, SMDs with IAHA ranged from 0.38–0.43 for knee pain and 0.32–0.34 for knee function (all P < 0.001). There were no statistically significant differences between IAHA and saline controls for any safety outcome, including serious adverse events (SAEs) ( P = 0.12), treatment-related SAEs ( P = 1.0), study withdrawal ( P = 1.0), and AE-related study withdrawal ( P = 0.46). We conclude that intra-articular injection of US-approved HA products is safe and efficacious in patients with symptomatic knee osteoarthritis.

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Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis

Scientific Reports ◽

10.1038/srep25247 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 29

Author(s):

Regina WS Sit ◽

Vincent CH Chung ◽

Kenneth D. Reeves ◽

David Rabago ◽

Keith KW Chan ◽

...

Keyword(s):

Systematic Review ◽

Knee Osteoarthritis ◽

Primary Outcome ◽

Meta Analysis ◽

Knee Oa ◽

Composite Scale ◽

Symptomatic Knee Osteoarthritis ◽

Symptomatic Knee ◽

Pain Subscale ◽

Hypertonic Dextrose

Abstract Hypertonic dextrose injections (prolotherapy) is an emerging treatment for symptomatic knee osteoarthritis (OA) but its efficacy is uncertain. We conducted a systematic review with meta-analysis to synthesize clinical evidence on the effect of prolotherapy for knee OA. Fifteen electronic databases were searched from their inception to September 2015. The primary outcome of interest was score change on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Three randomized controlled trials (RCTs) of moderate risk of bias and one quasi–randomized trial were included, with data from a total of 258 patients. In the meta-analysis of two eligible studies, prolotherapy is superior to exercise alone by a standardized mean difference (SMD) of 0.81 (95% CI: 0.18 to 1.45, p = 0.012), 0.78 (95% CI: 0.25 to 1.30, p = 0.001) and 0.62 (95% CI: 0.04 to 1.20, p = 0.035) on the WOMAC composite scale; and WOMAC function and pain subscale scores respectively. Moderate heterogeneity exists in all cases. Overall, prolotherapy conferred a positive and significant beneficial effect in the treatment of knee OA. Adequately powered, longer-term trials with uniform end points are needed to better elucidate the efficacy of prolotherapy.

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Safety of Intra-Articular Hyaluronic Acid for Knee Osteoarthritis: Systematic Review and Meta-Analysis of Randomized Trials Involving More than 8,000 Patients

Cartilage ◽

10.1177/1947603519888783 ◽

2019 ◽

pp. 194760351988878

Author(s):

Larry E. Miller ◽

Samir Bhattacharyya ◽

William R. Parrish ◽

Michael Fredericson ◽

Brad Bisson ◽

...

Keyword(s):

Systematic Review ◽

Hyaluronic Acid ◽

Adverse Events ◽

Knee Osteoarthritis ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Controlled Trials ◽

Knee Oa ◽

Randomized Controlled ◽

Symptomatic Knee

Objective The objective of this systematic review and meta-analysis was to report the safety of intra-articular hyaluronic acid (IAHA) in patients with symptomatic knee osteoarthritis (OA). Methods We identified randomized controlled trials reporting the safety of IAHA versus IA saline in adults with symptomatic knee OA. Main safety outcomes were adverse events (AEs), local AEs, serious adverse events (SAEs), study withdrawals, and AE-related study withdrawals. Results A total of 35 randomized controlled trials with 38 group comparisons comprising 8,078 unique patients (IAHA: 4,295, IA saline: 3,783) were included in the meta-analysis. Comparing IAHA with IA saline over a median of 6 months follow-up, there were no differences in the risk of AEs (42.4% vs. 39.7%, risk ratio [RR] = 1.01, 95% CI = 0.96-1.07, P = 0.61), SAEs (1.8% vs. 1.2%, RR = 1.44, 95% CI = 0.91-2.26, P=0.12), study withdrawals (12.3% vs. 12.7%, RR = 0.99, 95% CI = 0.87-1.12, P = 0.83), or AE-related study withdrawals (2.7% vs. 2.1%, RR = 1.37, 95% CI = 0.97-1.93, P = 0.08). Local AEs, all of which were nonserious, were more common with IAHA vs. IA saline (14.5% vs. 11.7%, RR = 1.21, 95% CI = 1.07-1.36, P = 0.003) and typically resolved within days. Conclusion IAHA was shown to be safe for use in patients with symptomatic knee OA. Compared with IA saline, IAHA is associated with an increased risk of nonserious, transient local reactions. There was no evidence to suggest any additional safety risks of IAHA.

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The Prevalence of Symptomatic Knee Osteoarthritis in Relation to Age, Sex, Area, Region, and Body Mass Index in China: A Systematic Review and Meta-Analysis

Frontiers in Medicine ◽

10.3389/fmed.2020.00304 ◽

2020 ◽

Vol 7 ◽

Author(s):

Danhui Li ◽

Shengjie Li ◽

Qiang Chen ◽

Xuesheng Xie

Keyword(s):

Systematic Review ◽

Body Mass Index ◽

Knee Osteoarthritis ◽

Body Mass ◽

Meta Analysis ◽

Symptomatic Knee Osteoarthritis ◽

Symptomatic Knee

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Relative Efficacy of Intra-articular Injections in the Treatment of Knee Osteoarthritis: A Systematic Review and Network Meta-analysis

The American Journal of Sports Medicine ◽

10.1177/03635465211029659 ◽

2021 ◽

pp. 036354652110296

Author(s):

Harsh Singh ◽

Derrick M. Knapik ◽

Evan M. Polce ◽

Carlo K. Eikani ◽

Amanda H. Bjornstad ◽

...

Keyword(s):

Systematic Review ◽

Knee Osteoarthritis ◽

Systematic Reviews ◽

Meta Analysis ◽

Effect Sizes ◽

Controlled Trials ◽

Cochrane Central Register ◽

Knee Oa ◽

Symptomatic Knee

Background: In younger patients and those without severe degenerative changes, the efficacy of intra-articular (IA) injections as a nonoperative modality for treating symptomatic knee osteoarthritis (OA)–related pain while maintaining function has become a subject of increasing interest. Purpose: To assess and compare the efficacy of different IA injections used for the treatment of knee OA, including hyaluronic acid (HA), corticosteroids (CS), platelet-rich plasma (PRP), and plasma rich in growth factors (PRGF), with a minimum 6-month patient follow-up. Study Design: Meta-analysis of randomized controlled trials; Level of evidence, 1. Methods: A systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the following databases: PubMed/MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Google Scholar. Mean or mean change from baseline and standard deviation for outcome scores regarding pain and function were recorded at the 6-month follow-up and converted to either a 0 to 100 visual analog scale score for pain or a 0 to 100 Western Ontario and McMaster Universities Osteoarthritis Index score for function. A frequentist network meta-analysis model was developed to compare the effects of HA, CS, PRP, PRGF, and placebo on patient-reported outcomes. Results: All IA treatments except CS were found to result in a statistically significant improvement in outcomes when compared with placebo. PRP demonstrated a clinically meaningful difference in function-related improvement when compared with CS and placebo due to large effect sizes. Studies evaluating outcomes of PRGF reported significant improvement when compared with placebo due to large effect sizes, whereas a potential clinically significant difference was detected in the same comparison parameters in pain evaluation. With regard to improvements in pain, function, and both combined, PRP was found to possess the highest probability of efficacy, followed by PRGF, HA, CS, and placebo. Conclusion: PRP yielded improved outcomes when compared with PRGF, HA, CS, and placebo for the treatment of symptomatic knee OA at a minimum 6-month follow-up. Further investigations evaluating different IA and other nonoperative treatment options for patients with knee OA are warranted to better understand the true clinical efficacy and long-term outcomes of nonsurgical OA management.

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