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.

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

Osteoarthritis and Cartilage ◽

10.1016/j.joca.2019.02.568 ◽

2019 ◽

Vol 27 ◽

pp. S503-S504

Author(s):

C. Hummer ◽

F. Angst ◽

E. Schemitsch ◽

C. Whittington ◽

C. Manitt ◽

...

Keyword(s):

Molecular Weight ◽

Hyaluronic Acid ◽

Knee Osteoarthritis ◽

High Molecular Weight ◽

Meta Analysis

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The synovial fluid neuropeptide PACAP may act as a protective factor during disease progression of primary knee osteoarthritis and is increased following hyaluronic acid injection

Innate Immunity ◽

10.1177/1753425919839125 ◽

2019 ◽

Vol 25 (4) ◽

pp. 255-264 ◽

Cited By ~ 5

Author(s):

Zheng-Ping Sun ◽

Shao-Peng Wu ◽

Can-De Liang ◽

Chuan-Xi Zhao ◽

Bing-Yin Sun

Keyword(s):

Hyaluronic Acid ◽

Synovial Fluid ◽

Knee Osteoarthritis ◽

Disease Progression ◽

Protective Factor ◽

Oxford Knee Score ◽

Diagnostic Value ◽

Pain Scale ◽

Roc Curve Analysis ◽

Knee Oa

The correlation of serum and synovial fluid (SF) pituitary adenylate cyclase-activating polypeptide (PACAP) levels with disease progression of primary knee osteoarthritis (OA) was explored. Radiographic severity of OA was determined by Kellgren–Lawrence (K-L) grades. PACAP levels were measured by ELISA before treatment, and 4 and 8 wk following hyaluronic acid (HA) injection. Levels of IL-1β and MMP-3 were also detected. The numeric pain scale (NPS), revised Oxford Knee Score (OKS), and American Knee Society Score (AKSS) were employed to evaluate to symptomatic severity. Receiver-operating-characteristic (ROC) curve analysis was carried out to compare the diagnostic value of PACAP, IL-1β, and MMP-3 for the K-L grade. PACAP concentrations in SF but not serum were significantly lower in OA patients compared with controls. SF PACAP levels were negatively associated with K-L grades and higher NPS as well as worse AKSS and OKS. Further analysis demonstrated that PACAP concentration in SF was negatively correlated with expressions of IL-1β as well as MMP-3 and may act as a marker for radiographic progression along with MMP-3. Last, we found SF PACAP levels exhibited an incremental trend after HA injection. These findings confirmed the crucial role of PACAP deficiency in the development of primary knee OA.

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Platelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis: a meta-analysis

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-020-01919-9 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Jia Zhu Tang ◽

Ming Jun Nie ◽

Jian Zhong Zhao ◽

Guang Cheng Zhang ◽

Qing Zhang ◽

...

Keyword(s):

Hyaluronic Acid ◽

Adverse Events ◽

Knee Osteoarthritis ◽

Platelet Rich Plasma ◽

Meta Analysis ◽

Womac Pain ◽

Significant Difference ◽

Vas Scores ◽

Eq Vas

Abstract Background This study aimed to evaluate the clinical efficacy of platelet-rich plasma (PRP) injection compared with hyaluronic acid (HA) injection for patients undergoing knee osteoarthritis. Methods We systematically searched electronic databases including PubMed, Embase, Web of Science, and the Cochrane Library on January 23, 2020 to identify relevant studies issued in English languages. The outcomes evaluating the efficacy of knee osteoarthritis (KOA) treatment were Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores (WOMAC pain, function, stiffness, and total scores) at 1, 3, 6, and 12 months; International Knee Documentation Committee (IKDC) scores, Lequesne Index score, Visual Analog Scale (VAS) scores, EQ-VAS scores, and KOOS scores. The pooled data were analyzed by Stata 12.0. Results A total of 20 RCTs were enrolled in the present meta-analysis. The pooled results demonstrated that platelet-rich plasma (PRP) injection reduced pain more effectively than hyaluronic acid (HA) injection at 6-month and 12-month follow-up evaluated by WOMAC pain scores and VAS scores. EQ-VAS in the patients treated with PRP injection was lower than that in patients with HA injection at 12 months. Moreover, the patients with PRP injection had a better function recovery than those with HA injection at 1-month, 3-month, 6-month, and 12-month follow-up, as evaluated by WOMAC function scores. WOMAC total scores showed significant difference at 6-month and 12-month follow-up. The IKDC scores indicated PRP injection was significantly more effective than HA injection at 3 months and 6 months. However, the Lequesne Index scores, KOOS scores, and adverse events did not show any significant difference between groups. Conclusion Intra-articular PRP injection appeared to be more efficacious than HA injection for the treatment of KOA in terms of short-term functional recovery. Moreover, PRP injection was superior to HA injection in terms of long-term pain relief and function improvement. In addition, PRP injection did not increase the risk of adverse events compared to HA injection.

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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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How to Choose Platelet-Rich Plasma or Hyaluronic Acid for the Treatment of Knee Osteoarthritis in Overweight or Obese Patients: A Meta-Analysis

Pain Research and Management ◽

10.1155/2020/7587936 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Pan Luo ◽

Zhencheng Xiong ◽

Wei Sun ◽

Lijun Shi ◽

Fuqiang Gao ◽

...

Keyword(s):

Hyaluronic Acid ◽

Knee Osteoarthritis ◽

Platelet Rich Plasma ◽

Meta Analysis ◽

Cochrane Library ◽

Obese Patients ◽

Knee Oa ◽

Significant Difference ◽

Better Than

Objective. The purpose of this meta-analysis was to determine whether platelet-rich plasma (PRP) was better than hyaluronic acid (HA) for the treatment of knee osteoarthritis (OA) in overweight or obese patients. Design. Two reviewers independently used the keywords combined with free words to search English-based electronic databases according to Cochrane Collaboration guidelines, such as PubMed, Embase, ScienceDirect, and Cochrane library. The pooled data were analyzed using RevMan 5.3. Results. Ten randomized controlled trials (RCTs) with 1096 patients were included. During the first two months of follow-up, there was no significant difference between the two groups. At the 3rd, 6th, and 12th months of follow-up, the pooled analysis showed that PRP was better than HA for the treatment of knee OA in overweight or obese patients. There were significant differences between the two groups at Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score (3 months: MD = −1.35, [95% CI: −2.19 to −0.50], P=0.002, I2 = 0%; 6 months: MD = −7.62, [95% CI: −13.51 to −1.72], P=0.01, I2 = 88%; 12 months: MD = −12.11, [95% CI: −20.21 to −4.01], P=0.003, I2 = 94%). Conclusions. For overweight or obese patients with knee OA, intra-articular injection of PRP in a short time was not necessarily superior to HA, but long-term use was better than HA in pain and functional relief.

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Comparing Patient-Reported Outcomes From Sham and Saline-Based Placebo Injections for Knee Osteoarthritis: Data From a Randomized Clinical Trial of Lorecivivint

The American Journal of Sports Medicine ◽

10.1177/03635465211067201 ◽

2022 ◽

pp. 036354652110672

Author(s):

Jeyanesh R.S. Tambiah ◽

Ismail Simsek ◽

Christopher J. Swearingen ◽

Sarah Kennedy ◽

Brian J. Cole ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Patient Reported Outcomes ◽

Rating Scale ◽

Numeric Rating Scale ◽

Womac Pain ◽

Time Points ◽

Knee Oa ◽

Patient Reported ◽

Mean Differences ◽

Numeric Rating

Background: Durable, meaningful symptom responses to intra-articular saline placebo injections are observed in knee osteoarthritis (OA) trials, but it is unclear if these are due to physiological effects. Purpose: To perform a prospective comparison of patient-reported outcome responses among participants with knee OA who underwent intra-articular injection of saline-based placebo or sham (dry needle). Study Design: Randomized controlled trial; Level of evidence, 2. Methods: From a 24-week randomized double-blind trial, participants with moderate to severe knee OA received 2-mL intra-articular injections of saline-based placebo (PBO; 99.45% PBS) or sham (dry needle) to the target knee. Least squares mean differences of changes from baseline to week 24 were compared between the PBO and sham groups for the following: pain Numeric Rating Scale; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and function; and patient global assessment. Bang Blinding Index was used to evaluate all-group blinding on day 1 and week 24. Results: In total, 116 and 117 participants were randomized to the PBO and sham groups, respectively. Within the full trial population, the mean ± SD age and body mass index were 59.0 ± 8.5 years and 28.97 ± 4.01, respectively. An overall 406 (58.4%) were female, and 394 (57.3%) had Kellgren-Lawrence grade 3 target knee OA. The PBO and sham groups demonstrated clinically meaningful improvements (≥10%) from baseline in all patient-reported outcomes at all time points (ie, weeks 4-24). Mean differences (95% CI) at week 24 between the PBO and sham groups were as follows: pain Numeric Rating Scale, –0.10 (–0.79 to 0.59; P = .78); WOMAC pain, –2.89 (–9.70 to 3.92; P = .40); WOMAC stiffness, –2.37 (–9.37 to 4.63; P = .51); and WOMAC function, –1.39 (–8.06 to 5.29; P = .68). Bang Blinding Index indicated that blinding was maintained. Conclusion: PBO and sham groups demonstrated equivalent patient-reported outcomes at all time points through week 24, suggesting that responses attributed to saline were contextual (ie, to the procedure) and not physiological. Registration: NCT03122860 (ClinicalTrials.gov identifier).

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Efficacy of mesenchymal stromal cells for the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-020-02128-0 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Huazheng Qu ◽

Shui Sun

Keyword(s):

Knee Osteoarthritis ◽

Randomized Controlled Trials ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Meta Analysis ◽

Biomedical Literature ◽

Womac Pain ◽

Controlled Trials ◽

Knee Oa ◽

Randomized Controlled

Abstract Background Mesenchymal stromal cells (MSCs) are used as an emerging new option for the treatment of knee osteoarthritis (OA). However, their efficacy remains controversial across studies with different doses of MSCs and cell processing methods. We conducted this meta-analysis to assess the efficacy of MSCs in the treatment of knee OA. Methods Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, China), and CNKI (National Knowledge Infrastructure, China) databases were systematically reviewed. The pain level and function improvements were evaluated using visual analog scale (VAS), McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC). The pooled estimate was calculated with weighted mean difference (WMD) with 95% confidence intervals (95%CIs). Results Nine RCTs involving 476 patients were included in this meta-analysis. The pooled estimate showed that the treatment of MSCs significantly reduced VAS, WOMAC pain, WOMAC stiffness, and WOMAC function scores at a long-term follow-up (12 or 24 months). However, for the IKDC and WOMAC total scores, MSCs also showed significant improvement in these outcomes, although this was not statistically significant when compared to the control. Conclusion Based on the current studies, our results suggested that MSCs were a promising option for the treatment of patients with knee OA. However, considering the potential limitations, more well-performed, large-scale RCTs are needed to verify our findings.

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Effect of a Single-Shot of a High-Density Viscoelastic Solution of Hyaluronic Acid in Patients with Symptomatic Primary Knee Osteoarthritis: The No-Dolor Study

10.21203/rs.3.rs-1088483/v1 ◽

2021 ◽

Author(s):

Joan Calvet ◽

Danial Khorsandi ◽

Laura Tío ◽

Jordi Monfort

Keyword(s):

Hyaluronic Acid ◽

Knee Osteoarthritis ◽

Visual Analog Scale Score ◽

High Density ◽

Womac Pain ◽

Single Shot ◽

Analog Scale ◽

Knee Oa ◽

Pain Subscale ◽

Inflammatory Drugs

Abstract Background Pronolis®HD mono 2.5% is a novel, one-shot, high-density sterile viscoelastic solution, recently available in Spain, which contains a high amount of intermediate molecular weight hyaluronic acid (HA), highly concentrated (120 mg in 4.8 mL solution: 2.5%). The objective of the study was to analyze the efficacy and safety of this treatment in symptomatic primary knee osteoarthritis (OA). Methods This observational, prospective, multicenter, single-cohort study involved 166 patients with knee OA treated with a single-shot of Pronolis®HD mono 2.5% and followed up as many as 24 weeks. Results Compared with baseline, the score of the Western Ontario and McMaster Universities Arthritis Osteoarthritis Index (WOMAC) pain subscale significantly reduced at the 12-week visit (primary endpoint, median: 9 interquartile range [IQR]: 7-11 versus median: 4; IQR: 2-6). The percentage of patients achieving >50% improvement in the pain subscale increased progressively from 37.9% (at 2 weeks) to 66.0% (at 24 weeks). Similarly, WOMAC scores for pain on movement, stiffness subscale, and functional capacity subscale showed significant reductions at the 12-week visit which were maintained up to the 24-week visit. The EuroQol visual analog scale score significantly increased after 12 weeks (median: 60 versus 70). The need for rescue medication (analgesics/nonsteroidal anti-inflammatory drugs) also significantly decreased in all post-injection visits. Three patients (1.6%) reported local adverse events (joint swelling) of mild intensity. Conclusions In conclusion, a single intra-articular injection of the high-density viscoelastic gel of HA is effective and safe for the relief of symptoms in patients with knee OA. Trial registration: ClinicalTrial# NCT04196764

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Comparison of the Effectiveness of Intraarticular Ozone Therapy and Platelet Rich Plasma Treatment in Patients with Knee Osteoarthritis

International Journal of Innovative Research in Medical Science ◽

10.23958/ijirms/vol05-i04/859 ◽

2020 ◽

Vol 5 (04) ◽

Author(s):

Ümit Yalçın

Keyword(s):

Hyaluronic Acid ◽

Platelet Rich Plasma ◽

Pain Scale ◽

Controlled Study ◽

Womac Pain ◽

Ozone Therapy ◽

Knee Oa ◽

Randomized Controlled ◽

Vas Score ◽

Long Time

Background: Platelet rich plasma (PRP) has been applied for a long time in osteoarthritis (OA). Although there are studies about PRP that examining the effectiveness with agents such as hyaluronic acid and corticosteroid, there are few published literature comparing with ozone therapy (OT). The aim of this study is to compare the pain severity and functional status of OA patients undergoing intraarticular ozone and PRP injections. Methods: In a study which is made as prospective, randomized controlled study (RCS), 49 patients were included the study. In the first group (n = 24) OT, in the second group (n = 25) PRP injections were administered intraarticularly 3 times in total with one week intervals. Visual pain scale (VAS) and severity of pain were compared with Western Ontario McMaster Osteoarthritis Index (WOMAC). Results: In the PRP group, WOMAC pain, physical function and WOMAC total score were significantly lower than the OT group (p ˂ 0.05). Although VAS score decreased significantly (p ˂ 0.05) after treatment in both groups compared to pretreatment, the VAS score in the PRP group was significantly (p ˂ 0.05) lower than the OT group after treatment. Conclusion: Our study contributes to the literature in terms of limited publication about OT. However, this study shows that the results of PRP treatment are superior to OT in the treatment of knee OA.

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Efficacy and Safety of Hylan G-F 20 Versus Intra-Articular Corticosteroids in People with Knee Osteoarthritis: A Systematic Review and Network Meta-Analysis

Clinical Medicine Insights Arthritis and Musculoskeletal Disorders ◽

10.1177/1179544120967370 ◽

2020 ◽

Vol 13 ◽

pp. 117954412096737

Author(s):

Xavier Chevalier ◽

Brendan Sheehan ◽

Craig Whittington ◽

Mir-Masoud Pourrahmat ◽

Lionel Duarte ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Bayesian Network ◽

Meta Analysis ◽

Direct Injection ◽

Credible Interval ◽

Efficacy And Safety ◽

Knee Oa ◽

Pain Outcome ◽

Short And Long Term

Background: Direct injection of corticosteroids into the joint is a standard treatment for knee osteoarthritis (OA). However, the treatment is somewhat controversial with regard to the benefit of both single and repeated injections; evidence that they are beneficial comes from small studies that show only modest improvements. The aim of this study was to estimate the short- and long-term clinical efficacy and safety of hylan G-F 20 versus intra-articular corticosteroids (IACS) for the treatment of pain in knee OA using Bayesian network meta-analysis. Methods: Based on a pre-specified protocol, MEDLINE, Embase, and CENTRAL were searched from inception to June 2018 to identify randomized controlled trials. The Cochrane Collaboration’s tool for assessing risk of bias in randomized trials was used to assess the included studies. Hylan G-F 20 and IACS were compared using Bayesian network meta-analysis. Efficacy was evaluated at 1, 3, and 6 months, and at the final follow-up for safety outcomes. A pain hierarchy was used to select 1 pain outcome per study. Results: Forty-two trials were included for analysis. The network meta-analysis of pain showed that hylan G-F 20 may be equivalent to IACS in the short-term, but by 6 months the benefit relative to IACS was statistically significant, standardized mean difference (95% credible interval): –0.13 (–0.26, –0.01). There were no statistical differences in adverse events. Conclusions: Hylan G-F 20 may perform better in relieving pain at 6 months post-injection compared to IACS. Both agents were relatively well tolerated, with no clear differences in safety.

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