scholarly journals Hyaluronic Acid Injections or Oral Nonsteroidal Anti-inflammatory Drugs for Knee Osteoarthritis: Systematic Review and Meta-analysis of Randomized Trials

2020 ◽  
Vol 8 (1) ◽  
pp. 232596711989790 ◽  
Author(s):  
Larry E. Miller ◽  
Michael Fredericson ◽  
Roy D. Altman

Background: Intra-articular hyaluronic acid (HA) injections and oral nonsteroidal anti-inflammatory drugs (NSAIDs) are common treatments for symptomatic knee osteoarthritis (OA). However, the comparative effects of these treatments are unclear. Purpose: To compare the efficacy and safety of intra-articular HA injections compared with oral NSAIDs for the treatment of knee OA. Study Design: Systematic review; Level of evidence, 1. Methods: We systematically searched Medline, Embase, and the Cochrane Central Register of Controlled Trials for randomized trials of knee OA treatment with HA injections compared with oral NSAIDs. The main outcomes were knee pain, knee function, adverse events (AEs), serious AEs, study withdrawals, and study withdrawals because of AEs. Pooled effect sizes were reported at the final follow-up with standardized mean difference (SMD) for efficacy outcomes and risk ratio (RR) for safety outcomes. Results: In 6 randomized trials of 831 patients (414 HA, 417 NSAIDs), with follow-up ranging from 5 to 26 weeks, HA injections were associated with small, statistically significant improvements in knee pain (SMD, 0.15; P = .04) and knee function (SMD, 0.23; P = .01) compared with oral NSAIDs. The risk of AEs was lower with HA compared with NSAIDs (19.8% vs 29.0%; RR, 0.74; P = .01). The risk of a serious AE (RR, 1.37; P = .71), study withdrawal (RR, 1.05; P = .68), or study withdrawal because of an AE (RR, 0.65; P = .22) was comparable between groups. Gastrointestinal concerns were the most frequent AE reported, occurring more often with NSAIDs (23.4% vs 14.1%; P = .001). AEs reported more frequently with HA injections were injection site pain (11.7% vs 4.7%; P < .001), headache (8.4% vs 4.4%; P = .03), and arthralgia (8.1% vs 2.9%; P = .001). Significant heterogeneity or publication bias was not observed for any outcome. Conclusion: Comparing short-term outcomes of HA injections with oral NSAIDs for treatment of knee OA, HA injections provided statistically significant but not clinically important improvements in knee pain and function, along with a lower overall risk of AEs.

2020 ◽  
Vol 49 (1) ◽  
pp. 249-260 ◽  
Author(s):  
John W. Belk ◽  
Matthew J. Kraeutler ◽  
Darby A. Houck ◽  
Jesse A. Goodrich ◽  
Jason L. Dragoo ◽  
...  

Background: Platelet-rich plasma (PRP) and hyaluronic acid (HA) are 2 nonoperative treatment options for knee osteoarthritis (OA) that are supposed to provide symptomatic relief and help delay surgical intervention. Purpose: To systematically review the literature to compare the efficacy and safety of PRP and HA injections for the treatment of knee OA. Study Design: Meta-analysis of level 1 studies. Methods: A systematic review was performed by searching PubMed, the Cochrane Library, and Embase to identify level 1 studies that compared the clinical efficacy of PRP and HA injections for knee OA. The search phrase used was platelet-rich plasma hyaluronic acid knee osteoarthritis randomized. Patients were assessed via the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS) for pain, and Subjective International Knee Documentation Committee (IKDC) scale. A subanalysis was also performed to isolate results from patients who received leukocyte-poor and leukocyte-rich PRP. Results: A total of 18 studies (all level 1) met inclusion criteria, including 811 patients undergoing intra-articular injection with PRP (mean age, 57.6 years) and 797 patients with HA (mean age, 59.3 years). The mean follow-up was 11.1 months for both groups. Mean improvement was significantly higher in the PRP group (44.7%) than the HA group (12.6%) for WOMAC total scores ( P < .01). Of 11 studies based on the VAS, 6 reported PRP patients to have significantly less pain at latest follow-up when compared with HA patients ( P < .05). Of 6 studies based on the Subjective IKDC outcome score, 3 reported PRP patients to have significantly better scores at latest follow-up when compared with HA patients ( P < .05). Finally, leukocyte-poor PRP was associated with significantly better Subjective IKDC scores versus leukocyte-rich PRP ( P < .05). Conclusion: Patients undergoing treatment for knee OA with PRP can be expected to experience improved clinical outcomes when compared with HA. Additionally, leukocyte-poor PRP may be a superior line of treatment for knee OA over leukocyte-rich PRP, although further studies are needed that directly compare leukocyte content in PRP injections for treatment of knee OA.


2019 ◽  
Vol 53 (18) ◽  
pp. 1162-1167 ◽  
Author(s):  
Marthe Mehus Lie ◽  
May Arna Risberg ◽  
Kjersti Storheim ◽  
Lars Engebretsen ◽  
Britt Elin Øiestad

BackgroundThis updated systematic review reports data from 2009 on the prevalence, and risk factors, for knee osteoarthritis (OA) more than 10 years after anterior cruciate ligament (ACL) tear.MethodsWe systematically searched five databases (PubMed, EMBASE, AMED, Cinahl and SPORTDiscus) for prospective and retrospective studies published after 1 August 2008. Studies were included if they investigated participants with ACL tear (isolated or in combination with medial collateral ligament and/or meniscal injuries) and reported symptomatic and/or radiographic OA at a minimum of 10 years postinjury. We used a modified version of the Downs and Black checklist for methodological quality assessment and narrative synthesis to report results. The study protocol was registered in PROSPERO.ResultsForty-one studies were included. Low methodological quality was revealed in over half of the studies. At inclusion, age ranged from 23 to 38 years, and at follow-up from 31 to 51 years. Sample sizes ranged from 18 to 780 participants. The reported radiographic OA prevalence varied between 0% and 100% >10 years after injury, regardless of follow-up time. The studies with low and high methodological quality reported a prevalence of radiographic OA between 0%–100% and 1%–80%, respectively. One study reported symptomatic knee OA for the tibiofemoral (TF) joint (35%), and one study reported symptomatic knee OA for the patellofemoral (PF) joint (15%). Meniscectomy was the only consistent risk factor determined from the data synthesis.ConclusionRadiographic knee OA varied between 0% and 100% in line with our previous systematic review from 2009. Symptomatic and radiographic knee OA was differentiated in two studies only, with a reported symptomatic OA prevalence of 35% for the TF joint and 15% for PF joint. Future cohort studies need to include measurement of symptomatic knee OA in this patient group.PROSPERO registration numberCRD42016042693.


2019 ◽  
Vol 32 (11) ◽  
pp. 1046-1057 ◽  
Author(s):  
Kavin Sundaram ◽  
Juan S. Vargas-Hernández ◽  
Tomas Roca Sanchez ◽  
Nestor Moreno Moreu ◽  
Michael A. Mont ◽  
...  

AbstractKnee osteoarthritis (OA) is a highly prevalent disease and treatment options for early stages of OA are needed. Intraosseous injections of bone substitute and biologic materials have been proposed to expand the therapeutic arsenal by potentially halting OA progression and delaying the need for knee arthroplasty in patients with early/moderate-stage disease. Therefore, the goal of this study was assessed the efficacy and safety of subchondral intraosseous injection for the treatment of knee OA. A systematic review was performed on PubMed-Medline, and the Cochrane Database of systematic reviews. English and Spanish retrospective and prospective studies assessing the results of subchondral intraosseous injection of bone substitute materials and/or biologicals in human patients with knee OA, with a minimum of 6 months of follow-up were collected. A total of 1,081 potential articles were identified through our search. Six studies were included with a total of 163 patients. The mean follow-up was 18 months (range: 6–24 months). Patient reported outcomes measures (PROMs), complications, and conversion to total knee arthroplasty (TKA) were collected. All six studies showed PROMs improvement relative to baseline. Overall, the five studies reporting visual-analog scale (VAS) pain outcomes improved from a baseline mean score of 6.68 to 2.74. Also, knee injury and osteoarthritis score (KOOS), Tegner-Lysholm, and/or international knee documentation committee (IKDC) scores rose compared with baseline scores in all studies. Overall, 2.5% (4/163) of patients had a complication attributed to study-related treatment. Most patients (81%, 86/106) remained TKA-free at a 1-year follow-up. Subchondral intraosseous injections of bone substitute materials and platelet-rich plasma (PRP) suggest (1) improved PROMs of pain and functional status, (2) low complication rate, and (3) relatively low rates of conversion to TKA. However, the current studies investigating these treatments exhibited high degree of heterogeneity in both measurement of outcomes and delivery of treatment, with a high risk of bias. This procedure should not be utilized in advanced knee OA. In light of the limitations of the current literature, advising in favor or against this therapy for early to moderate knee OA is challenging.


2013 ◽  
Vol 6 ◽  
pp. CMAMD.S12743 ◽  
Author(s):  
Larry E. Miller ◽  
Jon E. Block

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.


BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e017652 ◽  
Author(s):  
Christelle Nguyen ◽  
Isabelle Boutron ◽  
Gabriel Baron ◽  
Emmanuel Coudeyre ◽  
Francis Berenbaum ◽  
...  

IntroductionOsteoarthritis (OA) pathophysiology is driven in part by joint inflammation. Resveratrol has in vitro anti-inflammatory properties. We aim to assess the efficacy of oral resveratrol for knee pain at 3 months in people with knee OA.Methods and analysisWe will conduct a randomised double-blind placebo-controlled trial. Overall, 164 individuals with knee OA fulfilling 1986 American College of Rheumatology criteria will be recruited in three tertiary care centres in France and randomised to receive oral resveratrol, 40 mg (two caplets) two times per day for 1 week, then 20 mg (one caplet) two times per day or a matching placebo for a total of 6 months. Randomisation will be centralised and stratified by centre. The allocation ratio of assignments will be 1:1. The primary outcome will be the mean change from baseline in knee pain on a self-administered 11-point pain Numeric Rating Scale at 3 months. Secondary outcomes will be the mean change in knee pain at 6 months, the function subscore of the Western Ontario and McMaster Universities Arthritis Index score, patient global assessment, proportion of responders according to the Osteoarthritis Research Society International–Outcome Measures in Rheumatology criteria at 3 and 6 months, and self-reported number of intra-articular injections of corticosteroids or hyaluronic acid and consumption of analgesics and non-steroidal anti-inflammatory drugs since the last contact. Other interventions will be allowed and self-reported. Adherence will be monitored by capsule counts and a booklet and adverse events recorded at 3 and 6 months. Statisticians, treating physicians and participants will be blinded to the allocated treatment.Ethics and disseminationThe oral resveratrol in knee osteoarthritis (ARTHROL) trial has been authorised by theAgenceNationale de Sécurité du Médicament et des Produits de Santéand ethics were approved by theComité deProtection des Personnes Île-de-FranceIII. The findings of the study will be published in a peer-reviewed journal and disseminated at conferences. The design of ARTHROL will warrant the translation of its findings into clinical practice.Trial registration numberClinicalTrials.gov identifier:NCT02905799. Pre-results. First received: 14 September 2016. Last updated: 16 September 2016. Status: not yet recruiting.


2020 ◽  
Author(s):  
Jinlong Zhao ◽  
Hetao Huang ◽  
Guihong Liang ◽  
Ling-feng Zeng ◽  
Weiyi Yang ◽  
...  

Abstract Background Studies have shown that the combined application of hyaluronic acid (HA) and platelet-rich plasma (PRP) can repair degenerated cartilage and delay the progression of knee osteoarthritis (KOA). The purpose of this study was to explore the efficacy and safety of PRP combined with HA in the treatment of KOA compared with intra-articular injection of PRP or HA alone. Methods The PubMed, Cochrane Library, EMBASE and China National Knowledge Infrastructure (CNKI) databases were searched from inception to December 2019. Two orthopaedic surgeons conducted the literature retrieval and extracted the data. Outcome indicators include the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the Lequesne Index, the visual analogue scale (VAS) for pain, and adverse events (AEs). Results Seven studies (5 randomized controlled trials, 2 cohort studies) with a total of 941 patients were included. In the VAS comparison after 6 months of follow-up, PRP combined with HA was more likely to reduce knee pain than PRP alone (standardized mean difference (SMD): -0.31; 95% confidence interval (CI): -0.55 to -0.06; P=0.01 <0.05). PRP combined with HA for KOA achieved better improvement in WOMAC Function Score (SMD: -0.32; 95% CI: -0.54 to -0.10) and WOMAC Total Score (SMD: -0.42; 95% CI: -0.67 to -0.17) at the 12-month follow-up than the application of PRP alone. In a comparison of Lequesne Index scores at a 6-month follow-up, PRP combined with HA improved knee pain scores more than PRP alone (SMD: -0.42; 95% CI: -0.67 to -0.17). In terms of AEs, PRP combined with HA was not significantly different from PRP or HA alone (P>0.05). Conclusions Compared with intra-articular injection of PRP alone, PRP combined with HA can improve WOMAC Function Scores, WOMAC Total Score, 6-month follow-up VAS ratings, and Lequesne Index scores. However, in terms of the incidence of AEs, PRP combined with HA was not significantly different from PRP or HA alone.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Cesare Stagni ◽  
Martina Rocchi ◽  
Alessandro Mazzotta ◽  
Nicolandrea Del Piccolo ◽  
Nicola Rani ◽  
...  

Abstract Background A first-year interim analysis of this two-year study suggested that intra-articular injections of highly purified, natural-origin polynucleotides and hyaluronic acid (HA) as a fixed combination (PNHA) might improve knee function and joint pain more effectively than HA alone in patients with knee osteoarthritis (OA). The purpose of the second-year analysis herein described was to verify whether the first-year interim outcomes persist over the whole two-year period. Methods Randomised, double-blind, HA-controlled clinical trial in 100 knee OA patients (98 randomised, 79 completing the study) in a high-specialisation tertiary care setting. The hypothesised difference of efficacy between PNHA and HA for the original sample size estimate is 20%. Treatment cycle: three intra-articular knee injections of either PNHA or HA, at baseline and weekly for two weeks. Evaluations: Western Ontario and McMaster Universities (WOMAC) score and Knee Society Score (KSS) as, respectively, primary and secondary endpoints, evaluated at baseline and after 2, 6, 12, and 24 months; synovial fluid levels of mediators (at baseline and the end of the treatment cycle). Adverse effects investigated at each control visit. Statistical analysis: Kruskal-Wallis test for independent samples (nonparametric one-way analysis of variance) after correction of means for age, Body Mass Index and Kellgren-Lawrence grade. If significant, pairwise post-hoc Sidak multiple comparisons. Results KSS total score and KSS pain item: significant improvement in both groups, with significantly more pain improvement in patients treated with PNHA (2-point reduction) than HA (1-point reduction). Both groups experienced significant long-term reductions in WOMAC total scores: significantly stronger in PNHA-treated patients after 24 months with a steady difference of 16% favouring PNHA in WOMAC pain subscore. No clinically significant adverse events in either group. Conclusions The outcomes of the 2-year study confirmed that a short cycle of intra-articular treatment (3 weekly double-blind injections) with polynucleotides (long-acting viscosupplementation properties, chondrocyte activation, pain-relieving properties) in fixed combination with high molecular weight hyaluronic acid is more effective in improving knee function and pain in knee OA patients than HA alone. PNHA may be elective for viscosupplementation in knee OA patients with fastidious and resistant pain and worsening disease. Trial registration NCT02417610. Registration, 15/04/2015. ClinicalTrials.gov database link:


Cartilage ◽  
2019 ◽  
pp. 194760351988878
Author(s):  
Larry E. Miller ◽  
Samir Bhattacharyya ◽  
William R. Parrish ◽  
Michael Fredericson ◽  
Brad Bisson ◽  
...  

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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