The efficacy of intraarticular viscosupplementation after arthroscopic partial meniscectomy: a randomized controlled trial.

BACKGROUND: This study aimed to evaluate the efficacy of viscosupplementation after arthroscopic partial meniscectomy. METHOD: A randomized controlled trial of 47 patients who underwent arthroscopic partial meniscectomy was conducted between March 2020 and March 2021. Patients were randomized into two groups: a viscosupplementation group (n = 23) and a control group (n = 24). A single-dose intraarticular hyaluronic acid injection was used as viscosupplementation. The 100 mm visual analogue scale (VAS) for pain assessment was measured at baseline and at 1 day, 2 weeks, 6 weeks, and 3 months post-surgery. The International Knee Documentation Committee (IKDC), Tegner, Lysholm, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scores and range of motion (ROM) of the knee were measured at baseline, 2 weeks, 6 weeks, and 3 months. RESULTS: The 100 mm VAS score for pain was significantly lower in the viscosupplementation group at 2 weeks post-surgery (27.5 mm vs. 40.7 mm, P = 0.047). ROM was significantly greater in the viscosupplementation group than in the control group at 2 weeks (131.5° vs. 121.0°, P = 0.044) post-surgery. No significant differences were observed in the IKDC or in the Tegner, Lysholm, and WOMAC scores between the two groups. CONCLUSIONS: Viscosupplementation after arthroscopic partial meniscectomy significantly reduced pain at 2 weeks post-surgery and improved ROM of the knee at 2 weeks post-surgery. There might be some benefits in terms of pain and functional recovery of viscosupplementation after arthroscopic surgery. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. TRIAL REGISTRATION: This randomized controlled trial was registered at cris.nih.go.kr # KCT0004921 .

Rethinking Viscosupplementation: Ultrasound- Versus Landmark-Guided Injection for Knee Osteoarthritis.

OBJECTIVES: Viscosupplementation, intra-articular injection of hyaluronic acid (HA), for knee osteoarthritis has fallen somewhat out of favor, with studies failing to show consistent benefits in pain reduction. Hyaluronic acid must enter the joint space to be beneficial; however, landmark-guided injection can be substantially inaccurate, especially in obese patients. We aimed to determine whether ultrasound (US) guidance to ensure needle placement for HA knee injection resulted in improved outcomes as reflected by surgery-free survival compared to landmark-guided HA knee injection. METHODS: All community-dwelling patients in 6 contiguous surrounding counties receiving HA knee injection either by landmark guidance (n = 647) or by US guidance (n = 500) were analyzed for the degree of arthritis, body mass index, follow-up injection, and subsequent need for knee arthroplasty. A subgroup analysis of obese patients was also performed. RESULTS: The US- and landmark-guided HA injection cohorts were similar with respect to sex, body mass index, and the degree of arthritis. Of 1147 patients receiving knee HA injection, 462 subsequently underwent knee arthroplasty. Significantly fewer patients in the US-guided HA injection cohort went to surgery (33.2%) compared to the landmark-guided cohort (45.8%; P < .001). The subgroup analysis for obese patients showed even larger differences (34.8% versus 51.8%; P < .001). CONCLUSIONS: Knee osteoarthritis treatment by viscosupplementation can be optimized by US guidance, ensuring intra-articular needle placement. Using an objective surgical outcome, our study shows that rethinking viscosupplementation to ensure intra-articular delivery improves effectiveness. Patients receiving US-guided knee HA injection were significantly less likely to undergo subsequent knee arthroplasty than patients receiving landmark-guided HA injection.

The use of hyaluronic acid in the treatment of ankle osteoarthritis: a review of the evidence.

Ankle osteoarthritis (OA) is a progressive degenerative joint disease that causes ankle pain and functional limitation especially during walking. It tends to involve younger people with high functional request and has often a post-traumatic origin. Symptoms control through conservative treatment is essential to procrastinate as long as possible the need for surgery. Although few data are present in literature about the use of local viscosupplementation in ankle OA, their potential use for ankle OA has been suggested. We systematically reviewed literature to evaluate the best evidence about short and long term effectiveness of intra-articular HA injections in the treatment of ankle OA. After having screened titles and abstracts from PubMed, Ovid, Cochrane Reviews, Google Scholar, we identified 14 full text articles and collected the outcome rates of intra-articular cycles of HA injections in patients with symptomatic ankle OA. Only 4 randomized control trials were included. Ankle Osteoarthritis Scales (AOS), American Orthopedic Foot, Ankle Society (AOFAS) clinical rating score, visual analog scales (VAS), Western Ontario and McMaster Universities (WOMAC) OA Index of Pain, Stiffness, and Physical Function Score were most frequently used to evaluate outcomes. Although randomized trials showed scores improvement also in placebo-treated patients, current evidence suggests that viscosupplementation for treatment of ankle OA is a safe and effective method. More randomized controlled trials with a large number of patients that compare not only the different types, dosages and frequency of HA injections, but also the effectiveness of HA versus corticosteroids infiltrations and HA versus other types of conservative treatment are still needed.

AMSSM Scientific Statement Concerning Viscosupplementation Injections for Knee Osteoarthritis: Importance for Individual Patient Outcomes.

OBJECTIVE: Osteoarthritis (OA) is a disabling disease that produces severe morbidity reducing physical activity. Our position statement on treatment of knee OA with viscosupplementation injection [hyaluronic acid (HA)] versus steroid [intra-articular corticosteroid (IAS)] and placebo [intra-articular placebo (IAP)] is based on the evaluation of treatment effect by examining the number of subjects within a treatment arm that met the Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) criteria, which is different and more relevant than methods used in other reviews which examined if the average change across the treatment groups was clinically different. DATA SOURCES: We performed a systematic literature search for all relevant articles from 1960 to August 2014 in the MEDLINE, EMBASE, and Cochrane CENTRAL. We performed a network meta-analysis (NMA) of the relevant literature to determine if there is a benefit from HA as compared with IAS and IAP. MAIN RESULTS: Eleven articles met the inclusion criteria from the search strategy. On NMA, those subjects receiving HA were 15% and 11% more likely to respond to treatment by the OMERACT-OARSI criteria than those receiving IAS or IAP, respectively (P < 0.05 for both). CONCLUSIONS: In light of the aforementioned results of our NMA, the American Medical Society for Sport Medicine recommends the use of HA for the appropriate patients with knee OA.

Single- or multiple-session viscosupplementation protocols for temporomandibular joint degenerative disorders: a randomized clinical trial.

The aim of the study was to compare the effectiveness of two single-session protocols, either adopting high- (protocol A) or medium-molecular weight hyaluronic acid (protocol B), with the reference five-session protocol of temporomandibular joint (TMJ) lavage plus viscosupplementation (protocol C) in the management of chronic TMJ degenerative disorders. A randomized clinical trial (RCT) with ten participants per treatment group was designed, with multiple observation points, ending at 6 months after treatment. Pain levels on a 10-point VAS scale were selected as the primary outcome variable to rate treatment effectiveness, along with a number of secondary outcome parameters. Findings showed that Group C patients had the highest decrease in pain levels. Nonparametric permutation analyses revealed that the global effect of treatment was significantly different between the three protocols (P = 0·024). Pairwise comparisons showed that the differences of treatment effect between the two single-session interventions were negligible (global P-value = 0·93). On the contrary, the five-session protocol was significantly superior to both single-session protocols (global P-values ranging from 0·003 to 0·012). In conclusion, in a population of age-, sex-, and psychosocial aspects-matched study groups, the standard of reference five-session protocol proved to be superior at 6 months as far as the decrease in pain levels was concerned, whilst there were no differences between the two single-session interventions. The absence of differences in treatment effect as for some other secondary clinical outcome variables may suggest that there is further space for future investigations attempting to reduce the number of multiple interventions for TMJ viscosupplementation.

[Intra-articular use of sodium hyaluronate (2,2,-2,7 MDa) in the treatment of Moroccan patients with knee osteoarthritis: randomized controlled trial]. / Intérêt de la viscosupplémentation a l'hyaluronate de sodium (2,2-2,7 MDa) dans le traitement de la gonarthrose chez des patients marocains: etude randomisée contrôlée.

OBJECTIVE: To assess the efficacy of intra-articular sodium hyaluronate, administred once weekly for 3 weeks (3 injections) in Moroccan patients with knee osteoarthritis over 6-month period. MATERIAL AND METHODS: We prospectively studied the outcome of 75 patients with painful knee osteoarthritis in grade 1, 2 and 3 on ACR radiological criteria in our rheumatology clinic in Morocco. Group 1: 45 patients were treated with 3-weekly injections of intra-articular sodium hyaluronate (1%; 2,2-2,7 MDa). Group 2 : 30 patients treated with symptomatic slow-acting drugs for osteoarthritis (SYSADOA). The efficacy parameters were Visual Analogue Scale (VAS) and Lequesne index. RESULTS: In group 1: 35/45 were female, a mean age of patients was 57.2 (± 8.2) years, and a mean Body Mass Index (BMI) was 28 (± 1.4) kg/m2. In group 2: 23/30 were female, a mean age of patients was 58.6 (± 2.8) years, and a mean of BMI was 27.8 (± 1.4) kg/m2. Before treatment in group 1, the mean of VAS was 6.5 cm (± 1), and of Lequesne index 10.5 (± 2.1). At 3 and 6 months after the third injection of sodium hyaluronate, there was a significant improvement from baseline of Lequesne index and VAS (P = 0.001). In group 2 before treatment, the mean of VAS was 7 cm (± 0,7), and of Lequesne index 8 (+ 1.1), but the improvement from baseline at 3 and 6 months of treatment was lower than group 1. CONCLUSION: The results of this prospective study, showed the efficacy of 3-weekly injections of sodium hyaluronate in the treatment of knee osteoarthritis in Moroccan patients over a 6-month period.

Predictors of Clinical Benefit with Intra-articular Hyaluronic Acid in Patients with Knee Osteoarthritis - A Narrative Review.

BACKGROUND: There is conflicting evidence regarding the efficacy of viscosupplementation with intra-articular hyaluronic acid injections in knee osteoarthritis. One possible explanation for the inconsistent findings on its efficacy is that only certain subpopulations of patients benefit from this therapy. OBJECTIVE: The purpose of this narrative review is to succinctly summarize the existing data on the predictive factors of clinical response to intra-articular hyaluronic acid to identify the patient profile most likely to benefit from this therapy. METHODS: For this narrative review, a PubMed search was conducted in January 2023, with no date limits, to identify publications reporting predictive factors of response to viscosupplementation using the following terms: hyaluronic acid OR viscosupplem* AND osteoarthritis AND knee AND predict*. Searches were limited to randomized controlled trials, systematic reviews and meta- analyses, or observational studies written in English. Other relevant references were identified by searching the references of retrieved articles. RESULTS: The disease severity was found to reliably predict response to intra-articular hyaluronic acid injections; patients with less severe disease consistently had a more robust therapeutic response than those with more severe disease. Other clinical variables such as level of baseline pain did not reliably predict response. Body mass index, and possibly age, may also be independent predictors of the response. CONCLUSION: A review of the existing literature suggests that patients with less severe clinical symptoms and radiological findings, who are younger, and with a lower or normal body mass index are the best candidates for intra-articular hyaluronic acid therapy.

Demonstrating antibiotic stewardship while diagnosing and treating bilateral pseudoseptic arthritis: a case report.

INTRODUCTION: Although viscosupplementation is a commonly used treatment for osteoarthritis and is widely regarded as a safe treatment option, it is associated with the rare complication of pseudoseptic arthritis. Most existing case reports that cite this rare complication employed the use of early broad-spectrum antibiotics. CASE PRESENTATION: In this case report, we present a 61-year-old African American female patient who presented with bilateral knee pseudoseptic arthritis in the setting of viscosupplementation. She presented 3 days after bilateral viscosupplementation injections with bilateral knee swelling, discomfort, and pain with micromotion. Her white blood cell count (WBC) was 12.83 (4.5-11 normal), her C-reactive protein (CRP) level was 159 mg/L (0-10 normal), and her erythrocyte sedimentation rate (ESR) was 79 mm/hour (0-40 normal). Her left knee aspirate yielded 38,580 WBC with a negative gram stain and negative cultures. Her right knee aspirate yielded 29,670 WBC with a negative gram stain and negative cultures. Through the utilization of careful clinical monitoring, ice therapy, and non-steroidal inflammatory medication, we were able to successfully treat this patient while maintaining proper antibiotic stewardship. CONCLUSION: Pseudoseptic arthritis in the setting of viscosupplementation can be adequately treated and monitored without the use of antibiotics.

The Use of Intra-articular Platelet-Rich Plasma as a Therapeutic Intervention for Hip Osteoarthritis: A Systematic Review and Meta-analysis.

BACKGROUND: There is a cohort of patients in whom hip preservation surgery is not indicated, because they have developed signs of early osteoarthritis (OA), and nor can they have a hip replacement, as they are too early in the disease process. Management of this cohort of patients is not standardised and both pharmacological and nonpharmacological measures are utilised to reduce pain. Interventions available for early OA include intra-articular injections of steroids, viscosupplementation and more recently platelet-rich plasma (PRP). However, the use of PRP in hip OA has not yet been studied systematically. PURPOSE: To assess intra-articular PRP as a therapeutic intervention for hip OA, including the duration of efficacy, influence of dose and composition of PRP, and the incidence of adverse effects. STUDY DESIGN: A systematic review and meta-analysis; Level of evidence, 4. METHODS: We performed literature searches on the MEDLINE, EMBASE, CINAHL, WEB OF SCIENCE, COCHRANE, and SCOPUS databases, and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Data were pooled using random-effects meta-analysis. We assessed the quality of the included studies using the methodological index for non-randomized studies instrument, with an additional assessment for randomized controlled trials with the revised Cochrane risk of bias tool for randomized trials. This is the first study to concisely collate the available data on the use of PRP in hip OA. RESULTS: Eight studies were included in the analysis, with data from a total of 331 patients. PRP significantly reduced pain compared with the baseline at multiple time points, with the greatest effect at the 1- to 2-month follow-up, but PRP significantly improved function only at the 1- to 2-month follow-up. A significantly larger reduction in pain was achieved with a single injection of PRP compared with multiple injections, a total injected dose of PRP <15 mL compared with ≥15 mL, and use of a leukocyte-poor PRP preparation compared with leukocyte-rich PRP. There were no lasting adverse effects. CONCLUSION: Low- and moderate-quality evidence suggests that PRP reduces pain and improves function at the end-point follow-up of studies compared with the baseline. Moderate-quality evidence suggests that a larger reduction in pain is achieved with a single injection of PRP compared with multiple injections, and low-quality evidence attributes a larger reduction of pain with a total injected dose of PRP <15 mL compared with ≥15 mL and using leukocyte-poor PRP compared with leukocyte-rich PRP.

Ultrasound-guided viscosupplementation of subacromial space in elderly patients with cuff tear arthropathy using a high weight hyaluronic acid: prospective open-label non-randomized trial.

OBJECTIVE: To assess if ultrasound (US)-guided viscosupplementation can reduce pain and improve function in elderly patients with cuff tear arthropathy. PATIENTS AND METHODS: Ninety-three patients aged over 65 with grade 3 or above cuff tear arthropathy were included in this prospective open-label non-randomized trial. Institutional review board approval and informed consent were obtained. Thirty-three patients received intra-articular injections of sodium hyaluronate under US guidance. Sixty patients constituted the control group. Shoulder joint function was assessed with Constant scores (CS) and pain with a visual analogue scale (VAS). RESULTS: Compared with controls, treated patients reported a significant decrease in symptoms at 1 (mean CS 66±3.1 vs 37±6.9; mean VAS 1.9±1.2 vs 6.9±2.2), 2 (mean CS 65±3.2 vs 35±7.2; mean VAS 1.7±1.2 vs 6.8±2.5), 3 (mean CS 66±3.4 vs 33 6.1; mean VAS 2.3±1.2 vs 6.6±1.9), and 4 (mean CS 62±3.0 vs 34±6.5; mean VAS 3.3±1.4 vs 7.8±3.1) months, p<0.001. After 5 months there were no differences. CONCLUSION: US-guided viscosupplementation is a beneficial therapeutic option in the first months of treatment.

Viscosupplementation in the management of ankle osteoarthritis: a review.

INTRODUCTION: Osteoarthritis (OA) is a disease of synovial joints and is the most common cause of chronic pain. Viscosupplementation (VS) with hyaluronic acid (HA) is largely used for knee osteoarthritis therapy but the evidence for its usefulness in ankle osteoarthritis is limited. The objective of this review is to assess the efficacy of viscosupplementation treatment of ankle osteoarthritis in the current literature. METHODS: The following databases were searched: Medline (period 2006-2008), Database of Abstract on Reviews and Effectiveness and Cochrane Database of Systematic Reviews. Reference lists of relevant articles were controlled for additional references. The search terms Review, Viscosupplementation (VS), Osteoarthritis (OA), Hyaluronic acid (HA), Hyaluronan, Sodium hyaluronate, Ankle OA, Ankle joint were used to identify all studies relating to the use of VS therapy for the ankle OA. Methodological quality of included studies was assessed by assigning level of evidence as previously defined by the Centre for Evidence Based Medicine (CEBM). RESULT: Seven articles concerning the efficacy of a total of 275 patients undergoing VS treatment for ankle OA were included. One European study, one Taiwanese study, one Italian study, one Turkish study and three American studies with level of evidence ranging from I to IV evaluated the following products: Hyalgan, Synvisc, Supartz, Adant. CONCLUSION: Viscosupplementation is used widely in knee OA and is included in the professional guidelines for treatment of the disease in this joint. The potential for treating osteoarthritis of the ankle joint by viscosupplementation has been suggested in the literature, however, no dosing studies have been published to date, and dosing in the ankle joint remains an area for discussion. Viscosupplementation could potentially provide an useful alternative in treating such patients with painful ankle OA.

Injection route affects intra-articular hyaluronic acid distribution and clinical outcome in viscosupplementation treatment for knee osteoarthritis: a combined cadaver study and randomized clinical trial.

The coverage of hyaluronic acid (HA) on the impaired cartilage should be the precondition to exert its beneficial effect on knee osteoarthritis (KOA) according to the pharmacological mechanism. However, the intra-articular distribution of HA might be correlated with the route of drug delivery. Forty-two cadaver knees with radiographic evidence of osteoarthritis were given anteromedial (AM) or medial midpatellar (MMP) injection of HA (molecular weight 600-1500 kD) followed by gait stimulation. Although 2.5 ml HA delivered through both routes failed to cover the entire cartilage, HA covered 96.12% cartilage of patellofemoral joint (PFJ) and 71.44% of medial femorotibial joint (FTJ) through MMP route, whereas mainly distributed into FTJ and posterior condyles through AM route. HA in the MMP group distributed more in PFJ than that in the AM group (P < 0.001), but no significant difference presented in medial FTJ (P = 0.084). The clinical efficacy was also associated with the route of drug delivery. One hundred patients with unilateral mild-to-moderate KOA were recruited and randomly assigned to receive five weekly HA injections with AM route (n = 50) or MMP route (n = 50). Patients in the MMP group obtained better improvement in WOMAC index total score, pain score, stiffness score, and Lequesne index total score over the entire follow-up period, as compared to patients in the AM group (all P < 0.01). More patients in the MMP group claimed pain relief (71.7%, P = 0.024) and felt satisfying (63.1%, P = 0.007) than in the AM group at the end of follow-up. Therefore, intra-articular HA injection through MMP route is recommended in treating mild-to-moderate KOA. Graphical Abstract .

Molecular Weight of Hyaluronic Acid Has Major Influence on Its Efficacy and Safety for Viscosupplementation in Hip Osteoarthritis: A Systematic Review and Meta-Analysis.

BACKGROUND: This study aimed to compare the efficacy and safety of intra-articular hyaluronic acid (HA) injection with different molecular weights (MWs) for treating hip osteoarthritis (OA). METHODS: A systematic literature search for relevant studies was conducted in 3 electronic databases, including PubMed, BMJ Journals, and Cochrane Library, from inception to April 2020. Extracted outcomes included visual analogue scale (VAS) (1, 3, and 6 months), Lequesne index (3 and 6 months), and adverse effects. HAs were classified into low-molecular-weight (LMW), moderate-molecular-weight (MMW), high-molecular-weight (HMW), and ultra-high-molecular-weight (UHMW) groups. Meta-analysis was performed using Review Manager 5.3. RESULTS: A total of 15 studies with 614 patients were included. Our meta-analysis showed that the HMW HA group had the best improvement in VAS and Lequesne index compared with other HA groups for all the follow-up visits. Moreover, the HMW group demonstrated significantly better improvement than the other groups in VAS at 6-month follow-up and in Lequesne index at 3- and 6-month follow-ups. Analysis for adverse effects revealed low rates of systemic adverse effects (≤0.6%) in all groups and similar rate of local adverse effects (around 10%) among the groups except for UHMW HA group (37.5%). CONCLUSION: Among different MWs of HA for treating hip OA, HMW HA injection demonstrated the best efficacy for up to 6 months after treatment without increased risk of adverse effects. Further studies with more comprehensive data and a higher level of evidence are required to prove our results.

EUROVISCO Recommendations for Optimizing the Clinical Results of Viscosupplementation in Osteoarthritis.

OBJECTIVES: The 3 aims of the work were to identify population subgroups that can benefit the most from viscosupplementation (VS), to provide recommendations on injection techniques, and to discuss VS appropriateness in clinical situations that are commonplace in daily practice. METHODS: The task force members voted on their degree of agreement on 27 statements, 36 recommendations, and 22 clinical scenarios using a 9-point scale. The strength of agreement/appropriateness/recommendation (SOA/SOR) was classified as strong if the median agreement score was ≥8. The level of consensus (LOC) was also obtained. RESULTS: Among the assumed predictors for VS failure, obesity, radiographic severity, large synovial fluid effusion, severe patellofemoral involvement, major malalignment, and gross joint instability received a large majority of agreements. The lateral mid-patellar approach was recommended for knee injection. Imaging guidance was unanimously recommended for hip and ankle. Agreement was achieved to strictly respect the dosing regimen proven by controlled trials. There was agreement for treating with VS patients with mild to moderate knee and hip OA, with normal weight or moderate overweight, insufficiently improved by first-line therapies, or who do not wish get oral treatment or who have contraindications to pain killers. The group considered the patient's wishes as a key element in therapeutic decision making. CONCLUSION: Based on literature data and clinical experience, the EUROVISCO group proposed a set of recommendations for optimizing the results of VS, aimed to help practitioners, especially in some cases in which the patients' specificities make the therapeutic decision difficult.

Predictors of placebo response to local (intra-articular) therapy in osteoarthritis: an individual patient data meta-analysis protocol.

INTRODUCTION: Osteoarthritis (OA) is a highly prevalent and disabling condition with limited safe and effective treatment options. Intra-articular therapies are increasingly being used, however whether the effect of these agents is due to active treatment or placebo remains unclear. As the placebo response can be attributed to multiple factors, assessment of the placebo response using individual patient data (IPD) meta-analysis will give insight into the different modifiers of response to placebo. The aim of this IPD meta-analysis is to investigate the predictors of placebo response in intra-articular injection trials in OA. IPD meta-analysis is considered to be superior to conventional meta-analysis, as it combines multiple trial data, facilitates the standardisation of analyses across different studies and allows measuring derivation of the desired information. METHOD AND ANALYSIS: A systematic literature search will be conducted for randomised clinical trials comparing corticosteroid and viscosupplementation/hyaluronic acid intra-articular injections with placebo for knee and hip OA. Pubmed (Medline), EMBASE, Web of Science, Cochrane Central and SCOPUS will be searched from inception to September 2018. Corresponding authors of the original trials will be contacted to obtain IPD. Risk of bias will be assessed using the Cochrane Collaboration's tool. The primary outcome will be change in pain from baseline. Secondary outcomes will be change in function and patient's global assessment. Potential predictors of placebo response assessed will include patient's characteristics, pain mechanism characteristics, radiographic severity, pain severity, intervention characteristics and trial design characteristics. A multilevel logistic regression analyses will be applied. Results will be reported using the Preferred Reporting Items for Systematic review and Meta-Analysis -IPD guidelines. ETHICS AND DISSEMINATION: This study does not include identifiable data and ethical approval was obtained by the original investigators. Results of the IPD meta-analysis will be disseminated for publication in peer-reviewed journals and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42018095188.

Why we should definitely include intra-articular hyaluronic acid as a therapeutic option in the management of knee osteoarthritis: Results of an extensive critical literature review.

OBJECTIVES: There is a discrepancy between evidence in support of the widespread use of intra-articular hyaluronic acid (IAHA) to treat knee osteoarthritis (OA) in clinical practice, and the often discordant recommendations from multiple international guideline committees, which requires further investigation. METHODS: We conducted a literature review to determine the strength of evidence in support of the efficacy and safety of IAHA, from randomized controlled trials and meta-analyses. RESULTS: Our analysis shows that IAHA provides a moderate symptomatic benefit to knee OA patients and without major safety concerns. In fact, IAHA may offer one of the best benefit/risk ratios among pharmacologic options, as measured by improvements in knee OA health outcomes, overall gain in quality-adjusted life years and substantial delays in time to total knee replacement. CONCLUSIONS: We advocate for the consideration of recommending IAHA injection as a treatment option in the management of knee OA, tailored by disease stage and patient phenotype. Future research efforts should focus on identification of OA patient subgroups that demonstrate a more robust response to IAHA, determination of long-term effects of repeat IAHA injections on patient-reported outcomes and total knee replacement-sparing effect, further elucidation of disease-modifying effects, and the potential for combination therapy with other pharmacologic and non-pharmacologic therapies to optimize the management of knee OA.

Efficacy of viscosupplementation with hyaluronic acid in temporomandibular disorders: A systematic review.

OBJECTIVE: To perform a systematic review of the viscosupplementation effectiveness with hyaluronic acid (HA) in the articular Temporomandibular Dysfunctions (TMDs) clinical management. METHOD: Electronic searches were performed in the following databases: MEDLINE (via PubMed), Scopus, Web of Science, Cochrane Library, EMBASE, LILACS, BBO, SIGLE (System for Information on Grey Literature in Europe), ClinicalTrials.gov, and the Brazilian Clinical Trials Registry (ReBec). Only randomized clinical trials that evaluated the intra-articular administration of HA or its derivatives in osteoarthritis and/or anterior displacement of the temporomandibular joint (TMJ) disc were included. The primary outcomes evaluated were patients' self-report of pain and/or discomfort in the TMJ. Each study was assessed for the risk of bias, using the Cochrane collaboration's risk of bias tool. RESULTS: A total of 640 studies were obtained in the electronic search. After the application of the eligibility criteria, manual search, and duplicate removal, 21 articles were included. Five articles classified their volunteers with internal derangements of the TMJ, in 4 articles the treatment was directed to participants with disc displacement with reduction and the other articles evaluated HA therapy in osteoarthritis. The protocols presented heterogeneity, varying in the form of application, associated or not with arthrocentesis, number of applications, molecular weight, dose and concentration. Nine studies presented high risk of bias. CONCLUSION: Due to the heterogeneity and methodological inconsistencies of the studies evaluated, it was not possible to establish the efficacy of HA in articular TMDs.

Practical Aspects of Hyaluronic Acid Application in Biolevox HA Preparations - Report on Research.

HA preparations in intraarticular injections have been applied in medicine since 1986 and became widely used in Poland at the beginning of the 90s of the twentieth century. Since then, numerous cases of successful application of intra-articular injections (the so called viscosupplementation) have been described in Polish and foreign literature. Changes in the molecular mass of hyaluronic acid and the related specific spatial structure result in different metabolic and immunological properties. Presently, in clinical practice, it is indicated to use the preparations produced by selected manufacturers who offer different forms of HA, containing different percentage of active substance (1 to 2.5%) and different molecular mass, making the desired number (1-5) of intra-articular injec-tions possible, depending on the type and intensity of a specific disease unit. Numerous studies have been con-ducted to confirm the effectiveness of treatment using hyaluronic acid. In Poland a research program was implemented to assess the practical application of 2 ml of Biolevox HA preparation in 2.2% concentration. During the study 15,000 patients were subjected to analysis. The physicians participating in the study injected the hyaluronic acid, in that case, Biolevox HA, to the knee joint, in patients with osteoarthritis, chondromalacia, knee joint injuries and other conditions.

Decision Algorithms for the Retreatment with Viscosupplementation in Patients Suffering from Knee Osteoarthritis: Recommendations from the EUROpean VIScosupplementation COnsensus Group (EUROVISCO).

Background Viscosupplementation (VS) is a symptomatic treatment of knee osteoarthritis. Although systematic reviews of its repeat use showed favorable benefit/risk ratio, no study has focused on the indication of retreatment. Methods A task force was created to look at issues regarding retreatment with VS in knee osteoarthritis. An attempt was made to reach consensus on several issues: (1) to define treatment "success" and "failure," (2) to determine when to retreat patients successfully treated by a previous VS, (3) to determine how to retreat patients in whom VS failed, (4) to define what to do in case of adverse reaction following previous VS, and (5) to examine the interests of soluble biomarkers to manage retreatment. After debate and review of literature the working group voted on 88 issues. Two "decision trees" were built based on the results of the votes. Results In case of failure, the authors draw attention to the need of a rigorous clinical and radiological analysis, and consider evidence-based medicine. When VS was previously successful, retreatment can be considered after recurrence or increase in pain. However, in subjects with high risk of disease progression, in young patients, and in professional sportsmen, retreatment could be considered systematically, because of the probability of hyaluronic acid to slow osteoarthritis progression. Evidence on soluble biomarkers was not considered as enough strong to support their use as decision tools for patient retreatment. Conclusion The decision algorithms are intended to facilitate consideration of the therapeutic options, in patients with knee osteoarthritis previously treated with VS.