Injections For Osteoarthritis Research Articles

Platelet-Rich Plasma for Knee and Hip Osteoarthritis Pain: A Scoping Review.

Platelet-rich plasma (PRP) is an emerging biological intervention for osteoarthritis (OA), yet the outcomes remain uncertain. The purpose of this study was to review current literature regarding the use of PRP for knee and hip OA. Recent systematic reviews have found significant clinical improvements in outcomes after the administration of PRP compared to hyaluronic acid (HA) in patients with knee OA. One of these reviews included bone marrow aspirate concentrate (BMAC) as a comparison group and found no significant differences in outcomes between PRP and BMAC. Currently, the literature is lacking on whether leukocyte-rich or leukocyte-poor PRP is superior in patients with knee OA. The literature on PRP for hip OA has not provided consistent results as it has for the knee. Two recent systematic reviews evaluated RCTs for patients undergoing treatment with either PRP or HA for hip OA and found no significant differences in clinical outcomes between groups at final follow-up. Current literature regarding the association between OA grade and PRP efficacy has found varying results. The use of PRP injections in the treatment of knee OA appears to be favorable, resulting in clinically comparable or superior outcomes compared to other injection treatments. However, the clinical efficacy of PRP injections in hip OA is far less consistent. Evidence is lacking to suggest that the presence of leukocytes significantly influences clinical outcomes. Further randomized controlled trials on larger cohorts, with longer follow-up, and with comparable formulations are required before recommendations can be made regarding use of PRP for hip OA, the effect of leukocyte concentration, and clinical efficacy based on OA grade.

Efficacy of stromal vascular fraction for knee osteoarthritis: A prospective, single-centre, non-randomized study with 2 years follow-up.

Current osteoarthritis (OA) treatments focus on symptom relief without addressing the underlying disease process. In regenerative medicine, current treatments have limitations. In regenerative medicine, more research is needed for intra-articular stromal vascular fraction (SVF) injections in OA, including dosage optimization, long-term efficacy, safety, comparisons with other treatments, and mechanism exploration. To compare the efficacy of intra-articular SVF with corticosteroid (ICS) injections in patients with primary knee OA. The study included 50 patients with Kellgren-Lawrence grades II and III OA. Patients were randomly assigned (1:1) to receive either a single intra-articular SVF injection (group A) or a single intra-articular ICS (triamcinolone) (group B) injection. Patients were followed up at 1, 3, 6, 12, and 24 months. Visual analog score (VAS) and International Knee Documentation Committee (IKDC) scores were administered before the procedure and at all follow-ups. The safety of SVF in terms of adverse and severe adverse events was recorded. Statistical analysis was performed with SPSS Version 26.0, IBM Corp, Chicago, IL, United States. Both groups had similar demographics and baseline clinical characteristics. Follow-up showed minor patient loss, resulting in 23 and 24 in groups A and B respectively. Group A experienced a notable reduction in pain, with VAS scores decreasing from 7.7 to 2.4 over 24 months, compared to a minor reduction from 7.8 to 6.2 in Group B. This difference in pain reduction in group A was statistically significant from the third month onwards. Additionally, Group A showed significant improvements in knee functionality, with IKDC scores rising from 33.4 to 83.10, whereas Group B saw a modest increase from 36.7 to 45.16. The improvement in Group A was statistically significant from 6 months and maintained through 24 months. Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA. More adequately powered, multi-center, double-blinded, randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.

Comparison of ultrasound guidance with landmark guidance for symptomatic benefits in knee, hip and hand osteoarthritis: Systematic review and meta‐analysis of randomised controlled trials

AbstractIntroductionMore than half of the patients with moderate and severe osteoarthritis (OA) report unsatisfactory pain relief, requiring consideration of intra‐articular (IA) injections as the second‐line management. Ultrasound‐guided IA injection has proven evidence of higher accuracy in administering IA injectates into the joints than landmark‐guided or blind IA injections. However, questions remain about translating higher accuracy rates of ultrasound‐guided injection into better clinical improvements. Therefore, we examined the symptomatic benefits (pain, function and patient satisfaction) of ultrasound‐guided injection in knee, hip and hand OA compared with blind injections by synthesising a systematic review and meta‐analysis of randomised controlled trials (RCT).MethodsPubMed, Medline and Embase databases were searched for eligible studies from their inception to August 28, 2023.ResultsOut of 295 records, our meta‐analysis included four RCTs (338 patients with knee OA), demonstrating significant improvement in procedural pain [−0.89 (95% CI −1.25, −0.53)], pain at follow‐up [−0.51 (95% CI −0.98, −0.04)] and function [1.30 (95% CI 0.86, 1.73)], favouring ultrasound guidance. One single study showed higher patient satisfaction with ultrasound guidance.ConclusionUltrasound‐guided IA injection provided superior clinical outcomes compared with landmark‐guided IA injection.

Intra-Articular Hyaluronic Acid for Osteoarthritis of the Hip, Shoulder, and Ankle

What Is the Issue?
 
 Osteoarthritis (OA) is a chronic disease of the joints, such as the hip, shoulder, and ankle. OA causes the joints to be painful, unstable, and less functional. In adults 55 years and younger, joint trauma is a common cause of OA.
 Hyaluronic acid (HA) is a naturally occurring molecule found in human cells that provides lubrication when injected into the joint. HA injections are a less invasive option than surgery, with potentially fewer complications.
 To support decision-making about treating hip, shoulder, or ankle OA in adults 55 years and younger, it is important to understand the potential benefits and harms of using HA in this population.
 
 What Did We Do?
 
 We reviewed the clinical effectiveness of high molecular weight (MW) injection of HA in adults between the ages of 18 and 55 years with OA of the hip, shoulder, or ankle joints to guide decisions on the use of high MW HA injection.
 An information specialist searched for peer-reviewed and grey literature sources published on January 1, 2013 to December 12, 2023. One reviewer screened citations and selected and critically appraised the included studies.
 
 What Did We Find?
 
 The evidence for this report was based on observational before-and-after studies. We found no relevant comparative studies examining the effect of high MW HA versus placebo or no treatment.
 While most studies reported post-treatment outcome improvements, it is uncertain whether high MW injection of HA improves pain, function, and disability in adults 55 years and under with hip, shoulder, or ankle OA. This is due to the low-quality evidence, small sample sizes, and methodological problems. Serious side effects of high MW HA were not reported.
 
 What Does This Mean?
 
 Due to the uncertainty of the clinical effectiveness evidence, health care providers and decision-makers may consider other factors when considering high MW IA-HA for patients with hip, shoulder, or ankle OA; these factors could include acceptability, feasibility, costs, health equity, and patient values and preferences.
 Future research from randomized studies in large populations is needed to understand the effectiveness and safety of high MW HA injections for hip, shoulder, and ankle OA.

Microfragmented Adipose Tissue Is Equivalent to Platelet-Rich Plasma for Knee Osteoarthritis at 12 Months Posttreatment: A Randomized Controlled Trial.

Platelet-rich plasma (PRP) is an effective treatment for knee osteoarthritis (OA). Microfragmented adipose tissue (MFAT) is another orthobiologic that holds promise, but data supporting its use are limited. Previous studies showed that MFAT created using the Lipogems device was equivalent to PRP created via noncommercial laboratory-based processes. To perform a comparison of commercially available MFAT and PRP systems for treatment of knee OA. Randomized controlled trial; Level of evidence, 2. A total of 71 patients with symptomatic knee OA (Kellgren-Lawrence grades 1-4) were randomized to receive a single injection of either leukocyte-rich PRP (Angel; Arthrex) or MFAT (Lipogems) under ultrasound guidance. Patient-reported outcomes (Knee injury and Osteoarthritis Outcome Score [KOOS], visual analog scale for pain with activities of daily living [VAS pain], and Tegner activity level) were recorded at baseline and at 1, 3, 6, and 12 months after injection. The primary outcome was the KOOS-Pain subscale score at 12 months after injection. Overall, 49 patients completed their 12-month follow-up (PRP group, n = 23; MFAT group, n = 26). All demographic features were similar between groups, except that more men were randomized to the PRP group and more women to the MFAT group. At 12 months posttreatment, KOOS-Pain scores improved in both groups, with no significant group difference (PRP, 78 ± 17.9 vs MFAT, 77.8 ± 19.3; P = .69). Similarly, other KOOS subscales, VAS pain scores, and Tegner scores improved at 12 months, with no differences between treatment groups. Both PRP and MFAT injections for knee OA resulted in improved patient-reported outcomes at 12 months posttreatment, with no differences found between treatments. NCT04351087 (ClinicalTrials.gov identifier).

Intra-articular corticosteroid injections provide a clinically relevant benefit compared to placebo only at short-term follow-up in patients with knee osteoarthritis: A systematic review and meta-analysis.

To quantify the clinical relevance of intra-articular corticosteroid effects compared to placebo for the injective treatment of knee osteoarthritis (OA). The PubMed, Cochrane Libraryand Web of Science databases were searched on May3, 2023. This study was conducted in accordance with the PRISMA guidelines. The inclusion criteria were randomized controlled trials (RCTs), published in English, with no time limitation regarding publication date, comparing intra-articular corticosteroids and placebo injections for knee OA. The effects were quantified at short- (≤6 weeks), mid- (>6 weeks and ≤3 months), and long-term (≥6 months) follow-ups. The minimal clinically important difference (MCID) for the outcomes (visual analogue scale for pain - VAS: 1.4, Western Ontario and McMaster University Osteoarthritis Index - WOMAC: 9) was used to interpret the clinical improvement provided by intra-articular corticosteroid injections compared to placebo. The quality of each article was assessed using the Cochrane RoB 2 tool and the GRADE guidelines. Among the 1030 articles retrieved, 11 RCTs (842 patients) were included. A comparison of the two groups revealed statistically significant differences in the improvement of VAS and WOMAC scores in terms of the mean difference (MD); this difference was in favour of corticosteroids at short-term (p < 0.001, MD = -1.6 and p < 0.001, MD = -9.9, respectively) and mid-term follow-ups (p = 0.001, mean MD = -1.3 and p = 0.005, MD = -4.9, respectively). No difference was observed at the long-term follow-up. The MDs between the improvements in the two groups reached the MCID values for the VAS and WOMAC only at the short-term follow-up. The RoB 2 tool and the GRADE evaluations showed the presence of risk of bias and limited quality of evidence. This systematic review and meta-analysis demonstrated that intra-articular corticosteroid injections offer clinically perceivable pain relief and functional improvement higher than the placebo effect only at short-term follow-up in patients affected by knee OA, with benefits losing clinical relevance already after 6 weeks. These results, together with the low number and the limited quality of the RCTscomparing this treatment with placebo, question the indication for the use of corticosteroid injections in clinical practice for the treatment of knee OA. Level I.

Clinical and radiological efficacy of single-dose intra-articular high-molecular-weight hyaluronic acid in knee osteoarthritis.

While visco-supplementation is being used for the treatment of knee osteoarthritis (OA), the published reports vary widely in benefits afforded by this treatment. It was therefore proposed to assess the objective parameters along with subjective outcomes. Our study assessed the radiological and clinical efficacy of single-dose high-molecular-weight intra-articular hyaluronic acid (HMW-IAHA) injection in knee OA. This interventional cohort study was conducted in a calculated sample size of 44 patients with knee OA. Visual analog scale (VAS) and knee OA and outcome score (KOOS) were used for clinical assessment, and whole organ magnetic resonance imaging score (WORMS) for radiological assessment. The subjects were given a single dose of HMW-IAHA injection, 90 mg/3 ml, and were assessed on day 0 and day 90. Statistical Package for Social Sciences (SPSS) software was used. At the day 90 follow-up, there was an improvement in mean ± standard deviation values of VAS score (day 0: 8.53 ± 0.81, day 90: 5.97 ± 0.87), KOOS score (day 0: 27.33 ± 15.18, day 90: 57.26 ± 14.26), and the cartilage signal and morphology in the medial femorotibial joint (day 0: 11.02 ± 6.26 and day 90: 10.91 ± 6.22) and patellofemoral joint (day 0: 10.35 ± 4.36 and day 90: 10.28 ± 4.39) compartments. There was a decrease in synovitis score from 2.3 ± 1.61 to 1.3 ± 1.3 in the medial femorotibial joint compartment and total WORMS score (day 0: 66.57 ± 36.06, day 90: 65.14 ± 35.62). A single dose of intra-articular injection with high-molecular-weight hyaluronic acid produces improvement in the clinical symptoms and quality of life as well as is effective in maintaining the articular cartilage integrity and reducing synovial inflammation.

Statistical Fragility of Randomized Controlled Trials Evaluating Platelet-Rich Plasma Use for Knee Osteoarthritis: A Systematic Review.

Numerous studies have been published on the use of platelet-rich plasma (PRP) for knee osteoarthritis (OA), with conflicting results. To determine the fragility index (FI) and fragility quotient (FQ) of randomized controlled trials (RCTs) that evaluated the use of PRP to treat knee OA. Systematic review. RCTs evaluating the efficacy of PRP injections for knee OA from 2000 to 2020 were included for analysis according to PRISMA guidelines. The FI was determined by calculating the number of outcome event reversals required to change the statistical significance. The associated FQ was determined by dividing the FI by the sample size. Our initial search resulted in 41,149 studies, of which 8 RCTs (678 patients, 72 outcome events) were included in the analysis. One study failed to report PRP formulation details, whereas 87.5% of studies reported using either leukocyte-rich or leukocyte-poor PRP. The platelet concentration was reported in 25% of the included trials. The overall FI of the 72 outcome events was 8.5. Accounting for sample size, the associated FQ was determined to be 0.14, suggesting that the reversal of 14% of outcome events was required to change outcome significance. There were 51 statistically significant outcomes, of which the FI and FQ were 12 and 0.164, respectively. Comprehensive fragility analysis suggested that the published literature evaluating the efficacy of PRP use for knee OA may lack statistical stability. We recommend the reporting of both an FI and FQ in addition to P value analysis to provide a clear and thorough understanding of the statistical integrity of studies reporting on PRP use for knee OA.

Understanding the effects of mesenchymal stromal cell therapy for treating osteoarthritis using an in vitro co-culture model.

Osteoarthritis (OA) is a leading cause of chronic pain and disability, for which there is no cure. Mesenchymal stromal cells (MSCs) have been used in clinical trials for treating OA due to their unique ability to generate paracrine anti-inflammatory and trophic signals. Interestingly, these studies have shown mainly short-term effects of MSCs in improving pain and joint function, rather than sustained and consistent benefits. This may reflect a change or loss in the therapeutic effects of MSCs after intra-articular injection. The present study aimed to unravel the reasons behind the variable efficacy of MSC injections for OA using an in vitro co-culture model. Osteoarthritic human synovial fibroblasts (OA-HSFs) were co-cultured with MSCs to investigate their reciprocal effects on cell responses and whether a short-term exposure of OA cells to MSCs was sufficient for reducing their diseased characteristics in a sustained manner. Gene expression and histological analyses were performed. OA-HSFs exposed to MSCs showed short-term downregulation of inflammatory markers. However, the MSCs showed upregulation of inflammatory markers and impaired ability to undergo osteogenesis and chondrogenesis in the presence of OA-HSFs. Moreover, short-term exposure of OA-HSFs to MSCs was found to be insufficient for inducing sustained changes to their diseased behaviour. These findings suggested that MSCs may not provide long-term effects in correcting the OA joint environment due to them adopting the diseased phenotype of the surrounding tissues, which has important implications for the future development of effective stem-cell-based OA treatments with long-term therapeutic efficacy.

Evaluating the Effectiveness of Intra-articular Platelet Rich Plasma Injections for the Treatment of Knee Osteoarthritis: A Systematic Review

Introduction: Osteoarthritis (OA) is the most frequently presented joint disorder, and its treatment is often challenging. Current literature has controversial results regarding the efficacy of Platelet Rich Plasma therapy (PRP) when compared to placebo injections. This systematic review investigates the role of intra-articular PRP injections as a recommended treatment option for knee OA with the potential to establish appropriate guidelines for treating physicians. Method: This review used PUBMED, Cochrane and CINHAL database. A thorough review of literature examining PRP injections as treatment options for knee OA was performed. Two independent reviewers evaluated the studies against inclusion and exclusion criterias. The WOMAC stiffness score, VAS Score, and KOOS score were used to assess efficacy of PRP treatment. Twelve articles met the criteria for inclusion and were analysed in this study. Results: PRP injections caused a significantly better improvement in WOMAC stiffness score (25.5%), VAS Score (31.7%), and KOOS score (6.2%) after six months of treatment. Conclusion: This review demonstrated significant improvement in pain relief and stiffness levels in patients with knee OA receiving intra-articular PPR when compared to placebo. Further research is required to establish the optimum dose and duration of treatment with PRP injections for knee OA.

Safety and efficacy of intra-articular injection of platelet-rich plasma for the treatment of ankle osteoarthritis: a systematic review and meta-analysis.

To evaluate the safety and efficacy of platelet-rich plasma (PRP) intra-articular injective treatments for ankle osteoarthritis (OA). A systematic literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in PubMed, Scopus, Embase, Google Scholar, and the Cochrane library until May 2022. Both randomized and non-randomized studies were included with the assessment of the risk of bias. We recorded the participant's age, gender, type of PRP, injection volume, the kit used, and activating agent. We subsequently assessed the short-term and long-term efficacy of PRP using the functional scores and visual analog scale (VAS). We included four studies with a total of 127 patients, with a mean age of 56.1years. 47.2% were male (60/127), according to eligibility criteria. There were three cohort studies and one randomized controlled trial (RCT) study, and no study reported severe adverse events. All included studies used the Leukocyte-poor PRP. Short-term follow-up results suggested significant improvement of the American Orthopaedic Foot and Ankle Society (AOFAS) score in the PRP injection group compared to the control group (n = 87 patients; MD: 6.94 [95% CI: 3.59, 10.29]; P < 0.01). Consistently, there was a statistical difference in AOFAS score between PRP injection and control groups in the final follow-up (≥ 6months) (n = 87 patients; MD: 9.63 [95% CI: 6.31, 12.94]; P < 0.01). Furthermore, we found a significant reduction in VAS scores in the PRP groups at both the short-term follow-up (n = 59 patients; MD, - 1.90 [95% CI, - 2.54, - 1.26]; P < 0.01) and the ≥ sixmonths follow-up (n = 79 patients; MD, - 3.07 [95% CI, - 5.08, - 1.05]; P < 0.01). The improvement of AOFAS and VAS scores at ≥ sixmonths follow-up reached the minimal clinically important difference (MCID). Nevertheless, the treatment effect of AOFAS and VAS scores offered by PRP at short-term follow-up did not exceed the MCID. Substantial heterogeneity was reported at the ≥ sixmonths follow-up in VAS scores (I2: 93%, P < 0.01). This meta-analysis supports the safety of PRP intra-articular injection for ankle OA. The improvements of AOFAS and VAS scores in the PRP group at short-term follow-up do not exceed the MCID to be clinically significant. PRP injection provides significant improvement of AOFAS score and reduced pain at ≥ sixmonths follow-up. The efficacy of PRP should be interpreted with caution regarding the high heterogeneity and the scarcity of available literature, which urges large-scale RCTs with longer follow-up to confirm the potential efficacy of PRP injection for ankle OA.

Platelet-Rich Plasma Injection for Thumb Carpometacarpal Joint Osteoarthritis

ObjectiveTo assess the effects of platelet-rich plasma (PRP) injection among patients with thumb carpometacarpal (CMC) joint osteoarthritis (OA). DesignRetrospective chart review with follow-up questionnaires/surveys. Post-procedure, patients were sent standardized, automatically-generated follow-up questionnaires, and contacted for a survey regarding patient-reported outcomes. SettingSingle institution (tertiary care hospital) outpatient clinic from 2015 to 2020. ParticipantsNineteen adult patients (9 women; average age 65.0 [±6.3 years]) who received a PRP injection for OA of 1 or both thumb CMCs (N=19). InterventionsPlatelet-rich plasma injection. Main Outcome MeasuresOutcome measures included symptom improvement (subjective, visual analog scale), duration of benefit, subsequent procedures, satisfaction, and side effects/adverse events. Cellular composition of whole blood and PRP injectate (platelets, erythrocytes, leukocytes, neutrophils, lymphocytes, and monocytes) were analyzed. ResultsSubjects reported moderate or excellent symptom improvement in 68.8% of injected joints and were moderately or very satisfied with 68.8% of the procedures. Mean patient-reported duration of benefit was 15.6 months (±19.5) months (mean duration of follow-up: 32.4 [±18.1] months). There were no major complications attributed to the procedures, but 1 patient was diagnosed with presumed unrelated lymphoma 2 weeks post-procedure. PRP mean platelet concentration was 1787.77 (±687.14) × 109/L, resulting in a mean platelet concentration factor of 8.80 (±4.19) times baseline and mean platelet dose of 1881 × 106. Other PRP cell concentration factors were erythrocytes, 0.02; neutrophils, 0.14; lymphocytes, 3.76; and monocytes, 3.29. ConclusionsPRP injection appears to be a safe and potentially effective treatment option for pain related to first CMC OA. Further study is needed to optimize treatment protocols and better understand which patients are most likely to benefit.

Platelet-rich plasma use for hip and knee osteoarthritis in the United States

BackgroundHip and knee osteoarthritis (OA) are rising in prevalence and increasingly affecting younger patients. There is a rising demand for therapeutics to address its growing disease burden. Platelet-rich plasma (PRP) therapy has been used to treat various musculoskeletal conditions, but its role in OA treatment is not well understood. Even still, there is significant interest in this biologic for treatment of OA. The purpose of this study was to determine the PRP utilization trends in the United States for hip and knee OA. MethodsThis was a retrospective review from the PearlDiver Patient Record Database. International Classification of Diseases and Current Procedural Terminology codes were used to identify patients who had received PRP injections for hip and knee OA from 2010 to 2018. Injection incidence was evaluated on an annual basis and by patient demographics, geographic distribution, and medical specialty under which the treatment was administered. ResultsA total of 3,884 PRP injections were administered over the study period, 15% for hip OA and 85% for knee OA. PRP injections per 100,000 patient cases increased by an average year-over-year percentage of 53% and 12% for hip and knee OA, respectively. The highest injection incidences were observed in patients younger than 44 years of age. 58% of both hip and knee PRP injections were administered in general orthopaedic practices. ConclusionThese findings show that PRP is increasingly being used as a treatment modality for hip and knee OA. There is a need for further research on its long term outcomes.

Responsiveness of an activity tracker as a measurement tool in a knee osteoarthritis clinical trial (ACTIVe-OA study).

In osteoarthritis (OA) clinical trials, reliable and responsive outcome measures to document physical and functional improvements are limited. This study aimed to assess whether the use of an activity tracker in an OA clinical trial is a responsive measurement tool. Secondary objectives assessed feasibility and validity. We recruited 65 participants in a prospective cohort study nested in a placebo-controlled clinical trial of platelet-rich plasma injection in knee OA. Participants wore an activity tracker (Fitbit Flex 2), and a smartphone was preloaded with a mobile application (OApp) designed to monitor load rates as a surrogate of knee loading. Participants used the systems for 7 days at baseline and for 7 days before the 2-month follow-up assessment. Effect size (ES) and standardised response mean (SRM) were calculated for change in step count and knee loading rate and regularly used knee OA outcome measures. Correlation coefficients (r) were calculated to examine the strength of the association between outcome measures. . Step count showed a trivial ES and SRM and mean knee loading rate measurements a moderate ES and SRM. We found a weak but significant correlation between change in mean steps per day and global improvement overall (r=0.28) and Western Ontario and McMaster Universities Osteoarthritis Index function (r=-0.28). Compliance was high with the activity trackers. Despite good feasibility, this study did not show significant responsiveness or validity of the activity trackers as compared with currently recommended outcome measures in OA clinical trials. The main challenge is the lack of a gold standard outcome measure to validate against, and because of the complex interplay between pain and measured function, a lack of correlation does not necessarily represent a failed validation in this context. ACTRN12617000853347. This trial is a substudy of the "Platelet-rich plasma as a symptom-and disease-modifying treatment for knee osteoarthritis - the RESTORE trial".

Umbilical Cord–Derived Stem Cells for the Treatment of Knee Osteoarthritis: A Systematic Review

Background:The use of mesenchymal stem cells (MSCs) for the treatment of knee osteoarthritis (OA) has gained recent interest in the orthopaedics community.Purpose:To review the literature to evaluate the efficacy of umbilical cord–derived MSCs in the treatment of OA of the knee joint.Study Design:Systematic review; Level of evidence, 4.Methods:We searched the PubMed, Cochrane Library, and Embase databases to identify studies with evidence levels from 1 to 4 that evaluated the clinical efficacy of human umbilical cord–derived MSC (hUC-MSC) injections for knee OA. The search phrase used was “umbilical cord knee osteoarthritis.” In the studies reviewed, patients were assessed based on the macroscopic International Cartilage Regeneration & Joint Preservation Society (ICRS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS) for pain, and the subjective International Knee Documentation Committee (IKDC) score.Results:A total of 7 studies met inclusion criteria, including 385 patients undergoing injection of hUC-MSCs (mean age, 59.7 years). The mean follow-up was 23.4 months. Weighted averages of the WOMAC, macroscopic ICRS, subjective IKDC, and VAS scores all showed improvement from before to after treatment. No severe adverse reactions were recorded.Conclusion:Patients undergoing treatment of knee OA with hUC-MSCs might be expected to experience improvements in clinical outcomes. Additional high-quality randomized studies are needed to better determine the efficacy of hUC-MSC for the treatment of knee OA.

Do Glucocorticoid Injections Increase the Risk of Knee Osteoarthritis Progression Over 5 Years?

Recent findings have demonstrated that intraarticular (IA) glucocorticoid injections can be deleterious for knees with osteoarthritis (OA). This study was undertaken to assess, in a real-life setting, the risk of knee OA progression in patients who received IA glucocorticoid injections over a 5-year follow-up period. We used marginal structural modeling with inverse probability of treatment weighting to determine the causal association between IA glucocorticoid injections and the 5-year risk of disease progression in patients with symptomatic knee OA from the Knee and Hip Osteoarthritis Long-term Assessment cohort. OA progression was defined as an incident total knee replacement (TKR) and/or radiographic worsening (Kellgren/Lawrence [K/L] grade or joint space narrowing [JSN]). We also examined these outcomes in knees that received IA hyaluronan (IAHA) injections. Among the 564 patients with knee OA included in the study sample, 51 (9.0%) and 99 (17.5%) received IA glucocorticoid or IAHA injections, respectively, and 414 (63.1%) did not receive any injection during follow-up. Compared to untreated knees, those treated with IA glucocorticoid injections had a similar risk of incident TKR (hazard ratio [HR] 0.92 [95% confidence interval (95% CI) 0.20, 4.14]; P = 0.91) or K/L grade worsening (HR 1.33 [95% CI 0.64, 2.79]; P = 0.44). IAHA injections had no effect on the risk of TKR (HR 0.81 [95% CI 0.14, 4.63]; P = 0.81) or K/L grade worsening (HR 1.36 [95% CI 0.85, 2.17]; P = 0.20). Similar results were obtained for JSN, and when TKR and radiographic outcomes were combined. In this study, IA glucocorticoid injections for symptomatic knee OA did not significantly increase the 5-year risk of incident TKR or radiographic worsening. These findings should be interpreted cautiously and replicated in other cohorts.

Factors Influencing Physician Recommendation for Intraarticular Therapies in Osteoarthritis: Results From a Qualitative Study.

Several current and many emerging osteoarthritis (OA) treatments are intraarticular (IA) injections; however, little is known about physicians' perceptions and beliefs regarding IA injections or their considerations when deciding whether to recommend them to patients. We aimed to investigate physician-perceived benefits and drawbacks of offering IA injections. We conducted individual interviews with orthopedic surgeons, rheumatologists, and physiatrists who treat patients with knee OA. We conducted a thematic analysis to identify factors that physicians weigh when making IA injection recommendations. We interviewed 18 physicians from academic and community practices. We identified the following 4 categories of themes that influenced providers' recommendations to their patients regarding injections: 1) the physician's knowledge, beliefs, and concerns, including their propensity to rely on guidelines versus clinical experience, and understanding of the efficacy and risks associated with injectables, such as possible cartilage damage; 2) the characteristics of the injectable product, such as ease or number of administrations needed; 3) the individual patient-specific factors, including OA severity, comorbidities, and patient preference for and expectations of specific IA injections; and 4) the financial and administrative factors, including insurance coverage and out-of-pocket costs. Physicians factor the uncertain efficacy of injectable treatments and the need to manage patient expectations into their decision to offer IA therapies. Some providers relied on evidence and guidelines while others were swayed more by clinical experience. High out-of-pocket costs were seen as a barrier to use. These findings may help in the delivery of IA injections for OA and in the development of injectable products.

Intra-articular injections in the treatment of osteoarthritis

Local methods are widely used in the treatment of osteoarthritis (OA) and play a significant role in the complex therapy of this disease. A special place among them belongs to intra-articular (i/a) administration of drugs. The most widely used for this purpose are glucocorticoids (GC) and hyaluronic acid (HA) drugs. When comparing the effectiveness of these drugs, it was shown that during the 1st month, HA had more favorable results, after 3 months the results did not differ significantly, and after 6 months, the effectiveness of HA was higher. Some authors believe that the optimal result can be obtained with the combined use of HA and GC.The efficacy and tolerability of HA drugs in patients with OA have been studied in numerous randomized controlled trials (RCTs), and the data obtained in these studies have been summarized in a number of meta-analyses. At the same time, both in RCTs and in meta-analyses, the results of such treatment were assessed differently. However, when summarizing the materials of various meta-analyses within the framework of a systematic review, it was shown that i/a injections of HA are an effective and safe method of local treatment of OA. However, there are no generally accepted recommendations for the use of HA in the treatment of OA, and the question of their administration in each case is decided individually, taking into account the history, clinical picture, OA phenotype, and tolerability of therapy. The Russian Association of Rheumatologists recommends the use of i/a HA injections in knee OA with synovitis and the use of HA injections to reduce pain and improve joint function.

Comparison of Extracorporeal Shockwave Therapy with Non-Steroid Anti-Inflammatory Drugs and Intra-Articular Hyaluronic Acid Injection for Early Osteoarthritis of the Knees.

Conservative treatments for early osteoarthritis (OA) of the knee included the use of non-steroid anti-inflammatory drugs (NSAIDs) and intra-articular hyaluronic acid (HA) injection. Recently, several animal studies reported that extracorporeal shockwave therapy (ESWT) demonstrated chondroprotective effects on knee OA. The present study compared the efficacy of oral NSAIDs, HA injection, and noninvasive ESWT for early OA of the knee. Forty-five patients with early knee OA were randomized into three groups. NSAIDs group received celecoxib 200 mg daily for 3 weeks. HA group received intra-articular injection of HA once a week for 3 weeks. ESWT group received ESWT for 3 sessions at bi-weekly interval. All patients were followed up for one year. Evaluations included the visual analogue scale (VAS) score, serum enzyme-linked immunosorbent assay (ELISA), plain radiography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI). In addition, the functional scores were performed including, WOMAC (Western Ontario and McMaster Universities Arthritis Index) score, KOOS (knee injury and osteoarthritis outcome) score, and IKDC (International Knee Documentation Committee) score. All three groups showed significant improvement in VAS and functional scores as well as in the collected one-year follow-up data after treatments. ESWT group had better pain relief than NSAIDs and HA groups. ESWT group had better therapeutic effects in the functional scores than NSAIDs and HA groups. The bone mineral density (BMD) of proximal tibia is significantly increased after ESWT than others. In the serum ELISA, ESWT inhibited the expression of COMP in knee OA patients as compared with NSAIDs and HA groups. The parameters of MRI showed no significant differences between three groups after treatments. ESWT and intra-articular HA injection showed comparable results than NSAIDs. ESWT was superior in pain relief than HA and NSAIDs. The results demonstrated that ESWT was an effective and alternative therapy than HA and NSAIDs for early osteoarthritis of the knees.

Systematic Review and Meta-Analysis of Health State Utility Values for Osteoarthritis-Related Conditions.

Health state utility values (HSUVs) are a key input in health economic modeling, but HSUVs of people with osteoarthritis (OA)-related conditions have not been systematically reviewed and meta-analyzed. Our objective was to systematically review and meta-analyze the HSUVs for people with OA. Searches within health economic/biomedical databases were performed to identify eligible studies reporting OA-related HSUVs. Data on study design, participant characteristics, affected OA joint sites, treatment type, HSUV elicitation method, considered health states, and the reported HSUVs were extracted. HSUVs for people with knee, hip, and mixed OA in pre- and posttreatment populations were meta-analyzed using random effects models. A total of 151 studies were included in the systematic review, and 88 in meta-analyses. Of 151 studies, 56% were conducted in Europe, 75% were in people with knee and/or hip OA, and 79% were based on the EuroQoL 5-dimension instrument. The pooled mean baseline HSUVs for knee OA core interventions, medication, injection, and primary surgery treatments were 0.64 (95% confidence interval [95% CI] 0.61-0.66), 0.56 (95% CI 0.45-0.68), 0.58 (95% CI 0.50-0.66), and 0.52 (95% CI 0.49-0.55), respectively. These were 0.71 (95% CI 0.59-0.84) for hip OA core interventions and 0.52 (95% CI 0.49-0.56) for hip OA primary surgery. For all knee OA treatments and hip OA primary surgery, pooled HSUVs were significantly higher in the post- than the pretreatment populations. This study provides a comprehensive summary of OA-related HSUVs and generates an HSUV database for people with different affected OA joint sites undergoing different treatments to guide HSUV choices in future health economic modeling of OA interventions.