Intra-articular Therapies Research Articles

Genicular Nerve Block for Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

Genicular nerve block (GNB) has emerged as a novel nonsurgical therapy for symptomatic knee osteoarthritis (KOA). The objective was to evaluate GNB versus placebo and other intra-articular (IA) therapies. The Medline, Embase, and Scopus databases were searched from their inception to January 2021. Only randomized controlled trials (RCTs) were included. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was tested with the I2 index. Regarding pain statistically significant scores were demonstrated at 1 and 3 months overall total effect of 1.43 (95% CI, 0.86, 1.99; P= 0.00001; I2 =85%). Similarly, for knee function a total effect of 0.71 (95% CI, 0.35, 1.06; P= 0.00001; I2 =69%) at 1 and 3 months, statistically significant. The minimal clinically important difference regarding pain was achieved at 1 and 3 months. Although, GNB achieved the MCID for KOA pain and statistically significant results for knee functions. We cannot recommend its routine use besides being a safe procedure so far, evidence is fair on GNB for primary KOA due to study heterogeneity and limited follow-up.

The Potential of Intra-Articular Therapies in Managing Knee Osteoarthritis: A Systematic Review.

Knee osteoarthritis (KOA) is a common degenerative and progressive joint disorder that negatively influences patients' quality of life. Intra-articular therapies, such as hyaluronic acid (HA) and platelet-rich plasma (PRP), have garnered attention for their potential to manage osteoarthritis OA symptoms effectively. This systematic review aims to identify the effectiveness and safety of HA and PRP treatment modalities in treating KOA. A literature search was conducted across MEDLINE (PubMed), Web of Science Core Collection, and Science Direct Collection Elsevier. Twenty-three randomized controlled trials, cohort studies, and observational studies were included in the review. The selection criteria focused on studies published in English within the last 10 years, involving subjects with KOA treated with intra-articular injections of HA or PRP and reporting on pain, function, or overall treatment efficacy outcomes. The analysis showed that both HA and PRP significantly improve functionality and reduce pain in KOA patients. High molecular weight HA consistently reduced pain and improved joint mobility in various studies. PRP had better long-term outcomes when combined with HA, leading to greater pain reduction and functional improvement. Both therapies had generally favorable safety profiles, with only minor adverse events reported. However, there were potential biases identified across the studies, such as selection, performance, detection, and reporting biases, which impacted the reliability of the results. Intra-articular treatments with HA and PRP show promise in managing knee osteoarthritis, with personalized treatment plans and further research needed to confirm these findings.

Semi-invasive therapies for pain in knee osteoarthritis: A systematic review and network meta-analysis.

The increasing number of semi-invasive pain therapies in knee osteoarthritis poses challenges in decision-making. This review aimed to simultaneously compare established intra-articular therapies with newer peri-articular therapies and explore effect modifiers. Randomized controlled trials were searched from five electronic databases without date or language restrictions. Study selection and data extraction of reports, retrieved up to May 2024, were performed independently by paired assessors. The primary outcome was 6-month pain score. Nine treatments were included. The effect size (ES) for each treatment, relative to placebo, was estimated using standardized means difference and expressed with 95% confidence intervals (CI). The rigor of results was evaluated with subgroup/sensitivity analyses. A total of 111 studies (14,695 participants) were included, with intra-articular hyaluronic acid having the greatest number of participants. Neuroablation demonstrated the greatest ES (1.08, 95% CI: 0.07, 2.10). While platelet-rich plasma (PRP) ranked second (ES: 0.75, 95% CI: 0.28, 1.22), it was the only intervention demonstrating statistically significant effect at 3, 6, and 12 months. However, this statistical significance was lost in some sensitivity analyses. Larger estimates for biologics and PRP compared with prolotherapy, steroid, and hyaluronic acid injections were consistently observed across different timepoints and in multiple sensitivity analyses. Generally, no statistically significant difference was found between the nine types of therapies. Although there is robust evidence suggesting greater efficacy of PRP, potentially including biologics, over other interventions, future research is needed to identify the phenotype or patient subgroup that would benefit most from PRP.

The effect of intra-articular autologous protein solution on knee osteoarthritis symptoms.

Knee osteoarthritis (OA) is characterized by a chronic inflammatory process involving multiple cytokine pathways, leading to articular cartilage degeneration. Intra-articular therapies using pharmaceutical or autologous anti-inflammatory factors offer potential non-surgical treatment options. Autologous protein solution (APS) is one such product that uses the patient's blood to produce a concentrate of cells and anti-inflammatory cytokines. This study evaluated the effect of a specific APS intra-articular injection (nSTRIDE) on patient-reported outcome measures compared to saline in moderate knee OA. A parallel, double-blinded, placebo-controlled randomized controlled trial was conducted, where patients with unilateral moderate knee OA (Kellgren-Lawrence grade 2 or 3) received either nSTRIDE or saline (placebo) injection to their symptomatic knee. The primary outcome was the difference in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 12 months post-intervention. Secondary outcomes included WOMAC component scores, Knee injury and Osteoarthritis Outcome Score (KOOS), and visual analogue scale (VAS) scores at all follow-up timepoints (three, six, and 12 months). A total of 40 patients were analyzed (21 nSTRIDE; 19 saline) in the study. No significant difference was found between nSTRIDE and saline groups for WOMAC total score at 12 months (mean difference -10.4 (95% CI -24.4 to 3.6; p = 0.141). There were no significant differences in WOMAC or KOOS scores across all timepoints. VAS scores favoured the saline group for both rest and worst pain scales at 12 months post-injection (mean difference (worst) 12 months 21.5 (95% CI 6.2 to 36.8; p = 0.008); mean difference (rest) 12 months 17.8 (95% CI 2.2 to 33.4; p = 0.026)). There were no adverse events recorded in either study group. Our study demonstrates no significant differences between nSTRIDE and saline groups in KOOS and WOMAC scores over time. Notably, APS injection resulted in significantly worse pain symptoms at 12 months compared to saline injection.

Culture of Hoffa fat pad mesenchymal stem/stromal cells on microcarrier suspension in vertical wheel bioreactor for extracellular vesicle production

BackgroundMesenchymal stromal cells (MSCs) are increasingly employed in regenerative medicine approaches for their immunomodulatory and anti-inflammatory properties, which are encoded in their secretome including extracellular vesicles (EVs). The Hoffa fat pad (HFP) located infrapatellarly harbours MSCs that could assist in tissue homeostasis in osteoarthritic joints. Intraarticular injection therapies based on blood products could modulate the populations of released HFP-MSC-EVs in a quantitative manner.MethodsTo obtain amounts of HFP-MSC-derived EVs that allow pre-clinical evaluation, suitable EV production systems need to be developed. This work investigates the release of EVs from primary HFP-MSCs cultivated in a 3D environment using microcarrier suspension culture in a vertical wheel bioreactor in comparison to conventional 2D culture. To simulate an intraarticular blood product therapy, cultures were treated with citrate-anticoagulated platelet-rich plasma (CPRP) or hyperacute serum (hypACT) before EV collection. HFP-MSC-EVs are enriched via ultrafiltration and characterised via Western Blot, nanoparticle tracking analysis in scatter as well as fluorescence mode. EV potency was determined via RT-qPCR analysing the expression of type II and X collagen (COL2 and COL10), as well as inducible nitric oxide synthase (iNOS) in primary OA chondrocytes.ResultsBlood product supplementation elevated HFP-MSC metabolic activity as determined via XTT assay over the course of 14 days. 3D culture resulted in a roughly 100-fold EV yield compared to 2D culture and elevated number of EVs released per cell. Total protein content correlated with the EV concentration. While typical EV marker proteins such as CD9, CD63 or Alix were detected in total protein extracts, CD9 and CD73 colocalised on individual EVs highlighting their cell origin. The type of blood product treatment did not affect the size or concentration of EVs obtained from HFP-MSCs. Assessing potency of 3D culture EVs in comparison to 2D EVs revealed superior biological activity with regard to inhibition of inflammation, inhibition of chondrocyte hypertrophy and induction of cartilage-specific ECM production.ConclusionsHFP-MSCs proliferate in presence of human blood products indicating that animal serum in culture media can be avoided in the future. The culture of HFP-MSCs in the employed bioreactor was successfully used to generate quantities of EVs that could allow evaluation of HFP-MSC-EV-mediated effects in pre-clinical settings. In addition, EV potency of 3D EVs is superior to EVs obtained in conventional 2D culture flasks.

Comparative effectiveness of intra-articular therapies in knee osteoarthritis: a meta-analysis comparing platelet-rich plasma (PRP) with other treatment modalities.

Knee osteoarthritis (KOA) is a progressive joint disease commonly treated with intra-articular injections, including platelet-rich plasma (PRP), hyaluronic acid (HA), or corticosteroids (CS). This updated meta-analysis aims to enhance the statistical power of the results and provide comprehensive clinical evidence that reflects the most current research. By doing so, the authors aim to suggest a reliable estimate for the development of guidelines, addressing the pressing need for effective and minimally invasive treatment options. PubMed, Scopus, clinicaltrials.gov, Cochrane Central were searched until March 2023, for randomized controlled trials (RCTs) comparing the effectiveness of intra-articular injectable therapies, including PRP, HA, CS, and placebo, in KOA. Data extraction involved baseline characteristics and outcome measures [Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, Visual Analog Scale (VAS) pain scores, KOOS, and IKDC scores] at 1, 3, 6 and 12 months. Statistical analysis, including subgroup analysis, assessment of heterogeneity, and publication bias, was conducted using Review Manager. Our meta-analysis of 42 studies involving 3696 patients demonstrated that PRP treatment resulted in significant pain relief compared to HA injections, as evidenced by improved WOMAC pain (MD: -0.74; 95% CI: -1.02 to -0.46; P≤0.00001; I 2=94%) and VAS pain (MD: -0.65; 95% CI: -1.24 to -0.06; P=0.03; I2=97%) outcomes. Similarly, PRP showed greater efficacy in reducing WOMAC pain (MD: -8.06; 95% CI: -13.62 to -2.51: P=0.004; I 2=96%) and VAS pain (MD: -1.11; 95% CI: -1.64 to -0.59; P≤0.0001; I 2=68%) compared to CS injections, with the most significant improvement observed at 6 months. PRP is an effective treatment for KOA. It provides symptomatic relief, has the potential to reduce disease progression, and has sustained effects up to 12 months. PRP offers superior pain relief and functional enhancement compared to CS and HA injections.

Effects of intra-articular administration of hyaluronic acid or platelet-rich plasma as a complementary treatment to arthroscopy in horses with osteochondritis dissecans

Although arthroscopy is the treatment of choice for horses with osteochondritis dissecans (OCD), it is not yet known whether intra-articular therapies in the postoperative period can bring any benefit to the recovery of these animals. This study evaluated the effects of the intra-articular application of platelet-rich plasma (PRP), hyaluronic acid (HA) or lactated Ringer's solution (LR) in horses with OCD undergoing arthroscopy. Eighteen male and female Brazilian Sport horses aged between 2 and 6 years were evaluated. All animals presented OCD fragments in the middle crest of the tibia. Ten days after surgery, animals were randomly distributed into three groups and received intra-articular application of PRP (n = 6), HA (n = 6), or LR (control group, n = 6). Clinical, radiographic, ultrasound and synovial fluid evaluations were performed on the day of surgery and after 10, 30 and 60 days. An increase in the thickness of the joint capsule was observed 30 days after surgery in the three groups evaluated. In the control group, there was significant improvement in the flexion test 30 and 60 days after surgery, and in the PRP group, there was worsening of this parameter in the same evaluations. In the control group, there was a reduction in the degree of synovial effusion, and in the PRP and HA groups, there was increased effusion. There was a significant increase in the number of leukocytes in the HA group. Intra-articular use of PRP or HA ten days after arthroscopy did not promote positive effects on the recovery of horses with OCD.

Surface modified cationic PLGA microparticles as long-acting injectable carriers for intra-articular small molecule drug delivery

Controlled local delivery of therapeutics (small molecule drug crystals or biologics) for knee-associated diseases such as osteoarthritis necessitates patient compliance, ensuring that the injected depot does not trigger local tissue inflammation and immune responses. A local drug delivery strategy that releases drug at a controlled rate while ensuring minimal tolerability issues at the injection site would be an appealing paradigm in intra-articular (IA) therapies. Herein, we report the formulation development and characterization of surface modified PLGA microparticles (MPs) through the surface integration of a cationic lipid, DOTAP (1,2-Dioleoyl-3-trimethylammonium propane). Following IA administration, these particles are able to interact with anionic synovial fluid glycosaminoglycans (GAGs) to form an in-situ surface coating in the knee joint, thereby reducing the depot-associated local inflammatory response. The formulated microparticles were about 10–40 µm in size range, with a +19 to +33 mV overall surface charge after DOTAP lipid surface integration. These particles showed preferential surface adhesion with endogenous anionic GAGs (e.g., hyaluronic acid) due to electrostatic interactions in vitro, and approximately 65 % of the model drug triamcinolone acetonide (TCA) was released after 10 weeks in simulated synovial fluid. The uncoated and DOTAP-coated PLGA microparticles had no effect on mouse osteoblast MC3T3 cell viability and human macrophage inflammatory response. Further, DOTAP-coated particles showed a marginal decrease in pro-inflammatory cytokines in naïve rats following knee injection. Together, the results suggest that surface-modified PLGA particles may have promising potential as delivery carriers for long-acting injectables.

Knee health promotion and cell therapy for knee osteoarthritis

Knee health promotion and cell therapy for knee osteoarthritis Shaw-Ruey Lyu, Professor from Dalin Tzu-Chi Hospital, Tzu-Chi University, says that the knee health promotion option and cell therapy are a perfect combination for knee osteoarthritis. Knee osteoarthritis (knee OA) is commonly but mistakenly referred to as a degenerative process of the knee. The mainstream medical community has devoted uncounted resources and talents to identifying the cause of knee OA, but that effort has only produced controversial results. Consequently, sufferers of knee OA have not been able to rest, and the deteriorating course of knee OA symptoms, which typically start from stage I and worsen to stages II, III, IV, and V, puts the patients through increasingly agonising pain and discomfort. The mainstream medical community collectively has tried to offer relief to their knee OA patients, such as nonpharmacological interventions, systemic drug treatment, intra-articular therapies ranging from corticosteroids to hyaluronans to more recently platelet-rich plasma, and more invasive surgical procedures such as arthroscopy or corrective osteotomy.

Towards intra-articular therapies for more than just symptom management in osteoarthritis

Towards intra-articular therapies for more than just symptom management in osteoarthritis

302 A Systematic Review and Meta-Analysis of Intra-Articular Injections for Base of Thumb Osteoarthritis

Abstract Aim Current literature is equivocal surrounding intra-articular injections for the treatment of thumb base osteoarthritis (TBOA), which is reflected in national and international guidelines. This systematic review assesses the effectiveness of different intra-articular injections for TBOA on pain and functional outcomes. Method MEDLINE, EMBASE, Cochrane Central Register of Control Trials and CINAHL databases were searched from inception to April 2022. Randomised controlled trials and comparative case series which investigated an injection-based intervention with any comparator/s were included. The protocol was registered to PROSPERO (CRD42022337265). Results Fifteen studies were included in the descriptive analysis of this review, with 4 included in the meta-analysis. From the intra-articular injection therapies, hyaluronic acid (HA) in 11 studies, corticosteroid (CS) CS in 10 studies, platelet-rich plasma (PRP) in 2 studies, dextrose (DX) in 1, HA mixed with NSAID in 1 study and placebo (saline) in 3 studies. Meta-analysis of visual analogue scale (VAS) showed that there was no statistically significant improvement in pain in the short-, medium- or long-term time points between HA vs CS injection therapies. Meta-analysis of functional outcomes showed an improvement in function with HA vs CS ((standardised mean difference (SMD) −1.05, 95% CI −1.43 to −0.68)) at the long-term time point. No significant adverse effects were reported. Conclusions There is no superior type of intra-articular injection for improving pain and limited evidence for HA for improving function. The choice of injection should be based on availability, guidelines and cost-benefit analysis until further methodologically robust trials can be completed.

Diagnosis and treatment of patellofemoral joint arthritis

Background: Although patellofemoral arthritis is a common and debilitating orthopedic disorder, its treatment varies and remains controversial. This review aims to provide an overview of the current understanding of the pathophysiology of patellofemoral arthritis, as well as its various diagnostic and treatment options.Current Concepts: The pathophysiology of patellofemoral arthritis includes lower limb malalignment, trochlear and/or patellar dysplasia, patellar instability, trauma, and obesity. The disorder is characterized by chronic anterior knee pain aggravated by flexion of the knee joint. A critical imaging study of the Merchant and lateral knee radiographs may show the progression of patellofemoral arthritis and dysplasia of the patellofemoral joints. Non-pharmacologic treatment options for patellofemoral arthritis include patient education, self-management, exercise, weight loss, taping, bracing, and orthotics. Pharmacologic agents (non-steroidal anti-inflammatory drugs, acetaminophen, oral narcotics, and duloxetine) and intra-articular injection therapies (glucocorticoids, hyaluronic acid, platelet-rich plasma, and other regenerative therapies) can be helpful for symptom relief in patients with patellofemoral arthritis. The surgical treatment can begin with lateral retinacular release to realign and decompress the patellofemoral joint. If failure in the improvement of symptoms is noted, a tibial tubercle osteotomy can be considered in young and active patients. While the early design and technique of patellofemoral arthroplasty were less than encouraging, more recent implant design and surgical techniques have demonstrated robust results.Discussion and Conclusion: Patellofemoral arthritis is a unique entity compared with tibiofemoral arthritis marked by distinct epidemiology, biomechanics, and risk factors and treatment options. It is essential to understand its pathophysiology and ensure proper treatment options.

Comparative effectiveness of pharmacological interventions for hand osteoarthritis: a systematic review and network meta-analysis of randomised trials

ObjectiveTo explore the comparative effectiveness of pharmacological interventions for hand osteoarthritis (OA).MethodsWe systematically searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception until 26 December 2021,...

Magnetic Nanoemulsions for the Intra-Articular Delivery of Ascorbic Acid and Dexamethasone.

(1) Osteoarthritis (OA) is a progressive joint degenerative disease that currently has no cure. Limitations in the development of innovative disease modifying therapies are related to the complexity of the underlying pathogenic mechanisms. In addition, there is the unmet need for efficient drug delivery methods. Magnetic nanoparticles (MNPs) have been proposed as an efficient modality for the delivery of bioactive molecules within OA joints, limiting the side effects associated with systemic delivery. We previously demonstrated MNP's role in increasing cell proliferation and chondrogenesis. In the design of intra-articular therapies for OA, the combined NE-MNP delivery system could provide increased stability and biological effect. (2) Proprietary Fe3O4 MNPs formulated as oil-in-water (O/W) magneto nanoemulsions (MNEs) containing ascorbic acid and dexamethasone were tested for size, stability, magnetic properties, and in vitro biocompatibility with human primary adipose mesenchymal cells (ADSC), cell mobility, and chondrogenesis. In vivo biocompatibility was tested after systemic administration in mice. (3) We report high MNE colloidal stability, magnetic properties, and excellent in vitro and in vivo biocompatibility. By increasing ADSC migration potential and chondrogenesis, MNE carrying dexamethasone and ascorbic acid could reduce OA symptoms while protecting the cartilage layer.

Poster 302: The Influence of Industry Affiliation on PRP Randomized Controlled Trials

Objectives: Industry funding and corporate sponsorship have played a significant role in the advancement of medical research and technology. However, this relationship raises concerns of how industry association may bias research findings and influence perception of results. As novel therapies continue to emerge, it is necessary to evaluate the literature for reliable and evidence-based clinical research before implementing these therapies into practice. The purpose of this study was to determine whether industry affiliation plays a role in the outcome of randomized controlled trial (RCT) studies investigating platelet-rich plasma (PRP) versus hyaluronic acid (HA), corticosteroids (CS), or placebo for knee osteoarthritis (OA). Methods: A search of the PubMed, Cochrane, and MEDLINE databases for RCTs of Level 1 or 2 evidence published from 2011 to present comparing PRP versus HA, CS or placebo for the treatment of knee OA was performed by two independent reviewers. To determine industry affiliation, the conflicts of interest, funding and disclosure segments of publications were assessed and all authors were reviewed through the AAOS Disclosure and Open Payments databases. Industry affiliation by financial conflicts of interest were identified as license or royalty fees, paid consultant fees, advisory position or speaker, employee, stock options, or research funding from companies that synthesize PRP or manufacture devices to administer PRP. Studies were classified as industry affiliated (IA) or non-industry affiliated (NIA). The outcomes of each study were rated as favorable, analogous, or unfavorable according to predefined criteria based on previously published protocols and also statistical significance by comparing patient reported outcome measures. Favorable studies showed superior results, analogous studies demonstrated no significant difference, and unfavorable studies had inferior outcomes when comparing PRP to HA, CS or placebo. Results: A total of 37 (6 IA and 31 NIA) studies were available for analysis. All studies were of level 1 (67.6%) or level 2 (32.4%) evidence, with no statistically significant difference between IA and NIA studies (p = 0.4443). Nineteen (51.4%) studies reported PRP as favorable compared to other treatments, while 18 (48.6%) studies showed no significant differences between PRP and other treatments. No studies showed worse outcomes with PRP compared to HA, CS, or placebo. There was no significant difference in qualitative conclusions between the IA and NIA cohorts, with the IA cohort having 3 favorable studies and 3 analogous studies, while the NIA group included 16 favorable studies and 15 analogous studies (p = 0.8881). When comparing IA versus NIA studies, using 6 and 12-month WOMAC and IKDC scores, there were no significant differences in outcome measures. Conclusions: The results of this study demonstrate largely favorable and analogous results with PRP compared to other intra-articular injection therapies for knee OA in randomized controlled trial studies. Qualitative conclusions and outcome scores were found to not be associated with industry affiliation. Although the results of this study suggest there is no influence of industry association on RCTs involving PRP, it is still necessary to carefully evaluate pertinent corporate affiliations in published literature. [Table: see text][Table: see text][Table: see text]

Glucagon-like peptide-1 receptor agonists as a disease-modifying therapy for knee osteoarthritis mediated by weight loss: findings from the Shanghai Osteoarthritis Cohort

ObjectiveObesity is a risk factor for knee osteoarthritis (KOA) development and progression. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity. However, whether KOA...

Innovation in Targeted Intra-articular Therapies for Osteoarthritis

Osteoarthritis is the most common chronic joint disease characterized by progressive damage to the joints, leading to pain and loss of function. There is currently no cure or disease-modifying therapy for osteoarthritis. Hence, the increasing disease prevalence linked with ageing and obesity represents a substantial socio-economic burden. Intra-articular therapy by injection of drugs into affected joints can optimize local drug bioavailability, while reducing risks of systemic toxicity, a concern in an ageing patient population. In this review, we investigate the current landscape of intra-articular drug therapies for osteoarthritis, including established approaches and those in clinical development. We performed a literature review using PubMed, complemented with a search for clinical trials using the ClinicalTrials.gov repository. Additionally, conference abstracts and presentations were identified and systematic snowballing was applied. Identified drugs were divided into several groups by main mechanism of action, and include drugs that reduce inflammation (anti-inflammatory), drugs aiming to prevent or reverse structural damage (structure modifying), drugs that aim to reduce the pain, and other drugs with a specific target. Most studies have been performed for osteoarthritis of the knee, a joint that is easily accessible for intra-articular treatments. Optimal therapy would provide symptomatic relief, while preventing further damage to the joint. The field of intra-articular drug therapies for osteoarthritis is rapidly evolving with clear challenges identified: definition of relevant outcome measures, optimization of clinical trial set-ups, and dealing with placebo responses. While many uncertainties persist, it appears that the innovation in drug development and improved clinical trial set-up may finally deliver successful therapies for this important disease.

An update on the effect of intra-articular intervention strategies using nanomaterials in osteoarthritis: Possible clinical application.

Osteoarthritis (OA) is the most common progressive condition affecting joints. It mainly affects the knees and hips as predominant weight-bearing joints. Knee osteoarthritis (KOA) accounts for a large proportion of osteoarthritis and presents numerous symptoms that impair quality of life, such as stiffness, pain, dysfunction, and even deformity. For more than two decades, intra-articular (IA) treatment options for managing knee osteoarthritis have included analgesics, hyaluronic acid (HA), corticosteroids, and some unproven alternative therapies. Before effective disease-modifying treatments for knee osteoarthritis, treatments are primarily symptomatic, mainly including intra-articular corticosteroids and hyaluronic acid, so these agents represent the most frequently used class of drugs for managing knee osteoarthritis. But research suggests other factors, such as the placebo effect, have an essential role in the effectiveness of these drugs. Several novel intra-articular therapies are currently in the clinical trial processes, such as biological therapies, gene and cell therapies. Besides, it has been shown that the development of novel drug nanocarriers and delivery systems could improve the effectiveness of therapeutic agents in osteoarthritis. This review discusses the various treatment methods and delivery systems for knee osteoarthritis and the new agents that have been introduced or are in development.

Efficacy of an oral collagen therapy compared with intra-articular therapies (hyaluronic acid and platelet-rich plasma) to treat knee osteoarthritis

Efficacy of an oral collagen therapy compared with intra-articular therapies (hyaluronic acid and platelet-rich plasma) to treat knee osteoarthritis

Duloxetine in Addition with Platelet Rich Plasma in Managing Neuropathic Knee Pain: A Comparative Study

Background: Osteoarthritis of knee joint is one of the most prevalent forms of arthritis in the world. With the progressive ageing of the population, it becomes a major public health concern. Knee osteoarthritis with neuropathic pain further increase the sufferings resulting functional limitation. Various conservative and intra-articular therapies have been used but none proved to be ideal for the treatment of chronic osteoarthritis. Current research in investigating new methods for stimulating repair or replacing damaged cartilage by using biological agents like platelet rich plasma in chronic osteoarthritis. Combination of platelet rich plasma therapy along with orally given duloxetine can provide better outcome for neuropathic pain and functional limitation.Methods: This study was carried out in the Pain Clinic, Department of Anaesthesia, Analgesia and Intensive Care Medicine, BSMMU during the period of May 2019 to April 2020. The patients were randomly assigned to one of the two groups (group A= only intra articular PRP; group B= PRP with oral Duloxetine 20mg) using a computer generated random sampling. After providing the allocated treatment, all patients were undergone follow-up examination at 1st week, 1st month and 3rd month after the procedure by International Knee Documentation Committee (IKDC) score, DN4 questionnaire and VAS scale. Pain intensity and neuropathic pain status were assessed by visual analog scale (VAS) and DN4 questionnaire. Whereas IKDC score was used to assess functional impairment of affected knee joint. Follow up were carried out by visiting in Pain Clinic at mentioned intervals or over phone. The significance of the difference of the DN4 score, visual analogue scale (VAS) and International Knee Documentation Committee (IKDC) score at 1st week, 1st month, and 3rd month were tested by using unpaired t- test, chi-square test and fisher exact test.Results: To assess functional improvement of affected knee joint, group B mean IKDC score was more than Group A in all follow up period, but statistically significant results were observed in 1st month (50.92±3.85) and 3rd month (55.54±4.64) follow up. Mean DN4 score and VAS score at pretreatment and 1st week were not statistically significant between the groups. But at 1st month and 3rd month both DN4 score and VAS score showed statistically significant difference between the groups. Inter group comparison showed that, mean DN4 score in group B (2.45±0.59) grossly decreased than group A (5.20±0.51) which indicate statistically significant reduction of neuropathic pain between the groups. Group B mean VAS (2.15±0.36) score decreased more than Group A (4.75±0.43) showed statistically significant improvement of pain in group B than group A.Conclusion: Intra articular platelet rich plasma in combination with oral duloxetine provide better pain relief and improvement of functional status than PRP alone in chronic knee osteoarthritis with neuropathic pain.