Single Intra-articular Injection Research Articles

A Pilot Study of the Clinical Effectiveness of a Single Intra-Articular Injection of Stanozolol in Canines with Knee Degenerative Joint Disease and Its Correlation with Serum Interleukin-1β Levels.

Stanozolol shows promise as an anabolic and anti-catabolic agent for treating degenerative joint disease (DJD). This study assessed the clinical efficacy of a single intra-articular stanozolol injection in canine knees with DJD and its correlation with serum IL-1β levels. Thirty dogs (n = 30) were divided into a control group (CG, n = 10) and a study group (SG, n = 20) with DJD. Pain levels were assessed using the Brown query, and radiographs were taken at T0 and T3. IL-1β levels were quantified via ELISA. Apart from 2 patients, all showed reduced pain intensity, with 15 patients showing improvement at T1 and 3 patients at T2. A positive correlation (r = 0.84; p < 0.01) was found between pain level and IL-1β in 15 patients. No systemic effects were observed. Most patients (18/20) experienced reduced pain. This pilot study suggests stanozolol's potential in managing DJD in dogs. Further research is warranted to validate these findings and understand stanozolol's mechanism in DJD treatment.

Intra-Articular Injection of PLGA/Polydopamine Core-Shell Nanoparticle Attenuates Osteoarthritis Progression.

Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degeneration. Unfortunately, currently available clinical drugs are mainly analgesics and cannot alleviate the development of OA. Kartogenin (KGN) has been found to promote the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocytes for the treatment of cartilage damage in early OA. However, KGN, as a small hydrophobic molecule, is rapidly cleared from the synovial fluid after intra-articular injection. This study synthesized a KGN-loaded nanocarrier based on PLGA/polydopamine core/shell structure to treat OA. The fluorescence signal of KGN@PLGA/PDA-PEG-E7 nanoparticles lasted for 4 weeks, ensuring long-term sustained release of KGN from a single intra-articular injection. In addition, the polyphenolic structure of PDA enables it to effectively scavenge reactive oxygen species, and the BMSC-targeting peptide E7 (EPLQLKM) endows KGN@PLGA/PDA-PEG-E7 NPs with an effective affinity for BMSCs. As a result, the KGN@PLGA/PDA-PEG-E7 nanoparticles could effectively induce cartilage in vitro and protect the cartilage and subchondral bone in a rat ACLT model. This therapeutic strategy could also be extended to the delivery of other drugs, targeting other tissues to treat joint diseases.

PEDF peptide plus hyaluronic acid stimulates cartilage regeneration in osteoarthritis via STAT3-mediated chondrogenesis.

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC.

Single Shot of Knee Intraarticular Injection of Platelets Rich Plasma versus Hyaluronic Acid Injections for Symptomatic Knee Osteoarthritis. An Observational Prospective Study

The aim of this study was to evaluate the effectiveness and safety of intra-articular PRP and HA in KOA patients. Methods: The current work was prospective randomized observational. Participants were divided into two groups. Group 1; 1 intra-articular PRP injection (15 mL) in 72 patients and Group 2; A single intra-articular injection of HA (80 mg/4 mL) was administered to 72 patients. All patients were evaluated before infiltration and 1, 3, 6, and 12 months after injection. Results: No significant difference was detected in the demographic distribution (gender and age) and Grade RT, Grade RL, Grade II OA and Grade III OA classifications of patients who received intra-articular PRP or HA injection for knee OA (p&amp;gt;0.05). Compared with the HA group WOMAC mean of 48.8 and p&amp;lt;0.05, there was no significant change in the PRP groups with the WOMAC mean of 68.9. At month 3, each group had significantly reduced overall WOMAC score compared to baselines in both groups. The mean WOMAC was 48.2 in the HA and 47.9 in the PRP group (P&amp;lt;0.001). At 6 months, the average WOMAC score of the PRP group was 39.4, while this rate was 56.3 in the HA group (P&amp;lt;0.001). The PRP group showed a steady improvement, while those treated with HA showed a rapid deterioration. At 12 months, the HA group's WOMAC scores (74.1) returned to baseline levels. The mean WOMAC of the PRP group was (58.9) (P&amp;lt;0.001). Conclusion: The overall PRP improvement outweighs HA injections

Long-Term Efficacy Following Intra-articular Injection of Carboxymethyl-chitosan, a New Product Class for Knee Osteoarthritis: Results from an Observational Study in Germany.

Evaluate the real-world efficacy of a single intra-articular injection of carboxymethyl-chitosan (CM-chitosan), a new product class for knee osteoarthritis (OA). This post-marketing study included adult patients with knee OA, who received a single injection of 60mg CM-chitosan (currently marketed as KioMedinevsone) according to the instructions for use. Follow-up was performed at weeks1, 12, 24, and 36. Efficacy was evaluated using a Visual Analog Scale (VAS) score for pain, the Knee injury and Osteoarthritis Outcome Score (KOOS), Patient's Global Assessment (PGA), and overall patient satisfaction. Forty-nine patients were included in the study. VAS pain score significantly decreased from a median of 49.0mm at baseline to 24.0mm at week1 and to 18mm at week36. Pain improvement was stable since at week36; 91.8% of patients confirmed pain reduction. All KOOS subscales (symptoms, pain, activities of daily living, sports and recreational activities, quality of life) improved significantly compared to baseline at all time points. KOOS pain improved progressively from a median of 58.3% at baseline (mean 56.2 ± 18.8%) to 86.1% (mean 74.1 ± 24%) at week36 compared to baseline. Overall, more than 70% of patients reported a condition gain (PGA), matching well with the more than 75% of patients being satisfied with the treatment. At 6months, 72.7% of the patients could be classified as responder according to the OMERACT-OARSI proposed set of responder criteria. CM-chitosan showed a rapid onset of pain relief after 1week and with a duration of 9months. In a real-world setting, treatment with CM-chitosan would appear to be a potentially effective option to reduce pain and improve physical function and global condition in patients with knee OA, opening new perspectives in patients who are considered as refractory to current symptomatic therapies and where the unmet need is high. NCT04757051 (ClinicalTrials.gov).

Navigating the New EU Medical Devices Regulation: Retrospective Post-Market Follow-Up of Hyaluronic Acid Injections for Knee Osteoarthritis.

The entry into force of the new Medical Device Regulation (EU) 2017/745 highlights the need for post-market clinical follow-up to ensure the safety and efficacy throughout the life cycle of medical devices. This study evaluates the efficacy and safety of a single intra-articular hyaluronic acid injection in knee osteoarthritis in real-world conditions, over a six-month period, aligning with the summary of safety and clinical performance (SSCP) required by the new regulation. Patients over 18 years of age with knee osteoarthritis, treated with a single injection of HA (Adant® One, Meiji Pharma Spain, Spain) at a 3rd level hospital. Patients were treated and followed between January 1, 2020 and June 30, 2022. Demographic, clinical, and treatment-related data were collected, and efficacy regarding pain relief and/or function improvement was assessed using a Likert-type scale. Data were pseudo-anonymized and the comparison was performed using Fisher' or Mann Whitney' test. The study was approved by the Ethics Review Board of the Hospital Puerta de Hierro (Madrid, Spain). We followed 20 patients with knee osteoarthritis, with a mean age of 61 years, 80% women, and with a high burden of comorbidities (90%). A total of 60% of patients presented Kellgren-Lawrence grade III-IV. Four patients (20%) returned before 6 months due to lack of efficacy. Of the other patients, 65% showed a clinical response that lasted more than 12 months in 38.5% of cases. Time until medical appointment and taking concomitant medication for knee osteoarthritis were associated with better clinical response (p < 0.05). The administration of a Adant® One single intra-articular hyaluronic acid injection in knee osteoarthritis is effective, safe, and maintains the improvement over a six-month period. Our findings also emphasize the need of using standardized tools for accurate efficacy assessment and optimal patient care.

Clinical Evaluation of Safety and Efficacy of a Central Current Good Manufacturing Practices Laboratory Produced Autologous Adipose-Derived Stromal Vascular Fraction Cell Therapy Product for the Treatment of Knee Osteoarthritis.

Knee osteoarthritis (KOA) is a prevalent condition characterized by the progressive deterioration of the entire joint and has emerged as a prominent contributor to disability on a global scale. The nature of the disease and its impact on joint function significantly limit mobility and daily activities, highlighting its substantial influence on patients' overall well-being. Stromal vascular fraction (SVF) is a heterogenous, autologous cell product, containing mesenchymal stem cells, derived from the patient's subcutaneous adipose tissue with demonstrated safety and efficacy in the treatment of KOA patients. We conducted a single-arm, open-label, multisite, FDA approved clinical study in Kellgren-Lawrence severity grade 2-4 KOA patients. The cellular product was manufactured from patient-specific lipoaspirate in a centrally located FDA-compliant manufacturing facility. Twenty-nine subjects were treated with a quality tested single intra-articular injection of GMP manufactured SVF. Adverse events, laboratory values, vital signs, and physical examination findings were monitored during the study period. Robust tolerability, without any substantial safety issues, was demonstrated. Knee pain and function, assessed through the Knee Injury and Osteoarthritis Outcome Score (KOOS), demonstrated notable improvements. These positive benefits persisted for up to 12 months, and the majority of participants expressed satisfaction. SVF from each patient was stored in a liquid nitrogen freezer for future clinical treatments. Unique to this study of autologous cells is the shipment of lipoaspirate from the clinic to a central FDA-compliant manufacturing facility for cleanroom-controlled manufacturing. The cell product characterization data demonstrate that this method produces an equivalent product in terms of cell count and viability with the added benefit of further quality assurance testing, including sterility, endotoxin, and flow cytometry, before patient administration. Clinical Trial Registration Number: NCT04043819.

Nanoparticle-based inhibition of vascular endothelial growth factor receptors alleviates osteoarthritis pain and cartilage damage.

Osteoarthritis (OA) is characterized by cartilage damage, inflammation, and pain. Vascular endothelial growth factor receptors (VEGFRs) have been associated with OA severity, suggesting that inhibitors targeting these receptors alleviate pain (via VEGFR1) or cartilage degeneration (via VEGFR2). We have developed a nanoparticle-based formulation of pazopanib (Votrient), an FDA-approved anticancer drug that targets both VEGFR1 and VEGFR2 (Nano-PAZII). We demonstrate that a single intraarticular injection of Nano-PAZII can effectively reduce joint pain for a prolonged time without substantial side effects in two different preclinical OA rodent models involving either surgical (upon partial medial meniscectomy) or nonsurgical induction (with monoiodoacetate). The injection of Nano-PAZII blocks VEGFR1 and relieves OA pain by suppressing sensory neuronal ingrowth into the knee synovium and neuronal plasticity in the dorsal root ganglia and spinal cord. Simultaneously, the inhibition of VEGFR2 reduces cartilage degeneration. These findings provide a mechanism-based disease-modifying drug strategy that addresses both pain symptoms and cartilage loss in OA.

Treatment of osteoarthritis knee with bone marrow aspirate concentrate injection

To assess the clinical effectiveness and safety of bone marrow aspirate concentrate (BMAC) injections given intraarticularly as a potential treatment for knee osteoarthritis (OA). Data from 60 patients with knee osteoarthritis treated with BMAC injection at a single centre between December 2021 and December 2022 were retrospectively examined. We only included patients with idiopathic osteoarthritis. Post-traumatic osteoarthritis, prior knee surgery, ageless then 50 years or over 85 years, an active infection, uncontrolled diabetes mellitus, rheumatological or another systemic condition, cancer, or immunosuppressive medication use were all exclusion factors. A single-spin manual approach was used to aspirate and concentrate bone marrow from the iliac crest. The Numeric pain scale (NPS) and Oxford knee score (OKS) were used to evaluate patients both before and after the treatment. A 12-month follow-up period was used. The statistical analysis comprised a total of 60 patients. With a mean age of 67 years (range 50-85), there were 42 females and 18 males. At the end of the follow-up period, the mean NPS reduced from 8.12 to 4.31 (p&amp;#60; 0.001) and the mean OKS rise from 22.30 to 34.74 (p &amp;#60;0.001). There were no problems. A single BMAC intra-articular injection is a dependable and safe technique that improves the clinical condition of knee OA.

Safety and Efficacy of Hybrid Cooperative Complexes of Sodium Hyaluronate and Sodium Chondroitin for the Treatment of Patients with Symptomatic Knee Osteoarthritis.

Knee osteoarthritis (KOA) represents a widespread degenerative disease that causes pain and motor disability. Conservative treatments mainly focus on relieving symptoms, improving joint function, and trying to delay surgery. Safety and efficacy of hybrid cooperative complexes (2.4% sodium hyaluronate and 1.6% sodium chondroitin; HA-SC) for symptomatic KOA were investigated in a single-arm, prospective, pilot study. Patients with a visual analogue scale (VAS) pain score ≥ 4 and Kellgren-Lawrence Grade < 4 received a single intraarticular HA-SC injection. Patients with a VAS score change from baseline ≤ 1 received a second injection at day 30. Device-related adverse events (DR-AEs)/adverse events (AEs) were primary endpoints. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis Index LK 3.1 (WOMAC LK 3.1), VAS, patient global assessment of disease status (PtGA), and patient proportion needing a second injection. Of 83 patients with KOA (Kellgren-Lawrence Grade, 2-3), 34.9% had DR-AEs at day 7. No serious DR-AEs/AEs were reported. A significant (P < 0.0001) reduction over time in VAS pain score plus WOMAC pain, stiffness, physical function limitation, and total scores was reported. Median PtGA scores indicated a 'slight improvement' at most follow-up visits. Only 18.1% of patients required a second injection. A single intraarticular HA-SC injection was safe, well-tolerated, and did not lead to major deterioration in terms of reducing knee pain, stiffness, and physical function limitation in patients with symptomatic KOA.

The In Vivo Chondrotoxicity of Single Intra-articular Injection of Local Anesthetic in Rat Cartilage.

Introduction A constant infusion of local anesthetics through pain pumps has been shown to cause chondrolysis. However, there is no general consensus regarding the safety of a single intra-articular injection of local anesthetics. In this experimental study, we examined the rat cartilage for possible histological effects after a single intra-articular administration of lidocaine or ropivacaine. Material and methods Thirty-two male Sprague-Dawley rats, weighing 250-300 grams, were divided into two groups of 16 each. We injected 0.1 ml of either lidocaine 2% (20 mg/ml) or ropivacaine 0.75% (7.5 mg/ml) into the left knee of the rats. The right knee in both groups was used as a control, and an equal amount of normal saline was injected. Each group was further divided into subgroups of four, which were euthanized after one, seven, 21, and 60 days after the initial injection. Knees were excised and prepared for histopathological analysis. A modified version of the Mankin score was used for cartilage damage evaluation. Results No difference regarding cartilage damage was detected after the examination under light microscopy between lidocaine, ropivacaine, and placebo in all specimens. Time elapsed since the initial injection did not affect the results at any time point. Conclusion A single intra-articular injection of local anesthetic did not induce any histological changes in the rat cartilage. Further research is needed to demonstrate the safety of humans.

The Effects of Extracellular Matrix Allograft Administration on Knee Inflammation Following an Anterior Cruciate Ligament Injury in Mice

Background and Hypothesis:A human placental-derived extracellular matrix (ECM) allograft has previously been developed and is indicated by the manufacturer for reducing tissue inflammation and accelerated repair. To evaluate the efficacy of this product for reducing post-anterior cruciate ligament (ACL) injury inflammation, we used a novel murine in vivo ACL injury model. This model has previously been shown to induce significant synovitis, infrapatellar fat pad (IFP) fibrosis, and articular cartilage (AC) degradation within 2 weeks following an ACL injury. We hypothesized that intra-articular injections of the allograft would correspond with a decrease in synovitis, fibrosis, and articular cartilage degradation.&#x0D; Experimental Design or Project Methods:Ten-week-old C57BL/6J mice were randomly placed into 4 groups (n=10/group). For all mice, the right ACL was ruptured. One group served as sham controls, with a single intra-articular saline injection 24-hours following injury. The remaining three groups received 1, 2, and 6 allograft injections respectively beginning 24-hours after injury. Mice were euthanized 14 days after injury. Following euthanasia, the degree of IFP fibrosis, knee synovitis, and AC degradation were histopathologically evaluated.&#x0D; Results:Thus far, 5 mice per group have been analyzed. Within this subset of mice, those that received 6 injections demonstrated a significantly higher synovitis score (p &lt; 0.01) than the sham group. The 1-injection (p &lt; 0.01), 2-injection (p = 0.16), and 6-injection (p = 0.03) groups each displayed greater IFP fibrosis, relative to sham. No significant differences were found in AC degeneration across groups.&#x0D; Conclusion and Potential Impact:If the current results hold, following the analyses of the remaining mice, then this particular orthobiologic may not be suitable for reducing the post-ACL injury inflammatory response in mice. However, there are several limitations to this pilot study that will first need to be accounted for to confirm the lack of efficacy found.

Investigation Into the Effects of Intra-Articular Steroid on Post-Traumatic Osteoarthritis in Distal Radius Fractures: A Randomized Controlled Pilot Study

The aim of this prospective, randomized, controlled, double-blinded pilot study was to determine the rates of post-traumatic osteoarthritis and assess joint space width in the presence or absence of a single intra-articular injection of corticosteroid after an acute, intra-articular distal radius fracture (DRF). Forty patients received a single, intra-articular, radiocarpal joint injection of 4 mg of dexamethasone (DEX) (n= 19) or normal saline placebo (n= 21) within 2 weeks of a surgically or nonsurgically treated intra-articular DRF. The primary outcome measure was minimum radiocarpal joint space width (mJSW) on noncontrast computed tomography scans at 2 years postinjection. Secondary outcomes were obtained at 3 months, 6 months, 1 year, and 2 years postinjection and included Disabilities of the Arm, Shoulder, and Hand; Michigan Hand Questionnaire; Patient-Rated Wrist Evaluation; wrist range of motion; and grip strength. At 2-year follow-up, there was no difference in mean mJSW between the DEX group (2.2 mm; standard deviation, 0.6; range, 1.4-3.2) and the placebo group (2.3 mm; standard deviation, 0.7; range, 0.9-3.9). Further, there were no differences in any secondary outcome measures at any postinjection follow-up interval. Radiocarpal joint injection of corticosteroid within 2 weeks of an intra-articular DRF does not appear to affect the development of post-traumatic osteoarthritis within 2 years follow-up in a small pilot cohort. Therapeutic II.

The cost-effectiveness of adding an ultrasound corticosteroid and local anaesthetic injection to advice and education for hip osteoarthritis

Abstract Objectives Evidence for the comparative cost-effectiveness of intra-articular corticosteroid injection in people with hip osteoarthritis (OA) remains unclear. This study investigated the cost-effectiveness of best current treatment (BCT), comprising advice and education, with BCT plus a single ultrasound-guided intra-articular hip injection of 40 mg triamcinolone acetonide and 4 ml 1% lidocaine hydrochloride (BCT+US-T). Methods A trial-based cost–utility analysis of BCT+US-T compared with BCT was undertaken over 6 months. Patient-level cost data were obtained, and effectiveness was measured in terms of quality-adjusted life years (QALYs), allowing the calculation of cost per QALY gained from a UK National Health Service (NHS) perspective. Results BCT+US-T was associated with lower mean NHS costs (BCT+US-T minus BCT: −£161.6; 95% CI: −£583.95, £54.18) and small but significantly higher mean QALYs than BCT alone over 6 months (BCT+US-T minus BCT: 0.0487; 95% CI: 0.0091, 0.0886). In the base case, BCT+US-T was the most cost-effective and dominated BCT alone. Differences in total costs were driven by number of visits to NHS consultants, private physiotherapists and chiropractors, and hip surgery, which were more common with BCT alone than BCT+US-T. Conclusion Intra-articular corticosteroid injection plus BCT (BCT+US-T) for patients with hip OA results in lower costs and better outcomes, and is highly cost-effective, compared with BCT alone. Trial registration EudraCT: 2014-003412-37 (8 August 2015) and registered with Current Controlled Trials: ISRCTN 50550256 (28 July 2015). Trial protocol Full details of the trial protocol can be found in the Supplementary Appendix, available with the full text of this article at https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-018-2153-0, doi: doi.org/10.1186/s12891-018-2153-0.

A comparative study of oral diacerein and transdermal diacerein as Novasomal gel in a model of MIA induced Osteoarthritis in rats

Background: Osteoarthritis is a chronic pathology of the joints causing disability and morbidity. Diacerein is a disease-modifying agent indicated for osteoarthritis management with enhanced performance and have much lower side effects profile than conventional non-steroidal anti-inflammatory drugs. Oral administration of Diacerein is associated with a laxative effect , thus causing treatment discontinuation. Aim: This study aimed to evaluate the activity of Diacerein novasome-based transdermal gel compared with standard oral treatment in the management of induced osteoarthritis in a rat model. Materials and methods: A single intra-articular injection of monosodium iodoacetate was administered to the left knee joint, resulting in the development of Osteoarthritis. Disease progression and the effect of both routes of Diacerein treatment were evaluated by morphological, biochemical, histological, and radiological studies. Results: Osteoarthritis was successfully induced in rats’ knee joints. Morphological studies revealed that both Diacerein treatments significantly reduced joint swelling as compared to the untreated group. The serum TNF-α and IL-1β levels were significantly lower in both Diacerein treatment groups as compared to the untreated group throughout the course of the study. Histological and radiological findings confirmed that transdermal Diacerein treatment protects against cartilage degradation like oral treatment. Conclusion: Novasomal technology proved its efficacy as a carrier for the transdermal delivery of Diacerein. The in-vivo study on an animal model of osteoarthritis showed that Diacerein transdermal gels provided sufficient pharmacological activity for the attenuation of the disease. This finding could support its use as an alternative to the standard oral treatment to avoid side effects.

The Single Intra-Articular Injection of Platelet-Rich Plasma vs. Non-Steroidal Anti-Inflammatory Drugs as Treatment Options for Canine Cruciate Ligament Rupture and Patellar Luxation.

Cranial cruciate ligament rupture (CCLR) and patellar luxation (PL) are common pathologies affecting canines. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used as a non-surgical treatment plan in these cases. Clinical usage of platelet-rich plasma (PRP) is an emerging area of interest in veterinary medicine. There is a lack of studies comparing those two different treatment methods in veterinary medicine. The main purpose of this study was to evaluate and compare the use of oral NSAIDs and single intra-articular injection of PRP on treatment outcomes in cases of canine CCLR and PL. Dogs diagnosed with CCRL (n = 12) and PL (n = 10) were subgrouped by the severity of pathologies and administered treatment: half of the CCRL and PL groups were orally administered NSAIDs and supplements for 14 days, and the other half received a single intra-articular PRP injection into affected stifle joint. We measured serum TNF-α levels and clinical outcomes (lameness scores, painfulness to manipulations, goniometry of stifle joint in flexion and extension, and muscle strength) before treatment, at day 14 and day 28 of treatment. The results of TNF-α concentration indicates a significant difference between groups of differently treated partial CCLR groups on d14 (p = 0.006). Results of group CCLR-P1 on d14 were decreased, while results of group CCLR-P2 on d14 were increased. When comparing TNF-α concentration between all CCLR cases treated with NSAIDs and treated with PRP, there was a significant difference between those groups on d14 (p = 0.001). The results of TNF-α concentration indicates a significant difference between groups of differently treated PL-III on d28 (p = 0.036). Results of group PL-III1 indicate growth of TNF-α concentration, while at the same d28, results of group PL-III2 indicate decreased levels of cytokine, comparing results between the subgroups at the same time point and within subgroups from baseline. Results indicate a significant difference in muscle strength between group CCLR-P1 and group CCLR-P2 on d28 (p = 0.007), indicating an increment in muscle strength in group CCLR-P1 up to d14 and its reduction up to d28, and muscle strength of group CCLR-P2 increasing up to d28. When comparing the muscle strength between all CCLR cases treated with NSAIDs and treated with PRP, there was a significant difference between those groups on d28 (p = 0.007). In conclusion, a single intra-articular injection of PRP has a superior effect on management of inflammatory processes, has better clinical outcomes, and longer duration of action than oral NSAIDs, in the treatment of canine CCRL or PL.

POLYACRYLAMIDE HYDROGEL VERSUS HYALURONIC ACID IN KNEE OSTEOARTHRITIS: A SUBGROUP ANALYSIS OF A RANDOMIZED STUDY

AbstractIntroductionThe effectiveness of single intra-articular injections of polyacrylamide hydrogel (iPAAG) and hyaluronic acid (HA) was compared in subgroups of participants from an RCT based on baseline age, BMI or Kellgren-Lawrence (KL) grade.Methodology239 participants were randomised to 6 mL iPAAG (Arthrosamid; n=119) or 6 mL HA (Synvisc-One; n=120). Participants continued analgesics (except 48 hours prior to visits) and non-pharmacological therapy. Topical therapies and intra-articular corticosteroids were not allowed. Pre-specified subgroup analyses (age: &lt;70 years, ≥70 years; BMI: normal, overweight, obese; KL grade: 2, 3, 4, 2–3) of change from baseline in WOMAC pain subscale at 52 weeks were based on the least squares means for the treatment-by-week interaction effect using a mixed model for repeated measurement with a restricted maximum likelihood-based approach.ResultsAcross all patients, change from baseline in WOMAC pain subscale in the iPAAG group was non-inferior to HA at 26 weeks and approached superiority (p=0.0572) at 52 weeks. Treatment differences for change from baseline in WOMAC pain subscale in favour of iPAAG over HA were statistically significant for the age &lt;70 years (p=0.019), BMI normal (p=0.011) and KL grade 2–3 (p=0.033) subgroups. Treatment differences for all other subgroups favoured iPAAG, except for KL grade 4 which favoured HA, without reaching statistical significance.ConclusioniPAAG approached superiority to HA across all participants at 52weeks, but demonstrated statistical superiority in participants with normal BMI, participants &lt;70 years old or participants with KL score 2–3. iPAAG represents a useful alternative to HA for the treatment of knee OA.

Honey improves radiographic features of monosodium iodoacetate-induced stifle (knee) joint osteoarthritis in a rat model

Osteoarthritis (OA) is the most common form of joint disease with over half of all people older than 65 years demonstrating radiographic changes of  osteoarthritis in the knees. Honey is known to contain bioactive compounds that exert chondroprotective effects by counteracting the homeostatic  dysregulation of the joint. However, its effect on the radiographic features of osteoarthritis has not been proven. This study was carried out to evaluate  the effect of honey on radiographic features of monosodium iodoacetate (MIA)- induced knee osteoarthritis in female Wistar rats. Thirty female Wistar  rats were randomly divided into five groups of six animals each. Animals in group one were healthy (control) rats, while animals in groups two to five  were subjected to experimental osteoarthritis of the right knee joint induced by a single intra-articular injection of 1mg of MIA. The animals in groups  two, three, four, and five were treated with normal saline (1ml/kg b. w.), arthocare (glucosamine/chondroitin sulfate 6.67/8.33mg/kg b. w.), low dose  honey (250mg/kg b. w.) and high dose honey (1,000mg/kg b. w.) respectively. All treatments were administered orally once daily using an oral cannula for  twenty-one days. All animals were subjected to radiographic assessment of the right knee joint before and after induction of OA, and after treatment.  High and low-dose honey reversed the loss of joint space; sclerosis of the tibial plateau, medial, and lateral femoral condyles, when compared to the  arthocare-treated and untreated groups. In conclusion, honey improved radiographic features of knee osteoarthritis in a rat model induced by  monosodium iodoacetate. 

Efficacy and Safety of Stempeucel in Osteoarthritis of the Knee: A Phase 3 Randomized, Double-Blind, Multicenter, Placebo-Controlled Study

Background: Osteoarthritis is a chronic, progressive, and degenerative condition with limited therapy options. Recently, biologic therapies have been an evolving option for the management of osteoarthritis. Purpose: To assess whether allogenic mesenchymal stromal cells (MSCs) have the potential to improve functional parameters and induce cartilage regeneration in patients with osteoarthritis. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 146 patients with grade 2 and 3 osteoarthritis were randomized to either an MSC group or placebo group with a ratio of 1:1. There were 73 patients per group who received either a single intra-articular injection of bone marrow–derived MSCs (BMMSCs; 25 million cells) or placebo, followed by 20 mg per 2 mL of hyaluronic acid under ultrasound guidance. The primary endpoint was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. The secondary endpoints were WOMAC subscores for pain, stiffness, and physical function; the visual analog scale score for pain; and magnetic resonance imaging findings using T2 mapping and cartilage volume. Results: Overall, 65 patients from the BMMSC group and 68 patients from the placebo group completed 12-month follow-up. The BMMSC group showed significant improvements in the WOMAC total score compared with the placebo group at 6 and 12 months (percentage change: −23.64% [95% CI, −32.88 to −14.40] at 6 months and −45.60% [95% CI, −55.97 to −35.23] at 12 months P < .001; percentage change, −44.3%). BMMSCs significantly improved WOMAC pain, stiffness, and physical function subscores as well as visual analog scale scores at 6 and 12 months (P < .001). T2 mapping showed that there was no worsening of deep cartilage in the medial femorotibial compartment of the knee in the BMMSC group at 12-month follow-up, whereas in the placebo group, there was significant and gradual worsening of cartilage (P < .001). Cartilage volume did not change significantly in the BMMSC group. There were 5 adverse events that were possibly/probably related to the study drug and consisted of injection-site swelling and pain, which improved within a few days. Conclusion: In this small randomized trial, BMMSCs proved to be safe and effective for the treatment of grade 2 and 3 osteoarthritis. The intervention was simple and easy to administer, provided sustained relief of pain and stiffness, improved physical function, and prevented worsening of cartilage quality for ≥12 months. Registration: CTRI/2018/09/015785 (National Institutes of Health and Clinical Trials Registry–India).

Mid- to long-term success rate and functional outcomes of acromioclavicular injections in patients with acromioclavicular osteoarthritis.

Acromioclavicular (AC) osteoarthritis (OA) is a frequent pathology of the shoulder in elderly patients. Drug injection plays an important role in treatment of AC OA. Literature has demonstrated excellent short-term results regarding shoulder function and pain. However, mid- to long-term results are lacking. The aim of this study was to assess the efficacy of a single intra-articular AC injection in patients with AC OA and to identify predictive factors for success. A retrospective study was performed to analyze success rate, shoulder function, and pain perception after a single intra-articular injection in patients with AC OA. Success was defined as the absence of reinterventions such as additional injection or surgery. Outcome measures were 1-year success rate and clinical outcome scores of Numeric Rating Scale (NRS) for pain, Oxford Shoulder Score, and Subjective Shoulder Value. Ninety-eight patients participated in this study. At a median final follow-up of 0.8 years (interquartile range, 0-6), 57 of these patients (58%) had undergone a reintervention. The 1-year success rate was 47% (95% confidence interval, 37%-57%), with NRS at rest as the sole factor significantly associated with success. Thirty patients not requiring reintervention reported significant improvement from baseline for all reported outcome measures at final follow-up. AC injections offer a 1-year success rate of 47%. The AC injection produces good mid- to long-term clinical outcomes regarding shoulder function, quality of life, and pain perception in one-third of patients. Further research is essential to analyze mid- to longterm outcomes of AC injections. Level of evidence: Level IV.