Intra-articular Saline Research Articles

Intra-Articular Physiological Saline in Temporomandibular Disorders May Be a Treatment, Not a Placebo: A Hypothesis, Systematic Review, and Meta-Analysis.

Background: Intra-articular injections reduce pain in patients with temporomandibular joint (TMJ) disorders who are unresponsive to conservative treatment. Hyaluronic acid, blood products, and medications provide rapid relief when administered this way, although their mechanisms of action remain unclear. In control groups, which are intended to be untreated, 0.9% NaCl is typically delivered. The hypothesis that "normal saline injections in TMJ cavities produce a therapeutic effect" is proposed, with an exploration of its potential verification, alongside a systematic review and meta-analysis of studies on intra-TMJ 0.9% NaCl. Methods: Randomized controlled trials (RCTs) on patients with TMJ internal derangement, arthritis, or degeneration were selected under PRISMA 2020 and assessed with RoB2. Results: Seven RCTs with 359 patients were included. Weekly follow-ups revealed a decrease in articular pain by 23.72% (SE: 0.84%; 95% CI: 24.38-21.06%; p < 0.01), and monthly follow-ups indicated a decrease of 34.01% (SE: 1.09%; 95% CI: 36.16-31.86%; p < 0.01) compared to the baseline values. These findings were grounded in low-risk-of-bias evidence on 267 patients in five RCTs and 222 patients in four RCTs, respectively. Conclusions: The hypothesis warrants further testing to determine whether, in addition to the known biological activity of typical injectables, the mechanical action also contributes to pain relief.

Immunotherapeutic potential of collagen V oral administration in mBSA/CFA-induced arthritis.

We hypothesized that after synovial injury, collagen V (Col V) expose occult antigens, and Col V autoantibodies develop, indicating the loss of immune tolerance against this molecule, thus leading to damage to mesenchymal-derived cells as well as the extracellular matrix in experimental arthritis. Thus, the present study investigated the effects of oral administration of Col V on the synovium after the development of inflammation in mBSA/CFA-induced arthritis. After fourteen days of intraarticular administration of mBSA, 10 male Lewis rats were orally administered Col V (500 μg/300 μL) diluted in 0.01 N acetic acid (IA-Col V group). The arthritic group (IA group, n = 10) received only intraarticular mBSA. An intra-articular saline injection (20 μL) was given to the control group (CT-Col V, n = 5). IA group presented damaged synovia, the expansion of the extracellular matrix by cellular infiltrate, which was characterized by T and B lymphocytes, and fibroblastic infiltration. In contrast, after Col V oral immunotherapy IA-Col V group showed a significant reduction in synovial inflammation and intense expression of IL-10+ and FoxP3+ cells, in addition to a reduction in Col V and an increase in Col I in the synovia compared to those in the IA group. Furthermore, an increase in IL-10 production was detected after IA-Col V group spleen cell stimulation with Col V in vitro. PET imaging did not differ between the groups. The evaluation of oral treatment with Col V, after mBSA/CFA-induced arthritis in rats, protects against inflammation and reduces synovial tissue damage, through modulation of the synovial matrix, showing an immunotherapeutic potential in inhibiting synovitis.

Alpha-2-Macroglobulin Attenuates Posttraumatic Osteoarthritis Cartilage Damage by Inhibiting Inflammatory Pathways With Modified Intra-articular Drilling in a Yucatan Minipig Model

Background: Posttraumatic osteoarthritis (PTOA) arises secondarily to joint trauma and is driven by catabolic inflammatory pathways. Alpha-2-macroglobulin (α2M) is a naturally occurring proteinase inhibitor found in human serum and synovial fluid that binds proteases as well as proinflammatory cytokines involved in the pathogenesis of PTOA. Purpose: (1) To investigate the therapeutic potential of intra-articular α2M injections during the acute stages of PTOA by inhibiting inflammatory pathways driven by the cytokines expressed by the synovium in a large preclinical Yucatan minipig model and (2) to determine if 3 intra-articular α2M injections have greater chondroprotective effects compared with 1 intra-articular injection. Study Design: Controlled laboratory study. Methods: A total of 48 Yucatan minipigs were randomized into 4 groups (n = 12 each): (1) modified intra-articular drilling (mIAD) and saline (mIAD + saline), (2) mIAD and 1 intra-articular α2M injection (mIAD +α2M-1), (3) mIAD and 3 α2M injections (mIAD +α2M-3), and (4) sham control. Surgical hindlimbs were harvested at 15 weeks after surgery. Cartilage degeneration, synovial changes, inflammatory gene expression, and matrix metalloproteinase levels were evaluated. Gait asymmetry was measured before and after surgery using a pressure-sensing walkway system. Results: Macroscopic lesion areas and microscopic cartilage degeneration scores were lower in the mIAD +α2M-1 and mIAD +α2M-3 groups compared with the mIAD + saline group (P < .05) and similar to those in the sham group (P > .05). Synovial membrane scores of the mIAD +α2M-1 and mIAD +α2M-3 groups were lower than that of the mIAD + saline group (P < .05) and higher than that of the sham group (P < .05). Interleukin-1 beta, nuclear factor kappa B, and tumor necrosis factor alpha mRNA expression in the synovium and matrix metalloproteinase-1 levels in synovial fluid were significantly lower in the mIAD +α2M-1 and mIAD +α2M-3 groups compared with the mIAD + saline group (P < .05). No significant differences were observed between the mIAD +α2M-1 and mIAD +α2M-3 groups for all measured outcomes. There were early changes in gait (P < .05) between preoperative and postoperative time points for the mIAD + saline, mIAD +α2M-1, and mIAD +α2M-3 groups that normalized by 15 weeks. Conclusion: Animals receiving early α2M treatment exhibited less cartilage damage, milder synovitis, and lower inflammation compared with animals with no α2M treatment. These results exemplify the early anti-inflammatory effects of α2M and provide evidence that intra-articular α2M injections may slow the progression of PTOA. Clinical Relevance: In patients presenting with an acute joint injury, an early intervention with α2M may have the potential to reduce cartilage degeneration from catabolic pathways and delay the development of PTOA.

Autologous Bone Marrow Aspiration Concentrate (BMAC) Therapy for Primary Knee Osteoarthritis-An Observational and Dose Escalation Study.

Anti-inflammatory and anti-fibrotic properties maximize the therapeutic potential of bone marrow aspiration concentrate (BMAC) in osteoarthritis (OA) knee. There is a lack of studies to standardize the treatment procedure to make the studies done across various centers comparable to understand the lacunae better and develop further the deficiency in our understanding of BMAC for OA knee. We aimed to assess the degree of pain relief, functional outcome, and cartilage thickness with different doses of BMAC in primary OA knee. A single-centered prospective observational study was conducted with 80 patients of OA knee who were divided into 4 groups where group A (n = 20), group B (n = 20), group C (n = 20), and group D (n = 20) received intra-articular 1, 2, 5million BMAC cells per kg body weight, and intra-articular saline, respectively. All patients were followed up with Visual Analog Scale (VAS), knee Injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) scores both pre and post-procedurally at 1, 3, 6, and 12months follow-up. The study found no significant differences in demographics or co-morbidities across four participant groups (A, B, C, D). However, clinical outcomes varied markedly: Groups B and C showed significant improvements in pain perception (VAS scores), knee function, and quality of life (KOOS and WOMAC scores), while Group A showed marginal or non-significant changes, and Group D exhibited no significant improvements. These findings suggest that treatments in Groups B and C reached the Minimal Clinically Important Difference, significantly enhancing patient-reported outcomes. A dose of 2million BMAC cells per kg body weight for knee OA serves as the better regenerative modality of choice in cartilage regeneration. With our dose-escalation study, we would be able to standardize the treatment procedure and enable global comparison of the treatment method across various regions of the world.

The impact of an illness perception conversation on open-label placebo response in knee osteoarthritis: A randomised controlled trial

ObjectiveTo compare the effect of an illness perception conversation (IPC), relative to a research participation conversation (RPC), on 2-week changes in knee pain in patients with knee osteoarthritis. MethodThis was a randomised single-blind trial. Patients were randomised to two matched conversations. An Illness Perception (IP) conversation concerning the participant’s knee pain-related IP or a research participation conversation, concerning the participant’s motivation for participating in research. Both conversations were followed by an open-label intraarticular saline injection in the most symptomatic knee. The primary outcome was change in knee pain from baseline to 2 weeks follow-up on a 100 mm Visual Analogue Scale (VAS). Key secondary outcomes included the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales: Activities of daily living (ADL) and Quality of life (QoL). Main analyses were based on the intention-to-treat population using repeated measures mixed effects linear models. Results103 patients were randomised to the IPC group (n = 52) and the RPC group (n = 51). VAS knee pain scores changed statistically significantly from baseline to end of treatment in both groups, -13.7 (SE: 3.2) in the IPC group and -13.0 (SE: 3.1) in the RPC group with an adjusted between-group difference of -0.7 (95% CI: -8.3 to 6.9; P= 0.85). Likewise, no group differences were seen in KOOS ADL and KOOS QoL. ConclusionA conversation concerning knee pain-related IP did not augment the pain-relieving effect of an open-label placebo injection, when compared to a similar control conversation concerning motivations for participating in research. TRIAL REGISTRATIONNCT05225480

Three once-weekly intra-articular injections of Hylan G-F 20 significantly improve pain relief compared with placebo in patients with chronic idiopathic knee osteoarthritis: a single-centre, evaluator-blinded and patient-blinded, randomized controlled trial.

Clinical trials on the use of viscosupplementation with hyaluronic acid (HA) in patients with knee osteoarthritis (KOA) are inconsistent, making it challenging to determine its value in clinical practice. One issue is the availability of various HA products on the market; differences in their chemical features can impact patient outcomes. Herein, we assess the efficacy and safety of three once-weekly intra-articular (IA) injections of Hylan G-F 20, a high-molecular-weight and highly crosslinked HA product, in patients with KOA. We hypothesized that Hylan G-F 20 would provide significant pain relief with no increased safety risk compared with IA saline (placebo). This was a 26-week, patient-blinded and evaluator-blinded, single-centre, randomized placebo- controlled trial. Men or women ≥18 years of age with Larsen grade II or III KOA were included. Patients received IA injections of either Hylan G-F 20 or placebo once a week for 3 weeks. The primary endpoints were the week 12 and 26 visits. Primary efficacy outcomes included visual analogue scale (VAS) pain scores, patient activity level and an overall assessment of clinical condition. Secondary outcomes included adverse events (AEs) that emerged during treatment. The primary analysis included the intention-to-treat population. An alpha level of 0.05 was used in the statistical analysis. Thirty patients were included in the intention-to-treat population (15 per group). All efficacy outcomes were statistically significant in favour of Hylan G-F 20, except night pain and inactivity stiffness, for both patient- assessed (all p=0.0001 at week 12) and evaluator-assessed (all p=0.0001 at week 12 and p=0.0004-0.0180 at week 26) measurements. There was also a greater proportion of symptom-free patients and those with a >50% improvement in their VAS scores, except night pain, in the Hylan G-F 20 group (p=0.001-0.003 in patient-assessed scores and p<0.0001 to 0.002 in evaluator-assessed scores at week 12). Two patients, one in each group, experienced an AE; no sequelae occurred, and no special treatment was required for either AE. No patients withdrew from the study prematurely due to an AE. In patients with chronic idiopathic KOA, Hylan G-F 20 provides significant improvements in pain relief compared with placebo with no added safety concerns.

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.

Comparative Effects of Intra-Articular versus Intravenous Mesenchymal Stromal Cells Therapy in a Rat Model of Osteoarthritis by Destabilization of Medial Meniscus.

Transplanted mesenchymal stromal cells (MSCs) exhibit a robust anti-inflammatory and homing capacity in response to high inflammatory signals, as observed in studies focused on rheumatic diseases that target articular cartilage (AC) health. However, AC degradation in osteoarthritis (OA) does not necessarily coincide with a highly inflammatory joint profile. Often, by the time patients seek medical attention, they already have damaged AC. In this study, we examined the therapeutic potential of a single bone marrow MSC transplant (2 × 106 cells/kgbw) through two different routes: intra-articular (MSCs-IAt) and intravenous (MSCs-IVt) in a preclinical model of low-grade inflammatory OA with an established AC degeneration. OA was induced through the destabilization of the medial meniscus (DMM) in female Wistar Kyoto rats. The animals received MSCs 9 weeks after surgery and were euthanized 4 and 12 weeks post-transplant. In vivo and ex vivo tracking of MSCs were analyzed via bioluminescence and imaging flow cytometry, respectively. Cytokine/chemokine modulation in serum and synovial fluid was measured using a multiplex panel. AC degeneration was quantified through histology, and hindlimb muscle balance was assessed with precision weighing. To our knowledge, we are the first group to show the in vivo (8 h) and ex vivo (12 h) homing of cells to the DMM-OA joint following MSCs-IVt. In the case of MSCs-IAt, the detection of cellular bioluminescence at the knee joint persisted for up to 1 week. Intriguingly, intra-articular saline injection (placebo-IAt) resulted in a worse prognosis of OA when compared to a non-invasive control (placebo-IVt) without joint injection. The systemic cytokines/chemokines profile exhibited a time-dependent variation between transplant routes, displaying a transient anti-inflammatory systemic response for both MSCs-IVt and MSCs-IAt. A single injection of MSCs, whether administered via the intra-articular or intravenous route, performed 9 weeks after DMM surgery, did not effectively inhibit AC degeneration when compared to a non-invasive control.

Tranexamic acid administered intraarticularly to the knee is safer for the articular cartilage and anterior cruciate ligament compared to intravenous administration: Histological analysis of an experimental rat model.

In this study, the effects of tranexamic acid (TXA) on the knee's articular cartilage, anterior cruciate ligament (ACL), and joint capsule were assessed histologically. There were 15 rats in each of the 3 groups, totaling 45 rats. Intraarticular (IA) saline injections were applied for the first group, IA TXA injections for the second group, and intravenous (IV) TXA injections for the third group. Using samples taken from the knee joint 3weeks later, the medial/lateral femoral condyle and medial/lateral tibial plateau articular cartilages were evaluated with Osteoarthritis Research Society International (OARSI) scoring, while ACL diameter and joint capsule thickness were analyzed histologically. In comparisons of OARSI scores for the medial/lateral femoral condyle and medial/lateral tibial plateau cartilage regions, the scores obtained for the IV TXA group were significantly higher than those of the IA saline group (P < 0.001, P = 0.001, P = 0.003, P = 0.011). In comparisons of medial/lateral femoral condyle and medial/lateral tibial plateau OARSI scores, the scores obtained for the IV TXA group were again significantly higher than those of the IA TXA group (P < 0.001, P < 0.001, P < 0.001, P = 0.002). When ACL diameters were compared, a significant decrease was observed in the ACL diameters of the IV TXA group compared to the IA saline and IA TXA groups (P < 0.001, P = 0.039). Histologically, IV TXA damages the articular cartilage and ACL more than IA TXA. IA administration of TXA is more protective when the articular cartilage and ACL are preserved.

Debate: Intra-articular steroid injections for osteoarthritis – harmful or helpful?

Intra-articular corticosteroids injections are a widely used treatment for pain from symptomatic osteoarthritis. Systematic reviews show that the treatment effect is modest compared with intra-articular saline (often considered as placebo) and lasts for 2-4 weeks on average. Potentially as a consequence of limited therapeutic duration, repeated injections are often given up to 4 injections annually. In this context of repeat injections, recent evidence has emerged that intra-articular corticosteroids might be associated with more MRI-assessed quantitative cartilage thickness loss than saline injections. Guidelines vary in the recommendation for use of intra-articular corticosteroids. Given the frequency with which intra-articular corticosteroids injections are used, the size and scale of the population with osteoarthritis, it is critical to fully understand the benefits and drawbacks of intra-articular corticosteroids injections. That is the focus of this debate article.

A Blend of Tamarindus Indica and Curcuma Longa Extracts Alleviates Monosodium Iodoacetate (MIA)-Induced Osteoarthritic Pain and Joint Inflammation in Rats

Background and objective NXT15906F6 (TamaFlexTM) is a proprietary herbal composition containing Tamarindus indica seeds and Curcuma longa rhizome extracts. NXT15906F6 supplementation has been shown clinically effective in reducing knee joint pain and improving musculoskeletal functions in healthy and knee osteoarthritis (OA) subjects. The objective of the present study was to assess the possible molecular basis of the anti-OA efficacy of NXT15906F6 in a monosodium iodoacetate (MIA)-induced model of OA in rats. Methods Healthy male Sprague Dawley rats (age: 8–9 wk body weight, B.W.: 225–308 g (n = 12) were randomly assigned to one of the six groups, (a) vehicle control, (b) MIA control, (c) Celecoxib (10 mg/kg B.W.), (d) TF-30 (30 mg/kg B.W.), (e) TF-60 (60 mg/kg B.W.), and (f) TF-100 (100 mg/kg B.W.). OA was induced by an intra-articular injection of 3 mg MIA into the right hind knee joint. The animals received either Celecoxib or TF through oral gavage over 28 days. The vehicle control animals received intra-articular sterile normal saline. Results Post-treatment, NXT15906F6 groups showed significant (p < 0.05) dose-dependent pain relief as evidenced by improved body weight-bearing capacity on the right hind limb. NXT15906F6 treatment also significantly reduced the serum tumor necrosis factor-α (TNF-α, p < 0.05) and nitrite (p < 0.05) levels in a dose-dependent manner. mRNA expression analyses revealed the up-regulation of collagen type-II (COL2A1) and down-regulation of matrix metalloproteinases (MMP-3, MMP-9 and MMP-13) in the cartilage tissues of NXT15906F6-supplemented rats. Cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) protein expressions were down-regulated. Decreased immunolocalization of NF-κβ (p65) was observed in the joint tissues of NXT15906F6-supplemented rats. Furthermore, microscopic observations revealed that NXT15906F6 preserved MIA-induced rats’ joint architecture and integrity. Conclusion NXT15906F6 reduces MIA-induced joint pain, inflammation, and cartilage degradation in rats.

Pharmacokinetics of intra-articular buprenorphine in horses with lipopolysaccharide-induced synovitis.

The objective of this study was to describe the pharmacokinetics of intra-articular (IA) administered buprenorphine in horses with lipopolysaccharide (LPS)-induced synovitis. Radiocarpal synovitis was induced in six healthy adult horses with the IA injection of LPS (0.5ng/joint) on two occasions in a randomized cross-over design. Treatments (IA buprenorphine (IAB) at 5μg/kg plus intravenous saline; and intravenous buprenorphine (IVB) at 5μg/kg plus IA saline) were administered 4h following LPS injection. Concentrations of buprenorphine were assessed in plasma and synovial fluid (SF) at 0.5, 2, 6, 12, and 24 h after administration. Pharmacokinetic parameters after IVB and IAB in plasma and synovial fluid were calculated using a nonlinear mixed effects model. IAB was detectable in SF of all horses at 24 h [median concentration of 6.2 (3.46-22.6) ng/mL]. IAB resulted in a median plasma concentration of 0.59 (0.42-1.68) ng/mL at 0.5h and was detectable in all subjects for up to 6 h and in two horses for up to 12 h. IVB resulted in SF concentrations detected up to 6 h in all horses [median concentration of 0.12 (0.07-0.82) ng/mL]. Results suggest that IA buprenorphine remains present in the inflamed joint for at least 24 h and systemic absorption occurs.

Exercise and education vs intra-articular saline for knee osteoarthritis: a 1-year follow-up of a randomized trial

To assess the longer-term effect of the Good Life with osteoarthritis in Denmark (GLAD) exercise and education program relative to open-label placebo (OLP) on changes from baseline in core outcomes in individuals with knee osteoarthritis (OA). In this 1-year follow-up of an open-label, randomized trial, patients with symptomatic and radiographically confirmed knee OA were monitored after being randomized to either the 8-week GLAD program or OLP given as 4 intra-articular saline injections over 8 weeks. The primary outcome was the change from baseline in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale after 1 year in the intention-to-treat population. Key secondary outcomes were the KOOS function and quality of life subscales, and Patients' Global Assessment of disease impact. 206 adults were randomly assigned: 102 to GLAD and 104 to OLP, of which only 137 (63/74 GLAD/OLP) provided data at 1 year. At one year the mean changes in KOOS pain were 8.4 for GLAD and 7.0 for OLP (Difference: 1.5 points; 95% CI-2.6 to 5.5). There were no between-group differences in any of the secondary outcomes. In this 1-year follow-up of individuals with knee OA, the 8-week GLAD program and OLP both provided minor longer-term benefits with no group difference. These results require confirmation given the significant loss to follow-up. NCT03843931.

Comparison of clinical outcome, cartilage turnover, and inflammatory activity following either intra-articular or a combination of intra-articular with intra-osseous platelet-rich plasma injections in osteoarthritis knee: A randomized, clinical trial

BackgroundThe objective of the study was to determine the changes in clinical outcome (pain and knee activity) and assess bone/ cartilage biomarkers and inflammatory activity in persons with osteoarthritis (OA) knee following a single injection of intra-articular platelet-rich plasma (IA-PRP) and combination of intra-articular, intraosseous PRP (IA+IO-PRP). MethodsThis prospective, randomized, single-blind clinical trial was conducted at a tertiary care teaching hospital in India. Ninety-six persons with OA knee with a Kellgren-Lawrence score of 3 were randomized into three groups- Group-I (IA-PRP), Group-II (IA+IO-PRP)], Group-III, [intra-articular normal saline (IA-NS)]. The primary outcome was a visual analog scale (VAS) for pain. The secondary outcomes were the Knee Injury and Osteoarthritis Outcome Score (KOOS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), bone/ cartilage turnover biomarkers [C-telopeptide (CTX-II), N-telopeptide (NTX-I), cartilage oligomeric matrix protein (COMP), N-terminal propeptide of collagen type-IIA (PIIANP), and hyaluronic acid (HA)], ultrasonography (USG) findings of the knee joint. The outcome measures were assessed at baseline, 6, and 12 weeks of follow-up. ResultsCompared to IA-NS injection, IA-PRP and IA+IO-PRP injections significantly improved VAS-pain and KOOS scores at 6 and 12 weeks. Furthermore, both PRP groups showed a significant reduction in ESR, CRP, and CTX-II at 12 weeks following PRP injections. In addition, at 12 weeks, the IA+IO-PRP group showed a significant reduction (p=0.009) in NTX-I level. Persons in the IA+IO-PRP group reported significant reductions in the synovial-effusion and infra-patellar bursitis. ConclusionsSignificant clinical improvements were noticed following IA-PRP and IA-IO-PRP injections compared to IA-NS injections. Both PRP groups reported a significant reduction in ESR, CRP, and CTX-II levels at 12 weeks. Persons in the IA+IO-PRP group reported significant changes in u-NTX-I level and knee-USG findings.

Intra-articular remifentanil on postoperative pain in knee arthroscopic surgery; a double blind randomized clinical trial

BackgroundWe aimed to assess the efficacy of intra-articular remifentanil in relieving postoperative pain after knee arthroscopy. MethodsWe conducted a double-blind randomized clinical trial study on 60 patients. Patients were divided into two equal groups. The control group received 25 ml of intra-articular normal saline, and the intervention group received 200 μg of remifentanil dissolved in 25 ml of saline. We evaluated at rest postoperative pain at 1, 3, 6, 12, 18, and 24 h after the surgery using the Visual Analog Scale (VAS). Patients with VAS scores of 4 or more received meperidine (pethidine). The first time meperidine was requested and the total amount of meperidine consumed was recorded. ResultsOut of 60 patients, 49 were male (81.6%), and the mean age of participants was 32.71 (7.02) years. An hour after the surgery, the control group showed a mean VAS score of 8.66 (1.26), and decreased to 2.53 (1.67) at the end of 24 h. The intervention group started with a mean VAS score of 2.23 (1.81) and ended at 0.10 (0.305). All patients in the control group and 11 (36.7%) patients in the intervention group asked for analgesics during follow-up. The mean total meperidine dose in the control and intervention groups was 108.33 (23.97) mg and 13.33 (19.40) mg, respectively (P < 0.001; 95% confidence interval of the difference 83.72 to 106.27). ConclusionsIntra-articular remifentanil may decrease postoperative pain and analgesic requirements in patients undergoing knee arthroscopy.

Functional outcome of treatment of frozen shoulder using Hydrodilatation along with intraarticular steroid and saline injection

Introduction: Defined as idiopathic shoulder pain of at least one month duration accompanied by increasing limitations of active and passive glenohumeral movements in all the directions in the patients who have no identifiable general illness and whose radiological findings are entirely normalMaterial and Methods: This study was conducted in the department of orthopaedics, RMMCH (Government Cuddalore Medical College) from August 2020 to November 2022 in the selected candidates in the age group between 35 to 65 years. Clinical outcomes were measured with Shoulder Pain and Disability Index (SPADI).Result: SPADI score recorded at 1 and 6 months follow up gives a clear picture that all stages of frozen shoulder had good clinical outcome and early stages of frozen shoulder had excellent results.Conclusion: Intervention with corticosteroid injection with saline distension is better than any of corticosteroid, saline distension or physiotherapy alone.In the long run it was found that outcome is improved by intervention using Hydrodilatation with saline and steroid followed by physiotherapy. Hydrodilatation along with steroid provides early, medium and long term improvements in range of movements.

RADIOGRAPHIC COMPARATIVE REGENERATIVE EFFECTS OF HYALURONATE AND PIROXICAM IN OSTEOARTHRITIS MODELS OF RATS

Background: Osteoarthritis is the most common degenerative joint disease that affects commonly in old age. Standard treatment of this disease is still underdeveloped, however multiple drug groups delay progression or reduce the symptoms. Objective of this study was to assess and compare the regenerative effects of hyaluronate and piroxicam in a rat model of osteoarthritis at the radiographic level. Methods: This laboratory-based randomized trial was conducted at Department of Pharmacology Army Medical College, Rawalpindi, from May to July 2019. Resection of the medial meniscus and anterior cruciate ligament resulted in osteoarthritis in the right knee joints of 24 rats. They were separated into 3 groups of 8 rats each. For 4 weeks, groups I, II, and III received intra-articular saline, hyaluronate, and piroxicam, respectively. After one week, radiographs of the anaesthetized rats’ matching knee joints were collected. Results: Comparison of radiograph of control group with drug treated group confirmed regenerative effects of hyaluronate and piroxicam (p=0.001). However comparison of hyaluronate and piroxicam treated groups had p=0.335 that professed both drug have equal regenerative effects in rat model of osteoarthritis. Conclusion: In a rat model of osteoarthritis, intra-articular injection of hyaluronate acid and piroxicam had regenerating benefits at the radiological level. Both administered medicines had similar regeneration effects. Pak J Physiol 2022;18(3):19–22

Who are likely to benefit from the Good Life with osteoArthritis in Denmark (GLAD) exercise and education program? An effect modifier analysis of a randomised controlled trial

To identify contextual factors that modify the treatment effect of the 'Good Life with osteoArthritis in Denmark' (GLAD) exercise and education programme compared to open-label placebo (OLP) on knee pain in individuals with knee osteoarthritis (OA). Secondary effect modifier analysis of a randomised controlled trial. 206 participants with symptomatic and radiographic knee OA were randomised to either the 8-week GLAD programme (n=102) or OLP given as 4 intra-articular saline injections over 8 weeks (n=104). The primary outcome was change from baseline to week 9 in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale (range 0 (worst) to 100 (best)). Subgroups were created based on baseline information: BMI, swollen study knee, bilateral radiographic knee OA, sports participation as a young adult, sex, median age, a priori treatment preference, regular use of analgesics (NSAIDs or paracetamol), radiographic disease severity, and presence of constant or intermittent pain. Participants who reported use of analgesics at baseline seem to benefit from the GLAD programme over OLP (subgroup contrast: 10.3 KOOS pain points (95% CI 3.0 to 17.6)). Participants with constant pain at baseline also seem to benefit from GLAD over OLP (subgroup contrast: 10.0 points (95% CI 2.8 to 17.2)). These results imply that patients who take analgesics or report constant knee pain, GLAD seems to yield clinically relevant benefits on knee pain when compared to OLP. The results support a stratified recommendation of GLAD as management of knee OA. ClinicalTrials.gov Identifier: NCT03843931. EudraCT number 2019-000809-71.

Intra-articular botulinum toxin A injection for painful base-of-thumb osteoarthritis: a double-blind, randomised, controlled, phase 3 trial (RHIBOT).

Intra-articular botulinum toxin A injection might have analgesic effects in patients with joint diseases. We aimed to compare the effects of intra-articular botulinum toxin A injection with those of intra-articular saline injection for patients with painful base-of-thumb osteoarthritis. RHIBOT was a double-blind, randomised, controlled, phase 3 trial conducted at Cochin Hospital, Paris, France. We recruited adult patients with x-ray evidence of trapeziometacarpal osteoarthritis who fulfilled the 1990 American College of Rheumatology criteria for hand osteoarthritis and reported a pain intensity score of at least 30 on an 11-point numeric rating scale (0: no pain to 100: maximal pain). Participants were randomly assigned (1:1), using a computer-generated randomisation list with permuted blocks of variable size (4 or 6), to receive an ultrasound-guided injection of either botulinum toxin A (50 Allergan units) in 1 mL of saline (experimental group) or 1 mL of saline alone (control group) in the trapeziometacarpal joint, in addition to custom-made rigid splinting. The primary outcome was the mean change from baseline in base-of-thumb pain in the previous 48 h on a numeric rating scale at 3 months after injection, analysed by intention to treat. This study is registered with ClinicalTrials.gov, NCT03187626. Between Nov 2, 2018, and Nov 3, 2020, we assessed 370 individuals for eligibility and recruited 60 (16%) participants (mean age 64·9 years [SD 9·4], 47 [78%] women and 13 [22%] men), of whom 30 (50%) participants were randomly assigned to the experimental group and 30 (50%) to the control group. At baseline, base-of-thumb pain score was 60·0 of 100·0 (SD 15·9). At 3 months, the mean reduction in base-of-thumb pain was -25·7 (95% CI -35·5 to -15·8) in the experimental group and -9·7 (-17·1 to -2·2) in the control group (absolute difference -16·0 [-28·1 to -3·9]; p=0·043). Overall, 51 adverse events were reported in both groups: 27 (53%) in the experimental group and 24 (47%) in the control group. During follow-up, 14 (47%) participants in the experimental group and two (7%) participants in the control group reported mild transient motor deficit of the thenar muscle. No serious adverse events were reported. Botulinum toxin A could be considered as a fast-acting, intra-articular therapy targeting chronic pain in individuals with base-of-thumb osteoarthritis. Future studies are needed to investigate the potential mechanism of the effects observed in this trial, to replicate our findings, and to assess the effects of repeated injections over time and their clinical effectiveness, including an analysis of cost-effectiveness. Assistance Publique-Hôpitaux de Paris.

A Comparative Study of Short-Term Efficacy of Intra-articular Hypertonic Saline and Hypertonic Dextrose Prolotherapy in Knee Osteoarthritis: A randomized controlled trial (RCT)

A Comparative Study of Short-Term Efficacy of Intra-articular Hypertonic Saline and Hypertonic Dextrose Prolotherapy in Knee Osteoarthritis: A randomized controlled trial (RCT)