Osteoarthritis Pain Research Articles

Fibrocyte Phenotype of ENTPD1+CD55+ Cells and Its Association with Pain in Osteoarthritic Synovium.

Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage erosion, structural changes, and inflammation. Synovial fibroblasts play a crucial role in OA pathophysiology, with abnormal fibroblastic cells contributing significantly to joint pathology. Fibrocytes, expressing markers of both hematopoietic and stromal cells, are implicated in inflammation and fibrosis, yet their marker and role in OA remain unclear. ENTPD1, an ectonucleotidase involved in purinergic signaling and expressed in specific fibroblasts in fibrotic conditions, led us to speculate that ENTPD1 plays a role in OA pathology by being expressed in fibrocytes. This study aimed to investigate the phenotype of ENTPD1+CD55+ and ENTPD1-CD55+ synovial fibroblasts in OA patients. Proteomic analysis revealed a distinct molecular profile in ENTPD1+CD55+ cells, including the upregulation of fibrocyte markers and extracellular matrix-related proteins. Pathway analysis suggested shared mechanisms between OA and rheumatoid arthritis. Correlation analysis revealed an association between ENTPD1+CD55+ fibrocytes and resting pain in OA. These findings highlight the potential involvement of ENTPD1 in OA pain and suggest avenues for targeted therapeutic strategies. Further research is needed to elucidate the underlying molecular mechanisms and validate potential therapeutic targets.

The efficacy of curcumin in relieving osteoarthritis: A meta-analysis of meta-analyses.

Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases. Several meta-analyses have shown that curcumin could improve the function of the knee and alleviate pain in OA, while some meta-analyses demonstrate controversial results. Hence, we assessed curcumin's effects on knee OA in an umbrella meta-analysis. PubMed, Scopus, Embase, and Web of Science databases were employed to find English-language meta-analyses of randomized controlled trials investigating the effect of curcumin supplementation on OA outcomes up to September 2023. The visual analog scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, function, and stiffness scales were analyzed. Effect sizes and 95% confidence intervals were utilized to obtain the overall effect size. A random-effects model was applied to perform the meta-analysis. Heterogeneity was determined by I2 statistics and the Cochrane Q-test. The pooled effect of the 11 included meta-analyses showed that curcumin could significantly decrease the VAS score (weighted mean difference [WMD] and standardized mean difference [SMD]), WOMAC-total (SMD and WMD), WOMAC-Function (SMD and WMD), WOMAC-Pain (SMD), and WOMAC-Stiffness scores (SMD) (p ≤ 0.001, ≤0.001, ≤0.001, 0.007, ≤0.001, 0.002, ≤0.001, ≤0.001, respectively). The results strongly support curcuminoid supplementation in relieving pain, improving joint mobility and stiffness, and shortening medication usage of OA patients.

Pain Management Strategies in Osteoarthritis.

Pain is the major symptom of osteoarthritis (OA) and is an important factor in strategies to manage this disease. However, the current standard of care does not provide satisfactory pain relief for many patients. The pathophysiology of OA is complex, and its presentation as a clinical syndrome is associated with the pathologies of multiple joint tissues. Treatment options are generally classified as pharmacologic, nonpharmacologic, surgical, and complementary and/or alternative, typically used in combination to achieve optimal results. The goals of treatment are the alleviation of symptoms and improvement in functional status. Several studies are exploring various directions for OA pain management, including tissue regeneration techniques, personalized medicine, and targeted drug therapies. The aim of the present narrative review is to extensively describe all the treatments available in the current practice, further describing the most important innovative therapies. Advancements in understanding the molecular and genetic aspects of osteoarthritis may lead to more effective and tailored treatment approaches in the future.

Assessment of Clinical Outcomes in Patients With Osteoarthritis: Analysis From the UK Medical Cannabis Registry

Osteoarthritis accounts for 0.6% of disability-adjusted life years globally. There is a paucity of research focused on cannabis-based medicinal products (CBMPs) for osteoarthritic chronic pain management. This study aims to assess changes in validated patient-reported outcome measures (PROMs) and CBMP clinical safety in patients with osteoarthritis. A prospective case series from the UK Medical Cannabis Registry was analyzed. Primary outcomes were changes in the Brief Pain Inventory (BPI), McGill Pain Questionnaire (MPQ2), EQ-5D-5L, Generalized Anxiety Disorder-7 (GAD-7) questionnaire, and Single-Item Sleep Quality Scale (SQS) at 1-, 3-, 6-, and 12-month follow-ups from baseline. Common Terminology Criteria for Adverse Events v.4.0 was used for adverse event (AE) analysis. Statistical significance was defined as p < 0.050. Seventy-seven patients met inclusion criteria. CBMP initiation correlated with BPI pain severity (p = 0.004), pain interference (p = 0.005), and MPQ2 (p = 0.017) improvements at all follow-ups compared to baseline. There were improvements in the EQ-5D-5L index (p = 0.026), SQS (p < 0.001), and GAD-7 (p = 0.038) up to 6 and 3 months, respectively. Seventeen participants (22.08%) recorded 76 mild AEs (34.86%), 104 moderate AEs (47.71%), and 38 severe AEs (17.43%). Though causality cannot be assumed in this observational study, results support development of randomized control trials for osteoarthritis pain management with CBMPs.

Anti-Inflammatory, Analgesic, Functional Improvement, and Chondroprotective Effects of Erigeron breviscapus (Vant.) Hand.-Mazz. Extract in Osteoarthritis: An In Vivo and In Vitro Study.

Osteoarthritis (OA) is a degenerative bone disease characterized by inflammation as a primary pathology and currently lacks therapeutic interventions to impede its progression. Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) is an east Asian herbal medicine with a long history of use and a wide range of confirmed efficacy against cardiovascular and central nervous system diseases. The purpose of this study is to evaluate whether EB is worthy of further investigation as a treatment for OA based on anti-inflammatory activity. This study aims to assess the potential of EB as a treatment for OA, focusing on its anti-inflammatory properties. Analgesic effects, functional improvements, and inhibition of cartilage destruction induced by EB were evaluated in acetic acid-induced peripheral pain mice and monosodium iodoacetate-induced OA rat models. Additionally, the anti-inflammatory effect of EB was assessed in serum and cartilage tissue in vivo, as well as in lipopolysaccharide-induced RAW 264.7 cells. EB demonstrated a significant alleviation of pain, functional impairment, and cartilage degradation in OA along with a notable inhibition of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, matrix metalloproteinases 13, and nitric oxide synthase 2, both in vitro and in vivo, in a dose-dependent manner compared to the active control. Accordingly, EB merits further exploration as a potential disease-modifying drug for OA, capable of mitigating the multifaceted pathology of osteoarthritis through its anti-inflammatory properties. Nonetheless, additional validation through a broader experimental design is essential to substantiate the findings of this study.

Sex differences in osteoarthritis prevalence, pain perception, physical function and therapeutics

ObjectiveWomen have a higher prevalence of osteoarthritis (OA) and worse clinical courses than men. However, the underlying factors and therapeutic outcomes of these sex-specific differences are incompletely researched. This review examines the current state of knowledge regarding sex differences in OA prevalence, risk factors, pain severity, functional outcomes, and use and response to therapeutics. MethodsPubMed database was used with the title keyword combinations “{gender OR sex} AND osteoarthritis” plus additional manual search of the included papers for pertinent references, yielding 212 references. Additional references were added and 343 that were reviewed for appropriateness. ResultsGlobally, women account for 60% of people with osteoarthritis with a greater difference after age 40. The higher risk for women may be due to differences in joint anatomy, alignment, muscle strength, hormonal influences, obesity, and/or genetics. At the same radiographic severity, women have greater pain severity than men, which may be explained by biologically distinct pain pathways, differential activation of central pain pathways, differences in pain sensitivity, perception, reporting, and coping strategies. Women have greater limitations of physical function and performance than men independent of BMI, OA severity, injury history, amount of weekly exercise. Women also have greater use of analgesic medications than men but less use of arthroplasty and poorer prognosis after surgical interventions. ConclusionsThe recognition of sex differences in OA manifestations and management could guide tailoring of sex-specific treatment protocols, and analysis of sex as a biological variable in future research would enhance development of precision medicine.

Pain control and functional recovery as therapeutic goals in patients with chronic musculoskeletal pain: two experiences with tapentadol hydrochloride.

This study aimed to evaluate pain control, functioning, and quality of life (QoL) recovery in patients with chronic low back pain (cLBP) or post-traumatic osteoarthritis (OA) pain in the ankle/foot area, treated with tapentadol prolonged release and unresponsive to other treatments. Two observational retrospective studies were conducted using clinical practice datasets of patients with chronic pain in cLBP and OA foot/ankle at different time points (total follow-up=60-90 days). The studies assessed pain intensity by the Numerical Rating Scale (NRS) pain scale (patients were classified as responder in case of ≥30% pain reduction), QoL by the 5-level EQ-5D (EQ-5D-5L) questionnaire, patient satisfaction by the 7-point Patients' Global Impression of Change (PGIC) scale; cLBP health status by the Roland Morris Disability Questionnaire (RMDQ); foot and ankle functional status by European Foot and Ankle Society (EFAS) score; and treatment-related AEs. For the cLBP setting, 37 patients were enrolled, of which 86.50% were classified as responders (n=32; CI: 75.5% ÷ 97.5%). For the foot/ankle OA pain setting, 21 patients were enrolled. Pain assessment at final follow-up was available only for 11 patients, of which 72.73% (n=8; CI: 39.0% ÷ 94.0%) were classified as responders. Statistically significant improvements were seen in the RMDQ, EQ-5D-5L, and PGIC scores in cLBP. Improvements in the EFAS, EQ-5D-5L, and PGIC scores were seen in OA as well. The incidence of treatment-related adverse reactions was low in both studies. In the study population, tapentadol prolonged release was effective and well tolerated in treating cLBP and post-traumatic foot/ankle OA chronic pain when used in a multimodal manner. The reduction in pain was accompanied by clinically relevant improvements in patients' functionality and QoL.

Hip-Spine and Knee-Spine Syndrome: Is Low Back Pain Improved After Total Hip and Knee Arthroplasty?

Hip and knee osteoarthritis (OA) and low back pain (LBP) are prevalent diseases that can negatively impact daily activities. The concurrent existence of lumbar spine disorders with hip or knee issues forms two syndromes: hip-spine syndrome (HSS) and knee-spine syndrome (KSS). The primary objective of this study is to evaluate the relationship between hip and knee OA and LBP, as well as the changes to LBP after total hip arthroplasty (THA) and total knee arthroplasty (TKA). The secondary objective is to identify the cause of LBP among patients with hip and knee OA. The group of hip OA patients treated with THA consisted of 34 individuals, and the group of knee OA patients treated with TKA consisted of 45 individuals. In these two groups of patients, the LBP was assessed using the visual analog scale score preoperatively and four and 12 months postoperatively. To determine the cause of LBP, we compared preoperative and postoperative (12-month) pelvic obliquity and hip or knee pain in patients with and without preoperative LBP. For hip OA-THA, more than half (55.88%) of patients suffering from hip OA also experienced moderate to severe LBP. Improvement in LBP was noticed in 79% of these patients at both four and 12 months post-THA, with levels dropping from 6.84 to 2.58 and then 2.53, respectively. Moreover, improvements in hip pain and pelvic obliquity were observed in patient groups both with and without preoperative LBP following THA. This suggests that there's no obvious correlation between LBP and these parameters. For knee OA-TKA, most (62.22%) patients with knee OA experienced moderate to very severe LBP. In 50% of these patients, LBP showed improvement at four and 12 months post-TKA (6.39 → 4.79 → 4.04). Additionally, in both groups with and without preoperative LBP, knee pain and pelvic obliquity were improved after TKA, suggesting no clear association between LBP and these parameters. HSS and KSS were frequently observed in patients. A significant improvement in LBP was seen after THA or TKA, suggesting that total arthroplasty should be prioritized before spinal surgery. Furthermore, there is not a definitive link between LBP, joint pain, and pelvic obliquity.

Relationship of Body Mass Index on Patient-Reported Outcomes After Platelet-Rich Plasma Versus Microfragmented Adipose Tissue for Knee Osteoarthritis: A Secondary Analysis of a Randomized Controlled Trial.

Body mass index is known to contribute to outcomes for patients with knee osteoarthritis. Furthermore, body mass index influences the protein expression of orthobiologic treatments like platelet-rich plasma and microfragmented adipose tissue. We performed a secondary analysis of the association of body mass index with patient-reported outcomes for patients with knee osteoarthritis who received either platelet-rich plasma or microfragmented adipose tissue injections. Seventy-one patients with knee osteoarthritis were randomized to receive a single ultrasound-guided injection of platelet-rich plasma or microfragmented adipose tissue. Platelet-rich plasma was created from 180 cc of anticoagulated blood and processed using a double-spin, buffy-coat concentration system. Microfragmented adipose tissue was created using autologous lipoaspirate that was processed according to minimal manipulation guidelines. Patient-reported outcomes and osteoarthritis outcome scores (Knee Osteoarthritis and injury Outcome Score) were tracked for 12 mos. Forty-nine patients (platelet-rich plasma = 23, microfragmented adipose tissue = 26) completed 12-mo follow-up. Knee Osteoarthritis and injury Outcome Score quality of life and activity of daily living subscores were inversely correlated (both P < 0.05) with body mass index in the microfragmented adipose tissue but not platelet-rich plasmagroup. Knee Osteoarthritis and injury Outcome Score pain and sport subscores showed a trend toward inverse correlation with body mass index in the microfragmented adipose tissue group ( P = 0.07 and P = 0.06, respectively), but not platelet-rich plasma. Body mass index was negatively associated with patient-reported outcomes in patients who received microfragmented adipose tissue injections for knee osteoarthritis, but not for patients receiving platelet-rich plasma.

β-crosslaps in knee osteoarthritis – assessment and rehabilitation

Abstract: The bone turnover is important for the progression of osteoarthritis. The C-terminal telopeptide of type I collagen, β-CrossLaps (β-CTx) is considered as the first-choice bone resorption markers. Today, the biochemical markers have been associated with pain and disease severity in knee osteoarthritis (KOA) patients. We studied the association between β-CTx and functional status in KOA patients, pre- and postrehabilitation program. The primary goals of our study are both to establish the correlation between the serum level of β-CTx and other parameters of clinical and functional status in KOA patients and to compare the CTX-I values before and after rehabilitation program. We respected the actual international management recommendations for KOA. A total of 130 patients were randomly allocated into two distinct groups: Study Group (SG = 90 patients) performed 10 sessions of complete rehabilitation program (magnetodiaflux, transcutaneous nerve stimulation, ultrasound and low intensity laser treatment, kinetic measures), and Control Group (CG = 40 patients) performed 10 sessions of kinetic program. Both programs were performed daily, 5 days/week, 2 weeks. Evaluation of patients was carried out in two stages - initial (T1) and after 3 months (T2). Comparing the initial values with the final ones for β-CTx, we noticed a high significant difference between initial and final values only in SG patients. For the both T1 and T2 moments, there was no a statistically significant difference between β-CTx values from the two groups. Analyzing the differences between the values of clinical parameters (Six Minutes Walking Test, Timed Up-and-Go test, walk cadence and Symmetry index in walk) obtained between the patients from the two groups, we noticed that, for the T2 moment, there was a statistically significant difference between studied parameters, except walk cadence. In the assessment of global KOA patient status (clinical and functional status in accordance with bone-cartilage interface dynamics), β-CTx has significant value and could be used for monitoring the individualized rehabilitation program.

The Effects of GreenShell Mussel Powder (Brand-Named PERNAULTRA) on Physical Performance and Subjective Pain, Symptoms, and Function Measures in Knee Osteoarthritis: A 6-Mo Randomized, Double-Blind, Placebo-Controlled Trial

BackgroundOsteoarthritis (OA) can cause disability and reduce quality of life (QoL). ObjectivesThis study aimed to determine whether GreenShell mussel (GSM) powder (PERNAULTRA) consumption was more effective than placebo at improving physical performance and subjective measures of symptoms and function in adults with early signs of knee OA. MethodsThe Researching Osteoarthritis and GSM study was a 6-mo randomized, double-blind, placebo-controlled trial in adults aged 55–80 y, screened for signs of OA (n = 120, 65.9 ± 6.43 y, 63% female). Participants consumed either 3 g of powdered whole GSM or placebo (pea protein) daily. Baseline and end data collection included 30-s chair stand, stair test, 40-m fast-paced walk test, Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire categorized into 5 subscales [pain (P), symptoms except pain (S), function in activities of daily living (ADL), function in sports/recreation (SP), and QoL], a measure of Intermittent and Constant Osteoarthritis Pain, and visual analog scale of pain and symptoms. ResultsVisual analog scale symptoms showed a significantly greater reduction in percentage change for GSM than that for placebo [−28.1 (−59.2, 43.2) compared with 0.00 (−28.6, 100); P = 0.03]. Further, a trend for improvement in percentage change for GSM compared with placebo was seen in 40m fast-paced walk [2.51 (−3.55, 8.12) compared with 0.20 (−6.58, 4.92); P = 0.09], KOOS-SP [11.4 (−4.48, 27.0) compared with 0.00 (−11.1, 17.7); P = 0.09], and Intermittent and Constant Osteoarthritis Pain intermittent pain scale [−27.7 (−77.3, 0.00) compared with −14.6 (−50.0, 36.4); P = 0.08]. In those with body mass index (BMI; in kg/m2) <25, GSM consumption significantly improved KOOS-S compared with placebo [6.35 (3.49, 12.7) compared with 0.00 (−4.65, 4.49); P = 0.03] and showed a trend for improvement in KOOS-ADL [3.29 (1.01, 8.79) compared with 1.01 (−5.75, 4.30); P = 0.07]. Those with BMI of ≥25, consuming GSM showed a trend for improvement in KOOS-SP [13.6 (−4.76, 33.3) compared with 0.00 (−12.5, 20.0); P = 0.07]. ConclusionsThis research suggests consumption of GSM has potential to alleviate symptoms and improve functionality in OA.This trial was registered at Clinical Trial Registry as ACTRN12620001112954p (https://www.anzctr.org.au/ACTRN12620001112954p.aspx).

Concerns beyond ankle symptoms predominate healthcare professionals’ views of patients with ankle osteoarthritis: A qualitative study

ObjectivesExplore healthcare professionals’ perspectives on the main problems that their patients with ankle osteoarthritis experience and to propose health-related domains. MethodsA qualitative study using semi-structured interviews was conducted with an international multidisciplinary group of healthcare professionals identified as ankle experts. Eligibility criteria were aged ≥18 years, and a certified healthcare professional with ≥ 5-year experience post-qualification in working with ankle osteoarthritis and/or chronic ankle pain. Interviews were recorded, transcribed verbatim and thematically analysed. ResultsTwenty-one healthcare professionals (20 males; mean (range) age 49 (34–72) years) from four professions (orthopaedic surgeons (n = 9), athletic trainers (n = 5), physiotherapists (n = 4) and podiatrists (n = 3)) were interviewed. Four main themes were identified: 1) people with ankle osteoarthritis have difficulty with weight-bearing activities; 2) symptoms of pain and stiffness predominate, alongside swelling, instability, weakness and poor balance; 3) chronic pain in ankle osteoarthritis has psychosocial consequences; and 4) the loss of activities of daily living and independence compromises quality of life. We proposed 15 health-related domains that emerge from the interview data. ConclusionHealthcare professionals recognise that ankle osteoarthritis patients have difficulty in physical, sporting, and occupational weight-bearing activities, and they live with persistent ankle pain, stiffness and other symptoms that have physical and psychosocial consequences. The health-related domains derived from interviews with expert healthcare professionals will contribute to the development of a core domain set for ankle osteoarthritis.

Miao medicine Gu Yan Xiao tincture inhibits mTOR to stimulate chondrocyte autophagy in a rabbit model of osteoarthritis

Ethnopharmacological relevanceThe Gu Yan Xiao tincture, a blend of traditional Chinese herbs, is traditionally used for osteoarthritis and related pain. This study investigated its mechanism of action in order to rationalize and validate its therapeutic use. Aim of the studyThis study analyzed, in a rabbit model of knee osteoarthritis, whether and how Gu Yan Xiao tincture exerts therapeutic benefits by modulating chondrocyte autophagy. Materials and methodsThe active constituents within the GYX tincture were identified using liquid chromatography-mass spectrometry. The rabbit model was established by injecting animals with type II collagenase intra-articularly, and the effects of topically applied tincture were examined on osteoarthritis lesions of the knee using histopathology, micro-computed tomography and x-ray imaging. Effects of the tincture were also evaluated on levels of inflammatory cytokines, matrix metalloproteases, and autophagy in chondrocytes. As a positive control, animals were treated with sodium diclofenac. ResultsThe tincture mitigated the reduction in joint space, hyperplasia of the synovium and matrix metalloproteases in serum that occurred after injection of type II collagenase in rabbits. These therapeutic effects were associated with inhibition of mTOR and activation of autophagy in articular chondrocytes. Inhibiting mTOR with rapamycin potentiated the therapeutic effects of the tincture, while inhibiting autophagy with 3-methyladenine antagonized them. ConclusionsGu Yan Xiao tincture mitigates tissue injury in a rabbit model of osteoarthritis, at least in part by inhibiting mTOR and thereby promoting autophagy in chondrocytes. These results rationalize the use of the tincture not only against osteoarthritis but also potentially other diseases involving inhibition of autophagy in bones and joints.

Peri-articular Dextrose Prolotherapy: Investigating the Effect of Injection Site on Knee Osteoarthritis Pain: A Double-Blind, Randomized, Clinical Trial.

Osteoarthritis (OA) is a chronic health condition that affects millions of people worldwide. It not only causes pain and physical limitations but also impacts mental health, sleep, work participation, and even mortality. Peri-articular dextrose prolotherapy has been shown to reduce knee osteoarthritis pain; however, the effect of injection sites on its effectiveness is not clear. This study aimed to investigate the effect of injection points on pain intensity, joint stiffness, and physical activity in patients with knee osteoarthritis who underwent peri-articular dextrose prolotherapy. This double-blind clinical trial involved 26 patients with grade 2 and 3 bilateral knee osteoarthritis. Three times every one week, dextrose and lidocaine were injected as interventions. Injection sites were positioned within acupuncture points on one knee, but were relocated by 1.5 centimeters to the medial side of the same acupuncture points on the other knee. Pain intensity, joint stiffness, and physical activity were evaluated using the Visual Analog Pain Scale (VAS) and the Persian version of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) before the intervention and at each follow-up visit at 1 and 2 months post-injection. Pain intensity score, joint stiffness, physical performance, and WOMAC were significantly decreased one and two months after the intervention in both groups (P = 0.0001). The improvement in the patients of both groups was similar, and the two study groups did not have a statistically significant difference in terms of study outcomes (P = 0.37). Prolotherapy with dextrose is an effective treatment for knee osteoarthritis.

Unicompartmental knee arthroplasty improves mental health in patients with single compartment knee osteoarthritis.

The purpose of this study was to determine if preoperative mental health status improves following unicompartmental knee arthroplasty (UKA) in patients with single compartment knee osteoarthritis (OA). A total of 163 patients underwent UKA [115 (71%) medial, 48 (29%) lateral] (mean age = 65 ± 11) completed preoperative and minimum 2-year postoperative veterans RAND 12 item health survey (VR-12) mental component score (MCS). VR-12 MCS was the primary outcome measure. Secondary measures included VR-12 physical component summary score (PCS), knee osteoarthritis outcome score (KOOS) and KOOS patient acceptable symptom state at the final follow-up. The median VR-12 MCS improved from 50.5 [interquartile range (IQR): 43.7-56.8] to 55.0 [IQR: 52.3-57.0] (p < 0.001) at a mean follow-up of 9.5 ± 4 years (range 2-19 years) following UKA. Preoperative VR-12 MCS was significantly correlated with patients postoperative VR-12 PCS (ρ = 0.294, p < 0.01), KOOS pain (ρ = 0.201, p = 0.012), KOOS ADL (ρ = 0.243, p = 0.002) and KOOS quality of life (ρ = 0.233, p < 0.01). Sixty-three (39%) patients improved from low VR-12 MCS (<50) to normal VR-12 MCS (≥50). One hundred forty-two (87%) achieved a normal VR-12 MCS score (≥50) postoperatively. At a mean of 10-year follow-up, patients who underwent UKA for single compartment osteoarthritic knee pain demonstrated significant improvement in mental health scores. UKA resulted in normal mental health in a majority of patients (87%). The resultant improved mental health scores were associated with improved patient pain and activities of daily living. Level III retrospective cohort study.

Missed Monteggia Injuries in Children and Adolescents: A Treatment Algorithm.

Monteggia injuries are rare childhood injuries. In 25-50% of cases, however, they continue to be overlooked, leading to a chronic Monteggia injury. Initially, the chronic Monteggia injury is only characterized by a moderate motion deficit, which is often masked by compensatory movements. Later, however, there is a progressive valgus deformity, neuropathy of the ulnar nerve and a progressive deformity of the radial head ("mushroom deformity") with ultimately painful radiocapitellar arthrosis. In the early stages, when the radial head is not yet deformed and there is no osteoarthritis in the humeroradial joint, these injuries can be treated with reconstruction procedures. This can be achieved either by an osteotomy of the proximal ulna with or without gradual lengthening. If there is already a severe deformity of the radial head and painful osteoarthritis, only rescue procedures such as functional radial head resection or radial head resection with or without hemi-interposition arthroplasty can be used to improve mobility and, above all, to eliminate pain. In this review article, we provide an overview of the current treatment options of chronic Monteggia injury in children and adolescents and present a structured treatment algorithm depending on the chronicity and dysplastic changes.

Targeting STAT6-mediated synovial macrophage activation improves pain in experimental knee osteoarthritis

BackgroundPain from osteoarthritis (OA) is one of the top causes of disability worldwide, but effective treatment is lacking. Nociceptive factors are released by activated synovial macrophages in OA, but depletion of synovial macrophages paradoxically worsens inflammation and tissue damage in previous studies. Rather than depleting macrophages, we hypothesized that inhibiting macrophage activation may improve pain without increasing tissue damage. We aimed to identify key mechanisms mediating synovial macrophage activation and test the role of STAT signaling in macrophages on pain outcomes in experimental knee OA.MethodsWe induced experimental knee OA in rats via knee destabilization surgery, and performed RNA sequencing analysis on sorted synovial tissue macrophages to identify macrophage activation mechanisms. Liposomes laden with STAT1 or STAT6 inhibitors, vehicle (control), or clodronate (depletion control) were delivered selectively to synovial macrophages via serial intra-articular injections up to 12 weeks after OA induction. Treatment effects on knee and hindpaw mechanical pain sensitivity were measured during OA development, along with synovitis, cartilage damage, and synovial macrophage infiltration using histopathology and immunofluorescence. Lastly, crosstalk between drug-treated synovial tissue and articular chondrocytes was assessed in co-culture.ResultsThe majority of pathways identified by transcriptomic analyses in OA synovial macrophages involve STAT signaling. As expected, macrophage depletion reduced pain, but increased synovial tissue fibrosis and vascularization. In contrast, STAT6 inhibition in macrophages led to marked, sustained improvements in mechanical pain sensitivity and synovial inflammation without worsening synovial or cartilage pathology. During co-culture, STAT6 inhibitor-treated synovial tissue had minimal effects on healthy chondrocyte gene expression, whereas STAT1 inhibitor-treated synovium induced changes in numerous cartilage turnover-related genes.ConclusionThese results suggest that STAT signaling is a major mediator of synovial macrophage activation in experimental knee OA. STAT6 may be a key mechanism mediating the release of nociceptive factors from macrophages and the development of mechanical pain sensitivity. Whereas therapeutic depletion of macrophages paradoxically increases inflammation and fibrosis, blocking STAT6-mediated synovial macrophage activation may be a novel strategy for OA-pain management without accelerating tissue damage.

An injectable cartilage-coating composite with long-term protection, effective lubrication and chondrocyte nourishment for osteoarthritis treatment

The osteoarthritic (OA) environment within articular cartilage poses significant challenges, resulting in chondrocyte dysfunction and cartilage matrix degradation. While intra-articular injections of anti-inflammatory drugs, biomaterials, or bioactive agents have demonstrated some effectiveness, they primarily provide temporary relief from OA pain without arresting OA progression. This study presents an injectable cartilage-coating composite, comprising hyaluronic acid and decellularized cartilage matrix integrated with specific linker polymers. It enhances the material retention, protection, and lubrication on the cartilage surface, thereby providing an effective physical barrier against inflammatory factors and reducing the friction and shear force associated with OA joint movement. Moreover, the composite gradually releases nutrients, nourishing OA chondrocytes, aiding in the recovery of cellular function, promoting cartilage-specific matrix production, and mitigating OA progression in a rat model. Overall, this injectable cartilage-coating composite offers promising potential as an effective cell-free treatment for OA. Statement of significanceOsteoarthritis (OA) in the articular cartilage leads to chondrocyte dysfunction and cartilage matrix degradation. This study introduces an intra-articular injectable composite material (HDC), composed of decellularized cartilage matrix (dECMs), hyaluronan (HA), and specially designed linker polymers to provide an effective cell-free OA treatment. The linker polymers bind HA and dECMs to form an integrated HDC structure with an enhanced degradation rate, potentially reducing the need for frequent injections and associated trauma. They also enable HDC to specifically coat the cartilage surface, forming a protective and lubricating layer that enhances long-term retention, acts as a barrier against inflammatory factors, and reduces joint movement friction. Furthermore, HDC nourishes OA chondrocytes through gradual nutrient release, aiding cellular function recovery, promoting cartilage-specific matrix production, and mitigating OA progression.

Association of Muscle Quality and Pain in Adults With Symptomatic Knee Osteoarthritis, Independent of Muscle Strength: Findings From a Cross-Sectional Study.

Knee osteoarthritis (OA) is a leading cause of chronic pain in adults and shows wide interindividual variability, with peripheral and central factors contributing to the pain experience. Periarticular factors, such as muscle quality (eg, echo intensity [EI] and shear wave velocity [SWV]), may contribute to knee OA pain; however, the role of muscle quality in OA symptoms has yet to be fully established. Twenty-six adults (age >50 years) meeting clinical criteria for knee OA were included in this cross-sectional study. Quantitative ultrasound imaging was used to quantify EI and SWV in the rectus femoris of the index leg. Pearson correlations followed by multiple linear regression was used to determine associations between muscle quality and pain, controlling for strength, age, sex, and body mass index. EI and SWV were significantly associated with movement-evoked pain (b = 0.452-0.839, P = 0.024-0.029). Clinical pain intensity was significantly associated with SWV (b = 0.45, P = 0.034), as were pressure pain thresholds at the medial (b = -0.41, P = 0.025) and lateral (b = -0.54, P = 0.009) index knee joint line, adjusting for all covariates. Pain interference was significantly associated with knee extension strength (b = -0.51, P = 0.041). These preliminary findings suggest that EI and SWV may impact knee OA pain and could serve as malleable treatment targets. Findings also demonstrate that muscle quality is a unique construct, distinct from muscle strength, which may impact pain and treatment outcomes. More research is needed to fully understand the role of muscle quality in knee OA.

Estimating the Minimal Clinically Important Difference on the Visual Analogue Scale for Carpometacarpal Thumb Joint Osteoarthritis.

The minimal clinically important difference (MCID) is the smallest perceived treatment effect that patients deem clinically significant. There is currently no agreement on an appropriate MCID for the pain visual analogue scale (VAS) in the context of thumb osteoarthritis (OA). We approximated MCIDs using a distribution-based approach that pooled standard deviations (SDs) associated with baseline mean values of the pain VAS (0-100 mm). We extracted the data from randomized controlled trials (RCTs) included in a systematic review of adults with long-term OA of the thumb. We excluded RCTs that did not report baseline SD values. The MCIDs were derived at 0.4 and 0.5 SDs of the pooled SD and compared with previously published MCIDs for the pain VAS in OA. A total of 403 patients were pooled from 7 RCTs for the analysis. The mean baseline VAS pain score was 5.6 cm. We derived an MCID of 0.72 cm at 0.4 SDs and 0.91 cm at 0.5 SDs using baseline SDs. We found that MCIDs derived from a distribution-based approach approximated published MCIDs for the VAS for pain for OA in the knee and hip. The authors propose that a change of 0.7 to 0.9 cm on the VAS is clinically meaningful in the context of long-term OA of the thumb.