Symptomatic Knee Osteoarthritis Research Articles

Efficacy of diadynamic currents as an adjunct to exercise to manage symptoms of knee osteoarthritis in adults: A randomized controlled clinical trial

Objective To investigate the effect of diadynamic currents administered prior to exercises on pain and disability in patients with osteoarthritis of the knee. Design A randomized-controlled trial. Setting Special Rehabilitation Services in Taboão da Serra. Participants Patients with bilateral knee osteoarthritis. Intervention Participants were randomly allocated to Group I (diadynamic currents and exercises; n = 30, 60 knees) or Group II (exercises alone; n = 30, 60 knees) and were treated three times a week for 8 weeks. Main outcome measures The primary outcome measures were change in knee pain evaluated by visual analog scale and disability Index Score (Lequesne). Secondary outcomes included change in mobility (Timed Up and Go test), range of motion (goniometer), muscle strength (dynamometer), a composite score for pain and disability (Western Ontario and McMaster Universities Osteoarthritis questionnaire), and a drug diary to measure consumption of rescue pain medication (paracetamol). All measurements were collected at baseline, 8 weeks, and 6 months from baseline (follow-up). Results There were 60 participants with a mean (SD) age of 63.40 (8.20) years. Between-group differences in the follow-up (8 weeks and 6 months) were observed for pain at rest, pain during activities of daily living and disability. There was improvement in Group I that was maintained for the three variables 6 months after treatment. Mean difference for pain at rest was −3.08 points (95% confidence interval −4.13; −2.02), p < 0.01 with an effect size of 1.4; mean difference for pain during activities of daily living was −2.40 points (95% confidence interval −3.34; −1.45), p < 0.01 with an effect size of 1.24; and mean difference for disability was −4.08 points (95% confidence interval −5.89; −2.26), p < 0.01 with an effect size of 1.04. Conclusion Patients with symptomatic knee osteoarthritis receiving 8 weeks of treatment with diadynamic currents as an adjunct to a program of exercises had significantly greater improvements in pain and disability than those receiving exercises alone. Beneficial effects were sustained for 6 months.

Deformity in valgus knee malalignment is not only in the femurbut also in tibia or both, based on demographic and morphological analysis before and after knee osteotomies.

This study aims to identify the demographic and morphological features of valgus knee deformity with unilateral osteoarthritic knee in the coronal plane. A secondary aim was to identify the distinct phenotypes of valgus knees in Hirschmann's phenotype and the coronal plane alignment of the knee (CPAK) classifications before and after a knee osteotomy (KO). A total of 107 patients (57 female and 50 male) with a mean age of 42.4 ± 17.2 years, who underwent varisation osteotomy for symptomatic unilateral knee osteoarthritis (OA) and constitutional valgus deformity, were enrolled in the study, and the mean follow-up period was 29.1 ± 7.3 months. The included cases comprised 60 cases of distal femoral osteotomy, 10 cases of double-level osteotomyand 33 cases of high tibial osteotomy. All patients underwent preoperative and postoperative clinical, functional and radiological evaluations, analysed by analysis of variance tests. An analysis of the location of the valgus deformities demonstrated that 56 cases (52.3%) were femoral based, 18 cases (16.8%) were both femoral and tibial basedand 33 cases (30.9%) were tibial based. Twelve preosteotomy cases (11.2%)and 38 postosteotomy cases (35.5%) matched the most common eight Hirschmann's phenotypes, phenotyping the coronal lower limb alignment based on the native alignment in young patients without OA. Four (3.7%) preosteotomy cases and 89 postosteotomy cases (83.1%) matched the most common three CPAK phenotypes (Ⅰ, Ⅱ, Ⅴ) based on constitutional alignment and joint line obliquityin healthy and osteoarthritic knees. In valgus knee malalignment, the location of the deformity is not only solely femoral-basedbut also solely tibial-based or combined femoral and tibial-based. An individualised osteotomy approach would be recommended to achieve careful preoperative planning that considers the location of the deformity and the resultant joint line. Hirschmann's and CPAK classification would not be relevant when KO is considered. Level Ⅳ, retrospective case-control study.

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.

The potential impact of polymorphisms in METTL3 gene on knee osteoarthritis susceptibility

ObjectiveThis study was aimed to explore the correlation between METTL3 polymorphisms and susceptibility to knee osteoarthritis (KOA). MethodsThe relationship of five single nucleotide polymorphisms (SNPs) in the METTL3 gene with the susceptibility of KOA was analyzed through multinomial logistic regression analysis in this a case-control study. Genotyping was performed on 228 KOA patients and 252 unaffected individuals from South China based on the TaqMan method. The MDR software (version 3.0.2) was utilized for the analysis of SNP interactions. ResultsOut of the five SNPs examined, the T > G change in the METTL3 gene at the rs1061026 locus increased the risk of KOA, while rs1139130 A > G and rs1263802 C > T variants were found to be linked with a reduced risk of developing KOA with statistical significance. The rs1061027 A > C and rs1263801 C > G variants did not show significant association (p＞0.05). The rs1061026 TG/GG genotype showed a significant correlation with an increased risk of KOA in the following subgroups: the males, individuals with a BMI ranging from 24 to 28, smokers, those who were not engaged in physical exercise (PE), patients who had experienced KOA symptoms for eight years or longer, and those without a family history of the disease or reported swelling. On the other hand, the rs1139130 AG/GG genotype demonstrated a protective effect against KOA among the females, individuals with a BMI greater than or equal to 24, a unilateral KOA, or a KOA duration of 8 years or less, non-smokers, non-alcohol drinkers, those who were not engaged in PE, and those who had no injury or family history, or no experience of knee swelling. Additionally, it was observed that the rs1263802 CT/TT genotypes showed a protective effect among patients without a history of injury. Furthermore, individuals with the haplotypes GAT, GGC, TAT, and TGC were found to have a significantly lower susceptibility to KOA compared to the reference haplotype TAC. ConclusionsThe METTL3 gene variant rs1061026 could increase the risk of KOA, whereas the variants of rs1139130 as well as rs1263802 might exert a protective effect against KOA. These variants could potentially function as susceptibility markers for KOA among the population from South China.

Effect of Intravenous Zoledronic Acid on Total Knee Replacement in Patients With Symptomatic Knee Osteoarthritis and Without Severe Joint Space Narrowing: A Prespecified Secondary Analysis of a Two-Year, Multicenter, Double-Blind, Placebo-Controlled Clinical Trial.

To determine the effect of zoledronic acid (ZA) on the risk of total knee replacement (TKR) in patients with symptomatic knee osteoarthritis and without severe joint space narrowing (JSN). We included 222 participants (mean age 62 years, 52% female) from the two-year Zoledronic Acid for Osteoarthritis Knee Pain trial (113 received 5 mg of ZA annually and 109 received placebo) conducted between November 2013 and October 2017. Primary TKR were identified until February 22, 2022. The effect of ZA on TKR risk was evaluated using Cox proportional hazard regression models. Because the treatment effect failed the proportional hazards assumption, a time-varying coefficients analysis for treatment was conducted by splitting the study into two periods (ie, within and after two years of randomization). Over a mean follow-up of seven years, 39% and 30% of participants had any TKR in the ZA and placebo groups, and 28% and 18% had TKR in the study knee, respectively. Use of ZA was associated with a higher risk of TKR in any knee (hazard ratio [HR] 4.2, 95% confidence interval [CI] 1.2-14.7) and showed a trend in the study knee (HR 6.8, 95%CI 0.9-53.9) during the trial. In the posttrial period, the risk of TKR was similar in the ZA and the placebo groups for any knee (HR 1.2, 95%CI 0.5-1.8) and the study knee (HR 1.4, 95%CI 0.5-2.2). These results suggest that ZA is not protective against TKR in patients with symptomatic knee osteoarthritis and without severe JSN.

The association between obesity, knee pain, and gait during stair descent in older adults with knee osteoarthritis

BackgroundObesity and knee osteoarthritis adversely affect activities of daily living in older adults. Together, the complexities of their interaction on mobility, including stair negotiation, are unresolved. The purpose of this study was to determine the relationship between obesity, pain, and stair negotiation in older adults with knee osteoarthritis. MethodsOlder adults with symptomatic knee osteoarthritis and overweight or obesity participated in the study (n = 28; age range = 57.0–78.0 yrs.; body mass index range = 26.6–42.8 kg•m−2). The Western Ontario and McMaster Universities Osteoarthritis Index pain subscale was used to measure knee pain. Measurements included a three-dimensional biomechanical analysis during descent on a set of force plate-instrumented stairs and a timed stair descent test. Pearson's r was used to determine associations between body mass index and pain, stair descent weight-acceptance phase vertical ground reaction force (vGRF) variables and lower extremity joint kinematics and kinetics, and timed stair descent performance. FindingsSignificant correlations existed between body mass index and pain (r = 0.41; p = 0.03), peak vGRF (r = 0.39; p = 0.04), vertical impulse (r = 0.49; p = 0.008), and peak ankle plantar flexor moments (r = 0.50; p = 0.007) in older adults with knee osteoarthritis. InterpretationGreater obesity in older adults with knee osteoarthritis was associated with greater knee pain and higher ankle joint loads during stair descent. These results support the recommendations of osteoarthritis treatment guidelines for weight-loss as a first-line of treatment for older adults with obesity and knee osteoarthritis.

Chondroitin Sulfate for Osteoarthritis – Is There a Risk for Cancer: an Analysis of Osteoarthritis Initiative Data

The aim of this study was to evaluate the association between chondroitin sulfate (CS) use and incidence of self-reported cancer during 6-year follow up in the publicly available Osteoarthritis Initiative (OAI) cohort participants.&#x0D; Materials and Methods: The current study included analysis of 6-year longitudinal data obtained from the OAI progression (n= 1390) and incidence (n = 3284) subcohorts that are publicly available at https://nda.nih.gov/oai/. The inclusion criteria for OAI were the following: age between 45 and 79 years for both subcohorts, symptomatic tibiofemoral knee osteoarthritis (OA) for the progression subcohort, and the presence of established or putative risk factors for incident knee OA for the incidence subcohort. The OAI participants were recruited and enrolled between February 2004 and May 2006 at four recruitment centres in the United States. This study received ethical approval from each recruitment centre. All participants provided written informed consent. To reduce the risk of bias, only participants who did not take CS at baseline were included in the analysis (a “new-user” design).&#x0D; Results: 570 (18%) new users of CS and 2597 (82%) CS non-users were compared. In the CS user group, 294 (51.6%) participants received CS for more than one year, 291 (33.5%) for more than 2 years, 123 (21.6%) for more than 3 years, and 60 (10.5%) for more than 4 years. None of the participants received CS for more than 5 years. CS users and non-users were of the same age, had similar male/female ratio, and similar body mass index. In the non-user group, there were more African-American participants and there were more current smokers. 160 (6.2%) and 37 (6.5%) cases of incident self-reported cancer in the non-users and user groups were identified. There was no association between the use of CS and incident self-reported cancer in the non-adjusted analyses. The adjustments for age, race and smoking status did not change the results.&#x0D; Conclusion: The results of the current study did not show an association between CS use and self-reported cancers. Considering the complex function of CS in the development and progression of malignant tumors, there is a need for further epidemiological studies evaluating CS effects on specific types of cancers and in different genetic backgrounds.

Impact of a Semi-Rigid Knee Orthotic Intervention on Pain, Physical Activity, and Functional Capacity in Patients with Medial Knee Osteoarthritis.

Background: The effectiveness of knee orthoses as part of conservative treatment for patients with medial knee osteoarthritis has not been fully explored. The purpose of this study was to evaluate the effects of a novel semi-rigid knee orthosis on pain, physical activity, and functional capacity. Methods: Pain levels, physical activity, and functional capacity were assessed in 24 participants experiencing symptomatic medial knee osteoarthritis one week before (i.e., pretest) initiating a six-week orthosis intervention and again during the final week of the intervention (i.e., post-test). Results: Night pain, pain during walking, pain during stair climbing, and pain during sitting consistently decreased by 41% to 48% while wearing the knee orthosis. Device-based measured physical activity showed a 20.2-min increase in vigorous physical activity during the post-test, while light and moderate physical activity did not show significant changes. After six weeks of orthosis application, there was a 5% increased distance for the six-minute walk test, and participants reported fewer limitations both in everyday and athletic activities, as well as an enhanced quality of life. Conclusions: These findings highlight the potential effectiveness of a semi-rigid knee orthosis to enhancing functional capacity and quality of life. More extensive and longer clinical trials are needed to improve confidence in these findings and understand their impact on disease progression.

Timing is everything: Towards classification criteria for early-stage symptomatic knee osteoarthritis

Timing is everything: Towards classification criteria for early-stage symptomatic knee osteoarthritis

Clinical Evaluation of Maharasnadi Kvatha, Trayodashanga Guggulu, and Brihatsaindhavadya Taila in the management of knee osteoarthritis (Janugata Sandhivata): An open-label single-arm clinical study

Abstract INTRODUCTION: Osteoarthritis (OA) is the foremost prevalent progressive musculoskeletal disorder characterized by the gradual and persistent degradation of cartilage tissue within joints due to bone friction. The risk factors associated with the development of OA include the female gender, advanced age (geriatric population), elevated body weight or obesity, and a history of a prior knee injury. Ayurveda therapy has great potential in the management of OA and its progression. AIM: This clinical study aims to assess the effect of selected Ayurveda formulations in the management of knee OA. MATERIALS AND METHODS: This was a prospective, single-center, open-label study carried out on 60 participants with primary OA of the knee. Inclusion criteria encompassed individuals aged between 35 and 65 years, meeting the diagnostic criteria outlined by the American College of Rheumatology, and with radiographic abnormalities characteristic of OA. Therapeutic interventions in the study comprised Maharasnadi Kvatha (MK) (50 mL twice a day in an empty stomach), Trayodashanga Guggulu (TG) (1500 mg twice daily), and Brihatsaindhavadya Taila (BST) (for local fomentation twice daily) for the duration of 84 days. The primary outcome of the study was change in the Indian Western Ontario and McMaster Universities arthritis index (WOMAC) score. RESULTS: Out of 60 participants, 58 subjects completed the study, while one subject dropped out and one was withdrawn. The analysis yielded statistically significant results (P &lt; 0.001) in the Indian WOMAC (modified—clinical research data (CRD) Pune version) score and clinical symptoms and improvement in the quality of life (P &lt; 0.001). X-ray assessments revealed the disappearance of osteophytes in knee joints in 8.62% of cases. A change in the mean pain score as assessed by the visual analog scale was also noticed with P &lt; 0.001. CONCLUSION: The Ayurvedic interventions demonstrated significant effects in mitigating symptoms of knee OA, with no reported adverse events. This study substantiates the effectiveness of Ayurvedic management in alleviating symptoms of knee OA such as bony tenderness of joints, difficulty of physical function of knee joints, crepitus, and improvement in quality-of-life parameters. CTRI REGISTRATION: CTRI/2018/03/012292, dated 30-03-2020.

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

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

Higher conversion rate to knee arthroplasty in female patients following medial open-wedge high tibial osteotomy.

Most studies about medial open-wedge high tibial osteotomy (HTO) reported outcomes without focusing on gender differences. Therefore, the study compared the long-term survival rate and postoperative subjective knee function after HTO in female versus male patients with symptomatic medial compartment knee osteoarthritis. The data of three cohorts with long-term outcomes were analysed (n = 245; 32% females; age: 49 ± 7 years; Kellgren Lawrence Grade I 6.1%, II 32.7%, III 42.4%; IV 18.8%). The minimum follow-up was at least 6 years or an earlier conversion to total knee arthroplasty (TKA). The gender-specific survival rate after HTO was calculated after 5 and 10 years and compared using Kaplan-Meier analysis and the logrank test. Baseline characteristics and subjective knee function (International Knee Documentation Committee [IKDC]/Lysholm) were analysed between both genders. Forty of 78 (51.3%) women and 41 of 167 men (24.5%) underwent TKA. HTO survival in females was significantly lower (p = 0.0010). The 5- and 10-year survival rates were 85.9% and 62.6% for females and 93.4% and 77.7% for males. In females and males, from preoperative to the last follow-up, the IKDC (43 ± 15 to 58 ± 17; 47 ± 14 to 67 ± 18) and the Lysholm (42 ± 18 to 72 ± 18; 55 ± 22 to 77 ± 23) improved significantly (all p < 0.0001). Females had significantly lower preoperative and postoperative IKDC (p = 0.0438; p = 0.0035) and Lysholm scores (p = 0.0002; p = 0.0323). But the absolute improvements of the IKDC and Lysholm were not significantly different between genders. Females had higher conversion rates to TKA and lower knee function at the last follow-up. However, preoperative knee function was lower in females and the absolute improvement following HTO was similar for both genders. In general, females benefit from HTO to treat medial knee arthritis, and TKA could be postponed for half of female patients for more than 10 years. However, surgeons must be aware of the described inferior outcomes in females for realistic patient expectation management. Level II.

'I do hope more people can benefit from it.': The qualitative experience of individuals living with osteoarthritis who participated in the GLA:D™ program in Alberta, Canada.

The Good Life with osteoArthritis: Denmark (GLA:DTM) is an evidence-based program designed for individuals with symptomatic hip and knee osteoarthritis (OA). This program has reported improvement in pain, quality of life and self-efficacy, as well as delays in joint replacement surgery for adults with moderate to severe hip or knee OA. Evaluations of GLA:DTM implementation in several countries have focused on effectiveness, training, and feasibility of the program primarily from the provider perspective. Our objective was to examine how the GLA:DTM program was perceived and experienced by individuals with hip and knee OA to inform on-going program refinement and implementation. Thirty semi-structured telephone interviews were conducted with participants who completed the GLA:DTM program in Alberta. An interpretive description approach was used to frame the study and thematic analysis was used to code the data and identify emergent themes and sub-themes associated with participants' experience and perception of the GLA:DTM program. Most participants had a positive experience of the GLA:DTM program and particularly enjoyed the group format, although some participants felt the group format prevented one-on-one support from providers. Three emergent themes related to acceptability were identified: accessible, adaptable, and supportive. Participants found the program to be accessible in terms of location, cost, and scheduling. They also felt the program was adaptable and allowed for individual attention and translatability into other settings. Finally, most participants found the group format to be motivating and fostered connections between participants. The GLA:DTM program was perceived as acceptable by most participants, yet the group format may not be useful for all individuals living with OA. Recommended improvements included adapting screening to identify those suited for the group format, providing program access earlier in the disease progression trajectory, modifying educational content based on participants' knowledge of OA and finally, providing refresher sessions after program completion.

Association Between Occurrence of Knee Osteoarthritis and Physical Activity in Older Adults

Background: Knee osteoarthritis (OA) is a leading cause of disability among older adults, significantly affecting their quality of life and mobility. The relationship between physical activity and the severity of knee OA symptoms has been a subject of extensive research, with mixed results on whether physical activity exacerbates or alleviates OA symptoms. Objective: This study aimed to investigate the association between physical activity levels and the severity of knee osteoarthritis, as well as to assess the impact of physical activity on the health-related quality of life among individuals with knee OA. Methods: A cross-sectional study was conducted among 171 patients diagnosed with knee osteoarthritis at four medical institutions. Data on demographics, physical activity levels, and OA severity were collected through standardized questionnaires, including the SF-36 Health Survey and the Knee injury and Osteoarthritis Outcome Score (KOOS). Physical activity levels were categorized as poor, moderate, and good. The severity of knee OA was classified as no OA, moderate OA, and extreme OA. Statistical analysis was performed using SPSS version 25, employing descriptive statistics, chi-square tests for categorical variables, and Pearson's correlation to assess the association between physical activity levels and OA severity. Results: The study population comprised 35.1% males and 64.9% females, with a mean age of 71.1±3.9 years. Regarding physical activity, 30.4% engaged in poor, 46.8% in moderate, and 22.8% in good physical activity. The severity of knee OA was reported as extreme in 25.1% of patients, moderate in 49.1%, and absent in 25.7%. Statistical analysis revealed a significant association between physical activity levels and knee OA severity (Pearson Chi-Square = .000), indicating that higher levels of physical activity were associated with lower severity of OA symptoms. Conclusion: This study supports the notion that engaging in physical activity is associated with a reduced severity of knee osteoarthritis symptoms and suggests that physical activity could be beneficial for managing OA symptoms and improving the quality of life among individuals with knee OA. These findings highlight the importance of promoting physical activity as a key component of knee OA management strategies.

A Phase I Dose-Escalation Clinical Trial to Assess the Safety and Efficacy of Umbilical Cord-Derived Mesenchymal Stromal Cells in Knee Osteoarthritis.

Osteoarthritis (OA) is the most common degenerative joint disease. Mesenchymal stromal cells (MSC) are promising cell-based therapy for OA. However, there is still a need for additional randomized, dose-dependent studies to determine the optimal dose and tissue source of MSC for improved clinical outcomes. Here, we performed a dose-dependant evaluation of umbilical cord (UC)-derived MSC (Celllistem) in a murine model and in knee OA patients. For the preclinical study, a classical dose (200.000 cells) and a lower dose (50.000 cells) of Cellistem were intra-articularly injected into the mice knee joints. The results showed a dose efficacy response effect of Cellistem associated with a decreased inflammatory and degenerative response according to the Pritzker OARSI score. Following the same approach, the dose-escalation phase I clinical trial design included 3 sequential cohorts: low-dose group (2 × 106 cells), medium-dose group (20 × 106), and high-dose group (80 × 106). All the doses were safe, and no serious adverse events were reported. Nonetheless, 100% of the patients injected with the high-dose experienced injection-related swelling in the knee joint. According to WOMAC total outcomes, patients treated with all doses reported significant improvements in pain and function compared with baseline after 3 and 6 months. However, the improvements were higher in patients treated with both medium and low dose as compared to high dose. Therefore, our data demonstrate that the intra-articular injection of different doses of Cellistem is both safe and efficient, making it an interesting therapeutic alternative to treat mild and symptomatic knee OA patients. Trial registration ClinicalTrials.gov NCT03810521.

Essential Fatty Acids and Osteoarthritis.

Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Although n-3 fatty acids reduce inflammation, different n-3 fatty acids have different effects on inflammation and clinical outcomes, with eicosapentaenoic acid (EPA) having the strongest effect. We examined whether specific essential fatty acid levels affected the development of OA. We studied participants from the Multicenter Osteoarthritis Study (MOST) at risk of developing knee OA. As part of MOST, participants were asked repeatedly about knee pain, and knee radiographs and magnetic resonance images (MRIs) were obtained. Using baseline fasting samples, we analyzed serum fatty acids with standard assays. After excluding participants with baseline OA, we defined two sets of cases based on their status through 60 months' follow-up: those developing incident radiographic OA and those developing incident symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage damage and synovitis and worsening knee pain and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of specific n-3 and n-6 fatty acids, adjusting for age, sex, body mass index, education, physical activity, race, baseline pain, smoking, statin use, and depressive symptoms. We studied 363 cases with incident symptomatic knee OA and 295 with incident radiographic knee OA. The mean age was 62 years (59% women). We found no associations of specific n-3 fatty acid levels, including EPA, or of n-6 fatty acid levels with incident OA (eg, for incident symptomatic knee OA, the odds ratio per SD increase in EPA was 1.0 [95% confidence interval 0.87-1.17]). Results for other OA outcomes also failed to suggest a protective effect of specific n-3 fatty acids with OA outcomes. We found no association of serum levels of EPA or of other specific n-3 fatty acids or n-6 fatty acids with risk of incident knee OA or other OA outcomes.

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.

Cerebral Mechanism of Tuina on the Descending Pain Inhibitory System in Knee Osteoarthritis: Protocol for a Randomized Controlled Trial.

Knee osteoarthritis (KOA) is reputedly the most common musculoskeletal disease of the lower limbs and the main cause of pain and disability among older individuals. Pain is the most significant and widespread symptom of KOA. The descending pain inhibitory system has a cardinal role in normal pain consciousness, and its malfunction may be one of the pathophysiological mechanisms in KOA. Crucially, the rostral ventromedial medulla (RVM) and periaqueductal gray (PAG), as important components of the descending pain inhibitory system, directly modulate the activity of the spinal neurons involved in pain transmission. Tuina, a manual therapy, is effective and safe for reducing clinical symptoms of KOA; however, the mechanism that influences pain through the descending pain inhibitory system in KOA is unclear. This study aims to investigate the modulatory implications of Tuina on the RVM and PAG, which have critical roles in the descending pain inhibitory system in patients with KOA. This randomized controlled parallel trial will be conducted at the Tuina Clinic of the Third Affiliated Hospital of Henan University of Chinese Medicine (Zhengzhou, China). Patients with KOA will be randomly assigned (1:1) to 6 weeks of health education or Tuina. All patients in both groups will accept a resting-state functional magnetic resonance scan at the beginning and end of the experiment, and the resting-state functional connectivity and the voxel-based morphometry analysis will be performed to detect the RVM and PAG function and structure changes. The clinical outcome assessments will be (1) the pressure pain thresholds, (2) the Numerical Rating Scale, (3) the Hamilton Depression Scale (HAMD), and (4) the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Considering that this trial is a study of resting-state functional magnetic resonance imaging technology, resting-state functional connectivity and voxel-based morphometry are the primary outcomes, and clinical outcome assessments are secondary outcomes. Adverse events will be documented and assessed throughout. All main analyses will be carried out on the basis of the intention-to-treat principle. The outcome evaluators and data statisticians will be masked to the treatment group assignment to reduce the risk of bias. This trial was approved by the ethics committee of the Third Affiliated Hospital of Henan University of Chinese Medicine. Enrollment began in December 2023, and the results of this trial are expected to be submitted for publication in May 2025. This trial will identify a possible relationship between function and structure changes of RVM and PAG and the improvement of clinical variables, elucidating the effect of Tuina on the descending pain inhibitory system of patients with KOA. This trial will provide much-needed knowledge for Tuina for patients with KOA. Chinese Clinical Trial Registry ChiCTR2300070289; https://www.chictr.org.cn/showproj.html?proj=182570. PRR1-10.2196/52820.

Comparison of the clinical and radiological outcomes of Puddu and TomoFix plates for medial opening-wedge high tibial osteotomy: A two-year follow-up of a randomized controlled trial

PurposeOpening-wedge high tibial osteotomy (OWHTO) requires fixation devices for stabilization of the osteotomy gap. The two most commonly used fixation devices are the Puddu and the TomoFix plates. Based on its design, each implant generates a characteristic stability profile. The aim of this randomized controlled trial (RCT) was to investigate the short-term clinical and radiological outcomes of OWHTO using the Puddu and TomoFix plating systems. We hypothesized that the TomoFix plate would achieve superior clinical and radiographic results compared to the Puddu plate. MethodsA total of 60 patients were randomly allocated to undergo OWHTO either using the Puddu plate or the TomoFix plate if conservative treatment failed with symptomatic medial compartment knee osteoarthritis (OA) stage I or II according to Ahlbäck classification, and varus malalignment. All patients underwent clinical and radiological assessment preoperatively, and at 3, 6, 12, and 24months postoperatively. Radiological measurement of the hip-knee-ankle (HKA) angle, and posterior tibial slope (PTS) was performed. Functional assessment was carried out using the Hospital for Special Surgery Knee-Rating Scale (HSS) and the Western Ontario McMaster Universities (WOMAC) Osteoarthritis Index. Patients were also evaluated for intraoperative and postoperative complications throughout the follow-up period. ResultsThe mean angular correction was 9.6±4°, and 10.5±4.8° in the Puddu and TomoFix groups, respectively (p=0.488). The mean PTS change was significantly higher in the Puddu group (3.4±1.1°) compared to the TomoFix group (0.8±0.7°) (p<0.001). There was a statistically significant improvement in the mean HSS and WOMAC in both groups until one year postoperatively. Neither HSS nor WOMAC showed a statistically significant difference between the Puddu and TomoFix groups at any time during the first two postoperative years. The overall complication rate was not significantly different between the Puddu and TomoFix groups. However, the TomoFix group demonstrated higher incidence of symptomatic hardware (23% vs. 3.3%) and removal of metalwork (17% vs. 0%) than the Puddu group (p=0.023 and 0.020, respectively). ConclusionThis RCT suggests that the implant choice for OWHTO has no significant impact on functional outcomes during the first 2years postoperatively. While the Puddu plate was associated with an unintentional increase in the PTS during the surgery, both implants allowed coronal and sagittal plane corrections to be preserved postoperatively. The overall complication rates were similar, but the TomoFix required more material to be removed because it is more cumbersome. However, these results need to be confirmed on a larger scale. Level of evidenceII; randomized controlled trial.

The Association of Stair Climbing Behaviors With Hazard of All-Cause Mortality in Adults With or At Risk of Knee Osteoarthritis.

To investigate the association of stair climbing difficulty and stair climbing frequency with the risk of all-cause mortality over 13 years in adults with or at high risk for knee OA. We used data from the Osteoarthritis Initiative (OAI), a prospective cohort study of community-dwelling adults with or at high risk for symptomatic knee OA. The exposures were stair climbing difficulty and frequency, assessed at baseline using self-report questionnaires. The outcome was all-cause mortality, assessed from baseline through 13 years of follow-up. Kaplan-Meier survival curves and Cox proportional hazards regression were used to investigate the association between stair climbing exposures and all-cause mortality. Three hundred seven (6.81%) and 310 (6.84%) participants in the difficulty and frequency samples, respectively, died during 13 years of follow-up. Those who were limited in any capacity in terms of their stair climbing ability had 54% to 84% greater hazard of all-cause mortality, and those who climbed at least 7 flights of stairs per week had 38% lower hazard of all-cause mortality. Adults with or at high risk for knee OA who report difficulty with climbing stairs or who infrequently use stairs are at greater hazard of all-cause mortality. Stair climbing difficulty and frequency are simple to collect and changes may occur early in OA progression, allowing for early intervention. Brief questions about stair climbing behaviors can serve as a functional vital sign within the clinician's toolbox.