Selenium (Se) deficiency is a critical factor contributing to the imbalance of redox homeostasis in chondrocytes and the progression of osteoarthritis (OA). However, traditional selenium supplements face challenges such as a narrow therapeutic window and lack of targeting. To address this, we designed hyaluronic acid (HA)-modified selenium nanoparticles (HA-SeNPs) and developed a cascade-targeted delivery system (HA-SeNPs@AHAMA-HMs) based on a nano-micron combined strategy. The system involves loading HA-SeNPs into aldehyde-functionalized hydrogel microspheres prepared via microfluidic technology. Through Schiff base reactions between the aldehyde groups of the microspheres and amino groups of the cartilage, the system selectively adheres to the surface of damaged cartilage, achieving micron-scale targeting while continuously releasing HA-SeNPs. Then, HA-SeNPs achieve nanoscale targeting by binding to CD44, which is highly expressed on OA chondrocyte membranes, via their HA surface. Once taken up by the cells, HA-SeNPs exert their effects by directly scavenging ROS and promoting selenoprotein synthesis through the generation of selenite, forming a multifaceted antioxidant defense system. This effectively alleviates oxidative stress and optimizes mitochondrial function. In vivo and in vitro results demonstrated that this system significantly improved the oxidative phosphorylation pathway associated with mitochondrial function, which markedly reduced joint space narrowing and cartilage matrix degradation, and delayed the progression of OA. In summary, this study suggests that the cascade-targeting hydrogel microspheres designed and constructed based on a nano-micron combined strategy represent a promising prospective approach for precise Se supplementation and OA treatment.

As human lifespan increases and the proportion of obese people increases, the prevalence of knee osteoarthritis continues to increase. Its main clinical manifestations include joint pain, snapping, and decreased joint function. Due to the slow progression of the disease in KOA, patients have been troubled by the disease for a long time, affecting their quality of life. Therefore, the main purpose of treatment is to relieve symptoms and restore joint function. At present, most clinical studies focus on the joint function of postoperative KOA patients. However, in real life, there are still KOA patients who do not meet the surgical standards, and there are relatively few studies on this part. Therefore, this article reviews the relevant concepts, influencing factors and intervention measures for joint function in patients with non-surgical knee osteoarthritis in recent years, to provide a theoretical reference for subsequent research on improving joint function in patients with non-surgical knee osteoarthritis, and to improve patient's quality of life.

Osteoarthritis (OA) is a prevalent musculoskeletal condition leading to functional limitations, especially among the elderly. Current treatments focus on pain relief and functional improvement, however there is a lack of approaches which slow disease progression. A promising approach focusses on reducing knee joint loading, as excessive loading contributes to knee OA progression. This study explores kinematic variations in the knee OA population, utilizing principal component analysis (PCA) to examine gait variations (primitives) in both healthy individuals and those with knee osteoarthritis (KOA) and their implications for knee joint loading. The KOA population exhibited 14 modes of variation representing 95% of the cumulative variance, compared to 20 in the healthy population, indicating lower variability with KOA. The relation between identified gait primitives and knee loading parameters, revealed complex relationships. Surprisingly, modes with the largest kinematic variations did not consistently correspond to the highest variations in knee loading parameters revealing degrees of freedom which may have a larger role in determining joint loading. Moreover, potential gait-retraining strategies for KOA, associating specific kinematic combinations with altered knee loading were identified. The results showed a good agreement with previously applied strategies. However, this study highlights the importance of analyzing whole-body kinematics for effective gait retraining, as opposed to focusing on one single joint variation. The study's insights contribute to understanding the intricate interplay between gait pattern variations and knee joint loading changes in healthy and KOA populations, offering practical applications for guiding interventions and estimating loading parameters.

Angiogenesis plays a role in the mechanism underlying musculoskeletal pain; thus, embolization of blood vessels may exert an analgesic effect. Recent clinical studies have reported promising therapeutic outcomes for arterial embolization in knee osteoarthritis (OA). However, the placebo effect in human studies cannot be ignored, underscoring the need for objective evidence to validate the analgesic effects. However, basic research data supporting this role are limited. Thus, we investigated the analgesic effect of intraarterial administration of imipenem/cilastatin sodium (IPM/CS) in a model of knee OA induced by monosodium iodoacetate (MIA) using Sprague-Dawley rats. First, we infused IPM/CS in the right femoral artery and investigated the knee joint mechanical pressure threshold using pressure application measurement (PAM). Next, the nociceptive signals originating from the knee were analyzed via the spontaneous excitatory postsynaptic current (sEPSC) recording within the neural cells in the dorsal spinal horn using the in vivo patch-clamp recording. In the model of knee OA, the mechanical thresholds at the damaged knee were decreased compared with those of the contralateral knee, whereas these thresholds remained stable in the sham group (p < 0.05). The pressure threshold of the model of knee OA was significantly increased following intraarterial infusion of IPM/CS but not saline (p < 0.05). A notable decrease in the average sEPSC frequency in the model of knee OA following intraarterial infusion of IPM/CS but not saline (p < 0.05). These results indicated that intraarterial infusion of IPM/CS attenuated nociception caused by knee OA.

To examine the feasibility, safety and perceived patient response of a combined repetitive transcranial magnetic stimulation (rTMS) and quadriceps strengthening exercise intervention for knee osteoarthritis.

A two-arm, participant-blinded, therapist-blinded and assessor-blinded, randomised controlled trial with additional follow-up of pain and function at 3 months. Participants were randomised to receive active rTMS+exercise (AR+EX) or sham rTMS+exercise (SR+EX) twice weekly for 6 weeks while completing home exercises twice a week. Primary outcomes included recruitment rate, treatment attendance, dropouts, willingness to undergo therapy (11-point Numeric Rating Scale, 'not at all willing'=0 and 'very willing'=10), success of participant, therapist and outcome assessor blinding, adverse events and Global Perceived Effect Scale. Secondary outcomes were pain, function and measures of physiological mechanisms.

86 people were screened, 31 (36%) were randomised, 28 (90%) completed the treatments and 3 (10%) dropouts at 3-month follow-up. Both groups had high treatment attendance (98.4% and 100%). All participants scored at least 7 on the willingness to undergo therapy scale. Blinding was successful. No adverse events were reported. At the postintervention assessment, 80% in the AR+EX group and 75% in the SR+EX group reported an improvement on the Global Perceived Effect Scale. Both groups demonstrated within-group improvements in pain at the postintervention assessment but not at the 3-month follow-up. Function improved only in the AR+EX group at the postintervention assessment.

Combined rTMS and quadriceps strengthening exercise intervention for knee osteoarthritis is feasible, safe and well-received. A full-scale trial is justified to assess the clinical benefits of this novel treatment.

ACTRN12621001712897.

α-Solanine, a glycoalkaloid (GA) extracted from the stems of the potato plant, exhibits bioactivity and medicinal potential that necessitate further investigation. The impact and underlying mechanisms of α-Solanine on osteoarthritis (OA) remain to be elucidated. To achieve enhanced therapeutic outcomes, we have designed and synthesized a UIO-66-NH2@α-Solanine@PEI charged particle (USP) that amplifies the therapeutic effects of α-Solanine, demonstrating superior efficacy. Our approach involved the synthesis of a novel drug delivery system, the USP, to augment the therapeutic potential of α-Solanine in the treatment of OA. An OA rat model was established, and USP treatment was administered. The therapeutic effects were verified through histochemical staining and micro-CT. In vitro, α-Solanine significantly suppressed the expression of proteins related to glycolysis and notably inhibited ferroptosis. RNA sequencing revealed hypoxia-inducible factor-1α (HIF-1α) as a potential pathway mediating the effects of α-Solanine, and it was found that the co-addition of cycloheximide (CHX) led to a shortened decay time of HIF-1α. In vivo, rats with OA demonstrated significant inhibition of glycolysis and ferroptosis following treatment with USP, along with improvements in OA characteristics. These findings suggest that α-Solanine can inhibit the intense glycolysis associated with OA via the HIF-1α pathway and alleviate ferroptosis in chondrocytes. Treatment with USP demonstrated superior efficacy in the management of OA, providing a new therapeutic strategy for the disease.

Osteoarthritis and rheumatoid arthritis are debilitating joint diseases marked by pain, inflammation and cartilage destruction. Current osteoarthritis treatments only relieve symptoms, while rheumatoid arthritis therapies can cause immune suppression and provide variable efficacy. Here we developed an optimized small interfering RNA targeting matrix metalloproteinase 13 for preferential delivery to arthritic joints. Chemical modifications in a stabilizing 'zipper' pattern improved RNA resistance to degradation, and two independent linkers with 18 ethylene glycol repeats connecting to tandem C18 lipids enhanced albumin binding and targeted delivery to inflamed joints following intravenous administration. In preclinical models of post-traumatic osteoarthritis and rheumatoid arthritis, a single intravenous injection of the albumin-binding small interfering RNA achieved long-term joint retention, sustained gene silencing and reduced matrix metalloproteinase 13 activity over 30 days, resulting in decreased cartilage erosion and improved clinical outcomes, including reduced joint swelling and pressure sensitivity. This approach demonstrated superior efficacy over corticosteroids and small-molecule MMP inhibitors, highlighting the therapeutic promise of albumin 'hitchhiking' for targeted, systemic delivery of gene-silencing therapeutics to treat osteoarthritis and rheumatoid arthritis.

To compare home-based remote rehabilitation with usual rehabilitation care for knee osteoarthritis (OA).

PubMed, Cochrane, and Embase databases were searched for randomized controlled trials (RCTs) comparing home-based remote rehabilitation (telephone calls, video calls, apps, or websites) with usual in-person rehabilitation in patients with knee OA. Mean differences (MDs) or standardized mean differences (SMDs) were calculated for continuous outcomes and risk ratios (RRs) for binary outcomes, with 95 % confidence intervals (CIs). Statistical analyses were performed using R Software, version 4.4.1.

A total of 9 RCTs were included, comprising 974 patients with knee OA, of whom 483 (49.6 %) were randomized to home-based remote rehabilitation. Compared with usual rehabilitation, home-based remote rehabilitation significantly reduced pain severity (SMD -0.34; 95 % CI -0.67 to -0.02) and significantly improved physical activity levels (SMD -0.45; 95 % CI -0.85 to -0.05). Furthermore, the home-based remote rehabilitation group showed a significant reduction in pain assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (MD -0.95 points; 95 % CI -1.84 to -0.06), an improvement in functionality assessed with the Timed Up and Go test (MD -0.83 s; 95 % CI -1.64 to -0.02), and a greater patient satisfaction (RR 2.01; 95 % CI 1.46 to 2.76).

The results demonstrated that home-based remote rehabilitation reduced pain and increased patient satisfaction, however, there is insufficient evidence to state that remote rehabilitation significantly improved physical activity and functionality. Home-based remote rehabilitation appears to be a viable and effective alternative for patients with knee OA.

Physical therapy is commonly recommended for treating meniscus tears and knee osteoarthritis (KOA). However, data from randomized trials that compare the effectiveness of this treatment with that of glucocorticoid injections are lacking.

This randomized, single-blind, multicenter trial included 273 patients with KOA who were divided into either the physical therapy group (n = 133) or the glucocorticoid injection group (n = 140). The physical therapy included kinesiology tape, exercise protocols, and exercise training programs to increase core stability and periprosthetic muscle strength. The primary endpoint was the overall Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 1 year. Additionally, proprioception and safety were assessed. All analyses were performed with the use of the intention-to-treat approach. The data are reported as percentages (%) (n), and the threshold for statistical significance was p < 0.05.

There was no significant difference in the baseline characteristics between the two groups (p > 0.05). The average (± SD) WOMAC score at 1-year was 76.85 ± 2.50 in the physiotherapy group. And 99.55 ± 2.09 in the glucocorticoid injection group (mean difference = - 22.70; 95% confidence interval [95% CI] - 23.43 to - 21.96; p < 0.001). Compared with the glucocorticoid injection group, the physical therapy group exhibited superior performance in terms of proprioception, especially in the eyes-closed in situ stepping test (14.27 ± 0.75 versus 5.98 ± 0.74; mean difference = 8.29; 95% CI 8.09-8.50; p < 0.001). The incidence of serious adverse events at the 1-year follow-up was comparable between the two groups. Most of these events were determined to be complications arising from physical therapy and glucocorticoid injection.

The results revealed that pain, quality of life, and balance were greater in the physiotherapy group than in the glucocorticoid injection group within the 1-year study period. However, the long-term effects beyond this timeframe remain unknown, and future studies with extended follow-up times are needed to confirm the sustainability of these benefits.

The protocol was approved by the local ethics committee of the ethical commission of the Hebei Sports Science Research Institute (SEC20200213019) and Ethics Committee of Sichuan Taikang Hospital (SCTK-IRB-032). The study was registered at the Chinese Clinical Trial Registry (ChiCTR2000032508).

A growing body of research is exploring the role of antioxidant and anti-inflammatory dietary supplements in the treatment of osteoarthritis, highlighting an increasing emphasis on non-pharmacological interventions. Although more patients are turning to supplements to manage osteoarthritis, their actual effectiveness remains uncertain.

This study aims to provide a comprehensive evaluation of the available evidence concerning the efficacy of various dietary supplements in osteoarthritis treatment.

We searched PubMed, Embase, Cochrane Library and Web of Science for studies on the use of various dietary supplements in the treatment of osteoarthritis from the creation of each database until Jan 20, 2025.

(1) Research object: osteoarthritis. (2) Intervention measures: patients in the treatment group received dietary supplements, while the control group received placebos. (3) Research type: randomized controlled trials (RCTs).

Two researchers independently examined the literature and retrieved data based on predefined criteria. The information gathered included the first author, year of publication, sample size, participant demographics, length of the follow-up period, intervention and control measures, and inclusion indications. RCTs comparing dietary supplements to placebo with the pain and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) among patients with osteoarthritis were included. The optimal dietary supplement was identified based on the total ranking by summing the surface under the cumulative ranking curve (SUCRA) of these two scores. Furthermore, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to confirm the quality of the evidence.

Overall, 23 studies covering 21 dietary supplements and involving 2455 participants met the inclusion criteria. In the WOMAC pain score, the SUCRA of passion fruit peel extract was 91% (mean difference [MD]: -9.2; 95% confidence interval [CI]: [-16.0, -2.3]), followed by methylsulfonylmethane (89%), undenatured type II collagen (87%), collagen (84%), and Lanconone (82%). The SUCRA (99%) of passion fruit peel extract (MD: -41.0; 95% CI: [-66.0, -16.0]) ranked first in terms of the WOMAC function score, followed by Lanconone (95%), collagen (86%), ParActin (84%), and Lactobacillus casei strain Shirota (83%). The top three total rankings are passion fruit peel extract (95.0%), Lanconone (88.5%), and collagen (85.0%). However, the GRADE revealed low evidence quality.

Passion fruit peel extract was the best supplement for improving WOMAC pain and function scores in patients with osteoarthritis, followed by Lanconone and collagen. However, further large-scale, well designed RCTs are required to substantiate these promising findings. Please cite this article as: Chen CS, Wen L, Yang F, Deng YC, Ji JH, Chen RJ, Chen Z, Chen G, Gu JY. Effects of dietary supplements on patients with osteoarthritis: A systematic review and network meta-analysis. J Integr Med. 2025; Epub ahead of print.

The aims of this review was to investigate the effectiveness of closed kinetic chain exercise (CKCE) on pain, function, and proprioception in individuals with knee osteoarthritis (OA).

Nine databases were searched up to December 2023. Randomized controlled trials (RCTs) examining the effects of CKCE in individuals with knee OA were included. The methodological quality was assessed using the PEDro scale, and the level of evidence was evaluated with the GRADE system. A random-effects meta-analysis was conducted to assess differences between treatment groups for the primary outcomes (pain and function). Effect sizes were calculated using standardized mean differences (SMDs) with 95% confidence intervals (CIs).

A total of 24 studies were included in the descriptive analysis, and 18 studies were included in the quantitative analysis (meta-analysis). The meta-analysis results indicated that CKCE treatment led to greater improvements in pain (SMD = -0.76; 95% CI: -1.51, -0.01) and function (SMD = -1.25; 95% CI: -1.88, -0.62) compared to no treatment. A subgroup meta-analysis showed that the combined treatment of CKCE and conventional physical therapy (CPT) resulted in greater improvements in pain (SMD = -1.18; 95% CI: -1.70, -0.67) and function (SMD = -1.27; 95% CI: -1.79, -0.75) compared to CPT alone. The risk of bias assessment revealed that two studies were of low quality, nine were of fair quality, and the remaining 13 were of high quality. The GRADE system indicated a low quality of evidence for the effects of CKCE on both pain and function.

While CKCE shows promise in reducing pain and improving function in individuals with knee OA, the quality of evidence is considered low according to the GRADE system. Further high-quality RCTs with larger sample sizes are needed to confirm the effectiveness of CKCE in managing knee OA.

The main objective of this study is to examine the safety of oral acetaminophen at its therapeutic dose in adults aged ≥65 years.

This population-based cohort study used the Clinical Practice Research Datalink-Gold data. Participants were aged ≥65 years registered with a UK general practice for at least 12 months between 1998 and 2018. Acetaminophen exposure was defined as at least two acetaminophen prescriptions within six months of the first acetaminophen prescription, the first prescription date being the index date. Acetaminophen nonexposure was defined as the absence of two acetaminophen prescriptions within six months over the study period. We calculated propensity score (PS) for acetaminophen prescription and undertook inverse probability treatment weighting using PS and PS-matched analyses to account for confounding. Missing data were handled using multiple imputation. The adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) were calculated using the Cox proportional hazards regression model.

In total, 180,483 acetaminophen exposed and 402,478 unexposed participants were included in this study. Acetaminophen exposure was associated with an increased risk of perforation or ulceration or bleeding (aHR 1.24; 95% CI 1.16-1.34), uncomplicated peptic ulcers (aHR 1.20; 95% CI 1.10-1.31), lower gastrointestinal bleeding (aHR 1.36; 95% CI 1.29-1.46), heart failure (aHR 1.09; 95% CI 1.06-1.13), hypertension (aHR 1.07; 95% CI 1.04-1.11), and chronic kidney disease (aHR 1.19; 95% CI 1.13-1.24).

Despite its perceived safety, acetaminophen is associated with several serious complications. Given its minimal analgesic effectiveness, acetaminophen as the first-line oral analgesic option for long-term conditions in older people requires careful reconsideration.

Osteoarthritis (OA) is a degenerative joint condition leading to disability. The lack of effective treatment for OA creates a need for the development of new therapeutic approaches that may rely on stem cells including mesenchymal stem/stromal cells (MSCs) and their derivatives such as extracellular vesicles (EVs). The objective of this study was to evaluate the impact of MSCs derived from adipose tissue (AT-MSCs) and umbilical cord (UC-MSCs) and their EVs on cartilage-bone injury in vivo, to identify the specimen with the highest regenerative potential for further clinical applications in patients with OA. Humanized pigs underwent cartilage-bone injuries followed by intraarticular administration of products containing AT-MSCs, UC-MSCs, AT-MSC-EVs or UC-MSC-EVs mixed with hyaluronic acid (HA) or HA alone (for comparison). After 6-m follow-up, almost-fully-healed cartilage-bone defects were observed in the AT-MSC- and UC-MSC-treated pigs, and the defects were filled primarily with hyaline cartilage. In AT-MSC-EV- and UC-MSC-EV-treated pigs, a partial cartilage-bone tissue repair was observed, and the defects were filled primarily with fibrocartilage. The control pigs demonstrated limited regeneration capacity. The microcomputed tomography parameters of the subchondral bone indicated the ongoing progression of OA in controls, whereas in the MSC- and MSC-EV-treated pigs, the parameters indicated the cessation of OA progression. Moreover, no serious side effects were observed after the administration of products containing MSCs or MSC-EVs. The results indicate the safety and regenerative activity of MSCs on injured tissues, which favors not only the healing and improvement of bone structure but also the formation of hyaline cartilage. Superior tissue repair was observed after the administration of products containing AT-MSCs. The treatment of OA with MSC-EVs needs further standardization.

Aerobic exercise is recommended for the management of knee osteoarthritis (OA), but knee pain is often a barrier for participation. Some types of aerobic exercise may be less painful to undertake than others, though little is known about which are the most "knee friendly," that is, unlikely to exacerbate knee pain to an unacceptable level. This study aimed to identify aerobic exercise activities that (1) are knee friendly and (2) meet requirements for targeting cardiovascular health.

We conducted a three-phase international survey. In phase 1, persons living with knee OA provided descriptions of knee friendly exercise types, defined as activities that would cause shortness of breath and difficulty talking without worsening symptoms to an unacceptable level (cause severe symptoms and/or lasting more than 24 hours). In phase 2, exercise physiologists identified exercise activities meeting requirements for increasing aerobic fitness, which were grouped into broader aerobic exercise activities. In phase 3, participants nominated each aerobic exercise activity for "knee friendliness."

In phase 1, 487 respondents (Denmark: 259; the Netherlands: 144; Australia: 57; and North America: 15) provided a total of 1,590 exercise descriptions. In phase 2, 154 exercise activities were identified and grouped into a list of 30 broader aerobic exercise activities. In phase 3, 349 participants (Denmark: 195; the Netherlands: 114; Australia: 32; and North America: 8) nominated indoor biking and water exercise as most knee friendly (82% and 70%, respectively). Participants were predominantly women (60.7%), the mean ± SD age was 68.4 ± 8.81 years, the mean ± SD body mass index was 27.5 ± 5.8, the mean ± SD self-efficacy score was 7.3 ± 3.0 (0-10 scale), the mean ± SD symptom duration was 11.7 ± 9.05 years, and the mean ± SD current knee pain was 4.5 ± 2.2 (0-10 scale).

A catalog of 30 knee friendly aerobic exercise activities was generated for individuals living with knee OA. The catalog aims to empower individuals living with knee OA, offering suitable aerobic exercise options without exacerbating knee pain.

Osteoarthritis (OA), the most prevalent form of arthritis, is swiftly emerging as a chronic health condition, that poses the primary cause of disability and significant socioeconomic burden. Despite its prevalence, effective therapeutic options for OA remain elusive. This study seeks to explore the therapeutic potential of edaravone (EDA), a FDA-approved free radical scavenger, in the context of OA development and to elucidate its underlying mechanisms.

In vitro, oxidative stress models were induced by stimulating chondrocytes with t-butylhydroperoxide (TBHP); then, we investigated the influence of EDA on chondrocyte dysfunction, apoptosis, inflammatory responses and mitochondrial function in TBHP-treated chondrocytes, along with the underlying mechanisms. In vivo, destabilization of the medial meniscus (DMM) model was used to investigate the impact of EDA on OA progression. Nrf2 -/- mice were applied to determine the potential role of NRF2 as a target for EDA.

EDA notably alleviates chondrocyte dysfunction triggered by oxidative stress, safeguards chondrocytes from apoptosis and inflammatory responses, and preserves mitochondrial function and redox balance within chondrocytes. At the molecular level, EDA appears to halt the progression of OA by engaging and activating the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, which is crucial for maintaining mitochondrial function and redox equilibrium. Notably, the protective effects of EDA on OA are abolished in Nrf2 -/- mice, underscoring the significance of the NRF2 signaling pathway in mediating EDA's therapeutic effects.

EDA has the potential to mitigate chondrocyte degeneration, thereby slowing the progression of OA. Thus, EDA may represent a novel therapeutic agent for the treatment of OA, potentially expanding its clinical utility.

As a clinically licensed drug used for the treatment of neurological disorders, edaravone has shown promising therapeutic effects on OA development. Mechanistically, edaravone stabilized mitochondrial function and maintained redox homeostasis by activating NRF2 signaling pathway. The protective effects of edaravone against OA were verified in vivo and in vitro. These findings presented robust evidence for repurposing edaravone for the treatment of OA in clinic.

The causes of patellofemoral cartilage lesions or joint degeneration are multifactorial. Small, traumatic cartilage lesions can be treated without relevant cartilage regenerative therapies. Surgical treatment is recommended for larger lesions (> 1 cm2).

Conservative therapy is the mainstay of treatment for incipient or advanced patellofemoral osteoarthritis. Consequently, a thorough examination is essential to identify the underlying factors and to establish precise and efficient treatment planning. An individualized, stage-appropriate, and multimodal treatment strategy, supported by comprehensive patient education, is critical for therapeutic success. In the presence of functional or muscular imbalances, physiotherapy and exercise therapy, potentially supplemented by EMG biofeedback training, play a central role. When combined with weight reduction, patellar taping, cryotherapy, or extracorporeal shock wave therapy, these measures form the foundation of any conservative therapeutic approach. In the acute phase, nonsteroidal anti-inflammatory drugs or opioids may be employed for pain relief. If non-injection-based interventions remain ineffective, an injection therapy option may be considered.

Knee osteoarthritis (KOA) is primarily characterized by joint pain and dysfunction, and KOA has increasingly emerged as a public health concern in China and globally. This study aims to utilize data from the Global Burden of Disease (GBD) 2021 to summarize the disease burden of KOA in China and globally from 1992 to 2021, while also predicting the disease burden in 2030.

Using data from the GBD 2021 study, we compared and described the burden of KOA in China and globally. Joinpoint regression was applied to assess long-term trends in the burden of KOA based on GBD 2021 data. The impact of population growth, aging, and epidemiological trends on the burden of KOA was examined through decomposition analysis. Additionally, an age-period-cohort analysis (APC) was conducted to assess the effects of age, period, and cohort on the burden of KOA in China. Finally, we predicted the burden of KOA in 2030 using the Bayesian age-period-cohort (BAPC) and Norpred models.

In 2021, the number of patients with KOA in China was 10,957,472, reflecting an increase of 157.15% compared to 1992. Similarly, the incidence of KOA in China for the same year was 8,512,396, representing a rise of 123.45% since 1992. The and Years lived of disabled (YLDs) rate for KOA in China was 249.81 per 100,000 population, which is 116.44% higher than the rate observed in 1992. In 2021, the prevalence of KOA increased with age. Female exhibited higher estimates of prevalence, incidence, and YLDs than male across all age groups. Joinpoint regression analysis revealed fluctuating upward trends in prevalence, incidence, and YLDs, from 1992 to 2021. Decomposition analysis identified population growth as the primary driver of increased prevalence, incidence, and YLDs, particularly among female. Projections indicate that the number of KOA YLDs in China will continue to rise, potentially reaching a peak by 2030.

The disease burden of KOA in China remains significant, necessitating increased attention, particularly for female and the middle-aged and older adult populations, in order to develop more targeted preventive measures.

To systematically review the literature on the effectiveness, safety, and long-term outcomes of genicular artery embolization (GAE) for knee joint osteoarthritis (OA) associated pain.

After registering the protocol with the PROSPERO database, a search was conducted from inception until July 31, 2023, in MEDLINE, Cochrane Central Register of Controlled Trials, and ScienceDirect databases to gather studies evaluating GAE's safety and efficacy in knee OA. A total of 4979 studies were identified and evaluated against the inclusion criteria. Data on study characteristics, success parameters, and adverse events were collected and synthesized.

Twenty-three studies, primarily single-center prospective studies with a total of 657 patients, were included. Most studies reported a 100% technical success rates, except one study reporting a rate of 84.2%. Clinical success rates, defined variably across studies, ranged from 30% to 100%, depending on the study's follow-up period and outcome measures. The most frequent adverse events included skin discoloration without an ulcer (15.6%, n = 98) and transient post-procedural knee pain (10.2%, n = 64). Most studies were rated as fair in terms of quality, but the lack of robust randomized controlled trials highlighted the need for further comparative studies to standardize outcome reporting.

GAE appears to be a promising option for knee OA pain, particularly for patients unresponsive to conservative treatments or ineligible for surgery. High-quality studies are needed to confirm long-term effectiveness and standardize outcome measures.Clinical ImpactThis study highlights the safety and efficacy of genicular artery embolization as a minimally invasive treatment for knee osteoarthritis, particularly in patients who are unresponsive to conservative treatments or unsuitable for surgery. By targeting neovascularization and reducing inflammation, genicular artery embolization provides pain relief and functional improvement. Clinicians can consider genicular artery embolization as an alternative to surgery for mild-to-moderate OA, offering a lower adverse event rate and faster recovery.

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and pain, which leads to significant disability. IAHA is widely used because of its viscoelastic properties, which restore synovial fluid homeostasis and reduce symptoms. However, emerging evidence suggests that IAHA exerts additional biological effects including chondroprotection, inflammatory modulation, oxidative stress reduction, and pain modulation, which may influence disease progression. Objective: This narrative review examines the biological mechanisms underlying IAHA's role in OA management. The review explored IAHA's effects on synovial fluid viscoelasticity, inflammatory cytokine modulation, cartilage preservation, oxidative stress regulation, and pain pathways, emphasizing the influence of molecular weight variations on therapeutic efficacy. Additionally, this review evaluates IAHA's integration into multimodal treatment strategies, its potential disease-modifying effects, and future directions for personalized treatment approaches. Methods: A comprehensive literature review was conducted using PubMed, Cochrane Library, EMBASE, Scopus, and Web of Science for studies published between January 2000 and March 2024. The search focused on IAHA's molecular, cellular, and biochemical effects in OA and clinical findings assessing its impact on joint function, pain relief, and disease progression. Results: IAHA improves synovial fluid lubrication, reduces proinflammatory cytokines (IL-1β, TNF-α), inhibits matrix metalloproteinases (MMPs), scavenges reactive oxygen species (ROS), and modulates nociceptive pathways. High-molecular-weight IAHA demonstrates superior efficacy in advanced OA, while low-molecular-weight formulations may be better suited for early-stage disease. Although IAHA's symptom relief is comparable to corticosteroids and NSAIDs, its favorable safety profile and emerging disease-modifying potential support its long-term use in OA management. Conclusions: IAHA represents a multifaceted therapeutic approach bridging symptomatic relief and regenerative strategies. While long-term efficacy, optimal administration protocols, and patient-specific responses remain subjects of ongoing research, refining treatment selection criteria, dosing regimens, and combination strategies may enhance clinical outcomes. Future studies should explore biomarker-driven approaches, standardize treatment protocols, and assess IAHA's synergy with regenerative medicine to optimize its role in OA management.

To identify and quantify risk factors for incident knee osteoarthritis (KOA) across the lifespan.

This systematic review and meta-analysis identified eligible studies from seven electronic databases and three registries. Longitudinal cohort studies or randomised controlled trials evaluating participants who developed incident symptomatic and/or radiographic KOA were included. Two independent reviewers completed data screening and extraction. Estimates were pooled using a random effects model and reported as odds ratio (OR), hazard ratio, or risk ratio and corresponding 95% confidence intervals (95% CI). Grading of Recommendations, Assessment, Development and Evaluation was used to determine the certainty of evidence. Population attributable fractions were calculated, including risk factors significantly associated with radiographic KOA based on the pooled meta-analysis and where we could determine communality scores using existing clinical datasets.

We identified 131 studies evaluating > 150 risk factors. Previous knee injury, older age and high bone mineral density were associated with an increased risk of incident radiographic KOA based on the pooled analysis [OR (95% CI): 2.67 (1.41, 5.05), 1.15 (1.00, 1.33) and 1.82 (1.12, 2.94), respectively], with moderate-to-high certainty. Two risk factors (overweight/obesity and previous knee injury) accounted for 14% of incident radiographic KOA. Other modifiable risk factors, including occupational physical activity, also contribute to radiographic or symptomatic KOA.

Novel strategies addressing known modifiable risk factors including overweight/obesity, knee injuries and occupational physical activity are needed to reduce overall burden of KOA.

PROSPERO ID: CRD42023391187.

Telerehabilitation is promising for improving knee osteoarthritis, but the effect of different telerehabilitation strategies on knee osteoarthritis is unclear.

This study aimed to examine the effect of a clinic-based strengthening exercise (CbSE) and asynchronous video-based strengthening exercise (AVbSE) on pain, range of motion, muscle strength, quality of life, and physical function among patients with knee osteoarthritis.

A total of 52 consenting patients participated in this 8-week experimental study; they were assigned to the CbSE or AVbSE group at 2 different study sites. CbSE is a circuit exercise module comprising knee flexion and extension warm-up in sitting, quadriceps isometric setting, quadriceps strengthening exercise, hamstring clenches, wall squat, and a cooldown of knee flexion and extension. The AVbSE is an asynchronous video-based version of the CbSE.

This study spanned from March 31, 2021, to November 26, 2021. Eight out of 62 participants discontinued participation. Data collection and analysis have been completed. Significant differences were only observed in the mental health (t50=-3, P=.004), pain (t39.4=-3.6, P<.001), social support (t50=-2.7, P=.009), and social activities (t50=2.2, P=.03) domains of the Osteoarthritis Knee and Hip Quality of Life (OAKHQoL) questionnaire with higher scores in the AVbSE group at the end of week 4. At the end of week 8, significant differences were observed in mental health (t50=-2.1, P=.04) and pain (t37.3=-2.8, P=.008) measures with higher scores in AVbSE; however, a significantly higher score was observed in the CbSE group for the Quadruple Visual Analog Scale. No significant main effect of time was observed in this study, except in the muscle strength (F2100=1.5, P=.24), social support (F2100=2.5, P=.09), and social activity (F2100=0.7, P=.48) domains of the OAKHQoL questionnaire and activity limitation (F2100=0.1, P=.90), and performance restriction (F2100=1.3, P=.27) domains of the Ibadan Knee and Hip Osteoarthritis Outcome Measure (IKHOAM) questionnaire. There was no significant difference between groups in all OAKHQoL domains except social activities (mean 17.6, SD 1.2 vs 22.8, SD 1.2; P=.003) and average pain (2.8, SD 1.6 vs 2.3, SD 1.6; P=.03) with higher AVbSE mean scores. However, a higher score was observed for the CbSE group in the Quadruple Visual Analog Scale's least pain domain (1.2, SD 0.2 vs 0.7, SD 0.2; P=.04). Also, interaction effects showed that AVbSE scores were significantly higher for the OAKHQoL questionnaire's physical activity and mental health domains at all time points. However, the CbSE score was higher for the physical performance domain of the IKHOAM questionnaire in the eighth week.

CbSE circuit training and its AVbSE variant effectively improve treatment outcomes and increase the quality of life of patients. While AVbSE was associated with higher improvement in most health-related quality of life domains, CbSE led to higher improvement in average pain.

Pan African Clinical Trial Registry PACTR202208515182119, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=23943.

Background and Objectives: The aim of the study was to compare the effectiveness of proprioceptive studies according to radiological stages in patients with knee osteoarthritis and to determine at which stage of the disease it should be added to the rehabilitation program. Materials and Methods: This study is a prospective clinical trial. The study was registered with ClinicalTrials.gov (name of the registry: Evaluation of the Effectiveness of Proprioceptive Training According to Radiological Stages in Patients with Knee Osteoarthritis; trial registration number: NCT06150170; date of registration: 21 November 2023). The patients were divided into two groups, which were Grade 1-2 (Group 1) and Grade 3-4 (Group 2) knee osteoarthritis. Both groups underwent a strengthening plus proprioception exercise 3 times a week for 4 weeks. Our primary scale was the Western Ontario and McMaster Universities Arthritis (WOMAC) scale. The secondary outcome measures were pain intensity level, proprioception, range of motion, muscle strength, physical performance, physical activity, quality of life and patient satisfaction. All evaluations were performed twice, before treatment and after 4 weeks of treatment. Conclusions: After treatment, there were significant improvements in pain, range of motion, proprioception, muscle strength, functionality, physical performance and quality of life in both groups (p < 0.05). There was no significant difference between the total WOMAC scores among groups after treatment (p = 0.086). There was more improvement in hip external rotation range of motion in Group 1 (p = 0.022). No significant difference was found in other secondary outcomes (p > 0.05). As a result of this study, we found that proprioceptive training was effective on pain, joint position sense, range of motion, muscle strength, functionality, physical performance and quality of life in patients with knee osteoarthritis in all radiological stages. However, there was no difference between the groups, except for hip external rotation angles.

Genicular artery embolization (GAE) is an emerging minimally invasive procedure for managing knee osteoarthritis (OA), a condition affecting 365 million individuals globally. Initially developed to treat hemarthrosis, GAE selectively embolizes abnormal genicular vasculature, targeting synovial inflammation and reducing neoangiogenesis. This process alleviates pain and improves joint function, providing an alternative for patients with mild-to-moderate OA who are not candidates for surgical interventions due to comorbidities or other factors. Current evidence supports the use of GAE for patients with mild-to-moderate OA who experience persistent symptoms despite conservative treatments such as physical therapy, weight management, or intra-articular injections. The procedure effectively reduces pain, improves functionality, and provides sustained benefits. This review highlights the anatomical principles, procedural techniques, and patient selection criteria for GAE, as well as the clinical evidence supporting its safety and efficacy. It also explores potential future directions for research, including optimizing patient selection, evaluating long-term outcomes, and integrating GAE into routine OA management pathways.

Hip osteoarthritis constitutes a prevalent condition among individuals aged 55 and above, serving as one of the primary triggers for joint discomfort and impairment, and marking a substantial origin of chronic pain particularly affecting the elderly population. Our article provides an exhaustive summary of the mechanisms of action, therapeutic efficacy, and potential adverse consequences associated with novel therapeutic modalities including glucocorticoids, hyaluronic acid, platelet-rich plasma, mesenchymal stem cells, and stromal vascular fraction. Concurrently, we conducted a comprehensive evaluation of the clinical efficacy and potential applications of various medications.

In comparison to physical therapy, oral analgesics, and other nonsurgical modalities, intra-articular injection therapy is characterized by enhanced safety and greater efficacy. Moreover, when contrasted with surgical intervention, intra-articular injection demonstrates a lower degree of invasiveness and incurs fewer adverse reactions. Intra-articular treatments have shown excellent local efficacy while significantly minimizing adverse reactions in patients. These methods hold significant potential for development but require comprehensive research and thorough discussion within the academic community.

This meta-analysis evaluates the efficacy and safety of various topical dosage forms of diclofenac (gel, solution, and patch) for the treatment of knee osteoarthritis.

A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science for randomized controlled trials evaluating topical diclofenac formulations in knee osteoarthritis patients. Data on pain relief, functional outcomes, and adverse events were extracted. The primary outcomes were pain and function scores at different follow-up intervals (1-2 weeks, 3-6 weeks, 8-12 weeks), and safety outcomes.

A total of 12 randomized controlled trials (RCTs) were included in the analysis. Diclofenac gel, solution, and patch were all shown to significantly alleviate pain and improve function in patients with knee osteoarthritis. At 1-2 weeks, the diclofenac patch delivered the most pronounced short-term pain relief (SMD: -0.64; 95% CI: -0.90 to -0.39), while the gel and solution demonstrated sustained efficacy over the mid-term (3-6 weeks) and long-term (8-12 weeks). whereas skin-related adverse events, systemic side effects and withdrawal rates remained low across all formulations. The overall quality of evidence was assessed as moderate to high, reinforcing the robustness of the findings.

Topical diclofenac formulations (gel, solution, patch) significantly improve pain and function in knee osteoarthritis compared to placebo. All formulations were well-tolerated, with no significant increase in adverse events. These findings support the use of topical diclofenac for short-term pain relief and functional improvement in KOA patients.

Knee osteoarthritis (KOA) stands as a prevalent clinical condition that frequently affects individuals. A growing body of research has highlighted the potential advantages of dietary supplements, including glucosamine and chondroitin, in the management of KOA.

This study aims to ascertain the most efficacious dietary supplement for KOA, with a specific focus on reducing pain, alleviating stiffness, and enhancing joint function.

We conducted an exhaustive search of multiple databases, including PubMed, Web of Science, Embase, and the Cochrane Library, from inception to May 2023. We specifically focused on randomized controlled trials (RCTs) comparing various dietary supplements with the placebo group within the context of KOA. Assessment of outcomes among these groups relied on the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), with weighted mean differences (WMDs) and associated 95% confidence intervals (CIs) computed. Network meta-analyses were employed to compare outcomes across different supplement groups in comparison with the placebo. The surface under the cumulative ranking curve (SUCRA) was utilized to rank these supplements.

Our comprehensive analysis included 22 studies with 2,777 participants in total. The outcomes from our network meta-analysis yielded the following key findings: To reduce the total WOMAC score, the top three interventions were E-OA-7, LParActin, and LcS. For reducing the WOMAC score of pain, the most effective interventions were Aflapin, NEM, and PFP. In addressing the reduction of the WOMAC score of stiffness, NEM, Aflapin, and MSM emerged as the optimal interventions. Finally, for diminishing the WOMAC score of physical function, the most effective interventions were E-OA-7, LParActin, and LcS.

In comparison to the placebo, NEM (for stiffness), Aflapin (for pain), and E-OA-07 (for knee function and WOMAC total score) were discerned as the most effective interventions for the treatment of KOA.

https://www.crd.york.ac.uk/prospero/.

Knee osteoarthritis (OA) is a chronic, long-term disease with both physical and psychosocial consequences. In determining the treatment programs of patients diagnosed with knee OA and ensuring compliance with treatment, it is important to understand the emotional attitudes and experiences of patients regarding the physical and psychosocial effects of the disease. This study aimed to create a scale for evaluating the emotional attitudes of patients with knee OA as they manage and cope with the condition.

The research was a validity and reliability study designed using methodological methods. Study data were collected from the Department of Physical Therapy and Rehabilitation at a university hospital in Turkey between November and December 2024. The study sample included 90 patients diagnosed with knee OA. To establish the validity of the scale, content validity and construct validity were assessed. Internal consistency was determined using Cronbach's alpha reliability coefficient, item-total score correlations, and the Hotelling T2 test. The test-retest method was applied to determine the scale's stability over time.

The content validity index (CVI) values for the draft form of the scale ranged between 0.91 and 1.00. The exploratory factor analysis indicated that the scale consisted of a single factor, which explained 41.62% of the total variance. The scale demonstrated strong reliability, with a Cronbach's alpha coefficient of 0.86, item-total correlations ranging from 0.36 to 0.73, and a significant Hotelling T2 value (P < 0.001). Test-retest analysis indicated a positive and highly significant correlation for the overall scale (r = 0.964, P < 0.001).

The knee osteoarthritis emotional meaning scale (KOEMS) was demonstrated to be a valid and reliable instrument for this patient sample.

Osteoarthritis is a degenerative joint disease that worsens over time, often resulting in chronic pain. Eulophia nuda (Orchidaceae), a medicinal herb widely used by folklore and indigenous healers for treating arthritis but the active ingredients and the molecular mechanisms of action are yet to be explored. The present study systematically investigates the underlying anti-osteoarthritic mechanism of ENE through network pharmacology, molecular dynamics simulation and experimental assays. A comprehensive search on IMPPAT, KNApSAcK and Pubchem databases resulted 26 active compounds from E. nuda, of which 23 passed the drug-likeness criteria. A total of 2344 compound targets, 1370 osteoarthritis targets and 81 overlapping compound-disease targets were identified. The compound-disease target network resulted in five active constituents with degree > 23. Topological analysis of the protein-protein interaction network revealed six hub target genes. KEGG analysis revealed IL-17, TNF and AGE-RAGE signalling pathways as the enriched pathways involved in osteoarthritis. Molecular docking showed eulophiol had the good binding energy (>8.0 kcal/mol) with MMP9, JNK1, p38 and NF-kβ. The molecular dynamics simulations and the MMPBSA analysis indicate high stability and greater binding energy of eulophiol with the target proteins. ENE did not show cytotoxicity on SW982 cells up to a concentration of 100 μg/ml. ENE exhibited considerable anti-inflammatory effect by reducing PGE2, IL-6 and IL8 levels as well as reducing the mRNA expression of matrix metalloproteinases (MMP2 and MMP9). Furthermore, ENE effectively inhibited the NF-kβ nuclear translocation and phosphorylation of ERK2, p38 and JNK in SW982 cells. The current study showed that ENE may act as a potential drug candidate for treating osteoarthritis.

Knee osteoarthritis (OA) is a prevalent and debilitating condition that significantly impacts patients' quality of life and poses a substantial socioeconomic burden. Current treatments, including nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy, often provide only temporary relief and fail to halt disease progression, particularly in advanced stages where knee replacement surgery becomes the primary option. Regenerative cell therapies, particularly those utilizing mesenchymal stem cells (MSCs), have emerged as promising alternatives due to their anti-inflammatory and regenerative properties. This study investigates the efficacy of stromal vascular fraction (SVF) derived from autologous adipose tissue when injected into the infrapatellar (Hoffa's) fat pad, an approach that leverages the rich vascular and stem cell environment of the fat pad to potentially modulate inflammation and promote tissue repair.

Patients receiving therapy with SVF were invited to participate in the study. Inclusion criteria encompassed male and female patients aged 18 years or older with a Kellgren-Lawrence score up to 4, while exclusion criteria included malignant tumors, sepsis, or skin lesions at the site of collection or injection. A total of 25 patients were included in the study cohort, with two patients receiving bilateral treatment, resulting in 27 knees analyzed.For the correlation analysis, an additional four patients who had only completed the six-month follow-up were included, one of whom underwent bilateral treatment. This extended the correlation analysis cohort to 29 patients and 32 knees. However, these four patients were excluded from the final study analysis as they had not completed the two-year follow-up. Consequently, the final analysis focused exclusively on the 25 patients (27 knees) who completed the full two-year follow-up.

Significant improvements were observed in VAS pain scores and KOOS subscales for pain, activities of daily living (ADL), and quality of life (QOL) at 6 and 24 months (p < 0.05). The correlation between the number of injected cells and functional improvements was significant for ADL at 6 months (Spearman's rho = 0.31, p = 0.044). This time point was prioritized to evaluate early therapeutic responses, as it represents a critical window when cellular activity and therapeutic effects are believed to peak. Focusing on the six-month follow-up allowed for a detailed assessment of these early impacts while minimizing potential confounding factors observed in later stages. No major complications were reported.

SVF infiltration into the infrapatellar fat pad shows promising long-term benefits in pain relief and functional improvement for knee OA patients. Despite the lack of blinding and a control group, these findings suggest that SVF therapy could be a viable minimally invasive alternative to more invasive surgical interventions.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show substantial efficacy in regulating blood glucose levels and lipid metabolism, initially as an effective treatment for diabetes mellitus. In recent years, GLP-1RAs have become a focal point in the medical community due to their innovative treatment mechanisms, robust therapeutic efficacy, and expansive development prospects. Notably, GLP-1RAs benefit pain management through their neuroprotective and metabolic regulatory properties, such as inhibiting inflammation responses and oxidative stress, promoting β-endorphin release and modulating several other crucial biological pathways. Hence GLP-1RAs hold promise for repurposing as treatments for pain disorders. In this narrative review, we thoroughly trace the current preclinical and clinical evidence of seven pain modalities, including inflammatory pain, osteoarthritis, visceral pain, neuropathic pain, diabetic neuropathy, cancer pain and headache, to support the efficacy and underlying biological mechanisms of GLP-1RAs as therapeutic agents for pain suffering. Despite these promising findings, further research is necessary to establish their long-term efficacy, optimal dosing strategies, and potential synergistic interactions of GLP-1RAs with existing pain management therapies. Future clinical trials should aim to distinguish the direct analgesic effects of GLP-1RAs from their metabolic benefits and explore their broader applications in pain conditions. The ongoing exploration of new indications for GLP-1RAs further highlights their transformative potential in advancing medical treatments across diverse clinical fields.

Inflammation and cartilage degeneration are critical challenges in osteoarthritis (OA) treatment. Achieving sustained drug efficacy while mitigating the adverse effects of inflammation and reactive oxygen species remains a significant challenge. This study synthesizes a gallic acid-magnesium (GA-Mg) metal-organic framework (MOF) as a drug carrier for puerarin (PA). The PA-loaded GA-Mg MOF (pGM) is encapsulated within chondroitin sulfate methacrylate, forming monodisperse hybrid microspheres (CM@pGM) under ultraviolet light using microfluidic technology. The pGM is physically confined within the microspheres through a network of structural obstructions and noncovalent interactions. During degradation, GA and Mg2+ ions release from pGM, improving the inflammatory microenvironment of the articular cavity and mitigating oxidative stress. The sustained release of Mg2+ and PA supports chondrocyte anabolism and facilitates cartilage repair. In vitro studies confirm that injectable microspheres extend the drug release period to over 2 weeks. In vivo experiments demonstrate that CM@pGM significantly reduces osteophyte formation, alleviates degenerative changes in articular cartilage, and delays OA progression. In conclusion, CM@pGM, as a drug delivery platform that ameliorates the inflammatory microenvironment, alleviates oxidative stress, and promotes cartilage repair, holds significant potential for OA treatment.

Background/Objectives: Osteoarthritis (OA) is one of the most prevalent chronic conditions and significantly contributes to local and global disease burden. Common pharmaceuticals that are used to treat OA cause significant side effects, thus non-pharmaceutical bioactive alternatives have been developed that can impact OA symptoms without severe side-effects. One such alternative is the Red Algae Lithothamnion species (Litho). However, there is little mechanistic knowledge of its potential to effect OA gene expression, and a human in vitro model using commercially available cell lines to test its effectiveness has yet to be developed. Methods: Human osteoblast (hFOB 1.19. CRL-11372) and chondrocyte (C28/I2) cell lines were co-cultured indirectly using transwells. IL1-β was used to induce an inflammatory state and gene expression profiles following treatment were the primary outcome. Conclusions: Results indicated that the model was physiologically relevant, remained viable over at least seven days, untreated or following induction of an inflammatory state while maintaining hFOB 1.19. and C28/I2 cell phenotypic characteristics. Following treatment, Litho reduced the expression of inflammatory and pain associated genes, most notably IL-1β, IL-6, PTGS2 (COX-2) and C1qTNF2 (CTRP2). Confirmatory analysis with droplet digital PCR (ddPCR) revealed that Il-1β induced a significant reduction in C1qTNF2 at 7 days which was ameliorated with Litho treatment. These data present a novel and replicable co-culture model of inflammatory OA that can be used to investigate bioactive nutraceuticals. For the first time, this model demonstrated a reduction in C1qTNF2 expression that was mitigated by Red Algae Lithothamnion species.

Osteoarthritis is a degenerative joint disorder characterized by cartilage degradation, synovial inflammation, and altered subchondral bone structure. Recent insights have identified mitochondrial dysfunction as a pivotal factor in OA pathogenesis, contributing to chondrocyte apoptosis, oxidative stress, and extracellular matrix degradation. Disruptions in mitochondrial dynamics, including impaired biogenesis, mitophagy, and metabolic shifts from oxidative phosphorylation to glycolysis, exacerbate cartilage damage by promoting the production of reactive oxygen species and matrix-degrading enzymes such as ADAMTS and MMPs. This review explores the molecular mechanisms underlying mitochondrial dysfunction in OA, emphasizing its role in cartilage homeostasis and inflammation. Furthermore, it highlights emerging therapeutic strategies targeting mitochondrial pathways, including antioxidants, mitophagy enhancers, and metabolic modulators, as potential interventions to mitigate disease progression, which offer promising avenues for advancing personalized and disease-modifying treatments in OA.

To compare the effects of medical mud-pack (MMP) treatments applied at different temperatures on the pain and joint functions of patients with knee osteoarthritis (KOA). Kellgren Lawrence (KL) stage 3 or 4 KOA patients were included and randomized into three groups. Patients in groups 1, 2, and 3 took MMP treatment to both knees at 39 °C, 42 °C, and 45 °C, respectively. The treatment was performed for 12 days (only weekdays) and was 30 min long per day. The same blinded physician evaluated the patients at baseline and at the end of the treatment. The assessments were done before and after the intervention. The primary outcome was to achieve a minimal clinically important improvement (MCII) for KOA (decrease of at least 19 mm (-40.8%) on the VAS for pain, a decrease of 18.3 mm (-39%) on the patient's global assessment (PGA), and/or a decrease of at least 9.1 points (-26%) on the Western Ontario and McMaster Universities Osteoarthritis Index function subscale (WOMAC-FS). Secondary outcomes were pain (VAS), patient's global assessment (VAS), physician's global assessment (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Patient's health state, Patient Acceptable Symptom State (PASS). 217 patients were analyzed. Groups 1, 2, and 3 had 68, 81,68 patients, respectively. The MCII measurement revealed that MMP treatment did not show a significant difference between groups 2 and 3 (p > 0.05). Also, it was observed that more patients in groups 2 and 3 reached the MCII compared to group 1 (p < 0.001). For the secondary outcomes, significant improvements were observed within-group evaluations for each of the three groups (p < 0.001). Between groups comparisons, the improvements at the end of the treatment were found to be superior for group 2 and group 3 compared to group 1 (p < 0.001). There was no statistically significant difference between groups 2 and 3 for any parameters (p > 0.05). The number of patients who achieved the PASS was statistically lower for group 1 compared to groups 2 and 3 (p < 0.001). We observed significant improvements in all groups after treatment. The main result, as measured by MCII, suggests that MMP treatments at 42-45 °C is more effective than at 39 °C in managing severe KOA patients' pain and functional status. We found no significant difference in pain and joint function improvement between 42 °C and 45 °C after MMP.

People with knee osteoarthritis (OA) may have more thigh intermuscular and intramuscular adipose tissue (interMAT and intraMAT, respectively) compared to those without knee OA. Literature has not considered differences in body mass index (BMI) in the context of comparing intraMAT and interMAT between individuals with and without knee OA, matched for BMI (± 1 kg/m²). This study aims to compare interMAT and intraMAT, along with physical function (including knee extension strength), between individuals with and without knee osteoarthritis, matched by BMI.

Participants aged ≥ 40 years with symptomatic and radiological knee OA group (grade 2 and 3 on the Kellgren and Lawrence (KL) scale) were included in the affected group, while those with no knee pain and no radiological knee OA changes were included in the unaffected group. No participants were lost to assessment, ensuring complete data analysis for all participants. We used independent t-test and mean difference (95% CI) to compare thigh intraMAT and interMAT volume, self-reported measures (WOMAC questionnaire), physical function measures, and knee extension strength between groups.

Forty-six participants were analyzed (23 in each group). The affected group had significantly higher intraMAT compared to the unaffected group (p < 0.05), but no differences were observed for interMAT. Self-reported outcomes and physical function measures were worse in the affected group, as was knee extension strength.

People with knee OA present higher levels of intraMAT and poorer physical function compared to those without knee OA. These findings highlight the need for further research to explore the clinical significance of intraMAT and its potential impact on physical function in this population.

In recent years, various psychological interventions have garnered attention as effective support methods to promote self-management and comprehensively understand those with physical and psychological problems associated with knee pain. The purpose of this study was to implement an instructional design (ID) based self-management program for outpatients diagnosed with KOA and to verify the effectiveness of the program.

In this single-arm uncontrolled before‒after comparative intervention study, 41 subjects diagnosed with symptomatic knee osteoarthritis participated in an intervention program. Their pain, physical function, self-efficacy, self-care agency, and daily life difficulties were evaluated. A mixed-effects model was employed to examine the changes in each outcome from baseline to immediately before and after the intervention, and after one, three, and six months.

"Pain at the beginning of walking," "pain from standing to sitting position," and "pain after long-distance walking" reduced significantly immediately after the intervention and after one month. "Pain when climbing stairs" reduced significantly immediately after the intervention and after one, three, and six months. The sit-to-stand test showed significant improvement from baseline to immediately after and one, three, and six months after the intervention. Self-care agency scores improved significantly immediately after the intervention and after one and six months.

The intervention program effectively improved physical function, self-care agency, and self-efficacy, and reduced pain from one to six months. Innovation: This program could lead to an increase in the healthy life expectancy of the older adults.

Aerobic exercise is recommended to alleviate pain and protect the joint for patients with advanced knee osteoarthritis, however, its clinical implementation is challenging due to the potential for exacerbating pain.

The study aimed to compare the effects of anti-gravity treadmill training with traditional treadmill training in patients with advanced knee osteoarthritis.

This single-blinded randomized-controlled trial included 30 women with knee osteoarthritis. All participants received hotpack, transcutaneous electrical nerve stimulation, and therapeutic ultrasound. Additionally, group 1 received anti-gravity treadmill, while group 2 received traditional treadmill training. Group 3 served as the control. The interventions were administered three-times a week for eight-weeks. The visual analogue scale (VAS) pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), six-minute-walk-test distance (6MWD), and femoral cartilage thickness were evaluated at baseline and weeks 4 and 8.

VAS-pain significantly reduced over time in both anti-gravity (P < 0.001) and control (P = 0.004) groups. The anti-gravity group also showed significant improvements in WOMAC-pain (P = 0.008), WOMAC-total (P = 0.048), and 6MWD (P < 0.001). Post-hoc analysis indicated significant time (P < 0.001, effect size, ηp2 = 0.682) and interaction (P = 0.006, ηp2 = 0.271) effects on VAS, with no significant between-group differences. Femoral cartilage thickness showed no significant between-group differences, except within-group differences in the treadmill group (P = 0.037).

Anti-gravity treadmill training significantly improved pain, functionality, and functional capacity in patients with knee osteoarthritis, while traditional treadmill resulted in a reduction in femoral cartilage thickness. Further research should investigate long-term outcomes and more diverse populations.

NCT05319964.

» Corticosteroid injections (CSIs), including intra-articular, perineural, and those involving tendon sheaths or bursae, offer potential relief from osteoarthritic and inflammatory musculoskeletal pain, including gout attacks, as well as tarsal tunnel syndrome, plantar fasciitis, and interdigital neuromas.» CSI for musculoskeletal pain is commonly used as a nonoperative management option for both diagnostic and therapeutic purposes, offering pain relief, typically lasting from days to months.» CSIs are often performed prior to surgery as part of the nonoperative management of many conditions, with multiple CSIs within the year of surgery increasing postoperative infection risk in some major joints.» Despite the potential benefits of CSI, there are risks, including a potential increase in the risk of surgical site infection secondary to bacterial contamination and the immunomodulating effect of corticosteroids when given in the perioperative period.» To date, a multitude of studies across orthopaedic subspecialties has reported on perioperative infection risk associated with CSIs. However, heterogeneity in study design and patient populations has made standardized recommendations challenging. It is, therefore, difficult to elucidate, with a high level of evidence, the most appropriate perioperative timeline for CSI administration for which infection risk is nonsignificant.

A higher prevalence of knee pain in Southeast Asian countries, compared with non-Asian countries, is an established fact. This article hypothesizes that this fact, combined with personal, cultural, and environmental factors, may influence attitudes toward illness and treatment-seeking behavior and adherence.

This study aimed to determine current attitudes, stigma, and barriers of women to the management of chronic knee pain and treatment in two Southeast Asian countries.

Fourteen semi-structured interviews explored female lived perceptions of chronic knee pain in Southeast Asia. Using a phenomenological reduction process, open-ended questions allowed participants to voice their perceptions of their experience of this knee condition. Particular foci were potential stigma associated with the perceptions of others, health-seeking attitudes, and attitudes toward exercise.

The shared experiences of managing chronic knee pain revealed the impact of their condition on participants' normality of life and their struggles with pain, limitations, and fear for the future. Key individual, interpersonal, organizational and community barriers and facilitators impacted the health seeking attitudes and engagement with conservative rehabilitation programmes.

Improved socio-cultural competency and consideration for an individuals' intersectional identity and interpersonal relationships are key to designing rehabilitation and conservative management solutions. Co-creating alternative pathways for rehabilitation for individuals that are more distant from health facilities may help reduce socio-cultural barriers at a community level.