Gait kinematics differ by bout duration and setting.

BACKGROUND: Gait kinematics differ between settings and among young and older adults with and without knee osteoarthritis. Out-of-lab data has a variety of walking bout characteristics compared to controlled in-lab settings. The effect of walking bout duration on gait analysis results is unclear, and there is no standardized procedure for segmenting or selecting out-of-lab data for analysis. RESEARCH QUESTION: Do gait kinematics differ by bout duration or setting in young and older adults with and without knee osteoarthritis? METHODS: Ten young (28.1±3.5 yrs), ten older adults (60.8±3.3 yrs), and ten older adults with knee osteoarthritis (64.1±3.6 yrs) performed a standard in-lab gait analysis followed by a prescribed walking route outside the lab at a comfortable speed with four IMUs. Walking speed, stride length, and sagittal hip, knee, and ankle angular excursion (ROM) were calculated for each identified stride. Out-of-lab strides included straight-line, level walking divided into strides that occurred during long (>60 s) or short (≤60 s) bouts. Gait kinematics were compared between in-lab and both out-of-lab bout durations among groups. RESULTS: Significant main effects of setting or duration were found for walking speed and stride length, but there were no significant differences in hip, knee, or ankle joint ROM. Walking speed and stride length were greater in-lab followed by long and short bout out-of-lab. No significant interaction was observed between group and setting or bout duration for any spatiotemporal variables or joint ROMs. SIGNIFICANCE: Out-of-lab gait data can be beneficial in identifying gait characteristics that individuals may not encounter in the traditional lab setting. Setting has an impact on walking kinematics, so comparisons of in-lab and free-living gait may be impacted by the duration of walking bouts. A standardized approach for to analyzing out-of-lab gait data is important for comparing studies and populations.

Association between widespread pain and psychosocial factors in people with knee osteoarthritis: a cross-sectional study of patients from primary care in Denmark.

INTRODUCTION: The relationship between psychosocial factors and bodily pain in people with knee osteoarthritis (KOA) is unclear. PURPOSE: To examine whether widespread pain was associated with poorer self-efficacy, more anxiety, depression, and kinesiophobia in people with KOA. METHODS: This was a cross-sectional study based on data from Good Life with osteoArthritis in Denmark (GLA:D®). The association between widespread pain (multiple pain sites) and self-efficacy (Arthritis Self-Efficacy Scale), anxiety and depression (item from the EQ-5D-5 L), and kinesiophobia (yes/no) was examined using multiple linear tobit or logistic regression models. RESULTS: Among 19,323 participants, 10% had no widespread pain, 37% had 2 pain sites, 26% had 3-4 pain sites, and 27% had ≥5 pain sites. Widespread pain was associated with poorer self-efficacy (-0.9 to -8.3 points), and the association was stronger with increasing number of pain sites (p-value <.001). Significant increasing odds ratios (ORs) were observed for having anxiety or depression with 3-4 pain sites (OR 1.29, 95% CI 1.12; 1.49) and ≥5 pain sites (OR 1.80, 95% CI 1.56; 2.07). Having 2 and 3-4 pain sites were associated with lower odds of kinesiophobia compared to having no widespread pain. CONCLUSION: Widespread pain was associated with lower self-efficacy and more anxiety and depression but also lower kinesiophobia in people with KOA.

Osteocyte-derived exosomes regulate the DLX2/wnt pathway to alleviate osteoarthritis by mediating cartilage repair.

BACKGROUND: Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA. OBJECTIVE: This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms. METHODS: An injury cell model was established by treating chondrocytes with IL-1ß. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 in vivo. RESULTS: Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2. CONCLUSION: Osteocyte-derived exosomal DLX2 alleviated IL-1ß-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.

Is conventional radiofrequency ablation of the superolateral branch, one of the three genicular nerves targeted as standard, necessary or not? A non-inferiority randomized controlled trial.

Background: Radiofrequency ablation is an effective treatment modality in the symptomatic treatment of knee osteoarthritis. Our aim was to compare the efficacy of radiofrequency ablation of the superomedial and inferomedial genicular nerves (2 branches) with the superolateral, superomedial, and inferomedial genicular nerves (3 branches) and to show whether the 2-branch procedure is inferior to the 3-branch procedure. Methods: This study is a prospective, randomized, single-blind clinical study. Eligible participants were randomized into 2 groups: group A, which applied the procedure to the superomedial and inferomedial genicular nerves, and group B, which applied it to the superomedial, superolateral and inferomedial genicular nerves. Pain was evaluated with the numerical rating scale, quality of life with the Short Form-36 (SF-36), and disability with the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index before, and at 1 and 3 months after the procedure. Results: A total of 41 patients were included. There were no differences between the groups except for the SF-36 physical health sub-score at baseline. A significant improvement was seen in the numeric rating scale (NRS) score, SF-36 sub-scores, WOMAC Index total, as well as pain and physical function scores in both groups, though no significant difference was detected between the groups during follow-up. Conclusions: Although we were unable to establish the noninferiority of conventional radiofrequency ablation (CRFA) applied to 2 branches to CRFA applied to 3 branches, in this trial, significant and similar improvement was observed in NRS, WOMAC total, pain, and physical function and SF-36 scores in both groups.

UBE2I regulates the nuclear translocation of hnRNPA2B1 by contributing to SUMO modification in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a progressive condition affecting the joints that lacking effective therapy. However, the underlying molecular mechanism has not been fully clarified. METHODS: A model of OA was established in Sprague-Dawley (SD) rats through intra-articularly injected with monoiodoacetate (MIA). Western blot analysis was used to identify the levels of UBE2I and hnRNPA2B1 in articular cartilage. Overexpression and siRNA vectors for UBE2I were constructed and transfected into rat chondrocytes. CCK-8, TUNEL and transwell assay were utilized to assess the cell viability, apoptosis and migration ability. Western blot analysis was used to determine the levels of chondrogenic-specific genes including SOX9, COL2A1, Aggrecan, and PRG4. Then, molecular interactions were confirmed by immunoprecipitation. RESULTS: We observed significant upregulation of UBE2I and hnRNPA2B1 expression in articular cartilage samples of OA. The Pearson correlation analysis revealed positive correlation between UBE2I and hnRNPA2B1 levels. Functional experiments showed that increased UBE2I expression significantly suppressed cell growth, migration, and reduced the expression of chondrogenic-specific genes, while decreasing UBE2I levels had the opposite effects. Molecular interactions between UBE2I and hnRNPA2B1were determined via co-localization and immunoprecipitation. SUMO1 and SUMO3 proteins were enriched by immunoprecipitation using hnRNPA2B1 antibodies. Rescue experiments were performed using SUMOylation inhibitor (2-D08) and SUMOylation activator (N106). Overexpression of UBE2I increased the expression of hnRNPA2B1 in the cytoplasm and decreased the level in the nucleus, which was reversed by the treatment of 2-D08. Conversely, UBE2I knockdown and N106 treatment had the opposite effect. CONCLUSIONS: UBE2I modulated the nuclear translocation of hnRNPA2B1 by promoting SUMOylation in OA.

Associations amongst dynamic knee stiffness during gait, quadriceps stiffness, and the incidence of knee osteoarthritis over 24 months: a cohort study with a mediation analysis.

BACKGROUND: Decreased strength and increased stiffness of the quadriceps have been associated with a higher risk of developing knee osteoarthritis (OA) in elders. Dynamic joint stiffness (DJS) represents collective resistance from active and passive knee structures for dynamic knee motions. Elevated sagittal knee DJS has been associated with worsening of cartilage loss in knee OA patients. Altered quadriceps properties may affect DJS, which could be a mediator for associations between quadriceps properties and knee OA. Hence, this study aimed to examine whether DJS and quadriceps properties would be associated with the development of clinical knee OA over 24 months, and to explore the mediation role of DJS in associations between quadriceps properties and knee OA. METHODS: This was a prospective cohort study with 162 healthy community-dwelling elders. Gait analysis was conducted to compute DJS during the loading response phase. Quadriceps strength and stiffness were evaluated using a Cybex dynamometer and shear-wave ultrasound elastography, respectively. Knee OA was defined based on clinical criteria 24 months later. Logistic regression with generalized estimating equations was used to examine the association between quadriceps properties and DJS and incident knee OA. Mediation analysis was performed to explore the mediation role of DJS in associations between quadriceps properties and the incidence of knee OA. RESULTS: A total of 125 participants (65.6 ± 4.0 years, 58.4% females) completed the 24-month follow-up, with 36 out of 250 knees identified as clinical knee OA. Higher DJS (OR = 1.86, 95%CI: 1.33-2.62), lower quadriceps strength (1.85, 1.05-3.23), and greater quadriceps stiffness (1.56, 1.10-2.21) were significantly associated with a higher risk of clinical knee OA. Mediation analysis showed that the DJS was not a significant mediator for the associations between quadriceps properties and knee OA. CONCLUSIONS: Higher sagittal knee dynamic joint stiffness, lower quadriceps strength, and greater quadriceps stiffness are potential risk factors for developing clinical knee OA in asymptomatic elders. Associations between quadriceps properties and knee OA may not be mediated by dynamic joint stiffness. Interventions for reducing increased passive properties of the quadriceps and knee joint stiffness may be beneficial for maintaining healthy knees in the aging population.

Autologous bone grafting in combination with autologous chondrocyte implantation yields favourable outcomes in the treatment of osteochondral defects of the knee: A systematic literature review.

PURPOSE: This study addresses the gap in the current literature by evaluating the combined treatment of autologous bone grafting and autologous chondrocyte implantation (ABCI) for osteochondral defects of the knee. It aims to evaluate clinical outcomes against methodological quality and to summarize histological results and surgical techniques. METHODS: A thorough search was conducted across Pubmed, Cochrane and Embase databases. Studies reporting clinical outcomes of ABCI for osteochondral defects of the knee were included. Patient-reported outcome measures (PROMs), failure rates, methodological quality and potential conflicts of interest were evaluated. Histological results and surgical techniques were summarized. RESULTS: Eighteen studies with 344 analyzed patients met the eligibility criteria for inclusion. All studies showed a significant improvement (p < 0.05) across different PROMs (subjective International Knee Documentation Committee score, Cincinnati Knee Rating System, Visual Analogue Scale, Lysholm Score, Tegner Activity Scale, Knee injury and Osteoarthritis Outcome Score and Knee Society Score) compared to the preoperative status. Failure rates ranged from 0% to 17.6%, with a mean follow-up of 73.2 months (range: 9.0-143.6 months). Methodological quality was low to medium, including only one comparative study. Six studies reviewed reported a potential conflict of interest. The histological assessment showed effective bonding between autologous chondrocytes and bone graft. A large degree of variability was observed in the operative technique used. CONCLUSION: The current literature suggests that ABCI yields good clinical outcomes at mid- to long-term follow-up with favourable histological results for osteochondral defects of the knee. However, future research should focus on high-quality comparative studies to better guide treatment choices. Introducing ABCI as the standard abbreviation may enhance clarity in future research. LEVEL OF EVIDENCE: Level IV.

Adipocyte enhancer binding protein 1 knockdown alleviates osteoarthritis through inhibiting NF-κB signaling pathway-mediated inflammation and extracellular matrix degradation.

Inflammation promotes the degradation of the extracellular matrix, which contributes to the development of osteoarthritis (OA). Adipocyte enhancer binding protein 1 (AEBP1) participates in multiple pathological processes related to inflammatory diseases. However, the role of AEBP1 in OA development is unknown. We found a higher AEBP1 expression in articular cartilage of OA patients (n = 20) compared to their normal controls (n = 10). Thus, we inferred that AEBP1 might affect OA progression. Then mice with destabilization of the medial meniscus (DMM) surgery and chondrocytes with IL-1ß treatment (10 ng/mL) were used to mimic OA. The increased AEBP1 expression was observed in models of OA. AEBP1 knockdown in chondrocytes reversed IL-1ß-induced inflammation and extracellular matrix degradation, which was mediated by the inactivation of NF-κB signaling pathway and the increased IκBα activity. Co-immunoprecipitation assay indicated the interaction between AEBP1 and IκBα. Importantly, IκBα knockdown depleted the protective role of AEBP1 knockdown in OA. Moreover, AEBP1 knockdown in mice with OA showed similar results to those in chondrocytes. Collectively, our findings suggest that AEBP1 knockdown alleviates the development of OA, providing a novel strategy for OA treatment.

The predictors to self-reported and performance-based physical function in knee osteoarthritis patients: a cross-sectional study.

Background: Osteoarthritis (OA) knee patients have limited ability in physical function, or difficulties with physical tasks and activities may develop disability. This study aimed to observe the predictors of self-reported and performance-based physical function in patients with knee OA by analyzing the impacts of demographic, pathological, and muscle impairment factors. Methods: 135 knee OA patients participated in this study to complete self-reported questionnaires using Knee Injury and Osteoarthritis Outcome Score (KOOS). When measuring performance-based physical function, a 6-meter gait speed (6MGS) test was measured to evaluate their mobility, and a 5-time Sit-to-Stand test (5STS) was assessed to evaluate their balance. Pain intensity, knee extensor and flexor muscle strength, age, body mass index (BMI), durations of symptoms, and radiographic severity were also collected. Spearman correlation and stepwise multiple linear regression were used to explore the association and predictors in self-reported and performance-based physical function. Results: BMI and durations of symptoms did not indicate any significant correlation with either self-reported or performance-based physical function. Age is significantly negatively associated with 6MGS (r 2 = -0.383, p < 0.01), while knee extensor muscle strength has a moderate correlation with 5STS (r 2 = -0.528, p < 0.01). In the stepwise multiple linear regression models, pain intensity (ß = 0.712, p < 0.001), knee flexor muscle strength (ß = 0.112, p = 0.042) were significantly associated with self-reported physical function in daily activities and contributed to 55.0% of the variance in KOOS-PF score. Knee muscle strength, including knee extensor (5STS: ß = -0.428, p < 0.001) and flexor muscle strength (6MGS: ß = 0.367, p < 0.001), were the main predictors with performance-based physical function. Conclusion: Pain intensity was the leading risk factor of self-reported physical function, and knee flexor muscle strength contributed as well. The severity of knee OA, durations of symptoms and BMI did not contribute to physical function. However, knee extensor and flexor muscle strength were the main predictors of performance-based performance. Our results show that strengthening of weak knee muscles in both quadriceps and hamstring muscle strength should be considered a priory consideration in knee OA no matter if people are in the early or end-stage of knee OA.

Sexual dimorphism in peri-articular tissue anatomy - More keys to understanding sex-differences in osteoarthritis?

Objective: Osteoarthritis prevalence differs between women and men; whether this is the result of differences in pre-morbid articular or peri-articular anatomical morphotypes remains enigmatic. Albeit sex within humans cannot be reduced to female/male, this review focusses to the sexual dimorphism of peri-articular tissues, given lack of literature on non-binary subjects. Methods: Based on a Pubmed search and input from experts, we selected relevant articles based on the authors' judgement of relevance, interest, and quality; no "hard" bibliometric measures were used to evaluate the quality or importance of the work. Emphasis was on clinical studies, with most (imaging) data being available for the knee and thigh. Results: The literature on sexual dimorphism of peri-articular tissues is reviewed: 1) bone size/shape, 2) subchondral/subarticular bone, 3) synovial membrane and infra-patellar fad-pad (IPFP), 4) muscle/adipose tissue, and 5) peri-articular tissue response to treatment. Conclusions: Relevant sex-specific differences exist for 3D bone shape and IPFP size, even after normalization to body weight. Presence of effusion- and Hoffa-synovitis is associated with greater risk of incident knee osteoarthritis in overweight women, but not in men. When normalized to bone size, men exhibit greater muscle, and women greater adipose tissue measures relative to the opposite sex. Reduced thigh muscle specific strength is associated with incident knee osteoarthritis and knee replacement in women, but not in men. These observations may explain why women with muscle strength deficits have a poorer prognosis than men with similar deficits. A "one size/sex fits all" approach must be urgently abandoned in osteoarthritis research.

Micro-current stimulation could inhibit IL-1ß-induced inflammatory responses in chondrocytes and protect knee bone cartilage from osteoarthritis.

This study aimed to evaluate the inhibitory effects of micro-current stimulation (MCS) on inflammatory responses in chondrocytes and degradation of extracellular matrix (ECM) in osteoarthritis (OA). To determine the efficacy of MCS, IL-1ß-treated chondrocytes and monosodium iodoacetate (MIA)-induced OA rat model were used. To evaluate the cytotoxicity and nitric oxide (NO) production in SW1353 cells, the presence or absence of IL-1ß treatment or various levels of MCS were applied. Immunoblot analysis was conducted to evaluate whether MCS can modulate IL-1R1/MyD88/NF-κB signaling pathway and various indicators involved in ECM degradation. Additionally, to determine whether MCS alleviates subchondral bone structure destruction caused by OA, micro-CT analysis, immunoblot analysis, and ELISA were conducted using OA rat model. 25 and 50 µA levels of MCS showed effects in cell proliferation and NO production. The MCS group with IL-1ß treatment lead to significant inhibition of protein expression levels regarding IL-1R1/MyD88/NF-κB signaling and reduction of the nucleus translocation of NF-κB. In addition, the protein expression levels of MMP-1, MMP-3, MMP-13, and IL-1ß decreased, whereas collagen II and aggrecan increased. In animal results, morphological analysis of subchondral bone using micro-CT showed that MCS induced subchondral bone regeneration and improvement, as evidenced by increased thickness and bone mineral density of the subchondral bone. Furthermore, MCS-applied groups showed decreases in the protein expression of MMP-1 and MMP-3, while increases in collagen-II and aggrecan expressions. These findings suggest that MCS has the potential to be used as a non-pharmaceutical method to alleviate OA.

The effects of medial soft tissue release for varus deformity during medial open wedge supramalleolar osteotomy: a cadaveric study.

This study was performed to investigate the effects of fibular osteotomy and release of medial soft tissues including posterior tibial tendon (PTT), and deep deltoid ligaments, which act as medial stabilizing structures in medial open wedge SMO. Twelve fresh frozen human legs were obtained and disarticulated below the knee. Experiments were conducted in four steps. First, medial open wedge tibial osteotomy was performed. Second, fibular osteotomy was performed in an inferomedial direction at the same level as the tibial osteotomy. Third, the deep deltoid ligament was released from tibial attachments. Forth, total tenotomy of the PTT was performed behind the medial malleolus. After finishing each step, contact area and peak and mean pressures were measured in the tibiotalar and talofibular joints. Fibular osteotomy after medial open wedge SMO significantly decreased mean pressure in the tibiotalar joint, mean and peak pressures in the talofibular joint. Medial soft tissue release resulted in a remarkable lateral shift and decreased tibiotalar joint loading. However, no remarkable change was observed in the tibiotalar joint during releasing medial soft tissues. The overall peak pressure distribution tended to shift more laterally compared to the value of normal alignment. In conclusion, concomitant fibular osteotomy and release of the deltoid ligament and PTT provide a useful means of minimizing tibiotalar joint stress. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00370-7.

Simultaneous Concurrent Bilateral Total Knee Replacement in a Patient With Bilateral Lipoma Arborescens With End-Stage Osteoarthritis.

A 78-year-old Thai male presented with chronic bilateral knee pain and swelling. X-ray imaging revealed osteoarthritis in both knees, with a suspicious soft tissue shadow. Magnetic resonance imaging suggested lipoma arborescens (LA). The patient underwent LA excision with a complete synovectomy, followed by simultaneous bilateral total knee arthroplasty (SBTKA). Pathological examination confirmed LA. At the 2-year follow-up, the patient reported no complications, adverse outcomes, or recurrence. The intervention improved joint function and pain relief, allowing for early ambulation and full weight-bearing post-surgery. This case highlights the success of complete synovectomy with SBTKA, addressing bilateral knee pathology concurrently. The combined approach reduced operative time and significantly improved joint function and pain relief, emphasizing the benefits of timely surgical intervention and suggest potential advantages of SBTKA for optimal patient outcomes.

Topical Diclofenac Reduces Joint Synovitis in Hand Osteoarthritis: A Pilot Investigation Using Fluorescent Optical Imaging.

Purpose: Synovitis, the inflammation of joint synovia, is a prominent feature of osteoarthritis (OA) manifested by enhanced synovial vascularity, endothelial leakage, and perivascular oedema. In this pilot study, we assessed the effect of topical diclofenac in hand OA (HOA) using the established semi-quantitative methods Magnetic Resonance Imaging (MRI) and Ultrasonography (US), and compared them with Fluorescent Optical Imaging (FOI), an emerging imaging modality. Patients and Methods: Ten patients with symptomatic and diagnosed HOA used topical diclofenac for 14 days, with FOI, MRI, US, and subjective pain assessed at Baseline and after 7 (Day 8), and 14 (Day 15) days of treatment. Changes in synovitis were assessed for all 10 joints of the hand (via sum scores), and separately for the two joints most affected by synovitis. A new, fully quantitative approach for objective synovitis assessment based on the FOI images was also developed and applied. Results: The semi-quantitative analysis of the sum scores showed a small decrease in synovitis throughout the treatment duration across the different imaging modalities. The effect of the treatment was more prominent on the two most affected joints, with a synovitis reduction vs Baseline of 21.1% and 34.2% on Day 8 and Day 15, respectively, in the FOI. The quantitative FOI pixel analysis further strengthened the evidence for this effect, with observed reduction of 17.8% and 42.4% for Days 8 and 15, respectively. A similar trend was observed for subjective pain perception, with a reduction of 7.2 and 13.3 mm on Days 8 and 15. Conclusion: This pilot study evidenced the effect of topical diclofenac on reducing synovitis in hand OA in semi- and fully quantitative analyses, with the effect being stronger in the most affected joints. Further, supporting studies are needed to probe the accuracy of the quantitative pixel analysis of FOI images.

Outcome Comparison between Carpometacarpal Arthroplasty and Trapeziectomy in Patients with Carpometacarpal Osteoarthritis: A Systematic review.

Background: Osteoarthritis of the carpometacarpal (CMC) is considered a common musculoskeletal disorder. The treatment of carpometacarpal osteoarthritis could be either by conservative or surgical methods. surgical treatment, there are various alternatives, including trapeziectomy and arthroplasty. This study aims to perform a systematic review of the literature to determine the functional outcomes associated with trapeziectomy and arthroplasty in CMC arthritis. Objectives: To determine the functional outcomes associated with trapeziectomy and arthroplasty in CMC arthritis patients. Methods: A systematic review was conducted according to PRISMA guidelines and performed on August 2022 by one independent reviewer (author) using PubMed database, EBSCO Host, EMBASE, and ScienceDirect. The literature search will be based on Patients, Intervention, Control, and Outcome (PICO) criteria, as mentioned in the following: Patients with any carpometacarpal arthritis; with the intervention of using carpometacarpal arthroplasty as their method of surgery; control with trapeziectomy and primary outcome of functional outcome. Clinical outcomes using patient-reported outcome measures and complications were included. The quality of the included studies was evaluated with Cochrane risk-of-bias assessment tools. Quantitative analysis was performed by Review Manager 5.4. Results: Three studies met the inclusion criteria for the systematic review. Both treatments resulted in significant improvements in functional scores. When matching patients according to preoperative function, patients receiving arthroplasty had better postoperative function (Quick DASH: trapeziectomy = 25.1, ARPE = 16.8). Conclusion: This study showed that variable results of clinical outcomes improved after trapezeictomy and arthroplasty in patients with CMC arthritis. Evidence showed that arthroplasty allows for a better improvement in functional outcome.

Carbamazepine in osteoarthritis treatment: A novel approach targeting Nav1.7 channels.

Osteoarthritis (OA) presents a growing health concern, with substantial societal and healthcare burdens. Current management focuses on symptom relief, lacking disease-modifying options. Emerging research suggests the sodium channel Nav1.7 as a pivotal target in OA treatment. Preclinical studies demonstrate carbamazepine's efficacy in Nav1.7 blockade, offering significant joint protection in animal models. However, human trials are needed to validate these findings. Carbamazepine's repurposing holds promise for OA management, potentially revolutionizing treatment paradigms. Further research is essential to bridge the gap between preclinical evidence and clinical application, offering hope for improved OA management and enhanced patient quality of life.

Effects of the combination of various pharmacological treatments and exercise on knee osteoarthritis: a systematic review and network meta-analysis.

Purpose: The combination of pharmacological and non-pharmacological interventions is strongly recommended by current guidelines for knee osteoarthritis. However, few systematic reviews have validated their combined efficacy. In this study, we investigated the effects of the combination of pharmacological agents and exercise on knee osteoarthritis. Methods: Randomized controlled trials that investigated the efficacy of pharmacological agents combined with exercise for knee osteoarthritis were searched in PubMed, Embase, and Cochrane Library up to February 2024. The network meta-analysis was performed within the frequentist framework. Standardized mean difference (SMD) with 95% CI was estimated for pain and function. Grading of recommendations, assessment, development, and evaluations were used to evaluate the certainty of evidence. Results: In total, 71 studies were included. The combination therapy outperformed pharmacological or exercise therapy alone. Among the various pharmacological agents combined with exercise, mesenchymal stem cell injection was ranked the best for short-term pain reduction (SMD: -1.53, 95% CI: -1.92 to -1.13, high certainty), followed by botulinum toxin A, dextrose, and platelet-rich plasma. For long-term pain relief, dextrose prolotherapy was the optimal (SMD: -1.76, 95% CI: -2.65 to -0.88, moderate certainty), followed by mesenchymal stem cells, platelet rich in growth factor, and platelet-rich plasma. Conclusion: Exercise programs should be incorporated into clinical practice and trial design. For patients undergoing exercise therapies, mesenchymal stem cell, dextrose, platelet-rich plasma, platelet rich in growth factor, and botulinum toxin A may be the optimal agents.

Is There a Need for an Exogenous Activator Along with PRP for Early Knee Osteoarthritis? A Triple-Blinded Randomized Control Trial.

Background: In addition to other variables associated with PRP injections for Knee Osteoarthritis (OA), some confusion exists about the role of exogenous activators. The current study looks at matched groups getting PRP injections with or without activator (Calcium gluconate) in early knee OA patients. Methods: Patients of early OA knee meeting inclusion criteria were randomly divided into 2 groups; Group A (43 patients) received 8 ml PRP injection alone, and Group B (48 patients) received 8 ml PRP along with 2 ml Calcium gluconate as activator. The patients were evaluated at baseline, 6 weeks, 3 months and 6 months for WOMAC Pain and Total WOMAC scores; secondary variables assessed were VAS score and patient satisfaction. Results: The baseline characteristics of both groups were comparable. Leucocyte-depleted PRP with 5 times concentration and average absolute platelet numbers of 7.144 billion per knee was injected. Mean Pain WOMAC scores decreased in both groups from baseline (group A-8.68, group B-9.09) to final follow-up (group A-4.67, group B-5.11). Similarly, Mean Total WOMAC scores decreased from baseline (group A-37.81, group B-37.41) to (group A-21, group B-21.36) at the final follow-up in both groups. There was no significant difference between both groups, and both showed similar trends. Similar findings were noted for VAS scores. Patient satisfaction was also not different (group A, 90.69%, group B, 89.58%) at the end of 6 months. Conclusion: Our study concluded doubtful role of adding exogenous activator to PRP preparation. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-024-01159-7.

Chondroprotective Effects of a Single PRP Injection in a Spontaneous Osteoarthritis Model of Dunkin Hartley Guinea Pig: An Immunohistochemical Analysis.

Purpose of the Study: The evaluation of anti-apoptotic and chondroprotective properties of a single injection of PRP using immunohistochemistry (IHC). Methods: This was a placebo-controlled blinded experimental study. Ten healthy Dunkin Hartley guinea pigs were selected. One knee of each animal was injected with a single injection of PRP (Group A); the contralateral knee acted as a control and was injected with a single injection of normal saline (Group B). These groups were further divided into A3 and B3 based on the timeline of animal sacrifice (3 months) and A6 and B6 (6 months). The formalin-preserved articular cartilage blocks were subjected to IHC to stain Aggrecan, Caspase-3, and Collagen-2. Results: The mean IHC score was significantly low for Caspase-3 (p-0.029) in intervention group (A3) in comparison to placebo control group (B3) pointing towards decreased apoptosis. The mean IHC values were significantly higher for Collagen II (p-0.011) for intervention group (A6) in contrast to control group (B6); values were also significantly low for Caspase-3 (p-0.029) in A6 as compared to B6. The mean Caspase-3 values were significantly higher in A6 as compared to A3 (p-0.029). Conclusion: The impact of a solitary injection of PRP on upregulation of anabolic pathways inside cartilage is relatively slower as compared to its effect on downregulation of apoptotic pathways. Even a single PRP injection holds the potential to change cartilage microenvironment, but the effects are not long lasting.

Bone Marrow Aspirate Concentrate for Treatment of Primary Knee Osteoarthritis: A Prospective, Single-Center, Non-randomized Study with 2-Year Follow-Up.

Introduction: Knee osteoarthritis (OA) is a widespread, disabling condition with no intervention to fully restore cartilage or halt progression. Bone marrow aspirate concentrate (BMAC), an autologous product from bone marrow aspiration, has shown promise as a regenerative therapy due to its cell composition and chondrogenic effects. Our study aims to assess the functional outcomes, including pain, function, satisfaction, and complications post-BMAC injection in knee OA patients. Materials and Methods: In this prospective, single-center study, 63 patients with grade II-III knee OA (Kellgren-Lawrence (K-L) scale) unresponsive to conservative management underwent BMAC injection. The procedure involved bone marrow aspiration from the anterior iliac crest, processing to obtain a concentrate, followed by intra-articular injection. Patients were followed for 24 months, assessing outcomes using the Visual Analog Scale (VAS), International Knee Documentation Committee (IKDC) score, and MOCART 2.0 score. Results: The cohort, with a slight female predominance and predominantly aged 41-50 years, majorly comprised K-L grade III OA patients. BMAC treatment resulted in significant improvements in VAS pain scores, IKDC functional scores, and MOCART 2.0 scores over the 24-month follow-up. Conclusion: BMAC injection provides significant improvement in both pain and functional outcomes at mid-term follow-up in patients with mild-to-moderate OA of the knee. Further high-quality, adequately powered, multi-center, prospective, double-blinded, randomized controlled trials with longer follow-up are necessary to justify the routine clinical use of BMAC for treatment of patients suffering with knee OA.