Search

Inflammatory cytokines released by synovium after trauma disturb the gene regulatory network and have been implicated in the pathophysiology of osteoarthritis. A mechanistic understanding of how aging perturbs this process can help identify novel interventions. Here, we introduced network paradigms to simulate cytokine‐mediated pathological communication between the synovium and cartilage. Cartilage‐specific network analysis of injured young and aged murine knees revealed aberrant matrix remodeling as a transcriptomic response unique to aged knees displaying accelerated cartilage degradation. Next, network‐based cytokine inference with pharmacological manipulation uncovered IL6 family member, Oncostatin M (OSM), as a driver of the aberrant matrix remodeling. By implementing a phenotypic drug discovery approach, we identified that the activation of OSM recapitulated an "inflammatory" phenotype of knee osteoarthritis and highlighted high‐value targets for drug development and repurposing. These findings offer translational opportunities targeting the inflammation‐driven osteoarthritis phenotype. [ABSTRACT FROM AUTHOR]

Key points Accumulated fat in skeletal muscle (i.e. myosteatosis), common in sedentary older individuals, compromises skeletal muscle health and function. A mechanistic understanding of how physical activity levels dictate fat accumulation represents a critical step towards establishment of therapies that promote healthy ageing. Using a network medicine paradigm that characterized the transcriptomic response of aged muscle to exercise versus immobilization protocols, this study explored the shared molecular cascade that regulates the fate of fibro‐adipogenic progenitors (FAPs), the cell population primarily responsible for fat accumulation. Specifically, gene set enrichment analyses with network propagation revealed Pgc‐1α as a functional hub of a large gene regulatory network underlying the regulation of FAPs by physical activity in aged muscle, but not in young counterparts. Integrated in silico and in situ approaches to induce Pgc‐1α overexpression in aged muscle promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis. These findings suggest that the Pgc‐1α–mitochondrial fatty acid oxidation axis is a shared mechanism by which physical activity regulates age‐related myosteatosis. The network medicine paradigm introduced provides mechanistic insight into exercise adaptation in elderly skeletal muscle and offers translational opportunities to advance exercise prescription for older populations. Fat accumulation is a quintessential feature of aged skeletal muscle. While increasing physical activity levels has been proposed as an effective strategy to reduce the fat in skeletal muscle (i.e. myosteatosis), the molecular cascade underlying these benefits has been poorly defined. This study implemented a series of network medicine approaches and uncovered Pgc‐1α as a mechanistic driver of the regulation of fibro‐adipogenic progenitors (FAPs) by physical activity. Integrated in silico and in situ approaches to induce Pgc‐1α overexpression promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis. Together, the findings of the current study suggest a novel hypothesis that physical activity reduces myosteatosis via upregulation of Pgc‐1α‐mediated mitochondrial fatty acid oxidation and subsequent inhibition of FAP adipogenesis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case highlights the biomechanical influence of toe amputation on contralateral limb force elevation, possibly through reduced ipsilateral plantar flexor torque production. These findings provide insight into toe amputation‐related compensatory gait mechanics with greater inter‐limb asymmetry, which may increase the risk of musculoskeletal comorbidities, including osteoarthritis in contralateral limb. [ABSTRACT FROM AUTHOR]

The objective of this systematic review and meta-analysis is to clarify the effect of exercise therapy on the first peak knee adduction moment (KAM), as well as other biomechanical loads in patients with knee osteoarthritis (OA), and identify physical characteristics that influence differences in biomechanical load after exercise therapy. The data sources are PubMed, PEDro, and CINAHL, from study inception to May 2021. The eligibility criteria include studies evaluating the first peak (KAM), peak knee flexion moment (KFM), maximal knee joint compression force (KCF), or co-contraction during walking before and after exercise therapy in patients with knee OA. The risk of bias was independently assessed by two reviewers using PEDro and NIH scales. Among 11 RCTs and nine non-RCTs, 1119 patients with knee OA were included (average age: 63.7 years). As the results of meta-analysis, exercise therapy tended to increase the first peak KAM (SMD 0.11; 95% CI: −0.03–0.24), peak KFM (SMD 0.13; 95% CI: −0.03–0.29), and maximal KCF (SMD 0.09; 95% CI −0.05–0.22). An increased first peak KAM was significantly associated with a larger improvement in knee muscle strength and WOMAC pain. However, the quality of evidence regarding the biomechanical loads was low-to-moderate according to the GRADE approach. The improvement in pain and knee muscle strength may mediate the increase in first peak KAM, suggesting difficulty in balancing symptom relief and biomechanical load reduction. Therefore, exercise therapy may satisfy both aspects simultaneously when combined with biomechanical interventions, such as a valgus knee brace or insoles. Registration: PROSPERO (CRD42021230966) [ABSTRACT FROM AUTHOR]

Increased mechanistic insight into the pathogenesis of knee osteoarthritis (KOA) is needed to develop efficacious disease-modifying treatments. Though age-related pathogenic mechanisms are most relevant to the majority of clinically presenting KOA, the bulk of our mechanistic understanding of KOA has been derived using surgically induced posttraumatic OA (PTOA) models. Here, we took an integrated approach of meta-analysis and multi-omics data analysis to elucidate pathogenic mechanisms of age-related KOA in mice. Protein-level data were integrated with transcriptomic profiling to reveal inflammation, autophagy, and cellular senescence as primary hallmarks of age-related KOA. Importantly, the molecular profiles of cartilage aging were unique from those observed following PTOA, with less than 3% overlap between the 2 models. At the nexus of the 3 aging hallmarks, advanced glycation end product (AGE)/receptor for AGE (RAGE) emerged as the most statistically robust pathway associated with age-related KOA. This pathway was further supported by analysis of mass spectrometry data. Notably, the change in AGE-RAGE signaling over time was exclusively observed in male mice, suggesting sexual dimorphism in the pathogenesis of age-induced KOA in murine models. Collectively, these findings implicate dysregulation of AGE-RAGE signaling as a sex-dependent driver of age-related KOA. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KOA) is a leading cause of knee pain and disability due to irreversible cartilage degeneration. Previous studies have not identified modifiable risk factors for KOA. In this preliminary cross-sectional study, we aimed to test the following hypotheses: individuals with severe KOA would have a significantly lower quadriceps rate of force development (RFD) than individuals with early KOA, and the decrease in quadriceps RFD would be greater than the decrease in maximum quadriceps strength in individuals with severe KOA. The maximum isometric strength of the quadriceps was assessed in individuals with mild (Kellgren and Lawrence [K&L] grade 1–2) and severe KOA (K&L grade 3–4) using a handheld dynamometer. The RFD was analyzed at 200 ms from torque onset and normalized to the body mass and maximum voluntary isometric contraction torque. To test whether the quadriceps RFD was lowered and whether the lower in the quadriceps RFD was greater than the lower in maximum quadriceps strength in individuals with severe knee OA, the Mann–Whitney U-test and analysis of covariance were performed, respectively. The effect size (ES) based on Hedges' g with a 95% confidence interval (CI) was calculated for the quadriceps RFD and maximum quadriceps strength. Sixty-six participants were analyzed. Individuals with severe KOA displayed significantly lower quadriceps RFD (p = 0.009), the lower being greater than the lower in maximum quadriceps strength (between-group difference, ES: 0.88, -1.07 vs. 0.06, -0.22). Our results suggest that a decreased quadriceps RFD is a modifiable risk factor for progressive KOA. Our finding could help in the early detection and prevention of severe KOA. [ABSTRACT FROM AUTHOR]

Background: Postmenopausal women are at risk of fall and fracture with the physical decline. Distal radius fracture (DRF) is considered as the primary fragility fracture, and women with this fracture showed poor results in the usual Timed Up-and-Go (TUG) test, indicating a decline in balance and physical ability. The detailed physical characteristics of female DRF patients have not been extensively examined.Research Question: Is the novel laser TUG system able to detect and analyze the detailed gait characteristics in patients with DRF whose physical ability has tended to decline?Methods: In this cross-sectional case control study, the gait characteristics of 32 female patients　with DRF who had undergone surgery were evaluated at 2 weeks postoperatively with a　laser TUG system to analyze the detailed leg motion during normal TUG test.　Forty-three age- and sex-matched non-fractured women were evaluated by the laser TUG system as controls. Lifestyle and present illness were corrected at the time of TUG measurement. Detailed data during laser TUG in both groups were compared statistically, and odds ratio and thread shod of the fracture was elucidated through a　logistic regression analysis.Results: DRF patients showed slower speed and had to do more steps to complete the TUG test. Furthermore, asymmetric trajectory and significantly further distance from the marker were observed. Thirteen steps to complete the TUG test was the thread shod of DRF.Significance: Detailed gait characteristics of patients with DRF were detected by the laser TUG system. The gait decline and abnormality could be one of the reasons of consecutive fragility fracture. To prevent secondary fragility fractures, this system can be useful for screening. [ABSTRACT FROM AUTHOR]

Background: A waist-mounted sensor is an attractive option for detecting initial and end of foot contacts during gait in a clinical setting without disturbing the subject's natural gait.Research Question: To examine the current state of the field regarding waist-mounted sensor algorithms for gait event detection during locomotion in adults.Methods: A scoping review design was used to search peer-reviewed literature or conference proceedings published through October 2018 for algorithms for gait event detection. We analyzed data from the studies in a descriptive manner.Results: In total, 588 potentially relevant articles were selected, of which 14 (171 participants, mean age: 44.0 years) met the inclusion criteria. We identified 15 algorithms developed using biomechanical theories including the inverted pendulum model that represents gait during level walking. Most algorithms estimated gait events using triaxial acceleration data with an absolute error of approximately 50-100 ms in healthy adults. However, there was a large amount of inter-trial heterogeneity, and only a few algorithms were validated in patients with neurological diseases. Lower gait speed reduced the accuracy of gait event estimation.Significance: There was no algorithm that showed outstanding performance in the estimation of gait events during level walking using the waist-mounted sensor. More comparisons of all available algorithms with an established reference standard for one data-set are needed to identify the best algorithms. As patients with pathological conditions display altered trunk acceleration and slower gait speeds, the development of an algorithm that does not rely on particular signal characteristics and is robust for a wide range of gait speeds is needed before a specific algorithm can be recommended as a valid strategy for clinical practice. [ABSTRACT FROM AUTHOR]

This study aimed to examine the effect of transcutaneous electrical nerve stimulation (TENS) on stair climbing capacity in individuals with pre-radiographic to mild knee osteoarthritis (OA). This is a secondary analysis of data from a single, participant-blinded, randomized controlled trial with a pre-post design. Participants with pre-radiographic to mild knee OA (mean age, 59.1 years; 72.9% women) were randomly assigned into two groups, a TENS (n = 30) and a sham-TENS groups (n = 29). TENS or sham-TENS treatments were applied to all participants by using the prototype TENS device with pre-specified parameters. The primary outcome measures included valid and reliable functional measures for stair climbing (stair-climb test [SCT]), visual analog scale for knee pain during the SCT, and quadriceps muscle strength. TENS improved SCT time by 0.41 s (95% confidence interval [CI]: 0.07, 0.75). The time reduction in the transition phase explains the TENS therapeutic effect. Post-hoc correlation analyses revealed a non-significant but positive relationship between the pain relief effect and improved 11-step SCT time in the TENS group but not in the sham-TENS group. These results indicate that the TENS intervention may be an option for reducing the burden of early-stage knee OA. [ABSTRACT FROM AUTHOR]

Objective: The association between pain catastrophizing and ability to perform activities of daily living (ADL) requiring weight bearing, in particular stair climbing, standing from a seated position, and walking, in individuals with knee osteoarthritis (OA) is unclear. This study aimed to investigate the association between pain catastrophizing and ability to perform these ADLs by this population. Method: This cross-sectional study included individuals with knee OA (Kellgren and Lawrence grades 1–4). The ability to perform ADL was evaluated using the knee OA-related health domain measure (Japanese Knee Osteoarthritis Measure). Pain catastrophizing was evaluated using the Pain Catastrophizing Scale. The association between pain catastrophizing and ability to perform ADL, in particular stair climbing, standing from a seated position, and walking, was evaluated using the logistic regression analysis. Three types of sensitivity analysis were performed to validate the results of the logistic regression analysis. Results: A total of 151 participants were included in the final analysis. When adjusted for covariates, those with pain catastrophizing showed significantly decreased stair climbing ability (odds ratio 8.84; 95% confidence interval 1.37 to 56.92). Moreover, the results did not change even with sensitivity analysis. By contrast, when adjusted for covariates, those with pain catastrophizing did not show significantly decreased ability to stand from a seated position and walk. Conclusion: Pain catastrophizing in knee OA patients showed significantly decreased stair climbing ability. There is a need to consider the effect of pain catastrophizing in rehabilitation of knee OA patients with decreased ability to climb stairs. Key Points • Pain catastrophizing in knee OA patients showed significantly decreased stair climbing ability. • Ability to stand from a seated position and walk were not affected by pain catastrophizing. • There is a need to consider the effect of pain catastrophizing in rehabilitation of knee OA patients with decreased ability to climb stairs. [ABSTRACT FROM AUTHOR]

Introduction/objectives: This study aimed to investigate the association between hip abductor muscle strength and knee pain in patients with early-stage knee osteoarthritis (OA) while ascending and descending stairs. Method: This cross-sectional study included individuals with early-stage knee OA (Kellgren/Lawrence grades 1 or 2). Knee pain while ascending and descending stairs was evaluated using a knee OA-related health domain measure (Japanese Knee Osteoarthritis Measure). Knee extension and hip abductor muscle strength were also evaluated. The association between hip abductor muscle strength and knee pain while ascending and descending stairs was evaluated using multiple regression analysis. Results: A total of 157 participants were included in the final analysis. After the adjustment for age, sex, and knee extension strength, those with knee pain while descending stairs showed significantly decreased hip abductor muscle strength (β, − 0.09; 95% confidence interval [CI], − 0.19 to − 0.003). In contrast, after the adjustment for age, sex, and knee extension muscle strength, those with knee pain while ascending stairs did not have significantly decreased hip abductor muscle strength (β, − 0.06; 95% CI, − 0.15 to 0.02). Conclusions: Patients with early-stage knee OA and knee pain while descending stairs had significantly reduced hip abductor muscle strength. [ABSTRACT FROM AUTHOR]

Background: A growing clinical interest has been shown towards identifying knee osteoarthritis (OA) patients at earlier stages. The early detection of knee OA may allow for more effective interventions.Research Question: The aim of this study was to determine the discriminative ability of a stair-climb test (SCT) in identifying patients with early knee OA, and to determine if descending stair time during the SCT is better than ascending stair time for the identification of these patients.Methods: This study was a secondary, cross-sectional analysis of baseline data from a randomized controlled trial. Adults with moderate to severe knee pain were enrolled (n = 57; mean age 58.9 years; 71.9% women). Each participant performed an 11-step SCT (11-SCT) while wearing shoes with a pressure sensor insole. A receiver operating characteristic analysis was used to examine the discriminative power of 11-SCT for identifying early knee OA (Kellgren and Lawrence grade 1). The discriminative power was also compared between the ascending and descending 11-SCT time as evaluated by the pressure sensor.Results: The 11-SCT time in patients with early knee OA was 0.55 s longer than that in those with symptomatic non-radiographic OA. A one-second increase in the 11-SCT time was significantly associated with 1.9-fold increased odds of early knee OA being present. The 11-SCT value with the best balance of sensitivity and specificity for identifying early knee OA was 8.33 s (area under the curve: 0.711). The descending time was not significantly better than the ascending time for identifying early knee OA.Significance: This study determined the time values of an 11-SCT that may be useful for identifying early knee OA patients. These preliminary findings may serve as the foundation for future studies investigating the clinical hallmarks associated with early knee OA. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to examine the interaction effect between ambulatory physical activity (PA) and varus thrust on knee pain in individuals with knee osteoarthritis (OA). Method: Subjects (n = 207; mean age: 73.1 years, 71.5% women) in orthopedic clinics with diagnosed knee OA (Kellgren/Lawrence grade ≥ 1) were enrolled in this 12-month observational cohort study. Participants underwent gait observation for varus thrust assessment and pedometer-based ambulatory PA measurements at baseline and 12-month follow-up. Knee pain intensity was assessed using the Japanese Knee Osteoarthritis Measure pain subscale as a primary outcome measure. Multiple linear regression analyses were performed to evaluate ambulatory PA–thrust interaction on knee pain intensity. Results: Ninety-two subjects (mean age, 73.4 years; 68.5% women) completed the 12-month follow-up assessment. Baseline ambulatory PA–thrust interaction was significant (P = 0.017) in the cross-sectional analysis, adjusting for covariates, which yielded R2 = 0.310. Subgroup analysis showed that varus thrust was significantly associated with worse knee pain in subjects walking ≥ 5000 steps/day adjusting for covariates (beta: 7.94; 95% CI: 3.82, 12.1; P < 0.001) with a higher predictive ability (R2 = 0.664). In contrast, ambulatory PA–thrust interaction in the longitudinal analysis showed no significant association with knee pain changes. Conclusions: Ambulatory PA interacted with varus thrust in the association with knee pain, as coexisting high ambulatory PA and varus thrust had the strongest association with higher knee pain. Maximal pain relief effects might be achieved when both ambulatory PA and varus thrust are treated simultaneously, rather than treating each separately. [ABSTRACT FROM AUTHOR]

Abstract Clarifying proximal gait adaptations as a strategy to reduce knee joint loading and pain for individuals with knee osteoarthritis (OA) contributes to understanding the pathogenesis of multi-articular OA changes and musculoskeletal pain in other joints. We aimed to determine whether biomechanical alterations in knee OA patients during level walking is increased upper trunk lean in the frontal and sagittal planes, and subsequent alteration in external hip adduction moment (EHAM) and external hip flexion moment (EHFM). A literature search was conducted in PubMed, PEDro, CINAHL, and Cochrane CENTRAL through May 2018. Where possible, data were combined into a meta-analysis; pooled standardized mean differences (SMD) of between knee OA patients and healthy adults were calculated using a random-effect model. In total, 32 articles (2037 participants, mean age, 63.0 years) met inclusion criteria. Individuals with knee OA had significantly increased lateral trunk lean toward the ipsilateral limb (pooled SMD: 1.18; 95% CI: 0.59, 1.77) along with significantly decreased EHAM. These subjects also displayed a non-significantly increased trunk/pelvic flexion angle and EHFM. The GRADE approach judged all measures as " very low." These results may indicate that biomechanical alterations accompanying knee OA are associated with increased lateral trunk lean and ensuing alterations in EHAM. Biomechanical alterations in the sagittal plane were not evident. Biomechanical adaptations might have negative sequelae, such as secondary hip abductor muscle weakness and low back pain. Thus, investigations of negative sequelae due to proximal gait adaptations are warranted. [ABSTRACT FROM AUTHOR]

Background: Stair climbing is the task first affected in patients with knee osteoarthritis (OA); therefore, the precise measurement of time required to climb stairs is important to identify mobility limitations, particularly in the early phase of knee OA.Research Question: This study aimed to examine the test-retest reliability, measurement error, and concurrent validity of the stopwatch-based stair-climb test (SCT) in adults with pre-radiographic to mild knee OA.Methods: Fifty-nine participants (mean age, 59.1 [range, 50-69] years; 72.9% female) with Kellgren and Lawrence grade ≤2 disease underwent an 11-step SCT (11-SCT) in accordance with the Osteoarthritis Research Society International recommended method while wearing pressure sensor-mounted standard shoes that is used as a gold standard procedure. Test-retest reliability, measurement errors, and the concurrent validity of the stopwatch-based 11-SCT were evaluated.Results: The test-retest reliability of the stopwatch-based 11-SCT was excellent (intra-class correlation coefficient1,1 [ICC1,1], 0.952; 95% confidence interval [CI], 0.560 to 0.985; p <  0.001) and the minimal detectable change95 was 0.102 s. Concurrent validity was excellent (ICC2,1: 0.957; 95% CI: 0.661 to 0.986; p <  0.001).Significance: The stopwatch-based 11-SCT had high test-retest reliability and high concurrent validity, which justify its clinical use for identifying mobility limitations in individuals with pre-radiographic to mild knee OA. A difference of 0.2 s in the stopwatch-based 11-SCT time would be considered a true difference beyond a 95% measurement error. [ABSTRACT FROM AUTHOR]

To compare the efficacy and adherence rates of two parallel home exercise therapy programs—multiple exercise (training and stretching the knee and hip muscles) and control (training the quadriceps muscles)—on knee pain, physical function, and knee extension strength in community-dwelling elderly individuals with pre-radiographic knee osteoarthritis (OA). One hundred patients with medial knee pain were randomly allocated to one of two 4-week home exercise programs. Individuals with a Kellgren/Lawrence (K/L) grade 0 or 1 OA (pre-radiographic knee OA) in the medial compartment were enrolled. Primary outcomes were knee pain (visual analog scale), self-reported physical function (Japanese Knee Osteoarthritis Measure [JKOM]), and isometric maximum muscle strength of the knee extensor measured using a hand-held dynamometer. A total of 52 patients (28 [53.8%] in the multiple exercise group, 24 [46.2%] in the control group) completed the trial. The JKOM activities of daily living and general health conditions outcomes improved significantly in the multiple exercise group compared to the control group (JKOM activities of daily living, beta = − 0.76; 95% confidence interval [CI], − 1.39 to − 0.13; p = 0.01; JKOM general health conditions, beta = − 0.25; 95% CI, − 0.48 to − 0.01; p = 0.03). The home exercise compliance rates of the multiple exercise and control groups were 96.6 and 100%, respectively. When targeting pre-radiographic knee OA in community-dwelling elderly, it is important to implement home exercise programs that aim to improve muscle strength and joint flexibility rather than knee extension muscle power only. [ABSTRACT FROM AUTHOR]

This study aimed to develop a self-questionnaire index relevant to lower limb functional assessment reflecting clinical symptoms and activity restrictions associated with activities of daily living (ADL) for patients with knee osteoarthritis. This cross-sectional study enrolled patients with knee osteoarthritis (Kellgren/Lawrence grade ≥ 1). Participants evaluated clinical symptoms and activity restrictions using self-reported questionnaires. Radiographic evaluation, knee joint range of motion (ROM), and lower limb muscle strength were assessed. Associations between clinical symptoms, activity restrictions, and knee and hip joint function were evaluated using multiple and logistic regression analysis. Overall, 142 participants were included in the final analysis. Patients with knee pain while rising from a chair had lower knee and hip extension strength (knee extension β = − 0.28; 95% confidence interval (CI), − 0.41 to − 0.14; P < 0.0001; hip extension β = − 0.26; 95% CI, − 0.42 to − 0.08; P = 0.0034), and restricted knee extension ROM (odds ratio [OR] = 2.17; 95% CI, 1.02-4.63; P = 0.041). Patients with knee pain during stair climbing, turning or who were unable to stand on one leg without external support had reduced hip abduction muscle strength (β = − 0.17; 95% CI, − 0.27 to − 0.07; P = 0.0008). Patients with knee pain while rising from a chair or stepping showed more severe knee joint degeneration on radiographic evaluation (OR = 3.26; 95% CI, 1.11-10.91; P = 0.03). The self-questionnaire index reflected clinical symptoms and activity restrictions associated with ADL and was significantly associated with lower limb function in individuals with knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Background: Stair climbing was suggested to be the first affected task in individuals with knee osteoarthritis (OA).Research Question: This review aimed to identify consistent kinematic, kinetic, and spatiotemporal alterations of stair climbing exhibited by individuals with knee OA.Methods: A literature search published until September 2017 was conducted in PubMed, PEDro, CINAHL, and Cochrane CENTRAL. Reviewer extracted data in accordance with the Cochrane Handbook. Where possible, data were combined into a meta-analysis; the pooled standardized mean differences between individuals with knee OA and healthy adults were calculated using the random-effect model.Results: In total, 585 potentially relevant articles were selected, of which 12 (695 participants, mean age: 58.4 years) met the inclusion criteria. Meta-analysis revealed that kinematic and kinetic alterations during stair climbing associated with knee OA were lower external knee flexion moment in conjunction with a larger trunk/hip flexion angles and smaller knee flexion/ankle dorsiflexion angles. Individuals with knee OA showed a delayed quadriceps activation during stair ascent. A lack of evidence was detected for alterations in external knee adduction moment during stair climbing. Effect estimate in each meta-analysis was judged "very low" on the GRADE approach.Significance: No strong conclusion can be drawn because of the low quality of evidence; however, individuals with knee OA may exhibit altered kinematics and kinetics changes in sagittal plane during stair climbing, and have delayed quadriceps muscle activity. Further studies with adequate adjustment for confounders are warranted to facilitate clinical hallmarks of the knee OA, particularly in early stages of the disease. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine whether kilohertz-frequency alternating current (KFAC) is superior to low-frequency pulsed current (PC) in increasing muscle-evoked torque and lessening discomfort. Data sources: The electronic databases PubMed, PEDro, CINAHL, and CENTRAL were searched for related articles, published before August 2017. Furthermore, citation search was performed on the original record using Web of Science. Review methods: Randomized controlled trials, quasi-experimental studies, and within-subject repeated studies evaluating and comparing KFAC and PC treatments were included. The pooled standardized mean differences (SMDs) of KFAC and PC treatments, with 95% confidence intervals (CIs), were calculated using the random effects model. Results: In total, 1148 potentially relevant articles were selected, of which 14 articles with within-subject repeated designs (271 participants, mean age: 26.4 years) met the inclusion criteria. KFAC did not significantly increase muscle-evoked torque, compared to PC (pooled SMD: -0.25; 95% CI: -0.53, 0.06; P = 0.120). KFAC had comparable discomfort compared to that experienced using PC (pooled SMD: -0.06; 95% CI: -0.50, 0.38; P = 0.800). These estimates of the effects had a high risk of bias, as assessed using the Downs and Black scale, and were highly heterogeneous studies. Conclusions: This meta-analysis does not establish that KFAC is superior to PC in increasing muscle-evoked torque and lessening discomfort level. However, no strong conclusion could be drawn because of a high risk of bias and a large amount of heterogeneity. High quality studies comparing the efficacy between PC and KFAC treatments with consideration of potential confounders is warranted to facilitate the development of effective treatment. [ABSTRACT FROM AUTHOR]

The foot is speculated to play a role in knee joint kinematics. This exploratory cross-sectional study examined the association between static foot posture and the presence of varus thrust visualized during gait in patients with medial knee osteoarthritis (OA). Patients (n = 88 patients and 134 knees; age, 61-91 years; 68.2% female) with Kellgren/Lawrence (K/L) grade ≥1 in the medial compartment were included in this study and underwent gait observation for varus thrust. These patients' three-dimensional static foot posture while standing was evaluated and their tibiofemoral joint K/L grades and anatomical axis angles were also assessed as covariates. Knees with varus thrust (22 knees, 16.4%) on average had a 4° more inverted calcaneus relative to the floor than those without varus thrust (P < 0.001). A logistic regression analysis showed that an increased calcaneus inversion angle was significantly associated with higher odds of the presence of varus thrust with adjustments for age, sex, body mass index, K/L grade, and anatomical axis angle. The other predictors, such as navicular height, navicular height/foot length, and rearfoot angle relative to the lower leg, were not significantly associated with varus thrust. These results suggest that patients with varus thrust had a different static rearfoot posture as compared with those without varus thrust, a finding that may indicate an important role of static rearfoot posture in the pathogenesis of varus thrust. Furthermore, investigating the potential influence of foot posture on the efficacy of biomechanical interventions, such as lateral wedge insole use, on varus thrust would be of particular interest in the further studies. [ABSTRACT FROM AUTHOR]

ABSTRACT This cross-sectional study examined the relationship of flat feet with knee pain, disability, and physical performance in patients with knee osteoarthritis (OA). Orthopedic clinic participants ( n = 95; age 61-91 years; 68.4% women) with Kellgren-Lawrence (K/L) grade ≥1 in the medial compartment underwent evaluation of navicular height and foot length for flat feet. Knee pain intensity, disability, and physical performance were evaluated using the Japanese Knee Osteoarthritis Measure, 10-m walk, timed up and go, and five-repetition chair stand tests. Of the 95 enrolled patients, 24 (25.3%) had bilateral flat feet, and significantly higher knee pain compared to patients with no flat feet (11.3 ± 8.23 points vs. 6.58 ± 6.37 points; p = 0.043). A ordinal logistic regression analysis showed that bilateral flat feet were significantly associated with increased knee pain (proportional odds ratio: 5.48, 95% confidence interval: 1.96, 15.3; p = 0.001) compared with no flat feet, adjusted for age, sex, body mass index, and tibiofemoral joint K/L grade, which is consistent across various different cutoffs of the definition of flat feet. Physical performance was similar between patients with and without bilateral flat feet. The presence of unilateral flat feet was not significantly associated with any outcome measures. These findings indicate that bilateral, but not unilateral, flat feet are associated with worse knee pain. A prospective study investigating a causal relationship between bilateral flat feet posture and knee pain as well as disability would be of particular interest to verify the potential adverse effect of altered foot posture. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2490-2498, 2017. [ABSTRACT FROM AUTHOR]

This cross-sectional study investigated (i) the association of varus thrust during gait with the presence of patellofemoral osteoarthritis (PFOA) in patients with medial knee osteoarthritis (OA) and (ii) patellar alignment in the knees with varus thrust. Participants from orthopedic clinics (n=171; mean age, 73.4 years; 71.9% female) diagnosed with radiographic medial knee OA (Kellgren/Lawrence [K/L] grade ≥1) were included in this study, and underwent gait observation for varus thrust assessment using 2D video analysis. A radiographic skyline view was used to assess the presence of medial PFOA using the grading system from the Osteoarthritis Research Society International Atlas. The tibiofemoral joint K/L grade, patellar alignment (i.e., lateral shift and tilting angle), and knee pain intensity were also evaluated as covariates. Thirty-two (18.7%) of 171 patients exhibited varus thrust and they presented significantly higher knee pain (46.0±3.04mm vs. 32.4±2.73mm; P=0.024), a lower patellar tilting angle (P=0.024), and a higher prevalence of PFOA compared with those without varus thrust. A logistic regression analysis with adjustment of covariates showed that varus thrust was significantly associated with higher odds of the presence of mixed and medial PFOA, and trended to significantly associate with any PFOA, including lateral PFOA. This indicates that varus thrust was associated with PFOA in a compartment-nonspecific manner in patients with medial knee OA. Varus thrust may represent a clinical disease feature of more advanced and multicompartmental disease. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether knee pain during various activities of daily living (ADLs) is associated with physical activity in patients with early and severe knee osteoarthritis (OA). We hypothesized that the painful ADLs associated with decreased physical activity differ according to disease severity. This cross-sectional study enrolled 270 patients with medial knee OA, assigned to either the early (Kellgren Lawrence [K/L] grade 1-2) or the severe group (K/L grade 3-4). Physical activity was assessed using a pedometer. Knee pain during six ADLs (waking up in the morning, walking on a flat surface, ascending stairs, etc.) was evaluated using a questionnaire. We performed multiple regression and quantile regression analysis to investigate whether knee pain during each ADL was associated with physical activity. In the early group, the more knee pain they experienced while ascending stairs, the lower their physical activity was (75th regression coefficient = −1033.70, P = 0.018). In the severe group, the more knee pain they experienced while walking on a flat surface or bending to the floor or standing up, the lower their physical activity was (unstandardized coefficients = −1850.87, P = 0.026; unstandardized coefficients = −2640.35, P = 0.010). Knee pain while ascending stairs and while walking on a flat surface or bending to the floor or standing up was a probable limiting factor for physical activity in early and severe knee OA, respectively. These findings suggested that a reduction in task-specific knee pain according to disease severity could improve physical activity levels. [ABSTRACT FROM AUTHOR]

Objective. To investigate the association between knee pain during gait and 4 clinical phenotypes based on static varus alignment and varus thrust in patients with medial knee osteoarthritis (OA). Methods. Patients in an orthopedic clinic (n5266) diagnosed as having knee OA (Kellgren/Lawrence [K/L] grade ≥1) were divided into 4 phenotype groups according to the presence or absence of static varus alignment and varus thrust (dynamic varus): no varus (n5173), dynamic varus (n517), static varus (n550), and static varus1dynamic varus (n526).The knee range of motion, spatiotemporal gait parameters, visual analog scale scores for knee pain, and scores on the Japanese Knee Osteoarthritis Measure were used to assess clinical outcomes. Multiple logistic regression analyses identified the relationship between knee pain during gait and the 4 phenotypes, adjusted for possible risk factors, including age, sex, body mass index, K/L grade, and gait velocity. Results. Multiple logistic regression analysis showed that varus thrust without varus alignment was associated with knee pain during gait (odds ratio [OR] 3.30, 95% confidence interval [95% CI] 1.08-12.4), and that varus thrust combined with varus alignment was strongly associated with knee pain during gait (OR 17.1, 95% CI 3.19- 320.0). Sensitivity analyses applying alternative cutoff values for defining static varus alignment showed comparable results. Conclusion. Varus thrust with or without static varus alignment was associated with the occurrence of knee pain during gait. Tailored interventions based on individual malalignment phenotypes may improve clinical outcomes in patients with knee OA. [ABSTRACT FROM AUTHOR]

Objective: Despite the increased use of platelet-rich plasma in the treatment of osteoarthritis, whether and how age of the platelet-rich plasma donor affects therapeutic efficacy is unclear. Design: In vitro, male osteoarthritic human chondrocytes were treated with platelet-rich plasma from young (18–35 yrs) or old (≥65 yrs) donors, and the chondrogenic profile was evaluated using immunofluorescent staining for two markers of chondrogenicity, type II collagen and SOX-9. In vivo, we used a within-subjects design to compare Osteoarthritis Research Society International scores in aged mouse knee joints injected with platelet-rich plasma from young or old individuals. Results: In vitro experiments revealed that platelet-rich plasma from young donors induced a more youthful chondrocyte phenotype, as evidenced by increased type II collagen (P = 0.033) and SOX-9 expression (P = 0.022). This benefit, however, was significantly blunted when cells were cultured with platelet-rich plasma from aged donors. Accordingly, in vivo studies revealed that animals treated with platelet-rich plasma from young donors displayed a significantly improved cartilage integrity when compared with knees injected with platelet-rich plasma from aged donors (P = 0.019). Conclusions: Injection of platelet-rich plasma from a young individual induced a regenerative effect in aged cells and mice, whereas platelet-rich plasma from aged individuals showed no improvement in chondrocyte health or cartilage integrity. [ABSTRACT FROM AUTHOR]

Early detection of knee osteoarthritis (KOA) can improve treatment outcomes and prevent its progression. The aim of this systematic review was to identify the functional changes in early KOA. Electronic journal databases and platforms, including PubMed, the Physiotherapy Evidence Database, the Cochrane Central Register of Controlled Trials, and Scopus were searched. The inclusion criteria were as follows: (1) studies comparing patients with early KOA with an age-matched control group and (2) studies with objectively measured functional changes as outcomes. Studies that included individuals with Kellgren and Lawrence (K/L) grades > 2- were excluded. A random-effects model was constructed to calculate pooled standardized mean differences (SMDs). A total of nine articles were included in this systematic review. Seven studies used classification criteria to define early KOA, including knee pain; a K/L grade of 0, 1, or 2- (osteophytes only) for the medial compartment; and the presence of two out of four MRI criteria. The remaining two studies included K/L grade 1 confirmed by radiography. Early KOA participants had a significantly longer timed up-and-go test (TUG) time (pooled SMD: 0.57; 95% confidence interval: 0.15, 0.98). The two groups had similar knee extension muscle strength at 90° knee flexion. The quality of evidence for each measured outcome was "very low." In this review, longer TUG was identified as a functional manifestation of early KOA. Further studies involving functional assessments are needed to develop a screening method to detect early KOA. Key Points • There is a need for diagnostic criteria that include functional changes in patients with early knee osteoarthritis, since radiographic facilities are not available everywhere. • In this review, a long timed up-and-go test time was identified as a functional manifestation of early knee osteoarthritis. • If the findings of this study can be replicated, measurement of TUG may allow for earlier detection of knee osteoarthritis outside the hospital and in routine clinical practice without the use of MRI or X-rays. [ABSTRACT FROM AUTHOR]

Study Design: Cross-sectional study.Objective: This study aimed to objectively evaluate spastic gait and reveal its novel characteristics via analysis of gait in patients with cervical myelopathy (CM) using the Timed Up and Go (TUG) test with a laser range sensor.Summary Of Background Data: Among patients with CM, spastic gait is a common diagnostic symptom; thus, objective assessments of spastic gait would be useful for the diagnosis of CM and recognition of disease status. Although spastic gait has been objectively evaluated in previous studies, the methods employed in those studies are not suitable for clinical settings.Methods: In total, 37 and 24 participants were recruited for a control group and CM group, respectively. CM was diagnosed by spine surgeons. We developed a laser TUG test, in which the position and velocity of both the legs were captured. The parameter values for both groups were statistically compared, and odds ratios were calculated using logistic regression analyses.Results: The total TUG-test time, time to stand up, time to first step, number of steps, and trajectory error for the CM group were significantly higher than those for the control group, whereas the average velocity and average stride length for the CM group were significantly lower than those for the control group. There was a significant independent association between the total TUG-test time and CM. The optimal cutoff point of the total test time for CM risk was approximately 9 seconds.Conclusion: Through the use of the laser TUG test, we were able to identify characteristics of spastic gait, which leads to difficulty in standing and taking the first step, wobbling while walking, and an increased risk of falling. We found that the risk of CM was higher if the individual took longer than 9 seconds to complete the TUG test.Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

Laser range sensor-based timed up and go (laser-TUG) test can evaluate performance in TUG subtasks (sit-to-walk [STW], walking a short distance, and turning). This study aimed to test the hypothesis that weaker hip abductor muscle strength is more significantly associated with slowed turning speed than with the other TUG subtasks (STW and straight walking) after controlling for quadriceps muscle strength in patients with knee osteoarthritis (OA). Community-dwelling participants with knee OA (Kellgren and Lawrence [K&L] grade ≥ 1; mean age, 68.6 years; 70.3% women) underwent laser-TUG. Spatiotemporal gait parameters in TUG and the TUG subtasks were evaluated as outcome measures. The isometric muscle strength of the hip abductor and quadriceps was measured using a hand-held dynamometer. Multiple linear regression analysis was performed to examine the relationship between muscle strength as an independent variable and spatiotemporal parameters as dependent variables. The relative importance of hip abductor muscle strength was determined using the percentages of unique variance. Participants with weaker hip abductor muscle strength demonstrated 0.094 m/s slower turning speed after adjustment for covariates including quadriceps muscle strength. The unique variance explained by hip abductor muscle strength in turning speed was 2.1%. However, no significant relationships were confirmed between weak hip abductor muscle strength and the time to perform TUG and the straight walking (forward and return) phase. These findings indicate that turning motion may be more sensitive to aggravated hip abductor muscle weakness and may show better response to hip muscle strengthening exercises. Longitudinal studies are warranted to elucidate this issue. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (OA) progression is associated with an increase in peak external knee flexion torque (EKFT) during gait. However, the difference in the peak EKFT between individuals with knee OA and age-matched subjects was unclear. Therefore, to understand the kinematics, kinetics, and electromyogram characteristics in individuals with knee OA, we conducted a systematic review and meta-analysis of sagittal plane-dominant sit-to-stand (STS) motion. PubMed, PEDro, CINAHL, and Cochrane CENTRAL were used. Fourteen articles (knee-OA group: n = 323, mean age = 65.0 years, mean weight = 79.2 kg; control group: n = 224, mean age = 64.4 years, mean weight = 70.4 kg) were included, and the pooled standardized mean differences (SMDs) were calculated using a random-effects model. Meta-analysis showed that individuals with knee OA present significantly lower peak EKFT (pooled SMD: −1.62; 95% confidence interval [CI]: −2.36 to −0.88), significantly large trunk flexion angle (pooled SMD: 1.04; 95% CI: 0.69 to 1.39), and no significantly lower peak external knee adduction torque despite the significantly larger lateral-lean angle to the less affected side (pooled SMD: 1.04; 95% CI: 0.69 to 1.39). The quality of evidence for all outcomes was very low. The descriptive synthesis indicates that STS motion in individuals with knee OA might be an unsuitable motion strategy for knee muscle activity, force utilization from multiple joints to the knee joint, and their influence on knee joint cartilage, despite their lower peak EKFT. This information can help to better understand movement strategies and to optimize treatment approaches for individuals with knee OA. [ABSTRACT FROM AUTHOR]

Background: While abnormal rearfoot posture and its relationship to patellofemoral (PF) pain has been thoroughly discussed in the literature, its relationship to patellofemoral osteoarthritis (PFOA) has not been determined. This study aimed to examine whether rearfoot posture is associated with a higher prevalence of radiographic PFOA in a compartment-specific manner in patients with medial tibiofemoral osteoarthritis (TFOA). Methods: Participants from orthopedic clinics (n = 68, age 56–90 years, 75.0% female), diagnosed with radiographic medial TFOA (Kellgren/Lawrence [K/L] grade ≥ 2) were included in this study. The presence of PFOA and static rearfoot posture were evaluated using a radiographic skyline view and a footprint automatic measurement apparatus, respectively. The relationship between rearfoot posture and PFOA was examined using analysis of covariance and propensity score-adjusted logistic regression analysis. Results: On average, patients with coexisting PFOA and medial TFOA (n = 39) had an inverted calcaneus 3.1° greater than those with isolated medial TFOA (n = 29). Increased calcaneus inverted angle was significantly associated with a higher probability of the presence of medial PFOA (odds ratio: 1.180, 95% confidence interval: [1.005, 1.439]; p = 0.043). Calcaneus inverted angle was not associated with higher odds of lateral PFOA presence based on the adjusted values. Conclusions: The presence of an inverted rearfoot was associated with PFOA. Although these findings do not clearly indicate a biomechanical link between rearfoot posture and PFOA, this study shed light on the potential relationship between altered rearfoot posture and PFOA, as can be seen between rearfoot abnormality and PF pain. [ABSTRACT FROM AUTHOR]

Study Design: Cross-sectional study using radiological measurements and longitudinal data analysis.Objective: We aim to explore hip/pelvic geometry on anteroposterior radiographs and examine if such parameters are associated with clinical symptoms.Summary Of Background Data: Pregnancy-related sacroiliac joint pain is a common disease and is responsible to the disability of daily activities. The etiology is likely to be correlated with the biomechanical factors which are determined by trunk load and hip/pelvic geometry. Previous studies have already found the association between symptoms and weight increase during pregnancy. However, the relationship between bony anatomy and pregnancy-related sacroiliac joint pain remains unknown.Methods: In total, 72 women were included in the final analysis. In pregnant women with self-reported sacroiliac joint pain, pain scores at 12, 24, 30, and 36 weeks of pregnancy were recorded and included in a mixed-effect linear regression model as dependent variables. The radiological measurements were included as independent variables. Furthermore, to investigate the relationship between hip/pelvic geometry and the activity-specific nociceptive phenomenon, the radiological measurements between patients with and without activity-induced pain were compared using a binominal logistic regression model.Results: The relative bilateral is chial tuberosity distance (betta coefficient: 0.078; P = 0.015) and the relative bilateral femoral head length (betta coefficient: 0.011; P = 0.028) showed significant interactions with the slope of pain scores. Moreover, women whose pain exacerbate during prolonged walking had a higher odds in hip/pelvic geometry of the bilateral ischial tuberosity distance (odds ratio [OR]: 1.12; P = 0.050) and the bilateral femoral head length (OR: 1.16; P = 0.076) with approximately significant P-value.Conclusion: These data indicate hip/pelvic anatomical variations are associated with the degree of pain increasing and the activity-specific pain during pregnancy, which may help to have further understanding on the biomechanical factor in developing pregnancy-related sacroiliac joint pain.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Background: The differences of mechanical and histological properties between cartilage covered by menisci and uncovered by menisci may contribute to the osteoarthritis after meniscectomy and these differences are not fully understood. The purpose of this study is to investigate potential differences in the mechanical and histological properties, and in particular the collagen architecture, of the superficial cartilage layer and subchondral bone between regions covered and uncovered by menisci using immature knee.Methods: Osteochondral plugs were obtained from porcine tibial cartilage that was either covered or uncovered by menisci. Investigation of the thickness, mechanical properties, histology, and water content of the cartilage as well as micro-computed tomography analysis of the subchondral bone was performed to compare these regions. Collagen architecture was also assessed by using scanning electron microscopy.Results: Compared to the cartilage uncovered by menisci, that covered by menisci was thinner and showed a higher deformity to compression loading and higher water content. In the superficial layer of cartilage in the uncovered regions, collagen fibers showed high density, whereas they showed low density in covered regions. Furthermore, subchondral bone architecture varied between the 2 regions, and showed low bone density in covered regions.Conclusions: Cartilage covered by menisci differed from that uncovered in both its mechanical and histological properties, especially with regards to the density of the superficial collagen layer. These regional differences may be related to local mechanical environment in normal condition and indicate that cartilage covered by menisci is tightly guarded by menisci from extreme mechanical loading. Our results indicate that immature cartilage degeneration and subchondral microfracture may occur easily to extreme direct mechanical loading in covered region after meniscectomy. [ABSTRACT FROM AUTHOR]

ABSTRACT To date, there have been few studies on how temperature affects the phenotype and metabolism of human chondrocytes. Thus, the purpose of this study was to elucidate the effects of culture temperature on chondrocyte redifferentiation and extracellular matrix (ECM) formation using dedifferentiated mature human chondrocytes in vitro. Dedifferentiated chondrocytes were cultured in a pellet culture system for up to 21 days. The pellets were randomly divided into three groups with different culture temperature (32, 37, and 41°C). Chondrocyte redifferentiation and ECM formation were evaluated by wet weight, messenger ribonucleic acid (mRNA), histological, and biochemical analyses. The results showed that the wet weight and the mRNA expressions of collagen type II A1 and cartilage oligomeric matrix protein at 37°C were higher than the corresponding values at 32°C. The histological and biochemical analyses revealed that the syntheses of type II collagen and proteoglycan were promoted at 37°C compared to those at 32°C, whereas they were considerably inhibited at 41°C. In conclusion, the results obtained herein indicated that temperature affects chondrocyte redifferentiation and ECM formation, and modulation of temperature might thus represent an advantageous means to regulate the phenotype and biosynthetic activity of chondrocytes. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:633-639, 2015. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the influence of temperature on the ability of the chondrocytes to produce extracellular matrix (ECM). Materials and methods: Articular chondrocytes were isolated from porcine knee joints. The chondrocytes were cultured at three different temperatures: 32 °C, 37 °C, and 41 °C. The ability to produce ECM was assessed by gene expression analysis, histological, and biochemical evaluation in a pellet culture system. Results: Wet weight of the pellets generated after 21 days, was significantly heavier when cultured at lower temperatures. Picrosirius red staining, employed to evaluate collagen production, was higher at lower temperatures, and safranin-O staining, used to evaluate sulphated glycosaminoglycan (GAG), was lower at 32 °C than at 37 °C and 41 °C. Collagen type IIA1 mRNA expression was markedly up-regulated at 41 °C. However, picrosirius red staining was inhibited at 41 °C. GAG and DNA content were measured by 1,9-dimethylmethylene blue (DMMB) assay and PicoGreen® assay, respectively. The GAG content per pellet was significantly low at 41 °C compared to that at 32 °C and 37 °C. The DNA content per pellet was larger at lower temperatures. The GAG content normalised with the DNA content per pellet was significantly lower at 32 °C compared to that at 37 °C and 41 °C. Conclusion: Our results suggest that a culture temperature of approximately 41 °C inhibits ECM production by decreasing DNA content and perhaps by collagen misfolding. Taken together, the optimum temperature for ECM production in articular chondrocytes may be between 32 °C and 37 °C. [ABSTRACT FROM AUTHOR]

Background: Hallux valgus is the most common forefoot deformity and affects the transverse arch structure and its force loading patterns. This study aims to clarify the differences in the transverse arch structure and the force under the metatarsal heads individually, between normal feet and hallux valgus feet, and between hallux valgus feet with pain and without pain. We further test the association between the parameters of the transverse arch and hallux valgus angle and between the parameters and pain in hallux valgus. Methods: Women's feet (105 feet) were divided into normal group (NORM) and hallux valgus group (HVG); and further into subgroups: hallux valgus without pain (HV Pain (-)) and hallux valgus with pain (HV Pain (+)). Transverse arch height and metatarsal heads height were measured using weight-bearing ultrasound imaging. Force under the metatarsal heads was measured using force sensors attached directly on the skin surface of the metatarsal heads. The measurements were taken in three loading positions: sitting, quiet standing and 90% weight shift on the tested foot. Differences between the groups were compared using Student t-test and Wilcoxon Exact test. Multivariate logistic analysis with adjustment for physical characteristics was also conducted. Results: Transverse arch height was significantly higher in HVG than in NORM in all positions; there were no significant differences between HV Pain (+) and HV pain (-). Lateral sesamoid was significantly higher in HVG and HV Pain (+) than in NORM and HV Pain (-) respectively when bearing 90% of the body weight unilaterally. There was a trend of higher forces under the medial forefoot without significant difference. Transverse arch height and lateral sesamoid height were associated with the hallux valgus angle, while lateral sesamoid height was associated with forefoot pain in hallux valgus deformity. Conclusions: This study shows the differences in the transverse arch structure between normal feet and feet with hallux valgus, and between hallux valgus feet with and without pain. This finding is noteworthy when considering future treatments of painful feet, notably the height of the lateral sesamoid which seems to play a role in forefoot pain. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to clarify the effects of periodic mild heat stimuli on extracellular matrix (ECM) synthesis of adult human chondrocytes in 3-dimensional pellet culture. Results: Human articular chondrocytes were subjected to pellet culture at 37 °C for 3 days. Thereafter, the pellets were divided into three groups: 32 °C group which was cultured at 32 °C without heat stimuli, 32 °C + Heat group which was cultured at 32 °C and applied periodic heat stimuli, 37 °C group which was cultured at 37 °C. Heat stimuli were given by transferring the pellets into a CO2 incubator set at 41 °C for 20 min/day, 6 times/week. ECM synthesis ability was evaluated by analyzing the mRNA expressions. Additionally, the collagen and proteoglycan content in the pellet was quantified. DNA content was also measured for estimating the cell amount. We found that there were no significant differences in the mRNA expression of COL2A1, COL1A1, and ACAN between the 32 °C group and 32 °C + Heat group. However, the collagen content per cell and DNA content were significantly lower in the 32 °C + Heat group compared to other groups. Our results indicate that periodic mild heat stimuli may diminish ECM synthesis due to inhibition of collagen production and loss of cells. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine the effects of the lower-body positive pressure on surface blood flow during standing still and treadmill walking to explore cardiovascular safety for application to rehabilitation treatment. Thirteen healthy volunteers participated in the experiment and surface blood flows were measured in the forehead, thigh, calf, and the top of the foot during standing still and walking under various pressure conditions (0 kPa, 5 kPa, and 6.7 kPa). Results: Lower-body positive pressure decreased the blood flow in the forehead and the thigh during walking (p <.05 for each), whereas an increasing trend in blood flow was observed during standing still (p <.05). Furthermore, in the forehead and thigh, the extent of blood flow increase at the onset of walking was found to decrease in accordance with the applied pressure (p <.01 for each). These findings suggest that during walking, lower-body positive pressure modulates the blood flow, which implies safeness of this novel apparatus for use during orthopedic rehabilitation treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify ultrasound parameters reflecting subchondral porosity (Po), subchondral plate thickness (Tpl) and bone volume fraction at the trabecular bone region (BV/TVTb). Sixteen osteoarthritic human lateral femoral condyles were evaluated ex vivo using a 15-MHz pulsed-echo ultrasound 3-D scanning system. The cartilage-subchondral bone (C-B) surface region (layer 1) and inner subchondral bone region (layer 2) were analyzed; we newly introduced entropy (ENT) and correlation (COR) of ultrasound texture parameters of the parallel (x) or perpendicular (z) direction to the C-B interface for this analysis. Po, Tpl and BV/TVTb were evaluated as reference measurements using micro-computed tomography. ENTL1x (ENT of layer 1, x-direction) and ENTL1z were significantly correlated with Po (both r values = 0.58), CORL2x with Tpl (r = -0.73) and CORL2z with BV/TVTb (r = -0.66). These are efficient indicators of the characteristics of osteoarthritis-related subchondral bone; the other texture parameters were not significant. [ABSTRACT FROM AUTHOR]

Background: Low back pain (LBP) during pregnancy might be strongly related to posture and movements of the body, and its management is a clinically important issue. The purpose of this study was to investigate the activities related to LBP during pregnancy.Methods: Participants included 275 women before 12 weeks of pregnancy. The women were evaluated at 12, 24, 30, and 36 weeks of pregnancy. The intensity of LBP was assessed using the Numerical Rating Scale (NRS). Movements related to LBP were investigated by free descriptive answers. Descriptive statistics were used to compile the movements that pregnant women thought induced LBP at each evaluation. Subsequently, a linear regression analysis was performed to evaluate the degree of association of certain movements with LBP using the data of participants who had LBP. The intensity of LBP (NRS score) was specified as the dependent variable, the movements that were related to pain were specified as the independent variables at the analysis. A significance threshold was set at 0.05.Results: The final sample used in the analyses was 254, 249, 258, and 245 women at 12, 24, 30, and 36 weeks of pregnancy, respectively. There were 16 kinds of movements that induced LBP and all of them were daily activities rather than special movements that require extra task or effort. As pregnancy progressed, less number of participants attributed pain to a specific movement. At all evaluations, movements, especially sitting up, standing up from a chair, and tossing and turning were thought to be related to LBP. Furthermore, standing up from a chair and tossing and turning were significantly related to LBP throughout the pregnancy. In contrast, lying down and sitting up were significantly related to LBP but the relationship did not continue till late pregnancy.Conclusions: Daily routine activity is related to LBP during pregnancy. These results suggest that recommendations for pregnant women about basic physical movements, such as ways of standing up that reduce the load on the body might be useful in the management of LBP. [ABSTRACT FROM AUTHOR]

Background: To examine the association of radiographic frontal plane knee alignment with three-dimensional foot posture in patients with medial knee osteoarthritis (OA).Methods: Participants in orthopedic clinics with Kellgren/Lawrence (K/L) grade ≥1 (88 patients and 88 knees; age, 61-91 years; 65.9% female) were enrolled. An anteroposterior radiographic view was used to assess the anatomical axis angle (AAA) after subtracting a sex-specific correction factor. The three-dimensional foot posture was also evaluated.Results: Multiple regression analyses showed that increased corrected AAA (i.e., valgus direction) was independently associated with a decrease in the hallux valgus angle (regression coefficient: -0.40 per degree, 95% confidence interval [CI]: -0.72, -0.09; P = 0.013) and increase in the pronation angle of the calcaneus relative to floor (regression coefficient: 0.33 per degree, 95% CI: 0.10, 0.56; P = 0.005) adjusted for age, sex, and body mass index. The relationship between the corrected AAA and hallux valgus angle strengthened (regression coefficient: -0.60 per degree, 95% CI: -1.08, -0.13; P = 0.014) in varus-aligned knees examined separately (63 knees). The other foot postures (navicular height, navicular height/foot length, and rearfoot angle) were not significantly associated with corrected AAA.Conclusions: Radiographic frontal plane knee alignment was associated with hallux valgus angle and calcaneus angle relative to the floor in patients with medial knee OA, particularly in varus-aligned knees. These results indicate a connection between altered frontal knee alignment and foot posture, which may be helpful in understanding the pathogenesis of altered foot posture observed in patients with knee OA. [ABSTRACT FROM AUTHOR]

Background: This 1-year prospective cohort study aimed to compare the changes in clinical symptoms and functional disability between patients with coexisting patellofemoral (PF) and tibiofemoral (TF) osteoarthritis (OA) and those with isolated TFOA.Methods: Seventy-two patients with medial knee OA were enrolled. Knee pain and functional disability were assessed at baseline and at 1-year follow-up using the Japanese Knee Osteoarthritis Measure (JKOM) and a visual analog scale (VAS). We performed two-way analysis of covariance for the clinical outcome variables to examine, time (baseline and follow-up), group (coexisting PFOA and isolated TFOA), and time-group interaction effects. Furthermore, we conducted post-hoc exploratory analysis to address the possibility that dividing patients according to location of PFOA (i.e., isolated lateral, isolated medial, and mixed [bilateral]) may identify a distinct subgroup with different changes in clinical outcomes at 1-year follow-up.Results: We detected group effects only in scores of the JKOM pain subscale (P = 0.012) and VAS (P = 0.033), adjusted for age, sex, and body mass index. Patients with coexisting PFOA have stable moderate level knee pain and functional disability throughout the year which is significantly worse than that in those with isolated TFOA. Post-hoc subgroup analysis demonstrated that change of knee pain likely varied with location of PFOA. Patients with isolated lateral PFOA had mild/moderate level knee pain, and their VAS scores were likely to improve, whereas those with mixed PFOA exhibited stable to worsening moderate/severe knee pain.Conclusions: Although we did not detect differences in changes in clinical symptoms and functional disability between patients with coexisting PFOA and those with isolated TFOA, our findings indicate that patients with coexisting PFOA had worse clinical symptoms and functional disability than those with isolated TFOA. The results of the exploratory analysis suggested that patients with coexisting PFOA might have heterogeneous clinical outcomes, and presence of mixed PFOA might be an indicator of severe clinical knee OA. [ABSTRACT FROM AUTHOR]

We investigated the effect of low-intensity pulsed ultrasound (LIPUS) treatment combined with mesenchymal stromal cell (MSC) injection for cartilage repair and subchondral bone reconstitution for treatment of osteochondral defects. An osteochondral defect was created on both femur grooves of Wistar rats. Four weeks later, bone marrow MSCs were injected into the right knee joint. The rats were divided into two intervention groups: without or with LIPUS irradiation. Cartilage repair was evaluated histologically based on the Wakitani cartilage repair score. Subchondral bone reconstitution was evaluated as bone volume (BV)/tissue volume (TV) by micro-computed tomography analysis. MSC injection improved the cartilage repair score, and LIPUS irradiation improved BV/TV. Combination treatment promoted both cartilage repair and BV/TV improvement. Thus, MSC injection combined with LIPUS irradiation is more effective than either treatment alone in promoting concurrent cartilage repair and subchondral reconstitution. [ABSTRACT FROM AUTHOR]

An understanding of the articular cartilage degenerative process is necessary for the prevention and treatment of joint disease. The present study aimed to examine how long-term immobilization-induced cartilage degeneration is aggravated by remobilization. Sixty 8-week-old male Wistar rats were used in this study. The unilateral knee joint was immobilized using an external fixator for 8 weeks. The rats were killed at 0 and 3 days, and at 1, 2, 4 and 8 weeks after removing the fixator. After the rats were killed, the maximum knee extension angles were measured. Histological sections at the medial mid-condylar region (non-contact, transitional and contact regions of the femur and tibia) were prepared and scored. The cartilage thickness and number of chondrocytes were measured, and CD44 and Col2-3/4c expression levels were assessed immunohistochemically. The histological assessment revealed progressive aggravation of cartilage degeneration in the transitional region, with a decreased number of chondrocytes and CD44-positive chondrocytes as well as poor scoring over time, particularly in the tibia. Cyst formation was confirmed in the transitional region of the tibia at 8 weeks post-remobilization. The cartilage thickness in the transitional region was thicker than that in the contact region, particularly in the tibia. Col2-3/4c expression was observed in the non-contact and transitional regions, and the knee extension angle was recovered. In conclusion, immobilization-induced cartilage degeneration was aggravated by remobilization over time in the transitional region, followed by observations of a decreased number of chondrocytes and morphological disparity between different cartilage regions. [ABSTRACT FROM AUTHOR]

The repair of articular cartilage is challenging owing to the restriction in the ability of articular cartilage to repair itself. Therefore, cell supplementation therapy is possible cartilage repair method. However, few studies have verified the efficacy and safety of cell supplementation therapy. The current study assessed the effect of exercise on early the phase of cartilage repair following cell supplementation utilizing mesenchymal stromal cell (MSC) intra-articular injection. An osteochondral defect was created on the femoral grooves bilaterally of Wistar rats. Mesenchymal stromal cells that were obtained from male Wistar rats were cultured in monolayer. After 4 weeks, MSCs were injected into the right knee joint and the rats were randomized into an exercise or no-exercise intervention group. The femurs were divided as follows: C group (no exercise without MSC injection); E group (exercise without MSC injection); M group (no exercise with MSC injection); and ME group (exercise with MSC injection). At 2, 4, and 8 weeks after the injection, the femurs were sectioned and histologically graded using the Wakitani cartilage repair scoring system. At 2 weeks after the injection, the total histological scores of the M and ME groups improved significantly compared with those of the C group. Four weeks after the injection, the scores of both the M and ME groups improved significantly. Additionally, the scores in the ME group showed a significant improvement compared to those in the M group. The improvement in the scores of the E, M, and ME groups at 8 weeks were not significantly different. The findings indicate that exercise may enhance cartilage repair after an MSC intra-articular injection. This study highlights the importance of exercise following cell transplantation therapy. [ABSTRACT FROM AUTHOR]

Exposure to a microgravity environment leads to adverse effects in motion and musculoskeletal properties. However, few studies have investigated the recovery of altered locomotion and muscle atrophy simultaneously. The authors investigated altered locomotion in rats submitted to simulated microgravity by hindlimb unloading for 2 weeks. Motion deficits were characterized by hyperextension of the knees and ankle joints and forward-shifted limb motion. Furthermore, these locomotor deficits did not revert to their original form after a 2-week recovery period, although muscle atrophy in the hindlimbs had recovered, implying discordance in recovery between altered locomotion and muscle atrophy, and that other factors such as neural drives might control behavioral adaptations to microgravity. [ABSTRACT FROM AUTHOR]

The effects of intermittent hypergravity on gait alterations and hindlimb muscle atrophy in rats induced by 2 weeks of simulated microgravity were investigated. Rats were submitted to hindlimb unloading for 2 weeks (unloading period), followed by 2 weeks of reloading (recovery period). During the unloading period, animals were subjected to the following treatments: (1) free in cages (Control); (2) continuous unloading (UL); (3) released from unloading for 1 hour per day (UL + 1G); (4) hypergravity for 1 h per day using a centrifuge for small animals (UL + 2G). The relative weights of muscles to the whole body weight and kinematics properties of hindlimbs during gait were evaluated. UL rats walked with their hindlimbs overextended, and the oscillation of their limb motion had become narrowed and forward-shifted after the unloading period, and this persisted for at least 2 weeks after the termination of unloading. However, these locomotor alterations were attenuated in rats subjected to UL + 2G centrifugation despite minor systematic changes in muscle recovery. These findings indicate hypergravity application could counteract the adverse effects of simulated or actual microgravity environments. [ABSTRACT FROM AUTHOR]

Cell-based therapy has been explored for articular cartilage regeneration. Autologous chondrocyte implantation is a promising cell-based technique for repairing articular cartilage defects. However, there are several issues such as chondrocyte de-differentiation. While numerous studies have been designed to overcome some of these issues, only a few have focused on the thermal environment that can affect chondrocyte metabolism and phenotype. In this study, the effects of different culture temperatures on human chondrocyte metabolism- and phenotype-related gene expression were investigated in 2D and 3D environments. Human chondrocytes were cultured in a monolayer or in a pellet culture system at three different culture temperatures (32°C, 37°C, and 41°C) for 3 days. The results showed that the total RNA level, normalized to the threshold cycle value of internal reference genes, was higher at lower temperatures in both culture systems. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and citrate synthase (CS), which are involved in glycolysis and the citric acid cycle, respectively, were expressed at similar levels at 32°C and 37°C in pellet cultures, but the levels were significantly lower at 41°C. Expression of the chondrogenic markers, collagen type IIA1 (COL2A1) and aggrecan (ACAN), was higher at 37°C than at 32°C and 41°C in both culture systems. However, this phenomenon did not coincide with SRY (sex-determining region Y)-box 9 (SOX9), which is a fundamental transcription factor for chondrogenesis, indicating that a SOX9-independent pathway might be involved in this phenomenon. In conclusion, the expression of chondrocyte metabolism-related genes at 32°C was maintained or enhanced compared to that at 37°C. However, chondrogenesis-related genes were further induced at 37°C in both culture systems. Therefore, manipulating the culture temperature may be an advantageous approach for regulating human chondrocyte metabolic activity and chondrogenesis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the ultrastructural changes of surface cartilage collagen fibers, which differ by region and the length of the experimental period in an immobilization model of rat. Male Wistar rats were randomly divided into histological or macroscopic and ultrastructural assessment groups. The left knees of all the animals were surgically immobilized by external fixation for 1, 2, 4, 8 or 16 weeks ( n = 5/time point). Sagittal histological sections of the medial mid-condylar region of the knee were obtained and assessed in four specific regions (contact and peripheral regions of the femur and tibia) and two zones (superficial and deep). To semi-quantify the staining intensity of the collagen fibers in the cartilage, picrosirius red staining was used. The cartilage surface changes of all the assessed regions were investigated by scanning electron microscopy ( SEM). From histological and SEM observations, the fibrillation and irregular changes of the cartilage surface were more severe in the peripheral region than in the contact region. Interestingly, at 16 weeks post-immobilization, we observed non-fibrous structures at both the contact and peripheral regions. The collagen fiber staining intensity decreased in the contact region compared with the peripheral region. In conclusion, the alteration of surface collagen fiber ultrastructure and collagen staining intensity differed by the specific cartilage regions after immobilization. These results demonstrate that the progressive degeneration of cartilage is region specific, and depends on the length of the immobilization period. [ABSTRACT FROM AUTHOR]