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Purpose: Identification of responders/non-responders to unsupervised therapeutic exercise represents a critical challenge towards establishment of tailored self-management at home. Focusing on visualized varus thrust during gait as a possible effect moderator, this study determined whether and how varus thrust influences the therapeutic effects of home-based quadriceps exercise in individuals at increased risk of, or with, established knee osteoarthritis., Methods: This study is a secondary subgroup analysis of a randomized controlled trial (n = 50). Varus thrust at baseline was assessed via recorded gait movie. Analysis of covariance and subsequent mediation analysis were used to determine whether and how varus thrust influences the therapeutic effect of home-based quadriceps exercise after adjustment for covariates. To address the possible distinct impact of varus thrust on unsupervised and supervised exercise, the results were cross-checked with previous supervised exercise cohort using a meta-analysis., Results: Individuals without varus thrust displayed greater and clinically meaningful pain-relief after exercise after adjustment for covariates. The greater pain-relief in individuals without varus thrust was attributed, at least partly, to an improvement in knee flexion range of motion. Notably, the meta-analysis revealed that unsupervised and supervised exercise programs induce consistent and clinically meaningful pain reduction in individuals without varus thrust., Conclusions: Varus thrust is a robust effect moderator of the pain reducing effect of quadriceps exercise. Further, greater pain reduction may be a function of improvement of knee flexion range of motion. These studies provide evidence that varus thrust assessment represents valuable approach to identify responders/non-responders to quadriceps exercise even for unsupervised protocol at their home environment., Competing Interests: Conflict of Interest and Funding Source: This study was supported in part by (1) a JSPS KAKENHI (Grant Number: 23H03308) from the Japan Society for the Promotion of Science (https://www.jsps.go.jp/) for HI., (Copyright © 2024 by the American College of Sports Medicine.)

Tendons transmit the muscle contraction forces to bones and drive joint movement throughout life. While extensive research have indicated the essentiality of mechanical forces on tendon development, a comprehensive understanding of the fundamental role of mechanical forces still needs to be impaerted. This scoping review aimed to summarize the current knowledge about the role of mechanical forces during the tendon developmental phase. The electronic database search using PubMed, performed in May 2023, yielded 651 articles, of which 16 met the prespecified inclusion criteria. We summarized and divided the methods to reduce the mechanical force into three groups: loss of muscle, muscle dysfunction, and weight-bearing regulation. In contrast, there were few studies to analyze the increased mechanical force model. Most studies suggested that mechanical force has some roles in tendon development in the embryo to postnatal phase. However, we identified species variability and methodological heterogeneity to modulate mechanical force. To establish a comprehensive understanding, methodological commonality to modulate the mechanical force is needed in this field. Additionally, summarizing chronological changes in developmental processes across animal species helps to understand the essence of developmental tendon mechanobiology. We expect that the findings summarized in the current review serve as a groundwork for future study in the fields of tendon developmantal biology and mechanobiology., (© 2023 The Authors. Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

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., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

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. KEY POINTS: 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., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

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., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

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)., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

A mechanistic understanding of cell-autonomous skeletal muscle changes after injury can lead to novel interventions to improve functional recovery in an aged population. However, major knowledge gaps persist owing to limitations of traditional biological aging models. 2D cell culture represents an artificial environment, while aging mammalian models are contaminated by influences from non-muscle cells and other organs. Here, a 3D muscle aging system is created to overcome the limitations of these traditional platforms. It is shown that old muscle constructs (OMC) manifest a sarcopenic phenotype, as evidenced by hypotrophic myotubes, reduced contractile function, and decreased regenerative capacity compared to young muscle constructs. OMC also phenocopy the regenerative responses of aged muscle to two interventions, pharmacological and biological. Interrogation of muscle cell-specific mechanisms that contribute to impaired regeneration over time further reveals that an aging-induced increase of complement component 4b (C4b) delays muscle progenitor cell amplification and impairs functional recovery. However, administration of complement factor I, a C4b inactivator, improves muscle regeneration in vitro and in vivo, indicating that C4b inhibition may be a novel approach to enhance aged muscle repair. Collectively, the model herein exhibits capabilities to study cell-autonomous changes in skeletal muscle during aging, regeneration, and intervention., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Design: Systematic review using PRISMA guidelines., Purpose: To explore Relationship between ankle instability and ankle sprain recurrence in preventing recurrence of ankle sprains and to provide appropriate treatment., Methods: MEDLINE (the Cochrane Library) and the Physiotherapy Evidence Database (PEDro) were explored using key words related to ankle instability and ankle sprains in for April 2022. According to the inclusion criteria, studies that 1) targeted patients with ankle sprains, 2) assessed ankle instability, and 3) investigated ankle sprain recurrence rates, were extracted. The author names, publication year, patient characteristics, comparison groups, intervention methods, and outcome data (ankle instability and recurrence) were extracted. A correlation analysis between recurrence rate and ankle instability was conducted. In addition, A meta-analysis was performed on the correlation coefficients within each article., Results: Eight studies were extracted from 149 studies. A correlation analysis was conducted on five studies and meta-analysis was on three studies with the same post-intervention follow-up period and the same assessment methods for ankle instability and recurrence rate. Strong positive correlations were found for the same follow-up periods (r = 0.95: 95%CI [0.62-0.99]; 3-month, r = 0.97: 95%CI [0.75-0.10]; 1 year, p < .05). The correlation became stronger as the follow-up period increased. Furthermore, the meta-analysis showed that ankle instability as well as the main symptoms of sprain, such as pain and swelling, tended to be positively correlated with the recurrent rate of ankle sprains. These results suggest that ankle instability is strongly related to recurrence, and the longer the time since onset, the stronger the relationship., Conclusions: Ankle instability was a prognostic factor associated with recurrence of ankle sprains in patients with ankle sprains. Therefore, ankle instability is one of important factor in preventing recurrence of ankle sprains., Competing Interests: Declarations of interest There are no direct conflicts of interest, one or Corresponding Author received third party grants for a study associated with the subject of this manuscript., (Copyright © 2023. Published by Elsevier Ltd.)

Extracellular matrix stiffening is a quintessential feature of cartilage aging, a leading cause of knee osteoarthritis. Yet, the downstream molecular and cellular consequences of age-related biophysical alterations are poorly understood. Here, we show that epigenetic regulation of α-Klotho represents a novel mechanosensitive mechanism by which the aged extracellular matrix influences chondrocyte physiology. Using mass spectrometry proteomics followed by a series of genetic and pharmacological manipulations, we discovered that increased matrix stiffness drove Klotho promoter methylation, downregulated Klotho gene expression, and accelerated chondrocyte senescence in vitro. In contrast, exposing aged chondrocytes to a soft matrix restored a more youthful phenotype in vitro and enhanced cartilage integrity in vivo. Our findings demonstrate that age-related alterations in extracellular matrix biophysical properties initiate pathogenic mechanotransductive signaling that promotes Klotho promoter methylation and compromises cellular health. These findings are likely to have broad implications even beyond cartilage for the field of aging research., (© 2023. The Author(s).)

Patients with knee osteoarthritis show low stair climbing ability, but a diagnosis of stair performance time is not enough to identify the early stages of knee osteoarthritis. Therefore, we developed an indicator named range of the knee joint trajectory (RKJT) as a kinematic parameter to express more detailed characteristics than stair performance time. To achieve this, we used our developed "IR-Locomotion", a markerless measurement system that can track the knee joint trajectory when climbing stairs. This study aimed to test whether the RKJT effectively identifies patients with early knee osteoarthritis even after controlling stair performance time. Forty-seven adults with moderate to severe knee pain (mean age 59.2 years; 68.1% women) underwent the radiographic examination (Kellgren and Lawrence grade) of both knees and a stair climbing test on 11 stairs. The RKJT during the stair climbing test was calculated by "IR-Locomotion". A generalized linear mixed model was used to evaluate the discriminative capability of RKJT on early knee osteoarthritis (i.e., Kellgren and Lawrence grade of 1). As expected, patients with early knee osteoarthritis showed larger RKJT than non-radiographic controls (95% confidence interval: 1.007, 1.076). Notably, this finding was consistent even after adjusting stair performance time.

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., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

Background: Sarcopenia and knee osteoarthritis (OA) are two major risk factors for falls in older adults. The coexistence of these two conditions may exacerbate the risk of falls. This cross-sectional study aimed to test the hypothesis that older adults with coexisting sarcopenia and knee OA displayed an increased risk of falls experience., Methods: Participants recruited from an orthopedic clinic were divided into four groups according to the presence of sarcopenia and radiographic knee OA: isolated sarcopenia, isolated knee OA, sarcopenia + knee OA, and control (i.e., non-sarcopenia with non-OA) groups. We used questionnaires to assess falls experience in the prior 12 months. We performed logistic regression analyses to evaluate the relationship between the four groups and falls experience., Results: Of 291 participants (age: 60-90 years, 78.7% women) included in this study, 25 (8.6%) had sarcopenia + knee OA. Participants with sarcopenia + knee OA had 4.17 times (95% confidence interval: 0.84, 20.6) higher odds of recurrent falls (≥2 falls) than controls after adjustment for age, sex, and body mass index. The increased recurrent falls experience was not clearly confirmed in participants with isolated sarcopenia and isolated knee OA., Conclusions: People with coexisting of sarcopenia and knee OA displayed increased recurrent falls experience. This study suggests a new concept, "sarcopenic knee OA", as a subgroup associated with higher risk of falls, which should be validated in future large cohort studies., Trial Registration: Not applicable., (© 2021. The Author(s).)

Objective: To summarize the level of knowledge regarding the effects of microcurrent therapy (MCT) on musculoskeletal pain in adults., Data Sources: The PubMed, Physiotherapy Evidence Database, Cumulative Index to Nursing Allied Health Literature, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi database were searched from the time of their inception to December 2020., Study Selection: Randomized controlled trials (RCTs) investigating the effects of MCT on musculoskeletal pain were included. Additionally, non-RCTs were included to assess the adverse events., Data Extraction: The primary outcomes were pain and adverse events related to MCT. To assess the reproducibility of MCT, we evaluated the completeness of treatment description using the Template for Intervention Description and Replication (TIDieR) checklist. We also assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)., Data Synthesis: A comprehensive assessment of 4 RCTs and 5 non-RCTs that met the inclusion criteria revealed that MCT significantly improved shoulder pain (1 study, 40 patients) and knee pain (1 study, 52 patients) compared with sham MCT without any severe adverse events. MCT has clinically significant benefits for knee pain. This study also revealed a clinically significant placebo response in treating knee pain. This evidence highlights the substantial effect of placebo response in clinical care. These treatment effects on knee pain are further supported by the high quality of evidence in GRADE with high reproducibility in TIDieR., Conclusions: The findings of this meta-analysis highlight the effect of placebo response in treating knee pain. MCT is a potential, core nonpharmacologic treatment option in clinical care with minimal adverse events and should be further investigated. This study proposes a framework for the future investigation of the effect of MCT on musculoskeletal pain to enhance the study quality and reproducibility., (© 2021 The Authors.)

Objective: Knee osteoarthritis (OA) has been suggested to increase the risk of falls. Low back pain (LBP) is a potential risk factor for falls in people with knee OA, but this issue has not been addressed adequately in previous studies. The objective of this study was to investigate the relationship between LBP and falls in people with knee OA in a 12-month period., Methods: Participants with knee OA (Kellgren/Lawrence [K/L] grade ≥1) completed questionnaires for LBP and falls that occurred in the preceding 12 months. Binary and ordinal logistic regression analyses were performed to assess the relationship between LBP or moderate-to-severe LBP (numeric rating scale ≥4 points) and any fall (≥1 fall) or recurrent falls (≥2 falls) after adjustment for age, sex, K/L grade, knee pain severity, and quadriceps strength. Sensitivity analyses were performed excluding people with sciatica, nonchronic LBP, K/L grade 1, and those receiving pain medications., Results: We included 189 participants (ages 61-90 years, 78.3% women) in this study. Of these participants, 41 (21.6%) reported falls in the preceding 12 months. People with any LBP (n = 101) and those with moderate-to-severe LBP (n = 45) had 2.7- and 3.7-times higher odds of recurrent falls, respectively. Sensitivity analyses revealed a strong correlation between moderate-to-severe LBP and recurrent falls., Conclusion: Thorough investigation of LBP as a risk factor for recurrent falls in people with knee OA may provide a novel insight into the pathomechanics of recurrent falls in this population., (© 2020, American College of Rheumatology.)

Objective: To test the hypothesis that varus thrust visualized during gait is associated with a higher prevalence of low back pain (LBP) in individuals with knee osteoarthritis (OA)., Methods: Individuals with knee OA (Kellgren/Lawrence grade ≥1) underwent a gait observation to assess varus thrust. The participants identified LBP and its severity using questionnaires. Logistic regression analyses were performed to examine the association between varus thrust and LBP., Results: We included 205 participants (mean age 68.19 years; 72.20% women). A total of 45 participants (22.0%) showed varus thrust in their painful knee, in whom 31 (68.89%) and 18 (40.00%) were identified as having any LBP and moderate-to-severe LBP (numerical rating scale ≥4 points), respectively. Patients with varus thrust demonstrated a 3.6-fold higher risk of the presence of moderate-to-severe LBP (95% confidence interval [95% CI] 1.62-8.10). In patients with LBP, the presence of varus thrust was associated with more severe LBP intensity (proportional odds ratio 2.25 [95% CI 1.02-4.96])., Conclusion: This study highlights the novel relationship between varus thrust and LBP, which supports the idea of a biomechanical link, the so-called knee-spine syndrome. These findings provide new insight for clarifying the pathogenesis of LBP related to knee OA., (© 2019, American College of Rheumatology.)

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors did not receive financial support or other benefits from commercial sources for the work reported in this manuscript. Nor did they receive any other financial support that could create a potential conflict of interest or the appearance of a conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

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.

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., Competing Interests: Declaration of Competing Interest The authors did not receive financial support or other benefits from commercial sources for the work reported in this manuscript, or any other financial support that could create a potential conflict of interest or the appearance of a conflict of interest concerning the work., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

Case: A 77-year-old woman with knee osteoarthritis (OA) complained of right (ipsilateral) knee pain for more than 5 years with gait asymmetry. The OA and quadriceps muscle weakness were more severe in the left (contralateral) knee, but she had no pain. Bracing of the left knee led to decreased gait asymmetry, as determined with an inertial measurement unit, and reduced pain in the right knee., Conclusion: This case highlights the contralateral knee effect on ipsilateral chronic knee pain, possibly through gait asymmetry. These findings provide a mechanistic insight into knee OA-related pain in patients with gait asymmetry and suggest a new rehabilitative approach.

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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.

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.

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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 R 2  = 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 (R 2  = 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.

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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 coefficient 1,1 [ICC 1,1 ], 0.952; 95% confidence interval [CI], 0.560 to 0.985; p <  0.001) and the minimal detectable change 95 was 0.102 s. Concurrent validity was excellent (ICC 2,1 : 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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To investigate the effect of transcutaneous electrical nerve stimulation (TENS) on knee pain and comprehensive physical function in preradiographic knee osteoarthritis., Design: A single, participant-blinded, randomized controlled trial (RCT) with pre-post design., Setting: University research laboratory., Participants: Patients with knee pain belonging to Kellgren-Lawrence grade 0 or 1 (N=50; aged 50-69y) were randomly assigned to the TENS (n=25) and sham-TENS groups (n=25)., Interventions: All participants wore the TENS device under the patella of the symptomatic knee. After measurement, the TENS devices in the TENS group were turned on, and those in the sham-TENS group were not connected., Main Outcome Measures: The primary outcome measures included the stair climb test, timed Up and Go (TUG) test, 6-minute walk test (6MWT), and knee pain evaluated using the visual analog scale (VAS) for stair climb test, TUG test, and 6MWT. Secondary outcomes included knee extensor strengths and the 2-step test and stand-up test from the locomotive syndrome risk test., Results: Multiple regression analysis revealed that TENS intervention significantly improved the walk distance and VAS score of the 6MWT, after adjusting for premeasurement data (distance; P=.015, VAS; P=.030)., Conclusions: Use of TENS improved the VAS score for pain and the distance walked in the 6MWT for individuals with Kellgren-Lawrence grade 0 or 1 of the knee. Thus, TENS may be effective for long-distance walking in patients with preradiographic knee osteoarthritis., (Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: This study examined whether individuals who have mild medial osteoarthritis (OA) of the knee with coexisting lateral OA have less muscle strength than individuals who do not have lateral OA., Methods: A series of 153 individuals (84% of whom were women) between 48 and 88 years old who had Kellgren and Lawrence (KL) grade-2 OA in the medial compartment of the knee underwent radiographic evaluation to assess the presence of lateral OA, which was graded with the system of the Osteoarthritis Research Society International (OARSI) atlas as well as the KL system. The isometric maximum strengths of the quadriceps, the hip abductors, and the hip extensors were evaluated with use of a handheld dynamometer., Results: Individuals who had coexisting medial and lateral OA had more severe knee pain and weaker quadriceps than those who did not have lateral OA. The study adjusted for age and sex both for the OARSI atlas system (adjusted difference in mean strength: 0.272 Nm/kg, 95% confidence interval [CI]: 0.143 to 0.401 Nm/kg) and for KL grading (adjusted difference in mean strength: 0.185 Nm/kg, 95% CI: 0.061 to 0.309 Nm/kg). Logistic regression analysis showed that weakness of the quadriceps increased the odds of the presence of lateral OA sevenfold after adjustments using the OARSI atlas were made for age, sex, anatomical axis, range of motion of the knee, and intensity of pain in the knee., Conclusions: Individuals who had coexisting medial and lateral OA had weaker quadriceps than individuals who had mild medial OA alone. Paying close attention to quadriceps weakness might provide a key to clarifying the pathogenesis of bicompartmental disease in the tibiofemoral joint., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

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.

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 CO 2 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.

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.

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.

The aim of this study was to identify ultrasound parameters reflecting subchondral porosity (P o ), subchondral plate thickness (T pl ) and bone volume fraction at the trabecular bone region (BV/TV Tb ). 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. P o , T pl and BV/TV Tb were evaluated as reference measurements using micro-computed tomography. ENT L1x (ENT of layer 1, x-direction) and ENT L1z were significantly correlated with P o (both r values = 0.58), COR L2x with T pl (r = -0.73) and COR L2z with BV/TV Tb (r = -0.66). These are efficient indicators of the characteristics of osteoarthritis-related subchondral bone; the other texture parameters were not significant., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This systematic review with a meta-analysis aimed to summarize the current evidence of the effectiveness of mesenchymal stem cell (MSC) treatment for knee osteoarthritis (OA) and to examine whether rehabilitation is an effect modifier of the effect estimate of MSC treatment. A literature search yielded 659 studies, of which 35 studies met the inclusion criteria ( n  = 2385 patients; mean age: 36.0-74.5 years). The meta-analysis results suggested that MSC treatment through intra-articular injection or arthroscopic implantation significantly improved knee pain (standardized mean difference [SMD]: -1.45, 95% confidence interval [CI]: -1.94, -0.96), self-reported physical function (SMD: 1.50, 95% CI: 1.09, 1.92), and cartilage quality (SMD: -1.99; 95% CI: -3.51, -0.47). However, the MSC treatment efficacy on cartilage volume was limited (SMD: 0.49; 95% CI: -0.19, 1.16). Minor adverse events (knee pain or swelling) were reported with a wide-ranging prevalence of 2-60%; however, no severe adverse events occurred. The evidence for these outcomes was "very low" to "low" according to the Grades of Recommendation, Assessment, Development and Evaluation system because of the poor study design, high risk of bias, large heterogeneity, and wide 95% CI of the effects estimate. Performing rehabilitation was significantly associated with better SMD for self-reported physical function (regression coefficient: 0.881, 95% CI: 0.049, 1.712; P  = 0.039). We suggest that more high quality randomized controlled trials with consideration of the potential rehabilitation-driven clinical benefit would be needed to facilitate the foundation of effective MSC treatment and regenerative rehabilitation for patients with knee OA., Competing Interests: The authors declare no competing financial interests.

Rodent models of sciatic nerve lesion are regularly used to assess functional deficits in nerves. Impaired locomotor functions induced by sciatic nerve lesion are currently evaluated with scoring systems despite their limitations. To overcome these shortcomings, which includes low sensitivity, little significance, and the representation of only marginal components of motion profiles, some additional metrics have been introduced. However, a quantitative determination of motion deficits is yet to be established. We used a three-dimensional motion analysis to investigate gait deficits after sciatic nerve lesion in rats. This enabled us to depict the distorted gait motion using both traditional parameters and novel readouts that are specific for the three-dimensional analysis. Our results suggest that three-dimensional motion analysis facilitates a comprehensive understanding of the gait impairment specifically, but not limited to, a sciatic lesion rat model. A broad application of these methods will improve understanding and standardized motor assessment.

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., Competing Interests: The ethical committee of Kyoto University approved the study (approval number: E1923), and written informed consent was obtained from all participants before their enrollment.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Depressive symptoms are a major comorbidity in older adults with knee osteoarthritis (OA). However, the type of activity-induced knee pain associated with depression has not been examined. Furthermore, there is conflicting evidence regarding the association between depression and performance-based physical function. This study aimed to examine (i) the association between depressive symptoms and knee pain intensity, particularly task-specific knee pain during daily living, and (ii) the association between depressive symptoms and performance-based physical function, while considering other potential risk factors, including bilateral knee pain and ambulatory physical activity., Methods: Patients in orthopaedic clinics (n = 95; age, 61-91 years; 67.4% female) who were diagnosed with radiographic knee OA (Kellgren/Lawrence [K/L] grade ≥ 1) underwent evaluation of psychological health using the Geriatric Depression Scale (GDS). Knee pain and physical function were assessed using the Japanese Knee Osteoarthritis Measure (JKOM), 10-m walk, timed up and go (TUG), and five-repetition chair stand tests., Results: Ordinal logistic regression analysis showed that depression, defined as a GDS score ≥ 5 points, was significantly associated with a worse score on the JKOM pain-subcategory and a higher level of task-specific knee pain intensity during daily living, after being adjusted for age, sex, body mass index (BMI), K/L grade, and ambulatory physical activity. Furthermore, depression was significantly associated with a slower gait velocity and a longer TUG time, after adjusting for age, sex, BMI, K/L grade, presence of bilateral knee pain, and ambulatory physical activity., Conclusions: These findings indicate that depression may be associated with increased knee pain intensity during daily living in a non-task-specific manner and is associated with functional limitation in patients with knee OA, even after controlling for covariates, including bilateral knee pain and ambulatory physical activity.

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.