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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]

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]

Objective: To examine the clinical impact of coexisting lateral osteoarthritis (OA) in knees with mild medial OA.Design: In patients with Kellgren/Lawrence (K/L) grade 2 OA in the medial compartment (n = 100; age: 56-89 years; 80.0% female), anteroposterior knee radiography was used to assess the presence of lateral OA, using grading systems from the Osteoarthritis Research Society International (OARSI) atlas and the K/L classification. The Japanese Knee Osteoarthritis Measure (JKOM), knee range of motion (ROM), and performance-based functional measures (10 m walk, timed up and go and five repetition chair stand maneuvers) were evaluated. The outcomes were compared between patients with and without lateral OA using an analysis of covariance (ANCOVA) or nonparametric rank ANCOVA. Furthermore, ordinal logistic regression analysis was performed, with responses on individual JKOM pain questionnaires as the outcomes and lateral OA as the predictor.Results: Knees with coexisting lateral OA had a significantly worse score of JKOM pain question compared with those without, after adjusting for covariates. The presence of lateral OA was significantly associated with knee pain while ascending/descending stairs and standing. These results were consistent between different definitions of the K/L and OARSI grading systems. The knee ROM and performance-based functional measures were not significantly different between patients with and without lateral OA.Conclusion: Knees with concomitant lateral and mild medial OA may be more symptomatic compared to those without lateral OA. These findings might help to define a clinically distinct subgroup based on a simple radiographic finding in mild knee OA. [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]

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]

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]

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]

Purpose: Females typically present with a higher prevalence of knee osteoarthritis (KOA), and such a higher prevalence may be due to unique knee biomechanics during walking. However, the sex-dependent ambulatory mechanics has been yet to be clarified. To address this critical knowledge gap, this study implemented a series of computational approaches (1) to identify sex-related knee joint biomechanics during ambulation in persons with KOA and (2) to compare these biomechanical measures between individuals with vs. without KOA, stratified by sex., Methods: We searched five electronic databases for studies reporting sex-specific knee biomechanics in persons with and/or without KOA. Summary estimates were computed using random-effects meta-analysis and stratified by sex., Results: The systematic review identified eighteen studies (308 males and 383 females with KOA; 740 males and 995 females without KOA). A series of meta-analyses identified female-specific knee biomechanics in a disease-dependent manner. Females with KOA had lower first peak knee adduction moment and peak knee adduction compared to male counterparts. On the other hand, healthy females had lower peak knee flexion moment than male counterparts. Effect estimate in each meta-analysis display poor quality of evidence according to the GRADE approach., Conclusions: The current study is the first to consider sex as a biological variable into ambulatory mechanics in the development of KOA. We discovered that sex-dependent alterations in knee biomechanics is a function of the presence of KOA, indicating that KOA disease may be a driver of the sex-dependent biomechanical alterations or vice versa. Although no strong conclusion can be drawn because of the low quality of evidence, these findings provide new insight into the sex differences in ambulatory knee biomechanics and progression of KOA., Competing Interests: Conflict of Interest and Funding Source: This work was supported by a Grant-in-Aid for Early-Career Scientists (20K19411), (Copyright © 2024 by the American College of Sports Medicine.)

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.)

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).)

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).)

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.)

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.

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: 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.

A hypoxic environment is thought to be important for the maintenance of stemness and suppressing cell senescence, in stem cells. Therefore, a hypoxic condition is induced during cell expansion and/or induction of intended differentiation. However, the induction of these conditions requires a specially equipped hypoxia chamber and expensive gas mixtures, which are expensive and space-consuming. Owing to these restrictions, appropriate hypoxic conditions cannot be provided during cell transportation, which is increasingly required for regenerative medicine. Hence, a simple and economical culture system is required. The purpose of this study was to investigate the effects of short-term hypoxic conditions on human mesenchymal stem cell (MSC) proliferation, viability, and senescence, utilizing the CulturePal system (CulturePal-Zero and CulturePal-Five), a novel and simple hypoxic culture system with a built-in deoxidizing agent. The O2 concentration in the CulturePal-Zero was observed to reduce to <0.1% within 1 h, and to 5% within 24h in the CulturePal-Five system. Cell proliferation under these hypoxic conditions showed a sharp increase at 5% O2 concentration, and no noticeable cell death was observed even at severe hypoxic conditions (<0.1% O2) up to 72h. The p16(INK4A) (cell senescence marker) mRNA expression was retained under hypoxic conditions up to 72h, but it was up-regulated under normoxic conditions. Interestingly, the p16(INK4A) expression altered proportionately to the O2 concentration. These results indicated that the short-term hypoxic condition, at an approximate O2 concentration of 5%, would be suitable for promoting cell proliferation and repressing cell senescence, without aggravating the MSC viability. Therefore, the CulturePal systems may be suitable for providing an appropriate hypoxic condition in stem cell research and transportation.