Search

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.)

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

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. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

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

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

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

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

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

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

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

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]

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

Objective: To evaluate the clinical impact in knee osteoarthritis (OA) of coexisting patellofemoral (PF) joint OA (PFOA) in Japanese patients with medial tibiofemoral (TF) joint OA (TFOA).Methods: Patients with medial knee OA (n = 143) were enrolled. The radiographic severity of the TF and PF joints, anatomic axis angle of the TF joint, patellar alignment, trochlear morphology, patellar height, and passive range of motion (ROM) of the painful knee were evaluated. Additionally, the Japanese Knee Osteoarthritis Measure (JKOM) was used to investigate the association between the presence of PFOA and clinical symptoms.Results: PFOA was present in 98 of 143 patients (68.5%) with medial knee OA. Quantile regression analysis revealed that coexisting PFOA was associated with the pain-related subcategory of the JKOM. Furthermore, multiple logistic regression analysis showed that coexisting PFOA was associated with higher odds of reporting knee pain on using stairs while ascending (odds ratio [OR] 4.81 [95% confidence interval (95% CI) 1.73, 14.3]) and descending (OR 3.86 [95% CI 1.44, 10.8]). A more varus knee alignment and lower knee flexion ROM, which are features of patients with coexisting PFOA, were associated with knee pain while ascending/descending stairs. However, patellar alignment, trochlear morphology, and patellar height were not significantly associated with knee pain.Conclusion: PFOA coexisting with medial knee OA was associated with worse clinical symptoms, particularly while ascending/descending stairs, although patellar alignment did not contribute to reporting knee pain. Further studies that include evaluation of the PF joint are warranted to develop a basis for an optimal intervention based on compartmental involvement. [ABSTRACT FROM AUTHOR]

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

ABSTRACT The aim of this study was to elucidate whether the levels of serum biomarkers reflect the progression of osteoarthritis (OA) induced by different levels of exercise. Thirty-five Wistar rats subjected to anterior cruciate ligament transaction (ACLT) were divided into three groups: Control, moderate running, and intense running. Twelve rats (moderate running without ACLT) were allocated as a naive group. Running was performed on a motorized treadmill, at a speed of 18 m/min for 30 min/day (moderate and naive) or 60 min/day (intense) for 3 days per week. After 2 or 4 weeks, OA histopathology in the knees was evaluated using the Osteoarthritis Research Society International (OARSI) score, and the serum levels of cleaved collagen type II (C2C) and procollagen II C-propeptide (CPII) were analyzed. The OARSI score deteriorated in the intense running group after 2 weeks and the serum C2C/CPII ratio suggested the development of OA. At 4 weeks, the C2C/CPII ratio suggested there would be deterioration in the OARSI score but the score did not differ significantly between the moderate and intense running groups. C2C/CPII ratio had 13-25% correlation with the OARSI histological score. Thus, in rat experimental OA, the OARSI score could be partially predicted by the C2C/CPII ratio as a serum biomarker of OA. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1026-1031, 2013 [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]

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

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. [ABSTRACT FROM AUTHOR]

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

Objective To examine the association between pedometer-based ambulatory physical activity (PA) and physical function in patients with knee osteoarthritis (OA). Design Cross-sectional observational study. Setting Institutional practice. Participants Participants in orthopedic clinics (N=207; age, 56–90y; 71.5% women) with diagnosed radiographic knee OA (Kellgren/Lawrence [K/L] grade ≥1). Interventions Not applicable. Main Outcome Measures Ambulatory PA was objectively measured as steps per day. Physical function was assessed using the Japanese Knee Osteoarthritis Measure (JKOM) functional subcategory, 10-m walk, Timed Up and Go (TUG), and 5-repetition chair stand (5CS) tests. Results Patients walking <2500 steps/d had a low level of physical function with a slower gait speed, longer TUG time, and worse JKOM functional score compared with those who walk 2500 to 4999, 5000 to 7499, and ≥7500 steps/d adjusted for age, sex, body mass index [BMI], and K/L grade. Ordinal logistic regression analysis revealed that steps per day (continuous) was associated with better physical function adjusted for age, sex, BMI, and K/L grade. These relationships were still robust in sensitivity analyses that included patients with K/L grades ≥2 (n=140). Conclusions Although increased ambulatory PA had a positive relationship with better physical function, walking <2500 steps/d may be a simple indicator for a decrease in physical function in patients with knee OA among standard PA categories. Our findings might be a basis for counseling patients with knee OA about their ambulatory PA and for developing better strategies for improving physical function in sedentary patients 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]