Linking physical activity with clinical, functional, and structural outcomes: an evidence map using the Osteoarthritis Initiative.

Physical activity is consistently recommended across clinical practice guidelines for managing knee osteoarthritis, yet prescription rates are low. Evidence mapping uses a systematic approach to visually illustrate and summarize published evidence, highlight gaps in the literature, and formulate research questions. The purpose of this study was to review and summarize evidence published from the Osteoarthritis Initiative (OAI) linking physical activity with clinical, functional, and structural knee osteoarthritis outcomes. Electronic databases were searched until June 2021. Studies from the OAI reporting subjective (Physical Activity Scale for the Elderly, PASE) or objective (accelerometry) physical activity data were included. Scatter plots were created to represent each outcome group (clinical, functional, structural) and physical activity measure (PASE, accelerometry) to map the evidence by the directional effect (positive, interaction, negative, or no effect) associated with physical activity. Forty-two articles were included in this review. Physical activity was quantified using PASE (n = 21), accelerometry (n = 20), or both (n = 1). Studies reported consistently positive physical activity effects on clinical (n = 22) and functional (n = 20) outcomes, with few exceptions. Structural (n = 15) outcomes were largely reported as interaction effects by physical activity intensity or sex, or as no significant effect. A network of interconnected outcomes emerged, with clinical and functional outcomes often reported together, and structural outcomes reported individually. This study provides an overview of current evidence linking physical activity to multiple interrelated knee osteoarthritis outcomes using an OAI-driven model. These evidence maps can be used as a framework to guide future investigations of the effects of physical activity on knee osteoarthritis.

High day-to-day repeatability of lower extremity muscle activation patterns and joint biomechanics of dual-belt treadmill gait: A reliability study in healthy young adults.

PURPOSE: The reliability of lower extremity muscle activation patterns has not been clearly studied in a dual-belt instrumented treadmill environment. The primary study objective was to quantify the day-to-day reliability of quadriceps, hamstrings, gastrocnemius and gluteus medius activation patterns in healthy young adult gait. Secondarily, the reliability of spatiotemporal, and knee/hip motion and moment-based gait outcomes was assessed. SCOPE: 20 young adults were recruited and tested on two separate days. Using standardized procedures, participants were prepared for surface electromyography and lower extremity motion capture. All individuals walked on a dual-belt instrumented treadmill while muscle activation, segment motions and ground reaction forces were recorded. Sagittal plane motion and net external sagittal and frontal plane moments were calculated. Discrete biomechanical and muscle activation measures were calculated, and non-negative matrix factorization extracted amplitude and temporal muscle activation features. Intraclass Correlation Coefficients, Standard Error of Measurement and Minimum Detectable Change were calculated. CONCLUSIONS: High to excellent Intraclass correlation coefficients were found between visits for most primary and secondary outcomes. The absolute and relative reliability, including Minimum Detectable Change values, provided in this study support the use of dual-belt instrumented treadmill walking as an acceptable medium to collect biomechanical and lower extremity EMG outcomes for future studies.

Validation of a novel blinding method for measuring postoperative knee articular cartilage using magnetic resonance imaging.

OBJECTIVES: To test PEEK implant-associated MRI artifacts, a method for blinding MRI readers, the repeatability of cartilage thickness measures before and 6 weeks after high tibial osteotomy (HTO), and the sensitivity to change of cartilage thickness 12 months after HTO. MATERIALS AND METHODS: Ten patients underwent HTO using a PEEK implant and 3 T-MRI before, 6 weeks and 12 months after surgery. Masks were applied to hide implant visibility on 48 MRI pairs, which were assessed by 7 readers (blinded to time). One blinded reader measured femorotibial cartilage thickness from masked MRIs. RESULTS: No artifacts were produced. Readers were unable to identify scans by time greater than by chance. Cartilage thickness before and 6 weeks after surgery was not significantly different and indicated excellent repeatability. Medial cartilage thickness increases 12 M postoperatively approached statistical significance (p = 0.06), with no lateral changes observed. Half of the participants had an increase in medial cartilage thickness at 12 M that exceeded the minimal detectable change. Standardized response mean values were moderate-to-large. DISCUSSION: Postoperative measures of cartilage thickness are repeatable, consistent and sensitive to change when artifact is eliminated, and a validated blinding technique is used. These results provide proof of concept for accurately measuring increases in medial knee articular cartilage after medial opening wedge HTO.

MRI T2 and T1ρ relaxation in patients at risk for knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Magnetic resonance imaging (MRI) T2 and T1ρ relaxation are increasingly being proposed as imaging biomarkers potentially capable of detecting biochemical changes in articular cartilage before structural changes are evident. We aimed to: 1) summarize MRI methods of published studies investigating T2 and T1ρ relaxation time in participants at risk for but without radiographic knee OA; and 2) compare T2 and T1ρ relaxation between participants at-risk for knee OA and healthy controls. METHODS: We conducted a systematic review of studies reporting T2 and T1ρ relaxation data that included both participants at risk for knee OA and healthy controls. Participant characteristics, MRI methodology, and T1ρ and T2 relaxation data were extracted. Standardized mean differences (SMDs) were calculated within each study. Pooled effect sizes were then calculated for six commonly segmented knee compartments. RESULTS: 55 articles met eligibility criteria. There was considerable variability between scanners, coils, software, scanning protocols, pulse sequences, and post-processing. Moderate risk of bias due to lack of blinding was common. Pooled effect sizes indicated participants at risk for knee OA had lengthened T2 relaxation time in all compartments (SMDs from 0.33 to 0.74; p < 0.01) and lengthened T1ρ relaxation time in the femoral compartments (SMD from 0.35 to 0.40; p < 0.001). CONCLUSIONS: T2 and T1ρ relaxation distinguish participants at risk for knee OA from healthy controls. Greater standardization of MRI methods is both warranted and required for progress towards biomarker validation.

Association Between Knee Load and Pain: Within-Patient, Between-Knees, Case-Control Study in Patients With Knee Osteoarthritis.

OBJECTIVE: The association between knee loading and pain in patients with knee osteoarthritis is reported to be low and of questionable importance, but may be confounded by several factors that differ between patients. We aimed to elucidate the association between dynamic knee load and pain by minimizing confounding using a study design that was within the same patient, with knees discordant for pain. METHODS: A total of 265 patients with knees discordant for pain (530 knees) rated the pain in each knee before and after walking for 6 minutes, and then underwent 3-dimensional gait analysis. RESULTS: The peak knee adduction moment and knee adduction impulse (proxies for medial knee loading) were associated with increased pain (odds ratio [OR] 2.43 [95% confidence interval (95% CI) 1.77-3.33] and OR 6.62 [95% CI 3.46-12.7], respectively) and remained significant after controlling for radiographic disease severity. When split into quartiles, ORs indicated knees in the highest loading quartile had greater odds of experiencing increased pain with walking (OR 4.7 95% CI 2.3-9.5] for peak adduction moment; OR 9.0 [95% CI 4.0-20.1] for adduction impulse) compared to knees in the lowest loading quartile. CONCLUSION: When between-patient confounding is minimized, there is a strong association between medial knee load and increased knee pain during walking.

Postoperative Gait Mechanics After Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: Total hip arthroplasty is recommended by clinical practice guidelines for improving pain in patients with severe hip osteoarthritis, yet functional limitations may persist postoperatively. The effects of the surgical approach on postoperative gait biomechanics may influence these limitations after total hip arthroplasty but are currently not well established. The purpose of this study was to investigate the differences in postoperative gait biomechanical differences, at early and late follow-up, in patients with hip osteoarthritis who underwent total hip arthroplasty using different surgical approaches. METHODS: Four electronic databases were searched from their inception to December 2016. Four pairs of reviewers independently determined study eligibility, rated study quality, and extracted data. Pooled estimates for each meta-analysis were obtained using a random-effects model. Mean differences (MDs) and standardized mean differences (SMDs) were calculated for spatiotemporal, kinematic, and kinetic gait variables at early (≤3 months) and late (≥6 months) postoperative follow-up. The posterior, anterior, direct lateral, and anterolateral approaches were compared using the mean postoperative differences between approaches, standard deviations, and sample sizes. RESULTS: Nineteen studies (757 participants) were included. Individual and pooled effect sizes for the differences between approaches were inconsistent, with minimal significant differences at early or late follow-up. A significant increase in step length was observed after the posterior approach compared with the anterolateral approach at early (SMD = 0.68, p = 0.035) and late (SMD = 0.46, p = 0.032) follow-up, as well as a significant increase in hip adduction moment after the posterior approach compared with the lateral approach at early follow-up (SMD = 0.70, p = 0.020). Effect sizes ranged from small to very large, but too few studies comparing similar surgical approaches, as well as inconsistent reporting of outcome measures, limited the ability to pool data. CONCLUSIONS: These findings suggest little early or late postoperative difference in gait biomechanics between surgical approaches. Although some significant differences between surgical approaches exist, determining whether the reported postoperative gait value differences are clinically meaningful remains a substantial challenge for the interpretation of these findings. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

The Value of Preoperative Exercise and Education for Patients Undergoing Total Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: Existing evidence regarding the value of preoperative education and/or exercise (prehabilitation) for patients undergoing total joint replacement is conflicting. The purpose of this study was to conduct an updated, comprehensive systematic review with meta-analyses to determine the longitudinal effects and efficacy of prehabilitation on postoperative outcomes in patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). METHODS: We searched 11 electronic databases (MEDLINE, AMED, CINAHL, Embase, Scopus, ProQuest, PEDro, SportDiscus, PsycINFO, and Cochrane) from their inception to May 2016 for randomized controlled trials that compared changes in pain, function, strength, anxiety, and hospital length of stay following THA or TKA. Two reviewers independently determined study eligibility, rated study quality, and extracted data. There were no restrictions on study dates, patient characteristics, or the follow-up time point at which postoperative outcomes were measured. We excluded trials comparing 2 interventions. Methodological quality assessments were performed using the Cochrane risk-of-bias tool. We calculated pooled estimates, with 95% confidence intervals (CIs), of standardized mean differences (SMDs). RESULTS: Thirty-five studies with 2,956 patients were included. After a preoperative program, patients undergoing THA, but not TKA, had significantly less postoperative pain than controls (SMD = 0.15, 95% CI = 0.03 to 0.27, p = 0.017). Postoperative function was also significantly improved compared with controls, with similar improvement after THA (SMD = 0.32, 95% CI = 0.15 to 0.50, p < 0.001) and TKA (SMD = 0.32, 95% CI = 0.06 to 0.57, p = 0.015). Significantly greater quadriceps strength was observed after TKA (SMD = 0.42, 95% CI = 0.16 to 0.68, p = 0.002). No significant differences in hamstring strength were observed between groups after TKA (p = 0.132). Small-to-moderate but nonsignificant improvements in anxiety (SMD = 0.17, 95% CI = -0.05 to 0.39; p = 0.128) were observed after THA, and length of stay was significantly shorter after TKA (SMD = 0.54, 95% CI = 0.24 to 0.84, p < 0.001) and THA (p = 0.027). CONCLUSIONS: Overall effect sizes for prehabilitation were small to moderate. In patients undergoing TKA, significant improvements were observed in function, quadriceps strength, and length of stay. In patients undergoing THA, significant improvements were observed in pain, function, and length of stay. Included studies were inconsistent with regard to the types of outcome measures reported, and the quality of the interventions varied. A more standardized approach to reporting of clinical trial interventions and patient compliance is needed to thoroughly evaluate the effects of prehabilitation on postoperative outcomes. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Combined versus individual effects of a valgus knee brace and lateral wedge foot orthotic during stair use in patients with knee osteoarthritis.

The aim of this study was to investigate the combined and individual biomechanical effects of a valgus knee brace and a lateral wedge foot orthotic during stair ascent and descent in patients with knee osteoarthritis (OA). Thirty-five patients with varus alignment and medial knee OA were prescribed a custom valgus knee brace and lateral wedge foot orthotic. Knee angles and moments in the frontal and sagittal planes were determined from 3D gait analysis completed under four randomized conditions: (1) control (no knee brace or foot orthotic), (2) knee brace, (3) foot orthotic, and (4) combined knee brace and foot orthotic. Additional measures included the vertical ground reaction force, trunk lean, toe out and gait speed. During the combined use of a knee brace and foot orthotic, significant decreases in the knee adduction angle (2.17, 95%CI: 0.50-3.84, p=0.013) and 2nd peak EKAM (0.35, 95%CI: 0.17-0.52, p<0.001) were observed during stair descent; and significant increases in the EKFM were observed during stair ascent (0.54, 95%CI: 0.30-0.78, p<0.001) and descent (1stpk: 0.48, 95%CI: 0.15-0.80, p=0.005; 2ndpk: 0.55, 95%CI: 0.34-0.76, p<0.001). Fewer gait compensations were observed between conditions during stair descent compared to ascent, except for toe out. Findings suggest greater effects on gait when both knee brace and foot orthotic are used together, resulting in a more normal gait pattern. However, whether or not a true change in knee joint load can be inferred when using these orthoses remains unclear. Further research is required to determine the clinical importance of the observed changes.

Effects of Recombinant Human Growth Hormone for Osteoporosis: Systematic Review and Meta-Analysis.

Our objective was to evaluate the efficacy of recombinant human growth hormone (GH) on bone mineral density (BMD) in persons age 50 and older, with normal pituitary function, with or at risk for developing osteoporosis. We systematically reviewed randomized clinical trials (RCTs), searching six databases, and conducted meta-analyses to examine GH effects on BMD of the lumbar spine and femoral neck. Data for fracture incidence, bone metabolism biomarkers, and adverse events were also extracted and analysed. Thirteen RCTs met the eligibility criteria. Pooled effect sizes suggested no significant GH effect on BMD. Pooled effect sizes were largest, but nonsignificant, when compared to placebo. GH had a significant effect on several bone metabolism biomarkers. A significantly higher rate of adverse events was observed in the GH groups. Meta-analysis of RCTs suggests that GH treatment for persons with or at risk for developing osteoporosis results in very small, nonsignificant increases in BMD.

Longitudinal Changes in Magnetic Resonance Imaging-Based Measures of Femorotibial Cartilage Thickness as a Function of Alignment and Obesity: Data From the Osteoarthritis Initiative.

OBJECTIVE: To investigate the interaction between malalignment and body mass index (BMI) on cartilage thickness change in patients with knee osteoarthritis (OA). METHODS: Femorotibial cartilage thickness was measured from baseline to 2 years in 558 knees with radiographic OA. Cartilage thickness was determined in the central weight-bearing medial femorotibial cartilage (cMFTC) and lateral (cLFTC) compartments. Femorotibial angle (FTA) was stratified into neutral, minor, and definite malalignment. BMI was stratified using World Health Organization classifications for normal, overweight, and obese. Multivariable linear regression models were used to investigate the interaction between alignment and BMI, adjusting for age, sex, and disease severity. RESULTS: There was no significant interaction for continuous measures of alignment and BMI (P = 0.301 for cMFTC and P = 0.852 for cLFTC). Using BMI tertiles, the association between alignment and medial or lateral cartilage thickness loss was not moderated by BMI, despite a significant association of malalignment with greater cartilage thickness loss (P ≤ 0.005). Using FTA tertiles, the association between BMI and medial cartilage thickness loss was approximately 3 times greater in knees with definite malalignment (P = 0.149) and approximately 5 times greater in knees with minor malalignment (P = 0.006). Specifically, knees with minor varus significantly modified this relationship (P = 0.021). CONCLUSION: Malalignment was significantly associated with cartilage thickness loss per degree increase in malalignment, but was not moderated by BMI. BMI was significantly associated with greater rates of medial cartilage thickness loss per unit increase in BMI but only in knees with minor varus malalignment. These findings have implications for better understanding patient subgroups and intervention strategies targeting risk factors for knee OA.

Knee loading patterns of the non-paretic and paretic legs during post-stroke gait.

BACKGROUND: Post-stoke gait disorders could cause secondary musculoskeletal complications associated with excessive repetitive loading. The study objectives were to 1) determine the feasibility of measuring common proxies for dynamic medial knee joint loading during gait post-stroke with external knee adduction (KAM) and flexion moments (KFM) and 2) characterize knee loading and typical load-reducing compensations post-stroke. METHODS: Participants with stroke (n=9) and healthy individuals (n=17) underwent 3D gait analysis. The stroke and healthy groups were compared with unpaired t-tests on peak KAM and peak KFM and on typical medial knee joint load-reducing compensations; toe out and trunk lean. The relationship between KAM and load-reducing compensations in the stroke group were investigated with Spearman correlations. RESULTS: Mean (SD) values for KAM and KFM in the healthy group[KAM=2.20 (0.88)%BW*ht; KFM=0.64 (0.60)%BW*ht] were not significantly different from the values for the paretic [KAM=2.64 (0.98)%BW*ht; KFM=1.26 (1.13)%BW*ht] or non-paretic leg of the stroke group[KAM=2.23(0.62)%BW*ht; KFM=1.10 (1.20)%BW*ht]. Post hoc one sample t-tests revealed greater loading in stroke participants on the paretic (n=3), non-paretic (n=1) and both legs (n=2) compared to the healthy group. The angle of trunk lean and the angle of toe out were not related to KAM in the stroke group. DISCUSSION: Measurement of limb loading during a gait post-stroke is feasible and revealed excessive loading in individuals with mild to moderate stroke compared to healthy adults. Further investigation of potential joint degeneration and pain due to repetitive excessive loading associated with post-stroke gait is warranted.

Sensitivity of different measures of frontal plane alignment to medial and lateral joint space narrowing: From the osteoarthritis initiative.

OBJECTIVES: To explore cross-sectional relationships between a new radiographic measure of the femorotibial angle (FTA), the hip-knee-ankle angle (HKA), and the goniometry; to quantify sex differences between measures; and to evaluate the sensitivity of these measures to medial and lateral joint space narrowing (JSN). METHODS: Concurrent validity was evaluated in 2123 knees from the osteoarthritis (OA) initiative using Pearson correlation coefficients (r) and Bland-Altman plots (offsets). Diagnostic validity with respect to JSN was evaluated using areas under the receiver-operating characteristic curves (AUC) and standardized mean differences (SMD). Analyses were stratified by sex and JSN. RESULTS: JSN and sex contributed significantly to regression models predicting offsets between measures (p < 0.001), after controlling for age, BMI, and OA severity. There were weak correlations between FTA vs. goniometry (r: 0.16-0.22), and moderate correlations between FTA vs. HKA (r: 0.25-0.53) and HKA vs. goniometry (r: 0.40-0.67). The offset between the new FTA measure and HKA was larger in females than males (p < 0.001). Offsets between radiographic measures and goniometry also varied by sex and JSN (FTA: 2.9°-7.6°; HKA: 0.5°-2.4°). AUC (0.74-0.91) and SMD (0.53-3.80) between JSN strata were largest for FTA, whereas diagnostic validity was moderate for HKA (AUC: 0.69-0.80; SMD: 0.43-2.04) and weakest for handheld goniometry (AUC: 0.56-0.63; SMD: 0.07-0.90). CONCLUSIONS: Compared to HKA, goniometry demonstrated poor diagnostic validity with respect to JSN. The new FTA measure, in contrast, represented a reasonable surrogate of radiographic disease severity (JSN). The new FTA measure was skewed in the varus direction when compared to HKA and more so in females. This requires cautious interpretation when measurements are related to previous studies.

Valgus bracing for knee osteoarthritis: a meta-analysis of randomized trials.

OBJECTIVE: To evaluate the effects of valgus knee bracing on pain and function, and compliance and complications, in patients with medial knee osteoarthritis (OA). METHODS: A meta-analysis of randomized controlled trials that compared changes in patient-reported pain and/or function in patients with medial knee OA was performed. Seven databases were searched from their inception to January 2014. Two reviewers independently determined study eligibility, rated risk of bias, and extracted data. Pooled estimates and 95% confidence intervals (95% CIs) for standardized mean differences (SMDs) for the improvement in pain (and function) were calculated. Event rates (proportions) were calculated for studies that reported complications. RESULTS: Six studies were included in the meta-analysis. Overall, there was a statistically significant difference favoring the valgus brace group for improvement in pain (SMD 0.33 [95% CI 0.13, 0.52], P = 0.001) and function (SMD 0.22 [95% CI 0.02, 0.41], P = 0.03). When compared to a control group that did not use an orthosis, the effect size was moderate for pain (SMD 0.56 [95% CI 0.03, 1.09], P = 0.04) and function (SMD 0.48 [95% CI 0.02, 0.95], P = 0.04). When compared to a control group that used a control orthosis, only a small, statistically significant effect for pain remained (SMD 0.33 [95% CI 0.08, 0.58], P = 0.01). Instructions for brace use varied considerably and compliance ranged from 45% to 100%. Up to 25% of patients reported minor complications with brace use. CONCLUSION: Meta-analysis of randomized trials suggests valgus bracing for medial knee OA results in small-to-moderate improvements in pain. Effect sizes vary based on study design and warrant future research.

Osteoarthritis in 2014: Changing how we define and treat patients with OA.

Important advances in 2014 foster new perspectives on definitions of early and end-stage disease, and promote a shift in the clinical management of osteoarthritis (OA) through implementing treatment algorithms intended to minimize strain on current health-care models. Collectively, these changes shed new light on developing and optimizing approaches to OA treatment.

Outcomes for patients with the same disease treated inside and outside of randomized trials: a systematic review and meta-analysis.

BACKGROUND: It is unclear whether participation in a randomized controlled trial (RCT), irrespective of assigned treatment, is harmful or beneficial to participants. We compared outcomes for patients with the same diagnoses who did ("insiders") and did not ("outsiders") enter RCTs, without regard to the specific therapies received for their respective diagnoses. METHODS: By searching the MEDLINE (1966-2010), Embase (1980-2010), CENTRAL (1960-2010) and PsycINFO (1880-2010) databases, we identified 147 studies that reported the health outcomes of "insiders" and a group of parallel or consecutive "outsiders" within the same time period. We prepared a narrative review and, as appropriate, meta-analyses of patients' outcomes. RESULTS: We found no clinically or statistically significant differences in outcomes between "insiders" and "outsiders" in the 23 studies in which the experimental intervention was ineffective (standard mean difference in continuous outcomes -0.03, 95% confidence interval [CI] -0.1 to 0.04) or in the 7 studies in which the experimental intervention was effective and was received by both "insiders" and "outsiders" (mean difference 0.04, 95% CI -0.04 to 0.13). However, in 9 studies in which an effective intervention was received only by "insiders," the "outsiders" experienced significantly worse health outcomes (mean difference -0.36, 95% CI -0.61 to -0.12). INTERPRETATION: We found no evidence to support clinically important overall harm or benefit arising from participation in RCTs. This conclusion refutes earlier claims that trial participants are at increased risk of harm.

Combined tibial tubercle osteotomy with medial opening wedge high tibial osteotomy minimizes changes in patellar height: a prospective cohort study with historical controls.

BACKGROUND: Medial opening wedge high tibial osteotomy (HTO) for the treatment of varus gonarthrosis can be associated with inadvertent decreases in patellar height. HYPOTHESIS: Decreases in patellar height observed after medial opening wedge HTO can be minimized with the addition of a tibial tubercle osteotomy (TTO). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Twenty-nine patients undergoing medial opening wedge HTO with a concurrent TTO were matched with 29 controls who previously underwent medial opening wedge HTO without a TTO. Both groups had substantial varus malalignment (mean mechanical axis angle, -10° ± 3°) requiring large corrections. Measurements of patellar height and posterior tibial slope were calculated from standing lateral radiographs and compared preoperatively and 6 months postoperatively. Patellar height measures included the Blackburne-Peel index, Caton-Deschamps index, Miura-Kawamura index, Insall-Salvati ratio, and modified Insall-Salvati ratio. RESULTS: The changes in the Blackburne-Peel, Caton-Deschamps, and Miura-Kawamura indices were significantly less in the HTO/TTO group versus the HTO group. There were 3 of 29 (10%) new cases that met the radiographic criteria for patella infera in the HTO/TTO group versus 11 of 29 (38%) new cases of patella infera found postoperatively in the HTO group, suggesting an absolute risk reduction of 28% with TTO. The changes in the Blackburne-Peel and Caton-Deschamps indices were correlated to a larger preoperative varus deformity in the coronal plane (r = 0.52 and r = 0.41, respectively). CONCLUSION: The addition of a TTO when performing a medial opening wedge HTO minimizes the decreases in patellar height associated with the procedure.

Combined effects of a valgus knee brace and lateral wedge foot orthotic on the external knee adduction moment in patients with varus gonarthrosis.

OBJECTIVE: To test the hypothesis that a custom-fit valgus knee brace and custom-made lateral wedge foot orthotic will have greatest effects on decreasing the external knee adduction moment during gait when used concurrently. DESIGN: Proof-of-concept, single test session, crossover trial. SETTING: Biomechanics laboratory within a tertiary care center. PARTICIPANTS: Patients (n=16) with varus alignment and knee osteoarthritis (OA) primarily affecting the medial compartment of the tibiofemoral joint (varus gonarthrosis). INTERVENTIONS: Custom-fit valgus knee brace and custom-made full-length lateral wedge foot orthotic. Amounts of valgus angulation and wedge height were tailored to each patient to ensure comfort. MAIN OUTCOME MEASURES: The external knee adduction moment (% body weight [BW]*height [Ht]), frontal plane lever arm (cm), and ground reaction force (N/kg), determined from 3-dimensional gait analysis completed under 4 randomized conditions: (1) control (no knee brace, no foot orthotic), (2) knee brace, (3) foot orthotic, and (4) knee brace and foot orthotic. RESULTS: The reduction in knee adduction moment was greatest when concurrently using the knee brace and foot orthotic (effect sizes ranged from 0.3 to 0.4). The mean decrease in first peak knee adduction moment compared with control was .36% BW*Ht (95% confidence interval [CI], -.66 to -.07). This was accompanied by a mean decrease in frontal plane lever arm of .59cm (95% CI, -.94 to -.25). CONCLUSIONS: These findings suggest that using a custom-fit knee brace and custom-made foot orthotic concurrently can produce a greater overall reduction in the knee adduction moment, through combined effects in decreasing the frontal plane lever arm.

Rho activation regulates CXCL12 chemokine stimulated actin rearrangement and restitution in model intestinal epithelia.

Chemokines are critical regulatory factors that direct migration, proliferation and maturation of receptor expressing target cells within gut mucosa. The aim of the present study was to define the cellular mechanisms whereby engagement of the essential chemokine CXCL12 to CXCR4 regulates restitutive epithelial cell migration. Non-transformed IEC-6 cells or polarized T84 epithelial monolayers were wounded and F-actin accumulation assessed using fluorescence microscopy and flow cytometry. Immunoblot analysis, pull-down assays, fluorescence microscopy and wound healing assays defined activation of Rho, Rho-kinase (ROCK), and myosin light chain (MLC) and the role for those Rho effectors in CXCL12-regulated epithelial restitution. CXCL12 increased RhoGTP and F-actin localization to the leading edge of wounded IEC-6 and T84 monolayers. CXCL12 congruently stimulated an increase in active MLC that was inhibited by blockade of ROCK and myosin light chain kinase and regulated epithelial migration. Our data in model intestinal epithelia suggest CXCR4 and CXCL12 may function as an autocrine and paracrine mucosal signaling network regulating the competency of the epithelial barrier to withstand injury and mediate repair following damage.