Personalization improves the biomechanical efficacy of foot progression angle modifications in individuals with medial knee osteoarthritis.

Modifying the foot progression angle during walking can reduce the knee adduction moment, a surrogate measure of medial knee loading. However, not all individuals reduce their knee adduction moment with the same modification. This study evaluates whether a personalized approach to prescribing foot progression angle modifications increases the proportion of individuals with medial knee osteoarthritis who reduce their knee adduction moment, compared to a non-personalized approach. Individuals with medial knee osteoarthritis (N=107) walked with biofeedback instructing them to toe-in and toe-out by 5° and 10° relative to their self-selected angle. We selected individuals' personalized foot progression angle as the modification that maximally reduced their larger knee adduction moment peak. Additionally, we used lasso regression to identify which secondary kinematic changes made a 10° toe-in gait modification more effective at reducing the first knee adduction moment peak. Seventy percent of individuals reduced their larger knee adduction moment peak by at least 5% with a personalized foot progression angle modification, which was more than (p≤0.002) the 23-57% of individuals who reduced it with a uniformly assigned 5° or 10° toe-in or toe-out modification. When toeing-in, greater reductions in the first knee adduction moment peak were related to an increased frontal-plane tibia angle (knee more medial than ankle), a more valgus knee abduction angle, reduced contralateral pelvic drop, and a more medialized center of pressure in the foot reference frame. In summary, personalization increases the proportion of individuals with medial knee osteoarthritis who may benefit from a foot progression angle modification.

Corrigendum: Long-Term Cognitive Impairments and Pathological Alterations in a Mouse Model of Repetitive Mild Traumatic Brain Injury.

[This corrects the article DOI: 10.3389/fneur.2014.00012.].

Changes in foot progression angle during gait reduce the knee adduction moment and do not increase hip moments in individuals with knee osteoarthritis.

People with knee osteoarthritis who adopt a modified foot progression angle (FPA) during gait often benefit from a reduction in the knee adduction moment. It is unknown, however, whether changes in the FPA increase hip moments, a surrogate measure of hip loading, which will increase the mechanical demand on the joint. This study examined how altering the FPA affects hip moments. Individuals with knee osteoarthritis walked on an instrumented treadmill with their baseline gait, 10° toe-in gait, and 10° toe-out gait. A musculoskeletal modeling package was used to compute joint moments from the experimental data. Fifty participants were selected from a larger study who reduced their peak knee adduction moment with a modified FPA. In this group, participants reduced the first peak of the knee adduction moment by 7.6% with 10° toe-in gait and reduced the second peak by 11.0% with 10° toe-out gait. Modifying the FPA reduced the early-stance hip abduction moment, at the time of peak hip contact force, by 4.3% ± 1.3% for 10° toe-in gait (p = 0.005, d = 0.49) and by 4.6% ± 1.1% for 10° toe-out gait (p < 0.001, d = 0.59) without increasing the flexion and internal rotation moments (p > 0.15). Additionally, 74% of individuals reduced their total hip moment at time of peak hip contact force with a modified FPA. In summary, when adopting a FPA modification that reduced the knee adduction moment, participants, on average, did not increase surrogate measures of hip loading.

Tibiofemoral forces during FES rowing in individuals with spinal cord injury.

The purpose of this study is to determine the tibiofemoral forces during functional electrical stimulation (FES) rowing in individuals with spinal cord injury (SCI). We analysed the motion of five participants with SCI during FES rowing, with simultaneous measurements of (i) three-dimensional marker trajectories, (ii) foot reaction forces (FRFs), (iii) ergometer handle forces, and (iv) timestamps for electrical stimulation of the quadriceps and hamstrings muscles. We created full-body musculoskeletal models in OpenSim to determine subject-specific tibiofemoral forces during FES rowing. The peak magnitudes of tibiofemoral forces averaged over five participants with SCI were 2.43 ± 0.39 BW and 2.25 ± 0.71 BW for the left and right legs, respectively. The peak magnitudes of FRFs were 0.19 ± 0.04 BW in each leg. The peak magnitude of handle forces was 0.47 ± 0.19 BW. Peak tibiofemoral force was associated with peak FRF (magnitudes, R2 = 0.56, p = 0.013) and peak handle force (magnitudes, R2 = 0.54, p = 0.016). The ratios of peak magnitude of tibiofemoral force to peak magnitude of FRF were 12.9 ± 1.9 (left) and 11.6 ± 2.4 (right), and to peak magnitude of handle force were 5.7 ± 2.3 (left) and 4.9 ± 0.9 (right). This work lays the foundation for developing a direct exercise intensity metric for bone mechanical stimulus at the knee during rehabilitation exercises. Clinical Significance: Knowledge of tibiofemoral forces from exercises such as FES rowing may provide clinicians the ability to personalize rehabilitation protocols to ensure that an SCI patient is receiving the minimum dose of mechanical stimulus necessary to maintain bone health.

Rapid volumetric gagCEST imaging of knee articular cartilage at 3 T: evaluation of improved dynamic range and an osteoarthritic population.

Chemical exchange saturation transfer of glycosaminoglycans, gagCEST, is a quantitative MR technique that has potential for assessing cartilage proteoglycan content at field strengths of 7 T and higher. However, its utility at 3 T remains unclear. The objective of this work was to implement a rapid volumetric gagCEST sequence with higher gagCEST asymmetry at 3 T to evaluate its sensitivity to osteoarthritic changes in knee articular cartilage and in comparison with T2 and T1ρ measures. We hypothesize that gagCEST asymmetry at 3 T decreases with increasing severity of osteoarthritis (OA). Forty-two human volunteers, including 10 healthy subjects and 32 subjects with medial OA, were included in the study. Knee Injury and Osteoarthritis Outcome Scores (KOOS) were assessed for all subjects, and Kellgren-Lawrence grading was performed for OA volunteers. Healthy subjects were scanned consecutively at 3 T to assess the repeatability of the volumetric gagCEST sequence at 3 T. For healthy and OA subjects, gagCEST asymmetry and T2 and T1ρ relaxation times were calculated for the femoral articular cartilage to assess sensitivity to OA severity. Volumetric gagCEST imaging had higher gagCEST asymmetry than single-slice acquisitions (p = 0.015). The average scan-rescan coefficient of variation was 6.8%. There were no significant differences in average gagCEST asymmetry between younger and older healthy controls (p = 0.655) or between healthy controls and OA subjects (p = 0.310). T2 and T1ρ relaxation times were elevated in OA subjects (p < 0.001 for both) compared with healthy controls and both were moderately correlated with total KOOS scores (rho = -0.181 and rho = -0.332 respectively). The gagCEST technique developed here, with volumetric scan times under 10 min and high gagCEST asymmetry at 3 T, did not vary significantly between healthy subjects and those with mild-moderate OA. This further supports a limited utility for gagCEST imaging at 3 T for assessment of early changes in cartilage composition in OA.

pyKNEEr: An image analysis workflow for open and reproducible research on femoral knee cartilage.

Transparent research in musculoskeletal imaging is fundamental to reliably investigate diseases such as knee osteoarthritis (OA), a chronic disease impairing femoral knee cartilage. To study cartilage degeneration, researchers have developed algorithms to segment femoral knee cartilage from magnetic resonance (MR) images and to measure cartilage morphology and relaxometry. The majority of these algorithms are not publicly available or require advanced programming skills to be compiled and run. However, to accelerate discoveries and findings, it is crucial to have open and reproducible workflows. We present pyKNEEr, a framework for open and reproducible research on femoral knee cartilage from MR images. pyKNEEr is written in python, uses Jupyter notebook as a user interface, and is available on GitHub with a GNU GPLv3 license. It is composed of three modules: 1) image preprocessing to standardize spatial and intensity characteristics; 2) femoral knee cartilage segmentation for intersubject, multimodal, and longitudinal acquisitions; and 3) analysis of cartilage morphology and relaxometry. Each module contains one or more Jupyter notebooks with narrative, code, visualizations, and dependencies to reproduce computational environments. pyKNEEr facilitates transparent image-based research of femoral knee cartilage because of its ease of installation and use, and its versatility for publication and sharing among researchers. Finally, due to its modular structure, pyKNEEr favors code extension and algorithm comparison. We tested our reproducible workflows with experiments that also constitute an example of transparent research with pyKNEEr, and we compared pyKNEEr performances to existing algorithms in literature review visualizations. We provide links to executed notebooks and executable environments for immediate reproducibility of our findings.

Bone changes in the lower limbs from participation in an FES rowing exercise program implemented within two years after traumatic spinal cord injury.

Objective: To determine the effect of a functional electrical stimulation (FES) rowing program on bone mineral density (BMD) when implemented within two years after SCI.Design: Prospective.Setting: Health Care Facility.Participants: Convenience sample; four adults with recent (<2 years) traumatic, motor complete SCI (C7-T12 AIS A-B).Intervention: A 90-session FES rowing exercise program; participants attended 30-minute FES training sessions approximately three times each week for the duration of their participation.Outcome Measures: BMD in the distal femur and tibia were measured using peripheral Quantitative Computed Tomography (pQCT) at enrollment (T0) and after 30 (T1), 60 (T2), and 90 (T3) sessions. Bone stimulus was calculated for each rower at each time point using the average number of weekly loading cycles, peak foot reaction force, and bone mineral content from the previous time point. A regression analysis was used to determine the relationship between calculated bone stimulus and change in femoral trabecular BMD between time points.Results: Trabecular BMD in the femur and tibia decreased for all participants in T0-1, but the rate of loss slowed or reversed between T1-2, with little-to-no bone loss for most participants during T2-3. The calculated bone stimulus was significantly correlated with change in femoral trabecular BMD (P = 0.016; R2 = 0.458).Conclusion: Consistent participation in an FES rowing program provides sufficient forces and loading cycles to reduce or reverse expected bone loss at the distal femur and tibia, at least temporarily, in some individuals within two years after SCI.Trial Registration: NCT02008149.

Patellofemoral cartilage stresses are most sensitive to variations in vastus medialis muscle forces.

The purpose of this study was to evaluate the effects of variations in quadriceps muscle forces on patellofemoral stress. We created subject-specific finite element models for 21 individuals with chronic patellofemoral pain and 16 pain-free control subjects. We extracted three-dimensional geometries from high resolution magnetic resonance images and registered the geometries to magnetic resonance images from an upright weight bearing squat with the knees flexed at 60°. We estimated quadriceps muscle forces corresponding to 60° knee flexion during a stair climb task from motion analysis and electromyography-driven musculoskeletal modelling. We applied the quadriceps muscle forces to our finite element models and evaluated patellofemoral cartilage stress. We quantified cartilage stress using an energy-based effective stress, a scalar quantity representing the local stress intensity in the tissue. We used probabilistic methods to evaluate the effects of variations in quadriceps muscle forces from five trials of the stair climb task for each subject. Patellofemoral effective stress was most sensitive to variations in forces in the two branches of the vastus medialis muscle. Femur cartilage effective stress was most sensitive to variations in vastus medialis forces in 29/37 (78%) subjects, and patella cartilage effective stress was most sensitive to variations in vastus medialis forces in 21/37 (57%) subjects. Femur cartilage effective stress was more sensitive to variations in vastus medialis longus forces in subjects classified as maltrackers compared to normal tracking subjects (p = 0.006). This study provides new evidence of the importance of the vastus medialis muscle in the treatment of patellofemoral pain.

Effectiveness of conservative treatment for patellofemoral pain syndrome: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the evidence regarding the effectiveness of conservative treatment in reducing patellofemoral pain. DATA SOURCES: CENTRAL, MEDLINE, CINAHL, and PEDro databases. STUDY SELECTION: Adults with patellofemoral pain, randomized controlled trials only, any conservative treatment compared with placebo, sham, other conservative treatment, or no treatment. Two independent reviewers. DATA EXTRACTION: Data were extracted from the full-text of the articles, based on Cochrane Collaboration recommendations. The outcome of interest was the difference between groups regarding change in pain severity. DATA SYNTHESIS: The majority of studies were underpowered. More than 80% of the 37 trials did not show a clinically significant benefit. Clinically significant effects of different sizes were found for 7 trials (6 studies out of 7 had short follow-ups). These effects were found for: (i) pulsed electromagnetic fields combined with home exercise -33.0 (95% CI -45.2 to -20.8); (ii) hip muscle strengthening -65.0 (95% CI -87.7 to -48.3) and -32.0 (-37.0 to -27.0); (iii) weight-bearing exercise -40.0 (95% CI -49.4 to -30.6); (iv) neuromuscular facilitation combined with aerobic exercise and stretching -60.1 (95% CI -66.9 to -54.5); (v) postural stabilization -24.4 (95% CI -33.5 to -15.3); and (vi) patellar bracing -31.6 (95% CI -35.2 to -28.0). CONCLUSION: There is no evidence that a single treat-ment modality works for all patients with patellofemoral pain. There is limited evidence that some treatment modalities may be beneficial for some subgroups of patients with patellofemoral pain.

Subject-specific toe-in or toe-out gait modifications reduce the larger knee adduction moment peak more than a non-personalized approach.

The knee adduction moment (KAM) is a surrogate measure for medial compartment knee loading and is related to the progression of knee osteoarthritis. Toe-in and toe-out gait modifications typically reduce the first and second KAM peaks, respectively. We investigated whether assigning a subject-specific foot progression angle (FPA) modification reduces the peak KAM by more than assigning the same modification to everyone. To explore the effects of motor learning on muscle coordination and kinetics, we also evaluated the peak knee flexion moment and quadriceps-hamstring co-contraction during normal walking, when subjects first learned their subject-specific FPA, and following 20 min of training. Using vibrotactile feedback, we trained 20 healthy adults to toe-in and toe-out by 5° and 10° relative to their natural FPA, then identified the subject-specific FPA as the angle where each subject maximally reduced their larger KAM peak. When walking at their subject-specific FPA, 18 subjects significantly reduced their larger KAM peak; 8 by toeing-in and 10 by toeing-out. On average, subjects reduced their larger KAM peak by 18.6 ±â€¯16.2% when walking at their subject-specific FPA, which was more than the reductions achieved when all subjects toed-in by 10° (10.0 ±â€¯17.1%, p = .013) or toed-out by 10° (11.0 ±â€¯18.3%, p = .002). Quadriceps-hamstring co-contraction and the peak knee flexion moment increased when subjects first learned their subject-specific FPA, but only co-contraction returned to baseline levels following training. These findings demonstrate that subject-specific gait modifications reduce the peak KAM more than uniformly assigned modifications and have the potential to slow the progression of medial compartment knee osteoarthritis.

Pixel-Based DXA-Derived Structural Properties Strongly Correlate with pQCT Measures at the One-Third Distal Femur Site.

While bone mineral density has been traditionally used to quantify fracture risk for individuals with spinal cord injuries, recent studies are including engineering measurements such as section modulus and cross sectional moment of inertia. These are almost exclusively calculated by peripheral QCT scanners which, unlike DXA scanners, are rarely found in clinical settings. Using fifty-four fresh frozen femora, we developed and validated a pixel-by-pixel method to calculate engineering properties at the distal femur using a Hologic QDR-1000 W DXA scanner and compared them against similar parameters measured using a Stratec XCT-3000 peripheral QCT scanner. We found excellent agreement between standard DXA and pixel-by-pixel measured BMD (r 2 = 0.996). Cross-sectional moment of inertia about the anteroposterior axis measured using DXA and pQCT correlated very strongly (r 2 = 0.99). Cross-sectional moment of inertia about the anteroposterior axis measured using DXA also correlated strongly with pQCT measured bone strength index (r 2 = 0.99). These correlations indicate that DXA scans can measure equivalent pQCT parameters, and some existing DXA scans can be reprocessed with pixel-by-pixel techniques. Ultimately, these engineering parameters may help better quantify fracture-risk in fracture-prone populations such as those with spinal cord injuries.

FES-rowing attenuates bone loss following spinal cord injury as assessed by HR-pQCT.

Neurologically motor complete spinal cord injury (SCI) presents a unique model of bone loss whereby specific regional sites are exposed to a complete loss of voluntary muscle-induced skeletal loading against gravity. This results in a high rate of bone loss, especially in the lower limbs where trabecular bone mass decreases by ~50-60% and cortical bone mass decreases by 25-34% before the rate of bone loss slows. These SCI-induced losses that are likely superimposed on continual age-related bone losses, increase the risk of low-impact fragility fracture. The fracture incidence 20 years post SCI is reported to be 4.6% per year. An intervention that effectively prevents, attenuates, or reverses bone loss is therefore highly desirable. We present a case study of an individual with chronic complete SCI, where bone loss has been attenuated following long-term functional electrical stimulation (FES)-rowing training. In this case study, we characterize the ultradistal tibia and ultradistal radius of the FES-rower with chronic complete SCI using high-resolution-peripheral quantitative computed tomography. These data are compared with a group of FES-untrained individuals with chronic complete SCI and to a normative non-SCI cohort. The evidence suggests, albeit from a single individual, that long-term FES-rowing training can attenuate bone loss secondary to chronic complete SCI. Indeed, key FES-rower's bone metrics for the ultradistal tibia more closely resemble normative age-matched values, which may have clinical significance since the majority of fragility fractures in chronic SCI occur in the lower extremities.

T1ρ Dispersion in Articular Cartilage: Relationship to Material Properties and Macromolecular Content.

OBJECTIVE: This study assessed T1ρ relaxation dispersion, measured by magnetic resonance imaging (MRI), as a tool to noninvasively evaluate cartilage material and biochemical properties. The specific objective was to answer two questions: (1) does cartilage initial elastic modulus (E 0) correlate with T1ρ dispersion effects and (2) does collagen or proteoglycan content correlate with T1ρ dispersion effects? DESIGN: Cadaveric patellae with and without visible cartilage damage on conventional MR were included. T2 and T1ρ relaxation times at 500 and 1000 Hz spin-lock field amplitudes were measured. We estimated T1ρ dispersion effects by measuring T1ρ relaxation time at 500 and 1000 Hz and T2 relaxation time and using a new tool, the ratio T1ρ/T2. Cartilage initial elastic modulus, E 0, was measured from initial response of mechanical indentation creep tests. Collagen and proteoglycan contents were measured at the indentation test sites; proteoglycan content was measured by their covalently linked sulfated glycosaminoglycans (sGAG). Pearson correlation coefficients were determined, taking into account the clustering of multiple samples within a single patella specimen. RESULTS: Cartilage initial elastic modulus, E 0, increased with decreasing values of T1ρ/T2 measurements at both 500 Hz (P = 0.034) and 1000 Hz (P = 0.022). 1/T1ρ relaxation time (500 Hz) increased with increasing sGAG content (P = 0.041). CONCLUSIONS: T1ρ/T2 ratio, a new tool, and cartilage initial elastic modulus are both measures of water-protein interactions, are dependent on the cartilage structure, and were correlated in this study.

The Role of Cartilage Stress in Patellofemoral Pain.

PURPOSE: Elevated cartilage stress has been identified as a potential mechanism for retropatellar pain; however, there are limited data in the literature to support this mechanism. Females are more likely to develop patellofemoral pain than males, yet the causes of this dimorphism are unclear. We used experimental data and computational modeling to determine whether patients with patellofemoral pain had elevated cartilage stress compared with pain-free controls and test the hypothesis that females exhibit greater cartilage stress than males. METHODS: We created finite element models of 24 patients with patellofemoral pain (11 males and 13 females) and 16 pain-free controls (8 males and 8 females) to estimate peak patellar cartilage stress (strain energy density) during a stair climb activity. Simulations took into account cartilage morphology from magnetic resonance imaging, joint posture from weight-bearing magnetic resonance imaging, and muscle forces from an EMG-driven model. RESULTS: We found no difference in peak patellar strain energy density between those with patellofemoral pain (1.9 ± 1.23 J·m(-3)) and control subjects (1.66 ± 0.75 J·m(-3), P = 0.52). Females exhibited greater cartilage stress compared with males (2.2 vs 1.3 J·m(-3), respectively; P = 0.0075), with large quadriceps muscle forces (3.7 body weight in females vs 3.3 body weight in males) and 23% smaller joint contact area (females, 467 ± 59 mm2, vs males, 608 ± 95 mm2). CONCLUSIONS: Patients with patellofemoral pain did not display significantly greater patellar cartilage stress compared with pain-free controls; however, there was a great deal of subject variation. Females exhibited greater peak cartilage stress compared with males, which might explain the greater prevalence of patellofemoral pain in females compared with that in males, but other mechanical and biological factors are clearly involved in this complex pathway to pain.

Comparison of three methods of calculating strain in the mouse ulna in exogenous loading studies.

Axial compression of mouse limbs is commonly used to induce bone formation in a controlled, non-invasive manner. Determination of peak strains caused by loading is central to interpreting results. Load-strain calibration is typically performed using uniaxial strain gauges attached to the diaphyseal, periosteal surface of a small number of sacrificed animals. Strain is measured as the limb is loaded to a range of physiological loads known to be anabolic to bone. The load-strain relationship determined by this subgroup is then extrapolated to a larger group of experimental mice. This method of strain calculation requires the challenging process of strain gauging very small bones which is subject to variability in placement of the strain gauge. We previously developed a method to estimate animal-specific periosteal strain during axial ulnar loading using an image-based computational approach that does not require strain gauges. The purpose of this study was to compare the relationship between load-induced bone formation rates and periosteal strain at ulnar midshaft using three different methods to estimate strain: (A) Nominal strain values based solely on load-strain calibration; (B) Strains calculated from load-strain calibration, but scaled for differences in mid-shaft cross-sectional geometry among animals; and (C) An alternative image-based computational method for calculating strains based on beam theory and animal-specific bone geometry. Our results show that the alternative method (C) provides comparable correlation between strain and bone formation rates in the mouse ulna relative to the strain gauge-dependent methods (A and B), while avoiding the need to use strain gauges.