Associations of pain sensitivity and conditioned pain modulation with physical activity: findings from the Multicenter Osteoarthritis Study (MOST).

OBJECTIVE: Individuals with chronic pain due to knee osteoarthritis (OA) are insufficiently physically active, and alterations of facilitatory and inhibitory nociceptive signaling are common in this population. Our objective was to examine the association of these alterations in nociceptive signaling with objective accelerometer-based measures of physical activity in a large observational cohort. DESIGN: We used data from the Multicenter Osteoarthritis Study. Measures of peripheral and central pain sensitivity included pressure pain threshold at the knee and mechanical temporal summation at the wrist, respectively. The presence of descending pain inhibition was assessed by conditioned pain modulation (CPM). Physical activity was quantitatively assessed over 7 days using a lower back-worn activity monitor. Summary metrics included steps/day, activity intensity, and sedentary time. Linear regression analyses were used to evaluate the association of pain sensitivity and the presence of descending pain inhibition with physical activity measures. RESULTS: Data from 1873 participants was analyzed (55.9% female, age = 62.8 ± 10.0 years). People having greater peripheral and central sensitivity showed lower step counts. CPM was not significantly related to any of the physical activity measures, and none of the exposures were significantly related to sedentary time. CONCLUSIONS: In this cohort, greater peripheral and central sensitivity were associated with reduced levels of objectively-assessed daily step counts. Further research may investigate ways to modify or treat heightened pain sensitivity as a means to increase physical activity in older adults with knee OA.

Sex differences in osteoarthritis prevalence, pain perception, physical function and therapeutics.

OBJECTIVE: Women have a higher prevalence of osteoarthritis (OA) and worse clinical courses than men. However, the underlying factors and therapeutic outcomes of these sex-specific differences are incompletely researched. This review examines the current state of knowledge regarding sex differences in OA prevalence, risk factors, pain severity, functional outcomes, and use and response to therapeutics. METHODS: PubMed database was used with the title keyword combinations "{gender OR sex} AND osteoarthritis" plus additional manual search of the included papers for pertinent references, yielding 212 references. Additional references were added and 343 were reviewed for appropriateness. RESULTS: Globally, women account for 60% of people with osteoarthritis, with a greater difference after age 40. The higher risk for women may be due to differences in joint anatomy, alignment, muscle strength, hormonal influences, obesity, and/or genetics. At the same radiographic severity, women have greater pain severity than men, which may be explained by biologically distinct pain pathways, differential activation of central pain pathways, differences in pain sensitivity, perception, reporting, and coping strategies. Women have greater limitations of physical function and performance than men independent of BMI, OA severity, injury history, and amount of weekly exercise. Women also have greater use of analgesic medications than men but less use of arthroplasty and poorer prognosis after surgical interventions. CONCLUSIONS: The recognition of sex differences in OA manifestations and management could guide tailoring of sex-specific treatment protocols, and analysis of sex as a biological variable in future research would enhance development of precision medicine.

Gait Alterations and Association With Worsening Knee Pain and Physical Function: A Machine Learning Approach With Wearable Sensors in the Multicenter Osteoarthritis Study.

OBJECTIVE: The objective of this study was to identify gait alterations related to worsening knee pain and worsening physical function, using machine learning approaches applied to wearable sensor-derived data from a large observational cohort. METHODS: Participants in the Multicenter Osteoarthritis Study (MOST) completed a 20-m walk test wearing inertial sensors on their lower back and ankles. Parameters describing spatiotemporal features of gait were extracted from these data. We used an ensemble machine learning technique ("super learning") to optimally discriminate between those with and without worsening physical function and, separately, those with and without worsening pain over two years. We then used log-binomial regression to evaluate associations of the top 10 influential variables selected with super learning with each outcome. We also assessed whether the relation of altered gait with worsening function was mediated by changes in pain. RESULTS: Of 2,324 participants, 29% and 24% had worsening knee pain and function over two years, respectively. From the super learner, several gait parameters were found to be influential for worsening pain and for worsening function. After adjusting for confounders, greater gait asymmetry, longer average step length, and lower dominant frequency were associated with worsening pain, and lower cadence was associated with worsening function. Worsening pain partially mediated the association of cadence with function. CONCLUSION: We identified gait alterations associated with worsening knee pain and those associated with worsening physical function. These alterations could be assessed with wearable sensors in clinical settings. Further research should determine whether they might be therapeutic targets to prevent worsening pain and worsening function.

Hip Abductor Weakness and Its Association With New or Worsened Knee Pain: Data From the Multicenter Osteoarthritis Study.

OBJECTIVE: Hip abductors, important for controlling pelvic and femoral orientation during gait, may affect knee pain. Our objective was to evaluate the relation of hip abductor strength to worsened or new-onset frequent knee pain. Given previously noted associations of knee extensor strength with osteoarthritis in women, we performed sex-specific analyses. METHODS: We used data from the Multicenter Osteoarthritis study. Hip abductor and knee extensor strength was measured. Knee pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire and a question about frequent knee pain at baseline (144-month visit), and 8, 16, and 24 months thereafter. Knee pain outcomes were worsened knee pain (2-point increase in WOMAC pain) and incident frequent knee pain (answering yes to the frequent knee pain question among those without frequent knee pain at baseline). Leg-specific analyses tested hip abductor strength as a risk factor for worsened and new frequent knee pain, adjusting for potential covariates. Additionally, we stratified by knee extensor strength (high versus low). RESULTS: Among women, compared to the highest quartile of hip abductor strength, the lowest quartile had 1.7 (95% confidence interval [95% CI] 1.1-2.6) times the odds of worsened knee pain; significant associations were limited to women with high knee extensor strength (odds ratio 2.0 [95% CI 1.1-3.5]). We found no relation of abductor strength to worsening knee pain in men or with incident frequent knee pain in men or women. CONCLUSION: Hip abductor weakness was associated with worsening knee pain in women with strong knee extensors, but not with incident frequent knee pain in men or women. Knee extensor strength may be necessary, but not sufficient, to prevent pain worsening.

Osteoarthritis and Diabetes: Where Are We and Where Should We Go?

Diabetes mellitus (DM) and osteoarthritis (OA) are chronic noncommunicable diseases that affect millions of people worldwide. OA and DM are prevalent worldwide and associated with chronic pain and disability. Evidence suggests that DM and OA coexist within the same population. The coexistence of DM in patients with OA has been linked to the development and progression of the disease. Furthermore, DM is associated with a greater degree of osteoarthritic pain. Numerous risk factors are common to both DM and OA. Age, sex, race, and metabolic diseases (e.g., obesity, hypertension, and dyslipidemia) have been identified as risk factors. These risk factors (demographics and metabolic disorder) are associated with DM or OA. Other possible factors may include sleep disorders and depression. Medications for metabolic syndromes might be related to the incidence and progression of OA, with conflicting results. Given the growing body of evidence indicating a relationship between DM and OA, it is vital to analyze, interpret, and integrate these findings. Therefore, the purpose of this review was to evaluate the evidence on the prevalence, relationship, pain, and risk factors of both DM and OA. The research was limited to knee, hip, and hand OA.

Gait, physical activity and tibiofemoral cartilage damage: a longitudinal machine learning analysis in the Multicenter Osteoarthritis Study.

OBJECTIVE: To (1) develop and evaluate a machine learning model incorporating gait and physical activity to predict medial tibiofemoral cartilage worsening over 2 years in individuals without advanced knee osteoarthritis and (2) identify influential predictors in the model and quantify their effect on cartilage worsening. DESIGN: An ensemble machine learning model was developed to predict worsened cartilage MRI Osteoarthritis Knee Score at follow-up from gait, physical activity, clinical and demographic data from the Multicenter Osteoarthritis Study. Model performance was evaluated in repeated cross-validations. The top 10 predictors of the outcome across 100 held-out test sets were identified by a variable importance measure. Their effect on the outcome was quantified by g-computation. RESULTS: Of 947 legs in the analysis, 14% experienced medial cartilage worsening at follow-up. The median (2.5-97.5th percentile) area under the receiver operating characteristic curve across the 100 held-out test sets was 0.73 (0.65-0.79). Baseline cartilage damage, higher Kellgren-Lawrence grade, greater pain during walking, higher lateral ground reaction force impulse, greater time spent lying and lower vertical ground reaction force unloading rate were associated with greater risk of cartilage worsening. Similar results were found for the subset of knees with baseline cartilage damage. CONCLUSIONS: A machine learning approach incorporating gait, physical activity and clinical/demographic features showed good performance for predicting cartilage worsening over 2 years. While identifying potential intervention targets from the model is challenging, lateral ground reaction force impulse, time spent lying and vertical ground reaction force unloading rate should be investigated further as potential early intervention targets to reduce medial tibiofemoral cartilage worsening.

An open-label, single-arm trial of cryoneurolysis for improvements in pain, activities of daily living and quality of life in patients with symptomatic ankle osteoarthritis.

Objective: Cryoneurolysis, cold-induced reversible conduction block of peripheral nerves, is an effective treatment for reducing knee osteoarthritis (OA) symptoms and opioid use following knee arthroplasty. There are however, limited data concerning its use for ankle OA. Our aim was to assess clinically significant long-term symptomatic relief of ankle OA with cryoneurolysis. Method: This single-center, open-label trial included participants aged >18 years with radiographic tibiotalar OA, unilateral ankle pain ≥5/10 on Numerical Rating Scale (NRS), and with no ankle surgery within 6-months of screening. Following ultrasound-guided cryoneurolysis of nerves in the participant's pain distribution (sural, saphenous, superficial and/or deep fibular nerves), outcomes were assessed at clinic visits (6, 12 and 24-weeks) and by telephone interview (3, 9, 18-weeks). The primary endpoint was change in Foot and Ankle Outcome Score (FAOS) (pain subscale) at 12-weeks. Change in quality of life (FAOS-QoL), activities of daily living (FAOS-ADL), NRS-pain, and physical performance measures were also assessed. Longitudinal mixed models were constructed to evaluate changes from baseline at 6, 12- and 24-weeks post-treatment. Results: Forty participants enrolled (50% female, mean â€‹± â€‹SD age 63.0 â€‹± â€‹12.8 years). At 12-weeks post treatment, FAOS-pain (20.8, p â€‹< â€‹0.0001), ADL (18.1, p â€‹= â€‹0.0003), QoL (19.9, p â€‹= â€‹0.0003) and NRS-pain (-2.6, p â€‹< â€‹0.0001) were significantly improved from baseline. No difference in 40-m fast-paced walking test was detected at 12-weeks post-treatment (-1.2sec, p â€‹= â€‹0.59). For all outcomes, similar findings were observed at 6- and 24-week visits. Conclusion: Cryoneurolysis resulted in statistically significant improvements in ankle pain, physical function and QoL for up to 24-weeks in participants with unilateral, symptomatic ankle OA.

Relation of gait measures with mild unilateral knee pain during walking using machine learning.

Gait alterations in those with mild unilateral knee pain during walking may provide clues to modifiable alterations that affect progression of knee pain and osteoarthritis (OA). To examine this, we applied machine learning (ML) approaches to gait data from wearable sensors in a large observational knee OA cohort, the Multicenter Osteoarthritis (MOST) study. Participants completed a 20-m walk test wearing sensors on their trunk and ankles. Parameters describing spatiotemporal features of gait and symmetry, variability and complexity were extracted. We used an ensemble ML technique ("super learning") to identify gait variables in our cross-sectional data associated with the presence/absence of unilateral knee pain. We then used logistic regression to determine the association of selected gait variables with odds of mild knee pain. Of 2066 participants (mean age 63.6 [SD: 10.4] years, 56% female), 21.3% had mild unilateral pain while walking. Gait parameters selected in the ML process as influential included step regularity, sample entropy, gait speed, and amplitude dominant frequency, among others. In adjusted cross-sectional analyses, lower levels of step regularity (i.e., greater gait variability) and lower sample entropy(i.e., lower gait complexity) were associated with increased likelihood of unilateral mild pain while walking [aOR 0.80 (0.64-1.00) and aOR 0.79 (0.66-0.95), respectively].

Multiparametric 3-D analysis of bone and joint space width at the knee from weight bearing computed tomography.

Objective: Computed tomography (CT) can deliver multiple parameters relevant to osteoarthritis. In this study we demonstrate that a 3-D multiparametric approach at the weight bearing knee with cone beam CT is feasible, can include multiple parameters from across the joint space, and can reveal stronger relationships with disease status in combination. Design: 33 participants with knee weight bearing CT (WBCT) were analysed with joint space mapping and cortical bone mapping to deliver joint space width (JSW), subchondral bone plate thickness, endocortical thickness, and trabecular attenuation at both sides of the joint. All data were co-localised to the same canonical surface. Statistical parametric mapping (SPM) was applied in uni- and multivariate models to demonstrate significant dependence of parameters on Kellgren & Lawrence grade (KLG). Correlation between JSW and bony parameters and 2-week test-retest repeatability were also calculated. Results: SPM revealed that the central-to-posterior medial tibiofemoral joint space was significantly narrowed by up to 0.5 mm with significantly higher tibial trabecular attenuation up to 50 units for each increment in KLG as single features, and in a wider distribution when combined (p<0.05). These were also more strongly correlated with worsening KLG grade category. Test-retest repeatability was subvoxel (0.37 mm) for nearly all thickness parameters. Conclusions: 3-D JSW and tibial trabecular attenuation are repeatable and significantly dependent on radiographic disease severity at the weight bearing knee joint not just alone, but more strongly in combination. A quantitative multiparametric approach with WBCT may have potential for more sensitive investigation of disease progression in osteoarthritis.

Subject factors influencing blood flow restriction in the arm at low cuff pressures.

BACKGROUND: Limb circumference predicts the pressure needed for complete occlusion. However, that relationship is inconsistent at moderate pressures typical of effective blood flow restriction (BFR) training. The purpose of this study was to investigate the influence of subject factors on BFR at low restriction pressures in the arm. METHODS: Fifty subjects had arm anthropometrics assessed by peripheral quantitative computed tomography (pQCT), sum of skinfold thickness (sumSKF) and Gulick tape (Gulick tape circumference [Gulick Circ.]) at cuff level. Blood flow (BF) was measured with ultrasound at baseline and five restrictive pressures (20, 30, 40, 50 and 60 mmHg). Relationships between subject characteristics and BFR were assessed using Pearson's correlations and hierarchical regression. RESULTS: BF decreased (p < 0.05) at each incremental pressure. Regression models including percent muscle composition (%Muscle), pQCT circumference and systolic blood pressure (SBP), were significant at all five pressures (R2 = 0.18-0.49). %Muscle explained the most variance at each pressure. Regression models including sumSKF, Gulick Circ. and SBP, were significant at 30-60 mmHg (R2 = 0.28-0.49). SumSKF explained the most variance at each pressure. CONCLUSIONS: At low pressures (20-60 mmHg), there is considerable variability in the magnitude of BFR across individuals. Arm composition factors (muscle and fat) explained the greatest variance at each cuff pressure and may be the most important consideration when using BFR protocols.

Effect of Neuromuscular Electrical Stimulation During Walking on Pain Sensitivity in Women With Obesity With Knee Pain: A Randomized Controlled Trial.

OBJECTIVE: To assess the extent to which pain sensitivity is altered in women with obesity with frequent knee symptoms who walk with either a hybrid training system (HTS) that provides antagonist muscle electrical stimulation vs sensory transcutaneous electrical nerve stimulation (TENS). DESIGN: Randomized, double-blinded, controlled trial. SETTING: University-based fitness center. PARTICIPANTS: Twenty-eight women (N=28) with obesity, aged 40-70 years, with daily knee symptoms. INTERVENTIONS: Participants were randomized to 12 weeks of biweekly 30-minute walking exercise with either HTS (HTSW group) or sensory TENS (control group). MAIN OUTCOME MEASURES: Pressure pain thresholds (PPTs) at the more symptomatic knee (local PPT) and PPT at the ipsilateral pain-free wrist (remote PPT). RESULTS: After adjustment for preintervention values and body mass index (BMI), there was a statistically significant improvement in local PPT in the HTSW group compared with the control group (P=.039). After adjustment for pretraining value, age, and BMI, changes in remote PPT when comparing groups did not reach statistical significance, although the HTS group tended to demonstrate increased remote PPT (P=.052) compared with the control group. Moreover, after adjustment for pretraining value, knee pain, and quality of life, comparing groups did not reach statistical significance, although the HTS group tended to demonstrate decreased knee pain (P=.069) compared with the control group. CONCLUSIONS: Augmentation of walking exercise with HTS was more effective than application of sensory TENS in improving local pain sensitivity at the knee but not at the wrist in women with obesity with frequent knee symptoms.

Longitudinal Relationship Between Physical Activity and Joint Space Narrowing: Forty-Eight-Month Follow-Up Data From the Osteoarthritis Initiative.

OBJECTIVE: To determine whether the amount of physical activity (PA) is a determinant of joint space narrowing (JSN) worsening over 48 months in participants with knee osteoarthritis. METHODS: Data were obtained from the Osteoarthritis Initiative. PA, measured using the Physical Activity Scale for the Elderly (PASE), was defined as the mean value of the annual measurements conducted prior to development of worsening JSN. Worsening JSN was defined as at least a partial grade increase in the Osteoarthritis Research Society International JSN score over 48 months, in comparison with baseline. Restricted cubic spline function was used to group participants based on the linear association between PA and JSN worsening. A pooled logistic regression model was used to evaluate the association between PA and JSN worsening adjusted for confounders. RESULTS: A total of 2,167 participants were included. In total, 625 participants (28.8%) had JSN worsening over 48 months. Compared with a PASE score of 141-180, PASE scores of 101-140 and >220 were associated with an increased risk of JSN worsening in men, with odds ratios (ORs) of 1.73 (95% confidence interval [95% CI] 1.07-2.81) and 1.83 (95% CI 1.14-2.93), respectively. Similarly, in participants with Kellgren/Lawrence (K/L) grade 2, compared with a PASE score of 141-180, PASE scores of ≤100 and >220 were associated with increased risks of JSN worsening, with an OR of 1.69 (95% CI 1.13-2.54) and 1.64 (95% CI 1.05-2.56), respectively. CONCLUSION: Compared to moderate PA, higher or lower amounts of PA are associated with an elevated risk for JSN worsening in men and in participants with K/L grade 2 knees.

Longitudinal Relationship Between Tibiofemoral Contact Stress at Baseline and Worsening of Knee Pain Over 84 Months in the Multicenter Osteoarthritis Study.

OBJECTIVE: The aim of the study was to determine whether tibiofemoral contact stress predicts risk for worsening knee pain over 84 ms in adults aged 50-79 yrs with or at elevated risk for knee osteoarthritis. DESIGN: Baseline tibiofemoral contact stress was estimated using discrete element analysis. Other baseline measures included weight, height, hip-knee-ankle alignment, Kellgren-Lawrence grade, and Western Ontario and McMaster Universities Osteoarthritis Index pain subscale. Logistic regression models assessed the association between baseline contact stress and 84-mo worsening of Western Ontario and McMaster Universities Osteoarthritis Index pain subscale. RESULTS: Data from the dominant knee (72.6% Kellgren-Lawrence grade 0/1 and 27.4% Kellgren-Lawrence grade ≥ 2) of 208 participants (64.4% female, mean ± SD body mass index = 29.6 ± 5.1 kg/m 2 ) were analyzed. Baseline mean and peak contact stress were 3.3 ± 0.9 and 9.4 ± 4.3 MPa, respectively. Forty-seven knees met the criterion for worsening pain. The highest tertiles in comparison with the lowest tertiles of mean (odds ratio [95% confidence interval] = 2.47 [1.03-5.95], P = 0.04) and peak (2.49 [1.03-5.98], P = 0.04) contact stress were associated with worsening pain at 84 mos, after adjustment for age, sex, race, clinic site, and baseline pain. Post hoc sensitivity analyses including adjustment for body mass index and hip-knee-ankle alignment attenuated the effect. CONCLUSIONS: These findings suggest that elevated tibiofemoral contact stress can predict the development of worsening of knee pain.

Latest advancements in imaging techniques in OA.

The osteoarthritis (OA) research community has been advocating a shift from radiography-based screening criteria and outcome measures in OA clinical trials to a magnetic resonance imaging (MRI)-based definition of eligibility and endpoint. For conventional morphological MRI, various semiquantitative evaluation tools are available. We have lately witnessed a remarkable technological advance in MRI techniques, including compositional/physiologic imaging and automated quantitative analyses of articular and periarticular structures. More recently, additional technologies were introduced, including positron emission tomography (PET)-MRI, weight-bearing computed tomography (CT), photon-counting spectral CT, shear wave elastography, contrast-enhanced ultrasound, multiscale X-ray phase contrast imaging, and spectroscopic photoacoustic imaging of cartilage. On top of these, we now live in an era in which artificial intelligence is increasingly utilized in medicine. Osteoarthritis imaging is no exception. Successful implementation of artificial intelligence (AI) will hopefully improve the workflow of radiologists, as well as the level of precision and reproducibility in the interpretation of images.

Study TPX-100-5: intra-articular TPX-100 significantly delays pathological bone shape change and stabilizes cartilage in moderate to severe bilateral knee OA.

BACKGROUND: TPX-100, a promotor of osteoblast and chondroblast differentiation, is a potential osteoarthritis (OA) therapy. This retrospective study compared MRI 3D femoral bone shape changes (B-scores) after intra-articular TPX-100 or placebo and analyzed the relationship between cartilage thickness and bone shape change over 12 months. METHODS: One hundred and four participants with bilateral moderate to severe knee cartilage defects were randomized to receive TPX-100 (200 mg) or placebo. Each subject's contralateral placebo-treated knee served as a paired internal control. After MRI quality control, 78/93 subjects (84%; 156 knees) were analyzed for quantitative femoral B-score and cartilage thickness. All analyses were performed centrally, blind to treatment assignment and clinical data. RESULTS: TPX-100-treated knees (n = 78) demonstrated a statistically significant decrease in pathologic bone shape change compared with placebo-treated knees at 6 and 12 months: 0.0298 (95% C.I. - 0.037, 0.097) vs 0.1246 (95% C.I. 0.067, 0.182) (P = 0.02), and 0.0856 (95% C.I. 0.013, 0.158) vs. 0.1969 (95% C.I. 0.123, 0.271) (P = 0.01), respectively. The correlation between bone shape change and medial and total tibiofemoral cartilage thickness changes at 12 months was statistically significant in TPX-100-treated knees (P < 0.01). CONCLUSIONS: This is the first report of a potential therapy demonstrating a significant effect on bone shape measured by B-score in knee OA. These data, in combination with previously reported statistically significant and clinically meaningful improvements in WOMAC physical function versus placebo, support TPX-100 as a candidate for disease modification in knee OA. TRIAL REGISTRATION: NIH ClinicalTrials.gov, NCT01925261 . Registered 15 August 2013.

Gait Speed as a Predictor for Diabetes Incidence in People with or at Risk of Knee Osteoarthritis: A Longitudinal Analysis from the Osteoarthritis Initiative.

BACKGROUND: This study examined the association between baseline gait speed with incident diabetes mellitus (DM) among people with or at elevated risk for knee OA. MATERIALS AND METHODS: Participants from the Osteoarthritis Initiative, aged 45 to 79 years, where included. Participants with or at risk of knee OA from baseline to the 96-month visit were included. Participants with self-reported DM at baseline were excluded. DM incidence was followed over the 4-time points. Gait speed was measured at baseline using a 20-m walk test. Generalized estimating equations with logistic regression were utilized for analyses. Receiver operator characteristic curves and area under the curve were used to determine the cutoff score for baseline speed. RESULTS: Of the 4313 participants included in the analyses (58.7% females), 301 participants had a cumulative incidence of DM of 7.0% during follow-up. Decreased gait speed was a significant predictor of incident DM (RR 0.44, p = 0.018). The threshold for baseline gait speed that predicted incident DM was 1.32 m/s with an area under the curve of 0.59 (p < 0.001). CONCLUSIONS: Baseline gait speed could be an important screening tool for identifying people at risk of incident diabetes, and the determined cutoff value for gait speed should be examined in future research.

Quantitative Three-dimensional Assessment of Knee Joint Space Width from Weight-bearing CT.

Background Imaging of structural disease in osteoarthritis has traditionally relied on MRI and radiography. Joint space mapping (JSM) can be used to quantitatively map joint space width (JSW) in three dimensions from CT images. Purpose To demonstrate the reproducibility, repeatability, and feasibility of JSM of the knee using weight-bearing CT images. Materials and Methods Two convenience samples of weight-bearing CT images of left and right knees with radiographic Kellgren-Lawrence grades (KLGs) less than or equal to 2 were acquired from 2014 to 2018 and were analyzed retrospectively with JSM to deliver three-dimensional JSW maps. For reproducibility, images of three sets of knees were used for novice training, and then the JSM output was compared against an expert's assessment. JSM was also performed on 2-week follow-up images in the second cohort, yielding three-dimensional JSW difference maps for repeatability. Statistical parametric mapping was performed on all knee imaging data (KLG, 0-4) to show the feasibility of a surface-based analysis in three dimensions. Results Reproducibility (in 20 individuals; mean age, 58 years ± 7 [standard deviation]; mean body mass index, 28 kg/m2 ± 6; 14 women) and repeatability (in nine individuals; mean age, 53 years ± 6; mean body mass index, 26 kg/m2 ± 4; seven women) reached their lowest performance at a smallest detectable difference less than ±0.1 mm in the central medial tibiofemoral joint space for individuals without radiographically demonstrated disease. The average root mean square coefficient of variation was less than 5% across all groups. Statistical parametric mapping (33 individuals; mean age, 57 years ± 7; mean body mass index, 27 kg/m2 ± 6; 23 women) showed that the central-to-posterior medial joint space was significantly narrower by 0.5 mm for each incremental increase in the KLG (threshold P < .05). One knee (KLG, 2) demonstrated a baseline versus 24-month change in its three-dimensional JSW distribution that was beyond the smallest detectable difference across the lateral joint space. Conclusion Joint space mapping of the knee using weight-bearing CT images is feasible, demonstrating a relationship between the three-dimensional joint space width distribution and structural joint disease. It is reliably learned by novice users, can be personalized for disease phenotypes, and can be used to achieve a smallest detectable difference that is at least 50% smaller than that reported to be achieved at the highest performance level in radiography. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Roemer in this issue.

Knee Extensor and Flexor Torque Variability During Maximal Strength Testing and Change in Knee Pain and Physical Function at 60-Mo Follow-Up: The Multicenter Osteoarthritis Study (MOST).

ABSTRACT: As the population ages, there is a growing burden owing to musculoskeletal diseases, such as knee osteoarthritis, and subsequent functional decline. In the absence of a cure, there is a need to identify factors amenable to intervention to prevent or slow this process. The Multicenter Osteoarthritis Study cohort was developed for this purpose. In this study, associations between variability in peak knee flexor and extensor torque at baseline and worsening of pain and physical function over the subsequent 60 mos were assessed in a cohort of 2680 participants. The highest quartile of baseline knee flexor torque variability was found to be associated longitudinally with worsening pain (fourth quartile ß estimate, mean ± SE, 0.49 ± 0.19; P = 0.0115; with R2 = 0.28 and P for trend across quartiles = 0.0370) and physical function scores (fourth quartile ß estimate, mean ± SE, 1.39 ± 0.64; P = 0.0296; with R2 = 0.25 and P for trend across quartiles = 0.0371), after adjusting for baseline knee osteoarthritis and maximum knee flexor torque. There were no associations between baseline knee extensor torque and worsening pain or physical function by 60 mos. The presence of greater variability in maximum knee flexor strength may identify patients who may benefit from therapies aimed at preventing worsening knee pain and physical function.

The Association of Parity with Greater Dynamic Pronation of the Feet.

BACKGROUND: Postpartum women are at increased risk for lower limb musculoskeletal disorders. Foot arch collapse following pregnancy has been reported as a mechanism for this increased risk. However, dynamic changes during gait in postpartum women have not been reported. Therefore, we assessed the association between parity and dynamic foot pronation during gait. OBJECTIVE: To determine (1) if there is an association between parity and dynamic foot pronation (center of pressure excursion index, CPEI) during gait; and (2) the extent to which there is a dose-effect of parity on foot pronation. DESIGN: The Multicenter Osteoarthritis Study (MOST) Study is a longitudinal cohort study of adults with or at risk for knee osteoarthritis (OA). SETTING: Two communities in the United States, Birmingham, Alabama and Iowa City, Iowa. INTERVENTIONS: Not applicable PARTICIPANTS: A population-based sample of 1177 MOST participants who were female, had complete CPEI and parity data and completed the baseline, 30- and 60-month visits. MAIN OUTCOME MEASURES: Odds of a one quintile decrease in CPEI by parity group and mean CPEI by parity group. RESULTS: In 1177 women, mean age was 67.7 years and mean body mass index (BMI) was 30.6 kg/m2 . As parity increased, there was significantly greater foot pronation, lower mean CPEI: 19.1 (18.2-20.1), 18.9 (18.4-19.4), 18 (17.5-18.6) to 17.5 (16.4-18.6) in the 0 to 4 and >5 children groups, respectively; (P = .002), which remained significant after adjusting for race and clinic site (P = .005). There was a positive linear trend (ß = 1.08, 1.03-1.14) in odds ratios of a one quintile decrease in CPEI (greater pronation) with increasing parity level (P = .004), which remained significant after adjusting for race and clinic site (P = .01). After adjusting for age and BMI, these two associations were no longer statistically significant. CONCLUSIONS: This study indicates a positive correlation between parity and greater dynamic pronation of the feet.