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.

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.

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.

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.

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.

Predicting meniscal tear stability across knee-joint flexion using finite-element analysis.

PURPOSE: To analyse the stress distribution through longitudinal and radial meniscal tears in three tear locations in weight-bearing conditions and use it to ascertain the impact of tear location and type on the potential for healing of meniscal tears. METHODS: Subject-specific finite-element models of a healthy knee under static loading at 0°, 20°, and 30° knee flexion were developed from unloaded magnetic resonance images and weight-bearing, contrast-enhanced computed tomography images. Simulations were then run after introducing tears into the anterior, posterior, and midsections of the menisci. RESULTS: Absolute differences between the displacements of anterior and posterior segments modelled in the intact state and those quantified from in vivo weight-bearing images were less than 0.5 mm. There were tear-location-dependent differences between hoop stress distributions along the inner and outer surfaces of longitudinal tears; the longitudinal tear surfaces were compressed together to the greatest degree in the lateral meniscus and were most consistently in compression on the midsections of both menisci. Radial tears resulted in an increase in stress at the tear apex and in a consistent small compression of the tear surfaces throughout the flexion range when in the posterior segment of the lateral meniscus. CONCLUSIONS: Both the type of meniscal tear and its location within the meniscus influenced the stresses on the tear surfaces under weight bearing. Results agree with clinical observations and suggest reasons for the inverse correlation between longitudinal tear length and healing, the inferior healing ability of medial compared with lateral menisci, and the superior healing ability of radial tears in the posterior segment of the lateral meniscus compared with other radial tears. This study has shown that meniscal tear location in addition to type likely plays a crucial role in dictating the success of non-operative treatment of the menisci. This may be used in decision making regarding conservative or surgical management.

Lower Quadriceps Rate of Force Development Is Associated With Worsening Physical Function in Adults With or at Risk for Knee Osteoarthritis: 36-Month Follow-Up Data From the Osteoarthritis Initiative.

OBJECTIVE: To determine the association between quadriceps rate of force development (RFD) and decline in self-reported physical function and objective measures of physical performance. DESIGN: Longitudinal cohort study. SETTING: Community-based sample from 4 urban areas. PARTICIPANTS: Osteoarthritis Initiative participants with or at risk for knee osteoarthritis, who had no history of knee/hip replacement, knee injury, or rheumatoid arthritis (N=2630). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Quadriceps RFD (N/s) was measured during isometric strength testing. Worsening physical function was defined as the minimal clinically important difference for worsening self-reported Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function subscale score, 20-m walk time, and repeated chair stand time over 36 months. RESULTS: Compared with the slowest tertile of RFD, the fastest tertile had a lower risk for worsening of WOMAC physical function subscale score at 36-month follow-up, with an odds ratio (OR) of .68 (95% confidence interval [CI], .51-.92) after adjustment for age, sex, body mass index, depression, history of chronic diseases, and knee pain. In women, in comparison with the slowest tertile of RFD, the fastest tertile had a lower risk for worsening of WOMAC physical function subscale score at 36-month follow-up, with an adjusted OR of .57 (95% CI, .38-.86). This decreased risk did not reach statistical significance in men (OR, 0.81; 95% CI, 0.52-1.27). No statistically significant associations were detected between baseline RFD and walk or chair stand times. CONCLUSIONS: Our results indicate that higher RFD is associated with decreased risk for worsening self-reported physical function but not with decreased risk for worsening of physical performance.

Test-retest reliability of tibiofemoral joint space width measurements made using a low-dose standing CT scanner.

OBJECTIVE: To determine the test-retest reliability of knee joint space width (JSW) measurements made using standing CT (SCT) imaging. SUBJECTS AND METHODS: This prospective two-visit study included 50 knees from 30 subjects (66% female; mean ± SD age 58.2 ± 11.3 years; BMI 29.1 ± 5.6 kg/m2; 38% KL grade 0-1). Tibiofemoral geometry was obtained from bilateral, approximately 20° fixed-flexed SCT images acquired at visits 2 weeks apart. For each compartment, the total joint area was defined as the area with a JSW <10 mm. The summary measurements of interest were the percentage of the total joint area with a JSW less than 0.5-mm thresholds between 2.0 and 5.0 mm in each tibiofemoral compartment. Test-retest reliability of the summary JSW measurements was assessed by intraclass correlation coefficients (ICC 2,1) for the percentage area engaged at each threshold of JSW and root-mean-square errors (RMSE) were calculated to assess reproducibility. RESULTS: The ICCs were excellent for each threshold assessed, ranging from 0.95 to 0.97 for the lateral and 0.90 to 0.97 for the medial compartment. RMSE ranged from 1.1 to 7.2% for the lateral and from 3.1 to 9.1% for the medial compartment, with better reproducibility at smaller JSW thresholds. CONCLUSION: The knee joint positioning protocol used demonstrated high day-to-day reliability for SCT 3D tibiofemoral JSW summary measurements repeated 2 weeks apart. Low-dose SCT provides a great deal of information about the joint while maintaining high reliability, making it a suitable alternative to plain radiographs for evaluating JSW in people with knee OA.

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.

Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial.

PURPOSE: Knee osteoarthritis is a common, debilitating chronic disease. Prolotherapy is an injection therapy for chronic musculoskeletal pain. We conducted a 3-arm, blinded (injector, assessor, injection group participants), randomized controlled trial to assess the efficacy of prolotherapy for knee osteoarthritis. METHODS: Ninety adults with at least 3 months of painful knee osteoarthritis were randomized to blinded injection (dextrose prolotherapy or saline) or at-home exercise. Extra- and intra-articular injections were done at 1, 5, and 9 weeks with as-needed additional treatments at weeks 13 and 17. Exercise participants received an exercise manual and in-person instruction. Outcome measures included a composite score on the Western Ontario McMaster University Osteoarthritis Index (WOMAC; 100 points); knee pain scale (KPS; individual knee), post-procedure opioid medication use, and participant satisfaction. Intention-to-treat analysis using analysis of variance was used. RESULTS: No baseline differences existed between groups. All groups reported improved composite WOMAC scores compared with baseline status (P <.01) at 52 weeks. Adjusted for sex, age, and body mass index, WOMAC scores for patients receiving dextrose prolotherapy improved more (P <.05) at 52 weeks than did scores for patients receiving saline and exercise (score change: 15.3 ± 3.5 vs 7.6 ± 3.4, and 8.2 ± 3.3 points, respectively) and exceeded the WOMAC-based minimal clinically important difference. Individual knee pain scores also improved more in the prolotherapy group (P = .05). Use of prescribed postprocedure opioid medication resulted in rapid diminution of injection-related pain. Satisfaction with prolotherapy was high. There were no adverse events. CONCLUSIONS: Prolotherapy resulted in clinically meaningful sustained improvement of pain, function, and stiffness scores for knee osteoarthritis compared with blinded saline injections and at-home exercises.

Association between chair stand strategy and mobility limitations in older adults with symptomatic knee osteoarthritis.

OBJECTIVE: To determine which lower limb strength and joint kinetic and kinematic parameters distinguish sit-to-stand (STS) performance of older adults with symptomatic knee osteoarthritis (OA) with higher and lower chair stand time. DESIGN: Cross-sectional. SETTING: Motion analysis laboratory. PARTICIPANTS: Individuals (N=49; 26 men, 23 women) aged 50 to 79 years (mean ± SD age, 64.7±8.1y) with radiographic knee OA and daily symptoms, stratified by chair stand times. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Lower limb strength and STS strategy. RESULTS: The chair stand times (mean ± SD) in the high-, moderate-, and low-functioning groups in men were 6.5±0.7, 8.6±0.7, and 11.5±1.3 seconds, respectively, and in women were 7.6±1.2, 10.0±0.5, and 12.8±1.8 seconds, respectively. Chair stand time (P=.0391) and all measures of lower limb strength (all P<.0001) differed by sex. In men, no strength measure differed between groups, whereas in women hip abductor strength on the more affected side differed between groups. In men, sagittal hip range of motion (ROM) (P=.0122) differed between groups, and there was a trend toward a difference in sagittal knee power (P=.0501) during STS, while in women only sagittal knee ROM (P=.0392) differed between groups. CONCLUSIONS: Higher- and lower-functioning adults with symptomatic knee OA appear to use different strategies when standing from a chair. Higher-functioning men flexed more at the hip and produced greater knee power than lower-functioning men. Higher-functioning women used less knee flexion than lower-functioning women. Since STS is an important mobility task, these parameters may serve as foci for rehabilitation aimed at reducing mobility limitations.

Association between measures of patella height, morphologic features of the trochlea, and patellofemoral joint alignment: the MOST study.

BACKGROUND: Patellofemoral joint (PFJ) malalignment (lateral patella displacement and tilt) has been proposed as a cause of patellofemoral pain. Patella height and/or the morphologic features of the femoral trochlea may predispose one to patella malalignment. QUESTIONS/PURPOSES: The purposes of our study were to assess the associations among patella height, morphologic features of the trochlea, and measures of PFJ alignment and to determine which measures of patella height and morphologic features of the trochlea were the best predictors of PFJ alignment. METHODS: Measures of patella height (Insall-Salvati ratio and modified Insall-Salvati ratio), morphologic features of the trochlea (sulcus angle, trochlear angle, lateral trochlear inclination, medial trochlear inclination), and PFJ alignment (bisect offset and patella tilt angle) were assessed in 566 knees from the Multicenter Osteoarthritis Study. RESULTS: Bisect offset was correlated with the Insall-Salvati ratio (r = 0.25) and lateral trochlear inclination (r = -0.38). Patella tilt angle correlated with the trochlear angle (-0.27) and lateral trochlear inclination (-0.32). Linear regression models including the Insall-Salvati ratio and lateral trochlear inclination explained 20% and 11% of the variance in bisect offset and patella tilt angle, respectively. CONCLUSIONS: Of the variables measured in the current study, the Insall-Salvati ratio and lateral trochlear inclination were the best predictors of lateral patella displacement and lateral tilt. This knowledge will aid clinicians in the identification of anatomic risk factors for PFJ malalignment and/or PFJ dysfunction.

Lateral wedge insoles as a conservative treatment for pain in patients with medial knee osteoarthritis: a meta-analysis.

IMPORTANCE: There is no consensus regarding the efficacy of lateral wedge insoles as a treatment for pain in medial knee osteoarthritis. OBJECTIVE: To evaluate whether lateral wedge insoles reduce pain in patients with medial knee osteoarthritis compared with an appropriate control. DATA SOURCES: Databases searched include the Cochrane Central Register of Controlled Trials, EMBASE, AMED, MEDLINE, CINAHL Plus, ScienceDirect, SCOPUS, Web of Science, and BIOSIS from inception to May 2013, with no limits on study date or language. The metaRegister of Controlled Trials and the NHS Evidence website were also searched. STUDY SELECTION: Included were randomized trials comparing shoe-based treatments (lateral heel wedge insoles or shoes with variable stiffness soles) aimed at reducing medial knee load, with a neutral or no wedge control condition in patients with painful medial knee osteoarthritis. Studies must have included patient-reported pain as an outcome. DATA EXTRACTION AND SYNTHESIS: Trial data were extracted independently by 2 researchers using a standardized form. Risk of bias was assessed using the Cochrane Risk of Bias tool by 2 observers. Eligible studies were pooled using a random-effects approach. MAIN OUTCOME AND MEASURES: Change in self-reported knee pain at follow-up. RESULTS: Twelve trials met inclusion criteria with a total of 885 participants of whom 502 received lateral wedge treatment. The pooled standardized mean difference (SMD) suggested a favorable association with lateral wedges compared with control (SMD, -0.47; 95% CI, -0.80 to -0.14); however, substantial heterogeneity was present (I2 = 82.7%). This effect size represents an effect of -2.12 points on the 20-point Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale. Larger trials with a lower risk of bias suggested a null association. Meta-regression analyses showed that higher effect sizes (unstandardized ß, 1.07 [95% CI, 0.28 to 1.87] for trials using a no treatment control) were seen in trials using a no wedge treatment control group (n = 4 trials; SMD, -1.20 [95% CI, -2.09 to -0.30]) and lower effect sizes (unstandardized ß, 0.26 [95% CI, 0.002 to 0.52] for each bias category deemed low risk) when the study method was deemed at low risk of bias. Among trials in which the control treatment was a neutral insole (n = 7), lateral wedges showed no association (SMD, -0.03 [95% CI, -0.18 to 0.12] on WOMAC; this represents an effect of -0.12 points), and results showed little heterogeneity (I2 = 7.1%). CONCLUSIONS AND RELEVANCE: Although meta-analytic pooling of all studies showed a statistically significant association between use of lateral wedges and lower pain in medial knee osteoarthritis, restriction of studies to those using a neutral insole comparator did not show a significant or clinically important association. These findings do not support the use of lateral wedges for this indication.

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.

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.

Breaking the Law of Valgus: the surprising and unexplained prevalence of medial patellofemoral cartilage damage.

OBJECTIVES: To compare the prevalence of medial and lateral patellofemoral (PF) cartilage damage in three large osteoarthritis (OA) studies and determine the relationship of this damage to varus, neutral and valgus knee alignment. METHODS: In the Boston OA of the Knee, Framingham OA and Multicenter OA studies, MRIs were read for cartilage morphology at the medial and lateral patella and trochlea femoris using Whole-Organ MRI Scores (WORMS). WORMS scores ≥2 (any cartilage defect), ≥3 (areas of partial thickness loss), ≥4 (diffuse partial thickness loss) and ≥5 (extensive full thickness loss) were all variously considered as thresholds to identify damage that may indicate OA. Full-limb radiographs were measured for mechanical alignment, and varus (<-2°), neutral (-2° to 2°) and valgus (>2°) knees were identified. RESULTS: The prevalence of medial PF cartilage damage exceeded that of lateral damage in all three studies and according to nearly every threshold. Only among severely involved knees (WORMS ≥4 or ≥5) did the prevalence of lateral PF cartilage damage approximate that of medial damage. The high prevalence of medial PF damage persisted in all strata of knee alignment. Even among knees with valgus alignment, the prevalence of lateral PF cartilage damage equalled or surpassed that of medial PF damage only when the threshold was specific to severely involved knees. CONCLUSIONS: Medial PF cartilage damage is at least as prevalent within these older adult populations as lateral PF cartilage damage.

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.

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.

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.

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.