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ObjectiveKnee osteoarthritis (OA) is predominantly characterized by pain with weight-bearing activities. Pain at rest also occurs but the mechanisms for this are not clear. We evaluated the relations of nociceptive signal alterations to weight-bearing and non-weight-bearing pain in knee OA.DesignWe used data from a NIH-funded longitudinal cohort of older adults with or at risk of knee OA. We evaluated quantitative sensory testing (QST) measures (pressure pain threshold (PPT) at patellae and the wrist; mechanical temporal summation (TS); conditioned pain modulation (CPM)). Each WOMAC pain question was dichotomized as having at least moderate pain, and we further categorized them as weight-bearing pain and non-weight-bearing pain. We evaluated the relation of QST measures to each pain outcome using logistic regression, adjusting for potential confounders.Results2,749 participants (5,479 knees) were included (mean age 64 ± 11, 57% female). Each SD unit decrease in patellar PPT was associated with greater odds of both weight-bearing pain (OR 1.51 (95% CI 1.27, 1.79)) and non-weight-bearing pain (OR 1.46 (1.20-1.77)), while wrist PPT was associated with greater odds of weight-bearing pain (OR 1.27 (1.15, 1.39)) but only with pain during sitting/lying (OR 1.20 (1.01, 1.43)). TS was significantly associated with greater odds of pain with walking and stairs (OR 1.11 (1.01, 1.23), 1.11 (1.03, 1.20), respectively). CPM was not associated with any pain outcomes.ConclusionsOur findings challenge the hypothesis that non-weight-bearing pain may reflect greater pain sensitization and/or inefficient CPM than weight-bearing pain in knee OA, suggesting other mechanisms are likely responsible.

ObjectiveTo examine whether knee subchondral cysts, measured on magnetic resonance imaging (MRI), are associated with incident knee osteoarthritis (OA) outcomes.MethodsWe used longitudinal data from the Multicenter Osteoarthritis Study, a community-based cohort of subjects with risk factors for knee OA. Participants without a history of knee surgery and/or inflammatory arthritis (i.e., rheumatoid arthritis and gout) were followed up for 84 months for the following incident outcomes: 1) radiographic knee OA (Kellgren/Lawrence grade ≥2), 2) symptomatic radiographic knee OA (radiographic knee OA and frequent knee pain), and 3) frequent knee pain (with or without radiographic knee OA). In a subset of participants, subchondral cysts were scored on baseline MRIs of 1 knee. Multiple logistic regression, with adjustment for participant characteristics and other baseline knee MRI findings, was used to assess whether subchondral cysts were predictive of incident outcomes.ResultsAmong the participants with knees eligible for analyses of outcomes over 84 months, incident radiographic knee OA occurred in 22.8% of knees with no baseline radiographic knee OA, symptomatic radiographic knee OA occurred in 17.0% of knees with no baseline symptomatic radiographic knee OA, and frequent knee pain (with or without radiographic knee OA) occurred in 28.8% of knees with no baseline radiographic knee OA and 43.7% of knees with baseline radiographic knee OA. With adjustment for age, sex, and body mass index, the presence of subchondral cysts was not associated with incident radiographic knee OA but was associated with increased odds of incident symptomatic radiographic knee OA (odds ratio 1.92 [95% confidence interval 1.16-3.19]) and increased odds of incident frequent knee pain in those who had radiographic knee OA at baseline (odds ratio 2.11 [95% confidence interval 0.87-5.12]). Stronger and significant associations were observed for outcomes based on consistent reports of frequent knee pain within ~1 month of the study visit.ConclusionSubchondral cysts are likely to be a secondary phenomenon, rather than a primary trigger, of radiographic knee OA, and may predict symptoms in knees with existing disease.

ObjectiveTo examine the cross-sectional association of ascending pain mechanisms, implicated in pain sensitization, and descending pain modulation with pain patterns and unpredictability of pain.MethodsThe Multicenter Osteoarthritis Study is a longitudinal cohort of older adults with or at risk of knee osteoarthritis. Peripheral and central ascending pain mechanisms were assessed using quantitative sensory tests, pressure pain thresholds using a handheld pressure algometer (knee/peripheral and wrist/central), and temporal summation using weighted probes (wrist/central). Descending modulation was assessed by conditioned pain modulation using pressure pain thresholds and a forearm ischemia test. Pain patterns were characterized based on responses to the Intermittent and Constant Osteoarthritis Pain questionnaire: 1) no intermittent or constant pain, 2) intermittent pain only, 3) constant pain only, and 4) combined constant and intermittent pain. A question regarding frequency assessed unpredictable pain. We assessed the association of quantitative sensory test measures to pain patterns using regression models with generalized estimating equations.ResultsThere were 2,794 participants (mean age 63.9 years, body mass index 29.5 kg/m2 , and 57% female). Lower pain sensitization by wrist pressure pain threshold (odds ratio [OR] 0.80 [95% confidence interval (95% CI) 0.68, 0.93]) and adequate conditioned pain modulation (OR 1.45 [95% CI 1.10, 1.92]) were associated with having constant ± intermittent pain compared with intermittent pain only. Higher pain sensitization (by pressure pain thresholds and temporal summation) was associated with a higher likelihood of unpredictable pain.ConclusionKnee pain patterns appear to be related to peripheral ± central facilitated ascending pain mechanisms and descending modulatory mechanisms. These findings highlight the need for a broader approach to understanding pain mechanisms by symptomatic disease progression.

ObjectivesTo determine how many persons with knee pain have subsequent pain resolution and what factors are associated with resolution, focusing especially on types of physical activity.MethodsUsing data from MOST, an NIH funded longitudinal cohort study of persons with or at risk of knee osteoarthritis, we studied participants who at baseline reported knee pain on most days at both a telephone interview and clinic visit. We defined pain resolution if at 30 and 60 month exams, they reported no knee pain on most days and compared these participants to those who reported persistent pain later. In logistic regression analyses, we examined the association of baseline risk factors including demographic factors, BMI, depressive symptoms, isokinetic quadriceps strength and both overall physical activity (using the PASE survey) and specific activities including walking, gardening, and different intensities of recreational activities with pain resolution.ResultsOf 1,304 participants with knee pain on most days at baseline, 265 (20.3%) reported no knee pain at 30 and 60 months. Lower BMI and stronger quadriceps were associated with higher odds of pain resolution while overall physical activity was not. Of activities, walking decreased the odds of pain resolution (adjOR = 0.86 (95% CI 0.76, 0.98)), but gardening (adjOR = 1.59 (1.16, 2.18)) and moderate intensity recreational activities ((adjOR = 1.24 (1.05, 1.46)) increased it.ConclusionPain resolution is common in those with knee pain. Factors increasing the odds of pain resolution include lower BMI, greater quadriceps strength and gardening and moderately intensive recreational activities.

ObjectiveTo compare ground reaction force patterns (GRF) during walking among legs defined by presence or absence of knee pain and/or radiographic knee osteoarthritis (ROA).MethodPrincipal component analysis extracted major modes of variation (PCs) in GRF data from the Multicenter Osteoarthritis Study during self-paced walking. Legs were categorized as pain + ROA (n = 168), ROA only (n = 303), pain only (n = 476), or control (n = 1877). Relationships between group and GRF PCs were examined using Generalized Estimating Equations, adjusted for age, sex, body mass index, race, and clinic site with and without additional adjustment for gait speed.ResultsWith or without speed adjustment, pain + ROA had flatter vertical GRF waveforms than control (speed adjusted PC2 difference [95%CI]: -66 [-113,-20]), pain + ROA and ROA only had higher lateral GRF at impact and greater mid-stance medial GRF than control (speed adjusted PC3 difference: 9 [3,16] and 6 [2,10], respectively), and ROA only had higher early vs late medial GRF than control (speed adjusted PC2 difference: 7 [2,13]). Pain only had flatter vertical GRF waveforms and a smaller difference between anterior and posterior GRF than control only without speed adjustment.ConclusionIn this large sample, sustained mid-stance loading and higher impact loads were identified in legs with ROA or ROA and pain, even when adjusting for differences in gait speed and other confounders. While it remains to be seen whether these features precede or result from ROA and pain, the presence of these patterns in the speed-adjusted models could have implications on gait interventions aimed to change joint loading.

ObjectiveTo examine the relation of knee pain patterns to pain severity and to radiographic osteoarthritis (OA) severity and duration.MethodsThe Multicenter Osteoarthritis Study is a longitudinal cohort of older adults with or at risk of knee OA. Participants' Intermittent and Constant Osteoarthritis Pain (ICOAP) scores were characterized as 1) no intermittent or constant pain, 2) intermittent pain only, 3) constant pain only, and 4) a combination of constant and intermittent pain. Knee pain severity was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale and a visual analog scale (VAS). Radiographic knee OA (ROA) severity was defined as Kellgren/Lawrence grade ≥2, and ROA duration was defined according to the clinic visit at which ROA was first noted. We assessed the relation of ICOAP pain patterns to knee pain severity, ROA severity, and ROA duration using regression models with generalized estimating equations.ResultsThere were 2,322 participants (mean age 68.8 years, body mass index 31.0 kg/m2 , 60% female). Higher ICOAP pain patterns, i.e., a mix of constant and intermittent pain, were associated with greater WOMAC pain severity compared with those patients without either pain pattern (odds ratio [OR] 43.2 [95% confidence interval (95% CI) 26.4-61.3]). Results were similar for the VAS (OR 71.2 [95% CI 45.7-110.9]). Those patients with more severe and longer duration of ROA were more likely to have a mix of constant and intermittent pain compared with those without either pain (OR 3.7 [95% CI 3.1-4.6] and OR 2.9 [95% CI 2.5-3.5], respectively).ConclusionKnee pain patterns are associated with radiographic disease stage and duration, as well as pain severity, highlighting the fact that pain patterns are important for understanding symptomatic disease progression.

ObjectiveTo examine the associations of knee injury, radiographic osteoarthritis severity, and quadriceps strength with knee pain exacerbation during walking.DesignWithin-person knee-matched case-control study.MethodsParticipants from the Osteoarthritis Initiative who completed a 20-m walking test at the 24-month visit were included. Pain exacerbation was defined as an increase in pain intensity of 1 or more on a numeric rating scale (0 as no pain and 10 as the worst imaginable pain) while completing the 20-m walking test. We used conditional logistic regression to assess the relation of recent knee injury, Kellgren-Lawrence (KL) grade, and quadriceps strength to unilateral knee pain exacerbation during walking.ResultsWe included 277 people who experienced unilateral knee pain exacerbation during the walking test. Recent knee injury was associated with pain exacerbation during walking, with an odds ratio of 3.4 (95% confidence interval [CI]: 1.3, 9.2). Compared with knees with a KL grade of 0, the odds ratios of pain exacerbation during walking were 1.3 (95% CI: 0.7, 2.7), 3.3 (95% CI: 1.5, 7.1), and 8.1 (95% CI: 3.1, 21.1) for knees with KL grades of 2, 3, and 4, respectively. Painful knees with a deficit in quadriceps strength of greater than or equal to 4% had a 1.4-fold (95% CI: 1.0, 1.9) higher risk of pain exacerbation during walking than their pain-free counterparts.ConclusionRecent knee injury, more severe radiographic osteoarthritis, and lower quadriceps strength were associated with an increased risk of knee pain exacerbation during walking. J Orthop Sports Phys Ther 2021;51(6):298-304. Epub 10 May 2021. doi:10.2519/jospt.2021.9735.

OBJECTIVE: To assess the relation of symptomatic knee osteoarthritis (OA), knee pain, and radiographic knee OA to All-cause mortality and to identify mediators in the causal pathway. METHODS: Participants from the Osteoarthritis Initiative were divided into 4 groups: 1) symptomatic knee OA (i.e., both radiographic knee OA [Kellgren/Lawrence grade ≥2] and knee pain); 2) knee pain only; 3) radiographic knee OA only; and 4) neither radiographic knee OA nor knee pain. We examined the relation of knee OA status to All-cause mortality using a multivariable Cox proportional hazards model and assessed the extent to which the association was mediated by disability, physical component summary (PCS) and mental component summary (MCS) scores for quality of life (QoL), and use of oral pain-relief medications (i.e., nonsteroidal antiinflammatory drugs and opioids). RESULTS: Among 4,796 participants, 282 died over the 96-month follow-up period. Compared with those with neither radiographic knee OA nor knee pain, multivariable-adjusted hazard ratios (HRs) of mortality were 2.2 (95% confidence interval [95% CI] 1.6-3.1) for symptomatic knee OA, 0.9 (95% CI 0.6-1.4) for knee pain only, and 2.0 (95% CI 1.4-2.9) for radiographic knee OA only, respectively. Indirect effects (HRs) of symptomatic knee OA on mortality via disability and PCS of QoL were 1.1 (95% CI 1.0-1.4) and 1.2 (95% CI 1.0-1.4), respectively. No apparent mediation effect was observed through either MCS of QoL or oral pain-relief medications use. CONCLUSION: Participants with either symptomatic or radiographic knee OA were at an increased risk of All-cause mortality. Increased risk of mortality from symptomatic knee OA was partially mediated through its effect on disability and PCS of QoL.

ObjectiveTo compare early hip osteoarthritis (OA) features on magnetic resonance imaging (MRI) in high-impact athletes with and without hip and/or groin pain, and to evaluate associations between early hip OA features, the International Hip Outcome Tool (iHOT33) and Copenhagen Hip and Groin Outcome Score (HAGOS).DesignThis case-control study evaluated data of the femoroacetabular impingement and hip osteoarthritis cohort (FORCe). One hundred and eighty-two symptomatic (hip and/or groin pain >6 months and positive flexion-adduction-internal-rotation (FADIR) test) and 55 pain-free high-impact athletes (soccer or Australian football (AF)) without definite radiographic hip OA underwent hip MRI. The Scoring Hip Osteoarthritis with MRI (SHOMRI) method quantified and graded the severity of OA features. Each participant completed the iHOT33 and HAGOS.ResultsHip and/or groin pain was associated with higher total SHOMRI (0-96) (mean difference 1.4, 95% CI: 0.7-2.2), labral score (adjusted incidence rate ratio (aIRR) 1.33, 95% CI: 1.1-1.6). Differences in prevalence of cartilage defects, labral tears and paralabral cysts between symptomatic and pain-free participants were inconclusive. There was a lower prevalence of effusion-synovitis in symptomatic participants when compared to pain-free participants (adjusted odds ratio (aOR) 0.46 (95% CI: 0.3-0.8). Early hip OA features were not associated with iHOT33 or HAGOS.ConclusionsA complex and poorly understood relationship exists between hip and/or groin pain and early hip OA features present on MRI in high-impact athletes without radiographic OA. Hip and/or groin pain was associated with higher SHOMRI and labral scores.

Objective(s)It is well appreciated that traditional analgesic delivery routes used to treat pain associated with temporomandibular disorder (TMD) often have harmful unintended side effects as a consequence of systemic distribution. Further, localized delivery of analgesic medication via intra-articular injections involves a different set of issues limiting their clinical viability. As an option, transdermal analgesic delivery provides for prolonged pain relief and flexibility in dose administration, while limiting systemic exposure and minimizing adverse events. Incorporation of a novel electroporation technique may further increase transdermal drug penetration into synovial tissue/fluid and enhance pain reduction. The present feasibility study compares the effectiveness of an electroporation-enhanced transdermal application of diclofenac sodium to a conventional intra-articular injection of triamcinolone acetonide suspension (corticosteroids) to treat patients with TMD associated pain.MethodsPre- and post-treatment maximal incisal mouth opening (MIO), pain visual analog scale (VAS) and surface electromyography (EMG) of 22 patients treated with electroporation-enhanced diclofenac and 37 patients treated with corticosteroids injections were collected and analyzed.ResultsIn general, patients treated with electroporation exhibited better results in terms of pain improvement (corrected p-value = .01) compared to the standard treatment, but both methods were similarly effective for improvement of MIO (corrected p-value = .71) and improvement of all EMG indices (corrected p-values ≥ .05).ConclusionThe enhancing effect of electroporation in transdermal delivery of diclofenac sodium was demonstrated by decreased pain, increase MIO and EMG improvement to normal values. Its analgesic and inflammatory results are comparable with standard treatment offered by corticosteroids.

ObjectiveTo determine the frequency of chronic joint pain and stiffness 3 years after infection with chikungunya virus (CHIKV) in a Latin American cohort.MethodsA cross-sectional followup of 120 patients from an initial cohort of 500 patients who reported joint pain 2 years after infection from the Atlántico Department, Colombia. Patients were clinically diagnosed as having CHIKV during the 2014-2015 epidemic, and baseline and followup symptoms at 40 months were evaluated in serologically confirmed cases.ResultsOf the initial 500 patients enrolled in the study, 482 had serologically confirmed chikungunya infection. From this group, 123 patients reported joint pain 20 months after infection, and 54% of those patients reported continued joint pain 40 months after infection. Therefore, 1 out of every 8 people who tested serologically positive for CHIKV infection had persistent joint pain 3 years after infection. Participants who followed up in person were predominantly adult (mean ± SD age 51 ± 14 yrs) and female (86%). The most common type of pain reported in these patients at 40 months post-infection was pain with periods of relief and subsequent reoccurrence, and over 75% reported stiffness after immobility, with 39% experiencing morning stiffness.ConclusionTo our knowledge, this is the first report to describe persistent joint pain and stiffness 40 months after viral infection. The high frequency of chronic disease highlights the need to develop prevention and treatment methods. Further studies should be conducted to understand the similarities between post-chikungunya joint pain and rheumatoid arthritis.

ObjectiveOsteoarthritis (OA) and pain are both made more severe by low-grade inflammation. This study was undertaken to examine whether visceral fat, a major source of inflammatory cytokines and adipokines, is associated with an increased risk of knee OA or musculoskeletal pain.MethodsSubjects in the Multicenter Osteoarthritis Study cohort, who were age 50-79 years and had or were at high risk of knee OA, underwent whole-body dual x-ray absorptiometry (DXA) at baseline. At baseline, 30 months, and 60 months radiographs and magnetic resonance images (MRIs) of the knees were obtained, and patients were asked to score the severity of their knee pain and to identify sites of joint pain using a body homunculus. Baseline DXA scans were used to measure total body fat and visceral and subcutaneous fat in the torso. The association of fat depot size with structural outcomes (incident radiographic OA and cartilage loss and synovitis on MRI) and with pain outcomes (worsening knee pain, number of painful joints, and widespread pain) was assessed. Regression analyses were adjusted for age, sex, race, education level, smoking status, physical activity, body mass index (BMI), and depressive symptoms.ResultsOf the 2,961 participants at baseline, 60.7% were women. The mean age was 62.5 years and mean BMI was 30.5 kg/m2 . After adjustment for covariates, no fat measures were associated with any structural outcomes. However, total and visceral, but not subcutaneous, fat were positively associated with worsening knee pain (P = 0.0005 for total fat and P = 0.007 for visceral fat) and widespread pain (P = 0.001 for total fat and P = 0.02 for visceral fat), and the amount of visceral fat was associated with the number of painful joints (P = 0.07).ConclusionOur findings indicate that visceral fat is associated with an increased risk of musculoskeletal and widespread pain.

IntroductionMale youth in the United States commonly participate in gridiron (American) football. There are little data substantiating current popular opinion that it is associated with knee pain or osteoarthritis (OA) later in life. We aimed to evaluate the relationship of football with these outcomes in the Osteoarthritis Initiative (OAI).MethodsThis is a study of male OAI participants with knee x-ray readings, symptom assessments, and completed surveys on lifetime physical activity. The OAI is a multicenter, observational cohort recruited from the community not based on football participation status. A history of exposure to American football was ascertained via self-report. Knee radiographs were scored for Kellgren-Lawrence grade (0-4). Radiographic OA (ROA) was defined as Kellgren-Lawrence ≥ 2 in at least one knee. Frequent knee pain meant at least one knee with frequent knee pain. Symptomatic ROA required at least one knee with both ROA and frequent knee pain.ResultsA total of 1166 men had a mean age of 63.7 (SD, 9.2) yr and body mass index of 28.6 (SD, 4.2) kg·m. Thirty-one percent (365/1166) played football at some point in their lives, 95% of whom participated from ages 12 to 18 yr. The ORs for symptomatic ROA from the lowest to highest football participation were 1.2, 1.5, and 2.2, respectively (P for trend = 0.004). Findings were similar for football from ages 12 to 18 yr and for outcomes of knee pain and ROA.ConclusionThis is the first large epidemiologic study to suggest that football participation, including in the teen years, may be detrimental toward knee health. Prospective studies evaluating football players are warranted.

BackgroundArthralgia is a common and debilitating toxicity of aromatase inhibitors (AI) that leads to premature drug discontinuation. We sought to evaluate the clinical and genetic risk factors associated with AI-associated arthralgia (AIAA).MethodsWe performed a cross-sectional study among postmenopausal women with stage 0-III breast cancer who were prescribed a third-generation AI for adjuvant therapy. The primary outcome was patient-reported AIAA occurrence. We extracted and assayed germline DNA for single nucleotide polymorphisms (SNPs) of genes implicated in estrogen and inflammation pathways. Multivariable logistic regression models examined the association between demographic, clinical, and genetic factors and AIAA. Analyses were restricted to White participants.ResultsAmong 1049 White participants, 543 (52%) reported AIAA. In multivariable analyses, women who had a college education [Adjusted Odds Ratio (AOR) 1.49, 95% Confidence Interval (CI) 1.00-2.20], had a more recent transition into menopause (

OBJECTIVE: To evaluate racial and ethnic disparities in utilization of total knee arthroplasty (TKA) in relation to demographic, health, and socioeconomic status variables. DESIGN: Prospective study of 102,767 Womens Health Initiative postmenopausal women initially aged 50-79, examining utilization rates of primary TKA between non-Hispanic Black/African American, non-Hispanic White, and Hispanic/Latina women (hereafter referred to as Black, White, and Hispanic). A total of 8,942 Black, 3,405 Hispanic, and 90,420 White women with linked Medicare claims data were followed until time of TKA, death, or transition from fee-for-service coverage. Absolute disparities were determined using utilization rates by racial/ethnic group and relative disparities quantified using multivariable hazards models in adjusting for age, arthritis, joint pain, mobility disability, body mass index, number of comorbidities, income, education, neighborhood socioeconomic status (SES), and geographic region. RESULTS: TKA utilization was higher among White women (10.7/1,000 person-years) compared to Black (8.5/1,000 person-years) and Hispanic women (7.6/1,000 person-years). Among women with health indicators for TKA including diagnosis of arthritis, moderate to severe joint pain, and mobility disability, Black and Hispanic women were significantly less likely to undergo TKA after adjusting for age [Black: HR (95% confidence interval) = 0.70 (0.63-0.79); Hispanic: HR = 0.58 (0.44-0.77)]. Adjustment for SES modestly attenuated the measured disparity, but significant differences remained [Black: HR = 0.75 (0.67-0.89); Hispanic: HR = 0.65 (0.47-0.89)]. CONCLUSIONS: Compared to White women, Black and Hispanic women were significantly less likely to undergo TKA after considering need and appropriateness for TKA and SES. Further investigation into personal-level and provider-level factors that may explain these disparities is warranted.

ObjectiveTo investigate the TrkA inhibitor, ASP7962, for treatment of painful knee osteoarthritis.DesignPhase 2a, double-blind, placebo- and naproxen-controlled, double-dummy, parallel-group study. Adults with knee osteoarthritis were randomized (2:2:1) to ASP7962 (100 mg), placebo, or naproxen (500 mg) twice daily (BID) for 4 weeks. Primary endpoint: change from baseline to Week 4 in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale score. Secondary endpoints: change from baseline to Weeks 1, 2, and End of Treatment (EoT) in WOMAC pain subscale score; change from baseline to Weeks 1, 2, 4, and EoT in WOMAC physical function and stiffness subscales, walking pain and WOMAC total scores; and change from baseline in daily average pain score.Results215 participants were randomized (ASP7962 100 mg BID, n = 85; placebo, n = 87; naproxen 500 mg BID, n = 43). No significant difference was observed between ASP7962 and placebo in change from baseline to Week 4 in WOMAC pain subscale score (-0.14; 90% 2-sided CI: -0.62, 0.34; P = 0.316); a significant difference was observed between naproxen and placebo (-0.67; 80% 2-sided CI: -1.12, -0.23; P = 0.027). No differences were observed between ASP7962 and placebo in change from baseline in any WOMAC subscale score; statistically significant changes were observed between naproxen and placebo (P ≤ 0.01, all time points for all WOMAC endpoints). ASP7962 was safe and well-tolerated.ConclusionsFour-week treatment with ASP7962 (100 mg BID) did not improve pain or physical function in individuals with painful knee osteoarthritis. ClinicalTrials.gov, NCT02611466; EudraCT Number, 2014-004996-22.

ObjectiveTo investigate the 2-year association of varus knee thrust observed during walking to the odds of worsening Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain in older adults with or at risk of osteoarthritis (OA).MethodsVideo recordings of self-paced walking trials of Multicenter Osteoarthritis Study participants were assessed for the presence of varus thrust at baseline. Knee pain was assessed using the WOMAC questionnaire at baseline and at 2 years. Logistic regression was used to estimate the odds of worsening knee pain (defined as either any increase in WOMAC score or as clinically important worsening), adjusting for age, sex, race, body mass index, clinic site, gait speed, and static knee alignment. Analyses were repeated, stratified by baseline radiographic OA status and among the subset of knees without baseline WOMAC pain.ResultsA total of 1,623 participants contributed 3,204 knees. Varus thrust was observed in 31.5% of knees. Knees with varus thrust had 1.44 times (95% confidence interval [95% CI] 1.19-1.73) the odds of any worsening and 1.37 times (95% CI 1.11-1.69) the odds of clinically important worsening WOMAC pain compared to knees without thrust. Knees with thrust without baseline WOMAC pain had 2.01 times (95% CI 1.47-2.74) the odds of incident total pain.ConclusionResults indicate that varus thrust is a risk factor for worsening and incident knee pain. Targeting varus thrust through noninvasive therapies could prevent development or worsening of knee pain in older adults with or at risk for knee OA.

ObjectiveValidation of a symptom measure for early knee OA may help identify new treatments and modifiable risk factors. Symptom measures that consider pain in the context of activity level may provide better discrimination than pain alone. Therefore, we aimed to compare sensitivity to change for radiographic progression between Ambulation Adjusted Score for Knee pain (AASK), which accounts for self-reported ambulation, and Western Ontario McMaster Osteoarthritis (WOMAC) knee pain score.DesignParticipants were assessed annually up to 48 months using WOMAC, Physical Activity Scale for the Elderly (PASE) ambulation, and knee radiographs. AASK was defined as ((WOMAC pain) + 1)/((average daily hours of walking) + 1). Radiographs were scored for Kellgren-Lawrence (KL) grade. Linear regression, stratified by OA status, evaluated relationships between changes in AASK and WOMAC pain and KL grade over time.ResultsFor 4191 people (8030 knees), the mean age was 61.2 (+ 9.2) years old and BMI was 28.6 (+ 4.8) kg/m2; 58% female. Over 40% of knees had WOMAC pain scores of 0; by design, no knees had AASK scores of 0. Annual changes in AASK were more sensitive to changes in KL than changes in WOMAC in those without baseline OA (0.20 and 0.16 change per unit KL change, p = 0.005 and 0.070 respectively), but performed similarly in knees with OA.ConclusionAASK is simple to assess using existing validated questionnaires. AASK performs well in individuals with and without OA and should be considered in clinical trials and observational studies of early knee OA.

ObjectiveTo estimate the frequency of chronic joint pain after infection with chikungunya virus in a Latin American cohort.MethodsA cross-sectional follow-up of a prospective cohort of 500 patients from the Atlántico Department, Colombia who were clinically diagnosed as having chikungunya virus during the 2014-2015 epidemic was conducted. Baseline symptoms and follow-up symptoms at 20 months were evaluated in serologically confirmed cases.ResultsAmong the 500 patients enrolled, 485 had serologically confirmed chikungunya virus and reported joint pain status. Patients were predominantly adults (mean ± SD age 49 ± 16 years) and female, had an education level of high school or less, and were of Mestizo ethnicity. The most commonly affected joints were the small joints, including the wrists, ankles, and fingers. The initial virus symptoms lasted a median of 4 days (interquartile range [IQR] 3-8 days). Sixteen percent of the participants reported missing school or work (median 4 days [IQR 2-7 days]). After 20 months, one-fourth of the participants had persistent joint pain. A multivariable analysis indicated that significant predictors of persistent joint pain included college graduate status, initial symptoms of headache or knee pain, missed work, normal activities affected, ≥4 days of initial symptoms, and ≥4 weeks of initial joint pain.ConclusionThis is the first report to describe the frequency of chikungunya virus-related arthritis in the Americas after a 20-month follow-up. The high frequency of chronic disease highlights the need for the development of prevention and treatment methods.

ObjectiveEvaluate the efficacy and safety/tolerability of cryoneurolysis for reduction of pain and symptoms associated with knee osteoarthritis (OA).DesignRandomized, double-blind, sham-controlled, multicenter trial with a 6-month follow-up in patients with mild-to-moderate knee OA. Patients were randomized 2:1 to cryoneurolysis targeting the infrapatellar branch of the saphenous nerve (IPBSN) or sham treatment. The primary endpoint was the change from baseline to Day 30 in the Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain score adjusted by the baseline score and site. Secondary endpoints, including visual analogue scale (VAS) pain score and total WOMAC score, were tested in a pre-defined order.ResultsThe intent-to-treat (ITT) population consisted of 180 patients (n = 121 active treatment, n = 59 sham treatment). Compared to the sham group, patients who received active treatment had a statistically significant greater change from baseline in the WOMAC pain subscale score at Day 30 (P = 0.0004), Day 60 (P = 0.0176), and Day 90 (P = 0.0061). Patients deemed WOMAC pain responders at Day 120 continued to experience a statistically significant treatment effect at Day 150. Most expected side effects were mild in severity and resolved within 30 days. The incidence of device- or procedure-related adverse events was similar in the two treatment groups with no occurrence of serious or unanticipated adverse device effects (ADE).ConclusionsCryoneurolysis of the IPBSN resulted in statistically significant decreased knee pain and improved symptoms compared to sham treatment for up to 150 days, and appeared safe and well tolerated.

ObjectiveTo examine the longitudinal relationship of knee pain, radiographic osteoarthritis (OA), symptomatic knee OA, and knee pain severity to incident widespread pain.MethodsThe Multicenter Osteoarthritis Study is a longitudinal cohort of persons with or at risk of knee OA. Participants were characterized as having consistent frequent knee pain, radiographic OA (Kellgren/Lawrence scale grade ≥2), symptomatic OA, and knee pain severity at the 60-month visit (baseline). Widespread pain was categorized as pain above and below the waist, on both sides of the body and axially, using a standard homunculus, excluding knee pain. Incident widespread pain was defined as the presence of widespread pain at 84 months in those who were free of widespread pain at baseline. We assessed the relationship of baseline radiographic OA, symptomatic OA, consistent frequent knee pain, and knee pain severity, respectively, with incident widespread pain using logistic regression, adjusting for potential confounders, including models with and without pain severity.ResultsAt baseline, 1,129 subjects were eligible for analysis (mean ± SD age 66.7 ± 7.8 years; mean ± SD body mass index 30.1 ± 5.8 kg/m2 ; 52% women). Radiographic OA in either knee (adjusted odds ratio [ORadj ] 0.90 [95% confidence interval (95% CI) 0.63-1.30]; P = 0.587) was not associated with incident widespread pain. Baseline bilateral consistent frequent knee pain (ORadj 2.35 [95% CI 1.37-4.03]), bilateral symptomatic OA (ORadj 2.11 [95% CI 1.04-4.24]), and knee pain severity (worst knee) (ORadj 1.11 [95% CI 1.05-1.17]; P

ObjectiveMany persons with knee pain have joint pain outside the knee, but despite the impact and high frequency of this pain, its distribution and causes have not been studied. We undertook this study to test the hypothesis of those studying gait abnormalities who have suggested that knee pain causes pain in adjacent joints but that pain adaptation strategies are highly individualized.MethodsWe studied persons ages 50-79 years with or at high risk of knee osteoarthritis who were recruited from 2 community-based cohorts, the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative, and we followed them up for 5-7 years. We excluded those with knee pain at baseline and compared those who had developed knee pain at the first follow-up examination (the index visit) with those who had not. We examined pain on most days at joint regions outside the knee in examinations after the index visit. Logistic regression analyses examined the risk of joint-specific pain adjusted for age, sex, body mass index, and symptoms of depression, and we performed sensitivity analyses excluding those with widespread pain.ResultsIn the combined cohorts, 693 persons had knee pain at the index visit and 2,793 did not. A total of 79.6% of those with bilateral knee pain and 63.8% of those with unilateral knee pain had pain during follow-up in a joint region outside the knee, compared with 49.9% of those without knee pain. There was an increased risk of pain at most extremity joint sites, without a predilection for specific sites. Results were unchanged when those with widespread pain were excluded.ConclusionPersons with chronic knee pain are at increased risk of pain in multiple joints in no specific pattern.

ObjectiveTo determine the association of different types of meniscal pathology with knee pain, bone marrow lesion (BML) volume, and end-stage knee osteoarthritis (esKOA).DesignParticipants were selected from an ancillary project to the Osteoarthritis Initiative (OAI) who had at least one knee with symptomatic osteoarthritis. Baseline magnetic resonance images (MRI) were evaluated for meniscal pathology using a modified International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) classification system. We collapsed 10 types of meniscal pathology into five categories: normal, intrameniscal signal, morphological deformity/extrusion (altered meniscal shape and/or extrusion but no apparent substance loss), tear, and maceration. Outcomes included Western Ontario and McMaster Universities osteoarthritis index (WOMAC) knee pain and BML volume at baseline and after 2 years. We defined the prevalence of esKOA based on a validated algorithm. We performed logistic regression and adjusted for age, sex, and body mass index (BMI).ResultsThe 463 participants (53% male) included in the analysis had mean age 63 (9.2) years, BMI 29.6 (4.6) kg/m2, and 71% had Kellgren-Lawrence grade ≥2. Morphological deformity/extrusion and maceration, but no other types of meniscal pathology, were associated with BML volume (morphological deformity/extrusion odds ratio [OR] = 2.47, 95% CI: 1.49, 4.09, maceration OR = 5.85, 95% CI: 3.40, 10.06) and change in BML volume (morphological deformity/extrusion OR = 2.17, 95% CI: 1.37, 3.45, maceration OR = 3.12, 95% CI: 1.87, 5.19). Only maceration was associated with baseline WOMAC knee pain (OR = 2.82, 95% CI: 1.79, 4.43) and prevalence of esKOA (OR = 7.53, 95% CI: 4.25, 13.31).ConclusionsBased on MRI, morphologic deformity/extrusion and maceration rather than intrameniscal signal or tear were associated with osteoarthritis severity and progression, which highlights the importance of differentiating distinct types of meniscal pathology.

ObjectiveTo determine the association between changes in semiquantitative magnetic resonance imaging (MRI) biomarkers over 24 months and radiographic and pain progression over 48 months in knees with mild-to-moderate osteoarthritis (OA).MethodsWe undertook a nested case-control study as part of the Foundation for the National Institutes of Health Biomarkers Consortium Project. We used multivariable logistic regression models to examine the association between change over 24 months in semiquantitative MRI markers and radiographic and pain progression in knee OA. MRIs were read according to the MRI OA Knee Score system. We focused on changes in cartilage, osteophytes, meniscus, bone marrow lesions, Hoffa-synovitis, and effusion-synovitis.ResultsThe most parsimonious model included changes in cartilage thickness and surface area, effusion-synovitis, Hoffa-synovitis, and meniscal morphology (C statistic 0.740). Compared with no worsening, worsening in cartilage thickness in ≥3 subregions was associated with 2.8-fold (95% confidence interval [95% CI] 1.3-5.9) greater odds of being a case, and worsening in cartilage surface area in ≥3 subregions was associated with 2.4-fold (95% CI 1.3-4.4) greater odds of being a case. Worsening of meniscal morphology in any region was associated with 2.2-fold (95% CI 1.3-3.8) greater odds of being a case. Worsening effusion-synovitis and Hoffa-synovitis were also associated with a greater odds of being a case (odds ratios 2.7 and 2.0, respectively).ConclusionTwenty-four-month changes in cartilage thickness, cartilage surface area, effusion-synovitis, Hoffa-synovitis, and meniscal morphology were independently associated with OA progression, suggesting that these factors may serve as efficacy biomarkers in clinical trials of disease-modifying interventions for knee OA.

PurposeThe purpose of this nested case-control study was to identify baseline, incident, and progressive MRI findings visible on standard MRI clinical sequences that were associated with development of incident knee pain in subjects at risk for OA over a period of 48 months.MethodsWe analyzed 60 case knees developing incident pain (WOMAC(pain) = 0 at baseline and WOMAC(pain) ≥ 5 at 48 months) and 60 control knees (WOMAC(pain) = 0 at baseline and WOMAC(pain) = 0 at 48 months) from the Osteoarthritis Initiative. 3 T knee MRIs were analyzed using a modified WORMS score (cartilage, meniscus, bone marrow) at baseline and after 48 months. Baseline and longitudinal findings were grouped into logistic regression models and compared using likelihood-ratio tests. For each model that was significant, a stepwise elimination was used to isolate significant MRI findings.ResultsOne baseline MRI finding and three findings that changed from baseline to 48 months were associated with the development of pain: at baseline, the severity of a cartilage lesion in the medial tibia was associated with incident pain--(odds ratio (OR) for incident pain = 3.05; P = 0.030). Longitudinally, an incident effusion (OR = 9.78; P = 0.005), a progressive cartilage lesion of the patella (OR = 4.59; P = 0.009), and an incident medial meniscus tear (OR = 4.91; P = 0.028) were associated with the development of pain.ConclusionsOur results demonstrate that baseline abnormalities of the medial tibia cartilage as well as an incident joint effusion, progressive patella cartilage defects, and an incident medial meniscus tear over 48 months may be associated with incident knee pain. Clinically, this study helps identify MRI findings that are associated with the development of knee pain.

ObjectiveRadiographic disease and knee pain are thought to decrease physical activity in people with knee osteoarthritis (OA), but this has not been formally studied. We examined change in objectively measured daily walking over 2 years and evaluated the association of certain risk factors with reduced walking among adults with or at risk of knee OA.DesignSteps/day over 7 days were collected at baseline and 2 years later in subjects with or at risk of knee OA from the Multicenter Osteoarthritis Study using a StepWatch. We evaluated the presence of radiographic knee osteoarthritis (ROA), knee pain, worsening of ROA and pain over 2 years, obesity, depressive symptoms, living situation, catastrophizing, fatigue, widespread pain and comorbidities with 2-year change in daily walking using regression models adjusted for potential confounders.Results1318 met inclusion criteria (age 66.9 ± 7.7, 59% women, BMI 30.6 ± 5.9) and walked 126 ± 1700 steps/day fewer steps at 2 years (95% CI [-218, -35]). People with depressive symptoms at baseline walked 455 fewer steps/day [-872, -68], and there was a trend for people with ROA worsening to walk 183 fewer steps/day [-377.5, 11.7]. No other factors met statistical significance for change in daily walking.ConclusionAdults with or at risk of knee OA experienced only minimal declines in daily walking over 2 years. Nonetheless, depressive symptoms and may be worsening ROA are associated with a decline in steps/day in adults with or at risk of knee OA.

Study questionIs there concordance between hip pain and radiographic hip osteoarthritis?MethodsIn this diagnostic test study, pelvic radiographs were assessed for hip osteoarthritis in two cohorts: the Framingham Osteoarthritis Study (community of Framingham, Massachusetts) and the Osteoarthritis Initiative (a multicenter longitudinal cohort study of osteoarthritis in the United States). Using visual representation of the hip joint, participants reported whether they had hip pain on most days and the location of the pain: anterior, groin, lateral, buttocks, or low back. In the Framingham study, participants with hip pain were also examined for hip pain with internal rotation. The authors analysed the agreement between radiographic hip osteoarthritis and hip pain, and for those with hip pain suggestive of hip osteoarthritis they calculated the sensitivity, specificity, positive predictive value, and negative predictive value of radiographs as the diagnostic test.Study answer and limitationsIn the Framingham study (n=946), only 15.6% of hips in patients with frequent hip pain showed radiographic evidence of hip osteoarthritis, and 20.7% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of radiographic hip osteoarthritis for hip pain localised to the groin was 36.7%, specificity 90.5%, positive predictive value 6.0%, and negative predictive value 98.9%. Results did not differ much for hip pain at other locations or for painful internal rotation. In the Osteoarthritis Initiative study (n=4366), only 9.1% of hips in patients with frequent pain showed radiographic hip osteoarthritis, and 23.8% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of definite radiographic hip osteoarthritis for hip pain localised to the groin was 16.5%, specificity 94.0%, positive predictive value 7.1%, and negative predictive value 97.6%. Results also did not differ much for hip pain at other locations.What this study addsHip pain was not present in many hips with radiographic osteoarthritis, and many hips with pain did not show radiographic hip osteoarthritis. Most older participants with a high suspicion for clinical hip osteoarthritis (groin or anterior pain and/or painful internal rotation) did not have radiographic hip osteoarthritis, suggesting that in many cases, hip osteoarthritis might be missed if diagnosticians relied solely on hip radiographs.Funding, competing interests, data sharingSee the full paper on thebmj.com for funding. The authors have no competing interests. Additional data are available from bevochan@bu.edu.

ObjectiveTo examine a model addressing the roles of rheumatoid arthritis (RA) disease burden, mood disturbance, and disability as determinants of impairments in role functioning.MethodsIn a cross-sectional design, 103 RA patients recruited from the community to participate in a clinical trial completed assessments of self-assessed disease burden (total joint pain and disease activity), mood disturbance (Center for Epidemiological Studies Depression Scale depressed mood, somatic symptoms, lack of positive affect, and interpersonal problems), disability (Health Assessment Questionnaire disability index gross and fine motor), and role functioning (Short Form 36 health survey physical and social). Structural equation modeling (SEM) was used to examine direct and indirect mechanisms linking disease burden to role functioning.ResultsSEM results indicated that the model had excellent fit: S-Bχ(2)(30) = 38.59, P = 0.135; comparative fit index = 0.977, standardized root mean residual = 0.062, and root mean square error of approximation = 0.053. Mediational analyses demonstrated that, while disease burden was associated with poor role functioning, its effects were jointly mediated by mood disturbance and disability. After the effects of mood disturbance and disability were taken into account, the effect of disease burden on role functioning was not significant.ConclusionThe results indicate that mood disturbance and disability may serve as important pathways through which RA disease burden affects role functioning. Future longitudinal research is suggested to replicate these findings and further explore the mediational mechanisms examined in this study.

PurposeMusculoskeletal symptoms are the most common adverse effects of aromatase inhibitors (AIs) and can result in decreased quality of life and discontinuation of therapy. Omega-3 fatty acids (O3-FAs) can be effective in decreasing arthralgia resulting from rheumatologic conditions and reducing serum triglycerides.Patients and methodsWomen with early-stage breast cancer receiving an AI who had a worst joint pain/stiffness score ≥ 5 of 10 using the Brief Pain Inventory-Short Form (BPI-SF) were randomly assigned to receive either O3-FAs 3.3 g or placebo (soybean/corn oil) daily for 24 weeks. Clinically significant change was defined as ≥ 2-point drop from baseline. Patients also completed quality-of-life (Functional Assessment of Cancer Therapy-Endocrine Symptoms) and additional pain/stiffness assessments at baseline and weeks 6, 12, and 24. Serial fasting blood was collected for lipid analysis.ResultsAmong 262 patients registered, 249 were evaluable, with 122 women in the O3-FA arm and 127 in the placebo arm. Compared with baseline, the mean observed BPI-SF score decreased by 1.74 points at 12 weeks and 2.22 points at 24 weeks with O3-FAs and by 1.49 and 1.81 points, respectively, with placebo. In a linear regression adjusting for the baseline score, osteoarthritis, and taxane use, adjusted 12-week BPI-SF scores did not differ by arm (P = .58). Triglyceride levels decreased in patients receiving O3-FA treatment and remained the same for those receiving placebo (P = .01). No between-group differences were seen for HDL, LDL, or C-reactive protein.ConclusionWe found a substantial (> 50%) and sustained improvement in AI arthralgia for both O3-FAs and placebo but found no meaningful difference between the groups.

ObjectivesIt is not clear whether heightened pain sensitivity in knee osteoarthritis (OA) is related to sensitisation induced by nociceptive input from OA pathology ('state') versus other confounding factors. Conversely, some individuals may be predisposed to sensitisation irrespective of OA ('trait').MethodsThe Multicenter Osteoarthritis Study is a longitudinal cohort of persons with or at risk of knee OA. We obtained knee X-rays, pain questionnaires and comprehensive assessment of factors that can influence pain sensitivity. We examined the relation of sensitisation and sensitivity assessed by mechanical temporal summation (TS) and pressure pain thresholds (PPTs) to knee OA and knee pain severity. To test whether sensitisation and sensitivity is a 'state' induced by OA pathology, we examined the relation of PPT and TS to knee OA duration and severity.ResultsIn 2126 subjects (mean age 68, mean body mass index (BMI) 31, 61% female), PPT and TS were not associated with radiographic OA (ORs 0.9-1.0 for PPT and TS; p>0.05). However, PPT and TS were associated with pain severity (ORs: 1.7-2.0 for PPT; 1.3-1.6 for TS; p

ObjectiveTo examine the relation of cartilage loss and bone marrow lesions (BMLs) in the medial and lateral patellofemoral joint (PFJ) to knee pain.MethodsWe categorized the location of full-thickness cartilage loss and BMLs in the PFJ on knee magnetic resonance imaging (MRIs) from the Multicenter Osteoarthritis (MOST) and Framingham Osteoarthritis (FOA) Studies as no damage, isolated medial, isolated lateral, or both medial and lateral (mixed). We determined the relation of MRI lesions in each PFJ region to prevalent knee pain. Differences in knee pain severity were compared among categories of PFJ full-thickness cartilage loss and BMLs using quantile regression.ResultsIn MOST (n = 1137 knees), compared with knees without full-thickness cartilage loss, knees with isolated lateral or mixed PFJ full-thickness cartilage loss had 1.9 (1.3, 2.8) and 1.9 (1.2, 2.9) times the odds of knee pain, respectively, while isolated medial cartilage loss had no association with knee pain. BMLs in both the medial and lateral PFJ had 1.5 (1.1, 2.0) times the odds of knee pain compared with knees without BMLs. Knee pain severity was lowest in knees with isolated medial PFJ cartilage loss or BMLs. In FOA (n = 934 knees), neither isolated medial nor lateral cartilage loss was associated with knee pain, whereas isolated BMLs in either region were associated with pain.ConclusionsResults were not completely concordant but suggest that knee pain risk and severity is greatest with cartilage loss isolated to (MOST) or inclusive of (MOST and FOA) the lateral PFJ. While BMLs in either the medial or lateral PFJ are related to pain.

ObjectiveTo determine the diagnostic test performance of location of pain and activity-related pain in identifying knees with patellofemoral joint (PFJ) structural damage.MethodsThe Multicenter Osteoarthritis Study is a US National Institutes of Health-funded cohort study of older adults with or at risk of knee osteoarthritis. Subjects identified painful areas around the knee on a knee pain map and the Western Ontario and McMaster Universities Osteoarthritis Index was used to assess pain with stairs and walking on level ground. Cartilage damage and bone marrow lesions were assessed from knee magnetic resonance imaging. We determined the sensitivity, specificity, positive and negative predictive values for presence of anterior knee pain (AKP), pain with stairs, absence of pain while walking on level ground, and combinations of tests in discriminating knees with isolated PFJ structural damage from those with isolated tibiofemoral joint (TFJ) or no structural damage. Knees with mixed PFJ/TFJ damage were removed from our analyses because of the inability to determine which compartment was causing pain.ResultsThere were 407 knees that met our inclusion criteria. "Any" AKP had a sensitivity of 60% and specificity of 53%; and if AKP was the only area of pain, the sensitivity dropped to 27% but specificity rose to 81%. Absence of moderate pain with walking on level ground had the greatest sensitivity (93%) but poor specificity (13%). The combination of "isolated" AKP and moderate pain with stairs had poor sensitivity (9%) but the greatest specificity (97%) of strategies tested.ConclusionCommonly used questions purported to identify knees with PFJ structural damage do not identify this condition with great accuracy.

ObjectiveTo determine whether women experience greater knee pain severity than men at equivalent levels of radiographic knee osteoarthritis (OA).Design and methodsA cross-sectional analysis of 2712 individuals (60% women) without knee replacement or a recent steroid injection. Sex differences in pain severity at each Kellgren-Lawrence (KL) grade were assessed by knee using visual analog scale (VAS) scale and Western Ontario and McMaster Universities Arthritis Index (WOMAC) with and without adjustment for age, analgesic use, Body mass index (BMI), clinic site, comorbid conditions, depression score, education, race, and widespread pain (WSP) using generalized estimating equations. Effect sizes (Cohen's d) were also calculated. Analyses were repeated in those with and without patellofemoral OA (PFOA).ResultsWomen reported higher VAS pain at all KL grades in unadjusted analyses (d = 0.21-0.31, P

HypothesisThe purpose of this cross-sectional study is to determine whether the duration of symptoms influences the features seen in patients with atraumatic, full-thickness rotator cuff tears. Our hypothesis is that an increasing duration of symptoms will correlate with more advanced findings of rotator cuff tear severity on magnetic resonance imaging, worse shoulder outcome scores, more pain, decreased range of motion, and less strength.MethodsWe enrolled 450 patients with full-thickness rotator cuff tears in a prospective cohort study to assess the effectiveness of nonoperative treatment and factors predictive of success. The duration of patient symptoms was divided into 4 groups: 3 months or less, 4 to 6 months, 7 to 12 months, and greater than 12 months. Data collected at patient entry into the study included (1) demographic data, (2) history and physical examination data, (3) radiographic imaging data, and (4) validated patient-reported measures of shoulder status. Statistical analysis included a univariate analysis with the Kruskal-Wallis test and Pearson test to identify statistically significant differences in these features for different durations of symptoms.ResultsA longer duration of symptoms does not correlate with more severe rotator cuff disease. The duration of symptoms was not related to weakness, limited range of motion, tear size, fatty atrophy, or validated patient-reported outcome measures.ConclusionsThere is only a weak relationship between the duration of symptoms and features associated with rotator cuff disease.

ObjectiveTo evaluate health-related quality of life (HRQOL) and corticosteroid use in patients with moderate to severely active SLE enrolled in two international, multicentre, randomized controlled trials of epratuzumab (ALLEVIATE-1 and -2) and a long-term extension study (SL0006).MethodsNinety ALLEVIATE patients (43% BILAG A, mean BILAG score 13.2) were randomized to receive 360 mg/m(2) (n = 42) or 720 mg/m(2) (n = 11) epratuzumab or placebo (n = 37), plus standard of care, in 12-week cycles. Corticosteroid use, patient and physician global assessments of disease activity (PtGA and PGA) and 36-item Medical Outcomes Survey Short Form (SF-36) results were recorded at baseline and every 4 weeks. Both trials were prematurely discontinued due to a drug supply interruption; patients followed for ≥6 months were analysed. Twenty-nine patients continued in SL0006, with interim analysis at a median exposure of 120 (range 13-184) weeks.ResultsAt week 12, proportions of patients with a PGA ≥20% above baseline or with a PtGA improvement greater than or equal to the minimum clinically important difference were higher in the epratuzumab arms than the placebo arm. PGA and PtGA improvements were sustained but did not reach statistical significance. At week 24, mean cumulative corticosteroid doses with epratuzumab 360 and 720 mg/m(2) were 1051 and 1973 mg less than placebo (P = 0.034 and 0.081, respectively). At week 48, SF-36 scores approached or exceeded US age- and gender-matched norms in five domains with the 360 mg/m(2) treatment. Improvements were maintained in SL0006 over ∼2 years.ConclusionEpratuzumab treatment produced clinically meaningful and sustained improvements in PGA, PtGA and HRQOL and reductions in corticosteroid doses.

ObjectiveTo determine whether quadriceps weakness is associated with elevated risk of worsening knee pain over 5 years.MethodsThe Multicenter Osteoarthritis Study (MOST) is a longitudinal study of 50-79-year-old adults with knee osteoarthritis (OA) or known risk factors for knee OA. The predictor variable was baseline isokinetic quadriceps strength. Covariates included baseline body mass index (BMI), physical activity level, and history of knee surgery. The outcome was worsening pain reported on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale or knee replacement surgery between baseline and 5-year follow-up. Analyses were knee-based and used generalized estimating equations, stratified by sex to assess whether the lowest compared with the highest tertile of baseline quadriceps strength was associated with an increased risk of worsening knee pain at 5-year follow-up, controlling for age, BMI, history of knee surgery, and physical activity level as well as correlation between knees within participants.ResultsAnalyses of worsening knee pain included 4,648 knees from 2,404 participants (61% female). Men with lower quadriceps strength did not have a higher risk of worsening knee pain (RR {95% CI} = 1.01 {0.78-1.32}, P = 0.9183). However, women in the lowest compared with the highest strength tertile had a 28% increased risk of worsening knee pain (RR {95% CI} = 1.28 {1.08-1.52}, P = 0.0052).ConclusionQuadriceps weakness was associated with an increased risk of worsening of knee pain over 5 years in women, but not in men.

The fascia lata, or deep fascia of the thigh, is a complex anatomic structure that has not been emphasized as a potential source of pelvic and hip pain. This structure represents a broad continuum of fibrous tissue about the buttock, hip, and thigh that receives contributions from the posteriorly located aponeurotic fascia covering the gluteus medius muscle and from the more laterally located iliotibial band (ITB). At the pelvis and hip, the ITB consists of three layers that merge at the lower portion of the tensor fasciae latae muscle. The gluteal aponeurotic fascia and ITB merge at the buttock and hip before extending inferiorly to the Gerdy tubercle at the anterolateral tibia. Injuries to these anatomic structures are an underdiagnosed cause of pain and disability and may clinically mimic more common processes affecting the hip and proximal thigh. Categories of disease include overuse injuries, traumatic injuries, degenerative lesions, and inflammatory lesions. Familiarity with the anatomy and pathologic conditions of the fascia lata and its components is important in their recognition as a potential source of symptoms. This article illustrates the anatomy of this complex fascia through anatomic-pathologic correlation and describes the magnetic resonance imaging appearances of the pathologic conditions involving it.

ObjectiveTo better understand the relationship between knee pain and bilateral knee lesions, we compared focal knee lesions in knee pairs of subjects with no, unilateral, and bilateral knee pain, and risk factors for knee osteoarthritis (OA), but no radiographic knee OA.Materials and methodsWe examined both knees of 120 subjects from the Osteoarthritis Initiative database. We randomly selected 60 subjects aged 45-55 years with OA risk factors, no knee pain (WOMAC pain score=0) and no radiographic OA (KL-score ≤1) in both knees. We also selected two comparison groups with OA risk factors and no radiographic OA in both knees, but with knee pain (WOMAC pain score ≥5): 30 subjects with right only knee pain and 30 subjects with bilateral knee pain. All subjects underwent 3T MRI of both knees and focal knee lesions were assessed.ResultsStatistically significant associations between prevalence of focal lesions in the right and left knee with odds ratios up to 13.5 were found in all three subject groups. Focal knee lesions were generally not associated with pain in analyses comparing knee pairs of subjects with unilateral knee pain (p>0.05). The prevalence and severity of focal knee lesions were not significantly different in knee pairs of subjects with no knee pain and those with bilateral knee pain (p>0.05).ConclusionFocal knee lesions in the right and left knee of subjects with OA risk factors were positively associated with each other independent of knee pain status, and were not statistically significant different between knees in subjects with unilateral knee pain.

ObjectiveWhile depressive symptoms and knee pain are independently known to impede daily walking in older adults, it is unknown whether positive affect promotes daily walking. This study investigated this association among adults with knee osteoarthritis (OA) and examined whether knee pain modified this association.MethodsThis study is a cross-sectional analysis of the Multicenter Osteoarthritis Study. We included 1,018 participants (mean ± SD age 63.1 ± 7.8 years, 60% women) who had radiographic knee OA and had worn a StepWatch monitor to record their number of steps per day. High and low positive affect and depressive symptoms were based on the Center for Epidemiologic Studies Depression Scale. Knee pain was categorized as present in respondents who reported pain on most days at both a clinic visit and a telephone screening.ResultsCompared to respondents with low positive affect (27% of all respondents), those with high positive affect (63%) walked a similar number of steps per day, while those with depressive symptoms (10%) walked less (adjusted β -32.6 [95% confidence interval (95% CI) -458.9, 393.8] and -579.1 [95% CI -1,274.9, 116.7], respectively). There was a statistically significant interaction of positive affect by knee pain (P = 0.0045). Among the respondents with knee pain (39%), those with high positive affect walked significantly more steps per day (adjusted β 711.0 [95% CI 55.1, 1,366.9]) than those with low positive affect.ConclusionHigh positive affect was associated with more daily walking among adults with painful knee OA. Positive affect may be an important psychological factor to consider for promoting physical activity among people with painful knee OA.

ObjectivesAcupuncture utilization in the United States has increased in recent years, but is less common among racial/ethnic minorities and those of low socioeconomic status. Group-based, community acupuncture is a delivery model gaining in popularity around the United States, due in part to low-cost treatments provided on a sliding-fee scale. Affordable, community-based acupuncture may increase access to health care at a time when increasing numbers of people are uninsured. To assess the population using local community acupuncture clinics, sociodemographic factors, health status, and utilization patterns compared to national acupuncture users were examined.DesignData were employed from (1) a cross-sectional survey of 478 clients of two community acupuncture clinics in Portland, Oregon and (2) a nationally representative sample of acupuncture users from the 2007 National Health Interview Survey.ResultsPortland community acupuncture clients were more homogeneous racially, had higher educational attainment, lower household income, and were more likely to receive 10 or more treatments in the past 12 months (odds ratio=5.39, 95% confidence interval=3.54, 8.22), compared to a nationally representative sample of U.S. acupuncture users. Self-reported health status and medical reasons for seeking acupuncture treatment were similar in both groups. Back pain (21%), joint pain (17%), and depression (13%) were the most common conditions for seeking treatment at community acupuncture clinics.ConclusionsStudy findings suggest that local community acupuncture clinics reach individuals of a broad socioeconomic spectrum and may allow for increased frequency of treatment. Limited racial diversity among community acupuncture clients may reflect local demographics of Portland. In addition, exposure to and knowledge about acupuncture is likely to vary by race and ethnicity. Future studies should examine access, patient satisfaction, frequency of treatment, and clinical outcomes of group-based models of community acupuncture clinics located in racially and socioeconomically diverse communities.

BackgroundOsteoarthritis-induced arthralgia is a common cause of morbidity in both men and women worldwide. AR7 Joint Complex is a nutritional supplement containing various ingredients including sternum collagen II and methylsulfonylmethane. The product has been marketed in United States for over a decade, but clinical data measuring the effectiveness of this supplement in relieving arthralgia is lacking. The goal of this study was to determine the effect of AR7 Joint Complex on osteoarthritis.MethodsA total of 100 patients over the age of 50 who had osteoarthritis were recruited to the double-blind study and randomly assigned into either treatment or placebo control groups. The patients in the treatment group were given AR7 Joint Complex orally, 1 capsule daily for 12 weeks, while the patients in the control group were given a placebo for the same period of time. Prior to and at the end of the study, data including Quality of Life questionnaires (SF-36), visual analog scales (1 to 100 mm), and X-rays of affected joints were collected.ResultsA total of 89 patients completed the study: 44 from the treatment group and 45 from the control group. No significant change in X-ray results was found in either group after the study. However, there was a significant decrease in patients complaining of arthralgia and tenderness (P < 0.01) in the treatment group and there was also a significant difference between the treatment and control groups at the end of the study. In addition, for Quality of Life data, the body pain index (BP) in the treatment group was significantly improved (P < 0.05) compared to the control group. No significant toxicity was noted in either group.ConclusionAR7 Joint Complex appears to have short-term effects in relieving pain in patients with osteoarthritis. Whether such an effect is long-lasting remains to be seen.