Intra-Articular Mineralization on Computerized Tomography of the Knee and Risk of Cartilage Damage: The Multicenter Osteoarthritis Study.

OBJECTIVE: Intra-articular (IA) mineralization may contribute to osteoarthritis (OA) structural progression. We studied the association of IA mineralization on knee computed tomography (CT) with cartilage damage worsening on knee magnetic resonance imaging (MRI), with a focus on location- and tissue-specific effects. METHODS: Participants from the Multicenter Osteoarthritis Study with knee CT and MRI scans were included. Presence of IA mineralization on CT was defined as a Boston University Calcium Knee Score >0 anywhere in the knee. Cartilage worsening on MRI was defined as any increase in the MRI OA Knee Score, including incident damage. We evaluated the association of whole-knee, compartment-specific (ie, medial or lateral), and subregion-specific (ie, location-matched) IA mineralization at baseline with cartilage worsening at two years' follow-up in the corresponding locations using binomial regression with generalized estimating equations, adjusting for age, sex, and body mass index (BMI). RESULTS: We included 1,673 participants (mean age 60 years, 56% female, mean BMI 29). Nine percent had any IA mineralization in the knee, and 47.4% had any cartilage worsening on follow-up. Mineralization of any tissue in the knee, regardless of location, was not associated with MRI cartilage worsening. However, cartilage mineralization was associated with 1.39 (95% confidence interval 1.04-1.88) times higher risk of cartilage worsening in the same compartment, with similar results in subregion-specific analysis. CONCLUSION: CT-detected IA mineralization in the cartilage was associated with higher risk of MRI cartilage worsening in the same compartment and subregion over two years. These findings suggest potential localized, tissue-specific effects of IA mineralization on cartilage pathology in knee OA.

Assessing the association of epigenetic age acceleration with osteoarthritis in the Multicenter Osteoarthritis Study (MOST).

PURPOSE: Advancing age is one of the strongest risk factors for osteoarthritis (OA). DNA methylation-based measures of epigenetic age acceleration may provide insights into mechanisms underlying OA. METHODS: We analyzed data from the Multicenter Osteoarthritis Study in a subset of 671 participants ages 45-69 years with no or mild radiographic knee OA. DNA methylation was assessed with the Illumina Infinium MethylationEPIC 850K array. We calculated predicted epigenetic age according to Hannum, Horvath, PhenoAge, and GrimAge epigenetic clocks, then regressed epigenetic age on chronological age to obtain the residuals. Associations between the residuals and knee, hand, and multi-joint OA were assessed using logistic regression, adjusted for chronological age, sex, clinical site, smoking status, and race. RESULTS: Twenty-three percent met criteria for radiographic hand OA, 25% met criteria for radiographic knee OA, and 8% met criteria for multi-joint OA. Mean chronological age (SD) was 58.4 (6.7) years. Mean predicted epigenetic age (SD) according to Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks was 64.9 (6.4), 68.6 (5.9), 50.5 (7.7), and 67.0 (6.2), respectively. Horvath epigenetic age acceleration was not associated with an increased odds of hand OA, odds ratio (95% confidence intervals) = 1.03 (0.99-1.08), with similar findings for knee and multi-joint OA. We found similar magnitudes of associations for Hannum epigenetic age, PhenoAge, and GrimAge acceleration compared to Horvath epigenetic age acceleration. CONCLUSIONS: Epigenetic age acceleration as measured by various well-validated epigenetic clocks based on DNA methylation was not associated with increased risk of knee, hand, or multi-joint OA independent of chronological age.

Essential Fatty Acids and Osteoarthritis.

OBJECTIVE: Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Although n-3 fatty acids reduce inflammation, different n-3 fatty acids have different effects on inflammation and clinical outcomes, with eicosapentaenoic acid (EPA) having the strongest effect. We examined whether specific essential fatty acid levels affected the development of OA. METHODS: We studied participants from the Multicenter Osteoarthritis Study (MOST) at risk of developing knee OA. As part of MOST, participants were asked repeatedly about knee pain, and knee radiographs and magnetic resonance images (MRIs) were obtained. Using baseline fasting samples, we analyzed serum fatty acids with standard assays. After excluding participants with baseline OA, we defined two sets of cases based on their status through 60 months' follow-up: those developing incident radiographic OA and those developing incident symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage damage and synovitis and worsening knee pain and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of specific n-3 and n-6 fatty acids, adjusting for age, sex, body mass index, education, physical activity, race, baseline pain, smoking, statin use, and depressive symptoms. RESULTS: We studied 363 cases with incident symptomatic knee OA and 295 with incident radiographic knee OA. The mean age was 62 years (59% women). We found no associations of specific n-3 fatty acid levels, including EPA, or of n-6 fatty acid levels with incident OA (eg, for incident symptomatic knee OA, the odds ratio per SD increase in EPA was 1.0 [95% confidence interval 0.87-1.17]). Results for other OA outcomes also failed to suggest a protective effect of specific n-3 fatty acids with OA outcomes. CONCLUSION: We found no association of serum levels of EPA or of other specific n-3 fatty acids or n-6 fatty acids with risk of incident knee OA or other OA outcomes.

Relation of Intra-Articular Mineralization to Knee Pain in Knee Osteoarthritis: A Longitudinal Analysis in the MOST Study.

OBJECTIVE: Intra-articular (IA) calcium crystal deposition is common in knee osteoarthritis (OA), but of unclear significance. It is possible that low-grade, crystal-related inflammation may contribute to knee pain. We examined the longitudinal relation of computed tomography (CT)-detected IA mineralization to the development of knee pain. METHODS: We used data from the National Institutes of Health-funded longitudinal Multicenter Osteoarthritis Study. Participants had knee radiographs and bilateral knee CTs at baseline, and pain assessments every 8 months for 2 years. CT images were scored using the Boston University Calcium Knee Score. We longitudinally examined the relation of CT-detected IA mineralization to the risk of frequent knee pain (FKP), intermittent or constant knee pain worsening, and pain severity worsening using generalized linear mixed-effects models. RESULTS: We included 2,093 participants (mean age 61 years, 57% women, mean body mass index 28.8 kg/m2 ). Overall, 10.2% of knees had IA mineralization. The presence of any IA mineralization in the cartilage was associated with 2.0 times higher odds of having FKP (95% confidence interval [CI] 1.38-2.78) and 1.86 times more frequent intermittent or constant pain (95% CI 1.20-2.78), with similar results seen for the presence of any IA mineralization in the meniscus or joint capsule. A higher burden of IA mineralization anywhere within the knee was associated with a higher odds of all pain outcomes (odds ratio ranged from 2.14 to 2.21). CONCLUSION: CT-detected IA mineralization was associated with risk of having more frequent, persistent, and worsening knee pain over 2 years. Targeting IA mineralization may have therapeutic potential for pain improvement in knee OA.

Offspring neurodevelopmental outcomes born to parents with chronic inflammatory arthritis using antirheumatic therapies: A scoping review.

INTRODUCTION: Most women with rheumatic diseases discontinue antirheumatic therapies in anticipation of, or during pregnancy due to concerns around medication safety and fetal wellbeing. OBJECTIVE: We performed a scoping review of available evidence investigating the risks of adverse offspring neurodevelopmental outcomes amongst parents with chronic inflammatory arthritis, taking antirheumatic therapies during conception or pregnancy. METHODS: We designed a scoping review protocol and search strategy a priori in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed an exhaustive search in Cochrane Library, Embase, Google Scholar, Medline, and Web of Science for relevant literature in January 2023. Articles needed to include offspring neurodevelopmental outcomes born to parents with CIA who took antirheumatic therapies during conception or pregnancy. Independent reviewers extracted data from eligible articles using a standard abstraction tool and performed critical appraisal of study quality. RESULTS: Six studies were included for full data abstraction. Use of Nonsteroidal Anti-inflammatory Drugs, Tumor Necrosis Factor Alpha inhibitors, and exposure to methotrexate during early first trimester of pregnancy did not seem to increase risk for adverse offspring neurodevelopmental outcomes. Corticosteroid use during pregnancy seemed to pose an increased risk for attention deficit hyperactive disorders in offspring. CONCLUSION: Use of some antirheumatic therapies during pregnancy may not be associated with adverse offspring neurodevelopmental outcomes. Further investigations are needed to elucidate if other confounding factors affect long term offspring health outcomes born to parents with chronic inflammatory arthritis.

Development of a Magnetic Resonance Imaging-Based Definition of Knee Osteoarthritis: Data From the Multicenter Osteoarthritis Study.

OBJECTIVE: Although magnetic resonance imaging (MRI) is the imaging modality of choice for research, there is no widely accepted MRI definition of knee osteoarthritis (OA). We undertook this study to test the performance of different MRI definitions of OA. METHODS: We studied Multicenter Osteoarthritis Study participants with knee symptoms using posteroanterior and lateral knee radiographs and MRIs. Radiographic OA was defined as Kellgren/Lawrence grade ≥2 in the tibiofemoral (TF) and/or patellofemoral (PF) joint. Symptomatic OA was defined using a validated questionnaire. MRI findings of cartilage damage, osteophytes, bone marrow lesions (BMLs), and synovitis were scored using the Whole-Organ MRI Score system. We compared definitions using combinations of MRI features to the validation criteria of prevalent radiographic OA and symptomatic OA. All combinations included cartilage damage score ≥2 (0-6 scale) and osteophyte score ≥2 (0-6 scale); addition of BMLs and synovitis score was also tested. We also evaluated a Delphi panel definition that defined OA differently for the PF and TF joints. For each definition, we calculated sensitivity, specificity, and the area under the curve (AUC). RESULTS: We included 1,185 knees from 1,185 participants (mean age 66 years, 62% female, 89% White). Among the 1,185 knees, 482 knees had radiographic OA, and 524 knees had symptomatic OA. The MRI definitions with a cartilage score ≥2 and osteophyte score ≥2 and definitions which added BMLs or synovitis score ≥1 had the highest sensitivities (95.2% and 94.5%, respectively) for prevalent radiographic OA (AUCs 0.67 and 0.69, respectively), and also had the highest sensitivities for symptomatic OA. The Delphi panel definition had similar performance but was more complex to apply. CONCLUSION: An MRI OA definition requiring cartilage damage and a small osteophyte with or without BMLs or synovitis had the best performance and was simplest for identifying radiographic OA and symptomatic OA.

Meaning of patient global assessment when joint counts are low in rheumatoid arthritis.

OBJECTIVE: In patients with rheumatoid arthritis (RA) with low 28-joint tender and swollen joint counts but who assessed their disease as active, to evaluate whether activity reflected RA symptoms. METHODS: We carried out a cross-sectional study of patients in BRASS, a cohort of patients with established RA who had 28-joint counts assessed, scored their disease activity, identified their painful joints, and answered questions about other sites of pain and fatigue. Patients and their rheumatologists were asked about the presence of fibromyalgia. We examined whether patients reported pain in joints excluded from the 28-joint joint count (feet, ankles, hips, neck) and pain or symptoms probably unrelated to RA including low back pain, headache and fibromyalgia. Fatigue was not classified. Analyses were descriptive. RESULTS: Of 272 patients, 49 had tender and swollen joint counts <1 and a patient global assessment score of ≥3/10. 48/49 (95%) reported pain in joints excluded from the 28-joint count. Of these 49, 24 (45%) also had other symptoms especially low back pain. Fatigue was present in all patients. No patient had fibromyalgia. CONCLUSION: If joint counts <=1 are scored in 28 joints, patient global assessments of ≥3/10 often occur when there is pain in uncounted joints, joints that may respond to RA treatment.

Magnetic Resonance Imaging-Assessed Subchondral Cysts and Incident Knee Pain and Knee Osteoarthritis: Data From the Multicenter Osteoarthritis Study.

OBJECTIVE: To examine whether knee subchondral cysts, measured on magnetic resonance imaging (MRI), are associated with incident knee osteoarthritis (OA) outcomes. METHODS: We 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. RESULTS: Among 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. CONCLUSION: Subchondral 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.

Assessment of bone marrow oedema-like lesions using MRI in patellofemoral knee osteoarthritis: comparison of different MRI pulse sequences.

OBJECTIVE: To compare bone marrow oedema-like lesion (BML) volume in subjects with symptomatic patellofemoral (PF) knee osteoarthritis (OA) using four different MRI sequences and to determine reliability of BML volume assessment using these sequences and their correlation with pain. METHODS: 76 males and females (mean age 55.8 years) with symptomatic patellofemoral knee OA had 1.5 T MRI scans. PD fat suppressed (FS), STIR, contrast-enhanced (CE) T1W FS, and 3D T1W fast field echo (FFE) sequences were obtained. All sequences were assessed by one reader, including repeat assessment of 15 knees using manual segmentation and the measurements were compared. We used random-effects panel linear regression to look for differences in the log-transformed BML volume (due to positive skew in the BML volume distribution) between sequences and to determine associations between BML volumes and knee pain. RESULTS: 58 subjects had PF BMLs present on at least one sequence. Median BML volume measured using T1W FFE sequence was significantly smaller (224.7 mm3, interquartile range [IQR] 82.50-607.95) than the other three sequences. BML volume was greatest on the CE sequence (1129.8 mm3, IQR 467.28-3166.02). Compared to CE sequence, BML volumes were slightly lower when assessed using PDFS (proportional difference = 0.79; 95% confidence interval [CI] 0.62, 1.01) and STIR sequences (proportional difference = 0.85; 95% CI 0.67, 1.08). There were strong correlations between BML volume on PDFS, STIR, and CE T1W FS sequences (ρs = 0.98). Correlations were lower between these three sequences and T1W FFE (ρs = 0.80-0.81). Intraclass correlation coefficients were excellent for proton density fat-suppressed, short-tau inversion recovery, and CE T1W FS sequences (0.991-0.995), while the ICC for T1W FFE was good at 0.88. We found no significant association between BML volumes assessed using any of the sequences and knee pain. CONCLUSION: T1W FFE sequences were less reliable and measured considerably smaller BML volume compared to other sequences. BML volume was larger when assessed using the contrast enhanced T1W FS though not statistically significantly different from BMLs when assessed using PDFS and STIR sequences. ADVANCES IN KNOWLEDGE: This is the first study to assess BMLs by four different MRI pulse sequences on the same data set, including different fluid sensitive sequences and gradient echo type sequence.

Relation of therapies for ankylosing spondylitis and psoriatic arthritis to risk of myocardial infarction: a nested case control study.

BACKGROUND: Risk of myocardial infarction (MI) is elevated in ankylosing spondylitis and psoriatic arthritis (AS/PsA) compared to the general population. We evaluated the risk of MI related to the use of tumor necrosis factor inhibitor (TNFi) and other therapies in AS/PsA. METHODS: We conducted a nested case-control study using 1994-2018 data from OptumLabs® Data Warehouse, which includes de-identified medical and pharmacy claims, laboratory results, and enrollment records for commercial and Medicare Advantage enrollees. The database contains longitudinal health information on enrollees and patients, representing a diverse mixture of ages, ethnicities and geographical regions across the United States. Assessing AS/PsA separately, MI cases were matched to 4 controls by sex, age, diagnosis year and insurance type. We evaluated treatment within 6 months prior to MI including NSAIDs (AS referent), disease-modifying anti-rheumatic drug (DMARDs; PsA referent) and TNFi alone or in combinations. We evaluated the relation of treatment categories to MI risk using conditional logistical regression adjusting for confounders. RESULTS: Among 26,648 AS subjects, there were 237 MI cases and 894 matched controls. Among 43,734 PsA subjects, there were 404 cases and 1596 controls. In AS, relative to NSAID use, the adjusted odds ratio (aOR) for MI among TNFi only users was 0.85 (95% CI 0.39-1.85) and for DMARD only users was 1.04 (95% CI 0.65-1.68). In PsA, relative to DMARD use, the aOR among TNFi only was 1.09 (95% CI 0.74-1.60). Combination therapies also had no effect. CONCLUSIONS: Among AS/PsA, no combination of therapies appeared to be protective or harmful with regards to MI. Future studies should capture more AS and PsA patients and include longer term follow up to further investigate this question.

Knee osteoarthritis and time-to all-cause mortality in six community-based cohorts: an international meta-analysis of individual participant-level data.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population. METHODS: Seven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung-Knapp modification for random-effects meta-analysis. FINDINGS: 10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA. DISCUSSION: Participants with POA or PROA had a 35-37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality. FUNDING: Versus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International.

Relation of NSAIDs, DMARDs, and TNF Inhibitors for Ankylosing Spondylitis and Psoriatic Arthritis to Risk of Total Hip and Knee Arthroplasty.

OBJECTIVE: Ankylosing spondylitis (AS) and psoriatic arthritis (PsA) often affect the hip and/or knee. If effective, treatments might reduce risk of total hip or total knee arthroplasty (THA/TKA). We evaluated risk of THA/TKA related to use of medical therapies in AS/PsA. METHODS: We conducted a nested case-control study using 1994-2018 data from the OptumLabs Data Warehouse, which includes deidentified medical and pharmacy claims, laboratory results, and enrollment records for commercial and Medicare Advantage enrollees. Among those with AS/PsA, THA/TKA cases were matched up to 4 controls by sex, age, AS/PsA diagnosis, diagnosis year, insurance type, obesity, and prior THA/TKA. We assessed AS/PsA treatment 6 months prior to THA/TKA, including disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor inhibitors (TNFi), alone or in combination, stratified by nonsteroidal antiinflammatory drug (NSAID) use. We evaluated the relation of treatment to risk of THA/TKA using conditional logistical regression with adjustment for confounders. RESULTS: Among 16,748 adults with AS, there were 444 THA/TKA cases and 1613 matched controls. Among 34,512 adults with PsA, there were 1003 cases and 3793 controls. Adjusted ORs for treatment category and THA/TKA ranged from 0.60 to 1.92; however, none were statistically significant. Results were similarly null in several sensitivity analyses. CONCLUSION: Odds of THA/TKA were not reduced with any combinations of NSAIDs, DMARDs, or TNFi among persons with AS or PsA. Given current utilization patterns in this population of US adults with AS and PsA, these medical therapies did not appear to be associated with less end-stage peripheral joint damage.

Association of Visceral Adiposity With Pain but Not Structural Osteoarthritis.

OBJECTIVE: Osteoarthritis (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. METHODS: Subjects 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. RESULTS: Of 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). CONCLUSION: Our findings indicate that visceral fat is associated with an increased risk of musculoskeletal and widespread pain.

Testing different thresholds for patient global assessment in defining remission for rheumatoid arthritis: are the current ACR/EULAR Boolean criteria optimal?

OBJECTIVES: This study aimed to evaluate different patient global assessment (PGA) cut-offs required in the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean remission definition for their utility in rheumatoid arthritis (RA). METHODS: We used data from six randomised controlled trials in early and established RA. We increased the threshold for the 0-10 score for PGA gradually from 1 to 3 in steps of 0.5 (Boolean1.5 to Boolean3.0) and omitted PGA completely (BooleanX) at 6 and 12 months. Agreement with the index-based (Simplified Disease Activity Index (SDAI)) remission definition was analysed using kappa, recursive partitioning (classification and regression tree (CART)) and receiver operating characteristics. The impact of achieving each definition on functional and radiographic outcomes after 1 year was explored. RESULTS: Data from 1680 patients with early RA and 920 patients with established RA were included. The proportion of patients achieving Boolean remission increased with higher thresholds for PGA from 12.4% to 19.7% in early and 5.9% to 12.3% in established RA at 6 months. Best agreement with SDAI remission occurred at PGA cut-offs of 1.5 and 2.0, while agreement decreased with higher PGA (CART: optimal agreement at PGA≤1.6 cm; sensitivity of PGA≤1.5 95%). Changing PGA thresholds at 6 months did not affect radiographic progression at 12 months (mean ꙙsmTSS for Boolean, 1.5, 2.0, 2.5, 3.0, BooleanX: 0.35±5.4, 0.38±5.14, 0.41±5.1, 0.37±4.9, 0.34±4.9, 0.27±4.7). However, the proportion attaining HAQ≤0.5 was 90.2%, 87.9%, 85.2%, 81.1%, 80.7% and 73.1% for the respective Boolean definitions. CONCLUSION: Increasing the PGA cut-off to 1.5 cm would provide high consistency between Boolean with the index-based remission; the integer cut-off of 2.0 cm performed similarly.

Total Serum Testosterone and Western Ontario and McMaster Universities Osteoarthritis Index Pain and Function Among Older Men and Women With Severe Knee Osteoarthritis.

OBJECTIVE: To investigate whether serum total testosterone level is associated with knee pain and function in men and women with severe knee osteoarthritis (OA). METHODS: We enrolled 272 adults age ≥60 years (mean ± SD age 70.4 ± 4.4 years, 53% women) who underwent unilateral total knee replacement (TKR) due to severe knee OA. Serum testosterone levels and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function of the operated and contralateral knee were measured at 6-8 weeks after surgery. At the nonoperated knee, 56% of participants had radiographic knee OA with a Kellgren/Lawrence grade ≥2. Cross-sectional analyses were performed by sex and body mass index (BMI) subgroups, using multivariable regression adjusted for age, physical activity, and BMI. RESULTS: At the operated knee, higher testosterone levels were associated with less WOMAC pain in men (B = -0.62, P = 0.046) and women (B = -3.79, P = 0.02), and less WOMAC disability scores in women (B = -3.62, P = 0.02) and obese men (B = -1.99, P = 0.02). At the nonoperated knee, testosterone levels were not associated with WOMAC pain in men or women, but higher testosterone levels were associated with less disability in women (B = -0.95, P = 0.02). Testosterone levels were inconsistently associated with pain and disability in BMI subgroups among men. Only among obese women, testosterone levels were inversely associated with radiographic knee OA (odds ratio = 0.10, P = 0.003). CONCLUSION: Higher total testosterone levels were associated with less pain in the operated knee in men and women undergoing TKR and less disability in women. At the nonoperated knee, higher testosterone levels were inconsistently associated with less pain and disability.

Efficacy of Computer-Based Telephone Counseling on Long-Term Adherence to Strength Training in Elderly Patients With Knee Osteoarthritis: A Randomized Trial.

OBJECTIVE: To determine whether the Boston Overcoming Osteoarthritis through Strength Training Telephone-Linked Communication (BOOST-TLC) program, a novel telephone-based, motivational, strength-training exercise-adherence counseling intervention, improved adherence to a strength-training exercise program over 2 years. METHODS: Participants were recruited for this 2-year, single-blind, parallel-arm randomized controlled trial from knee osteoarthritis patient registries, community newspapers, and online websites in Massachusetts. Eligibility criteria included age 50 years or older, painful knee osteoarthritis, and ability to use a telephone. Exclusion criteria included medical conditions precluding exercise, inflammatory arthritis, current regular strength training, planned knee replacement surgery, dementia, inability to follow exercise instructions, and inability to use the TLC system. After participating in a group exercise class, participants were randomized to receiving motivational telephone calls through the BOOST-TLC program for 24 months or the control. Both control and intervention participants received a monthly automated phone message reminder to continue the program. Exercise adherence was ascertained by a single self-report item scored 0-10, where 10 represented complete adherence. Outcomes were evaluated at 6, 12, 18, and 24 months. RESULTS: A total of 104 subjects were randomized, and 89 subjects (44 control, 45 TLC) completed the 24-month follow-up. There was no significant difference in adherence at 24 months between groups (mean for control group 4.01 [95% confidence interval (95% CI) 3.03, 4.99], mean for TLC subjects 3.63 [95% CI 2.70, 4.56]; P = 0.57). CONCLUSION: In those with knee osteoarthritis who had participated in an exercise program, frequent motivational telephone reminders did not increase adherence to strength-training exercise.

Step Rate and Worsening of Patellofemoral and Tibiofemoral Joint Osteoarthritis in Women and Men: The Multicenter Osteoarthritis Study.

OBJECTIVE: To determine the association of self-selected walking step rate with worsening of cartilage damage in the patellofemoral (PF) joint and tibiofemoral (TF) joint compartments at a 2-year follow-up visit. METHODS: The Multicenter Osteoarthritis Study (MOST) is a prospective cohort of men and women with or at risk of knee osteoarthritis. Self-selected step rate was measured using an instrumented GAITRite walkway (CIR Systems) at the 60-month visit. Cartilage damage was semiquantitatively graded on magnetic resonance images at the 60- and 84-month visits in the medial and lateral PF and TF compartments. Step rate was divided into quartiles, and logistic regression was used to determine the association of step rate with the risk of worsening cartilage damage in men and women separately. Analyses were adjusted for age, body mass index, and knee injury/surgery. RESULTS: A total of 1,089 participants were included. Mean ± SD age was 66.9 ± 7.5 years, mean ± SD body mass index was 29.6 ± 4.7 kg/m2 , and 62.3% of the participants were women. Women with the lowest step rate had increased risk of lateral PF (risk ratio [RR] 2.1 [95% confidence interval (95% CI) 1.1-3.8]) and TF (RR 1.8 [95% CI 1.1-2.9]) cartilage damage worsening 2 years later compared to those with the highest step rate. Men with the lowest step rate had increased risk of medial TF cartilage damage worsening 2 years later (RR 2.1 [95% CI 1.1-3.9]). CONCLUSION: Lower step rate was associated with increased risk of cartilage damage worsening in the lateral PF and TF compartments in women and worsening medial TF joint damage in men. Future research is necessary to understand the influence of step rate manipulation on joint biomechanics in women and men.

Influence of Antagonistic Hamstring Coactivation on Measurement of Quadriceps Strength in Older Adults.

BACKGROUND: There is limited understanding of how antagonist muscle coactivation relates to measurement of strength in both individuals with and without knee osteoarthritis (KOA). OBJECTIVE: This study sought to determine whether hamstring coactivation during a maximal quadriceps activation task attenuates net quadriceps strength. DESIGN: Cross-sectional cohort analysis was conducted using data from the 60-month visit of the Multicenter Osteoarthritis Study (MOST). SETTING: Laboratory. PARTICIPANTS: A sample of 2328 community-dwelling MOST participants between the ages of 55 and 84 years, with or at elevated risk for KOA, completed the 60-month MOST follow-up visit. Of these, 1666 met inclusion criteria for the current study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Quadriceps strength; percentage of combined hamstring coactivation (HC), medial HC, and lateral HC. Quadriceps and hamstring strength were assessed using an isokinetic dynamometer. Surface electromyography was used to assess muscle activation patterns. General linear models, adjusted for age, BMI, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Kellgren-Lawrence (KL) grade and study site, modeled the relationship between antagonist hamstring coactivation and quadriceps strength. RESULTS: Men had significantly greater quadriceps strength (P < .001), history of knee injury (P < .001) and surgery (P = .002), and greater presence of varus malalignment (P < .001). Women had greater pain (P < .001) and proportion of KL grade ≥2 (P = .017). Gender-specific analyses revealed combined HC (P = .013) and lateral HC inversely associated with quadriceps strength in women (P = .023) but not in men (combined HC P = .320, lateral HC P = .755). A nonlinear association was detected between quadriceps strength and medial HC. Assessment of quartiles of medial HC revealed the third quartile had reduced quadriceps strength when compared to the lowest quartile of coactivation in both men and women. CONCLUSIONS: Hamstring coactivation attenuates measured quadriceps strength in women with or at elevated risk for KOA. LEVEL OF EVIDENCE: II.

Mediating Role of Bone Marrow Lesions, Synovitis, Pain Sensitization, and Depressive Symptoms on Knee Pain Improvement Following Substantial Weight Loss.

OBJECTIVE: Massive weight loss leads to marked knee pain reduction in individuals with knee pain, but the reason for the reduction in pain is unknown. This study was undertaken to quantify the contribution of magnetic resonance imaging (MRI)-evidenced changes in pain-sensitive structures, bone marrow lesions (BMLs), and synovitis, and changes in pain sensitization or depressive symptoms, to knee pain improvement after substantial weight loss. METHODS: Morbidly obese patients with knee pain on most days were evaluated before bariatric surgery or medical weight management and at 1-year follow-up for BMLs and synovitis seen on MRI, the pressure pain threshold (PPT) at the patella and the right wrist, depressive symptoms (using the Center for Epidemiologic Studies Depression scale [CES-D]), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain survey. Natural-effects models were used to quantify the extent that achieving a minimum clinically important difference (MCID) of ≥18% on the WOMAC pain scale could be mediated by weight loss-induced changes in BMLs, synovitis, PPT, and depressive symptoms. RESULTS: Of 75 participants, 53.3% lost ≥20% of weight by 1 year. Of these, 75% attained the MCID for pain improvement, compared with 34.3% in those who had <20% weight loss. Mediation analyses suggested that, in those with at least 20% weight loss, the odds of pain improvement increased by 62%, 15%, and 22% through changes in patella PPT, wrist PPT, and CES-D, respectively, but pain improvement was not mediated by MRI changes in BMLs or synovitis. CONCLUSION: Weight loss-induced knee pain improvement is partially mediated by changes in pain sensitization and depressive symptoms but is independent of MRI changes in BMLs and synovitis.