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PURPOSE: Hip osteoarthritis (OA) is a major cause of pain and disability worldwide. Lack of effective therapies may reflect poor knowledge on its aetiology and risk factors, and result in the management of end-stage hip OA with costly joint replacement. The Worldwide Collaboration on OsteoArthritis prediCtion for the Hip (World COACH) consortium was established to pool and harmonise individual participant data from prospective cohort studies. The consortium aims to better understand determinants and risk factors for the development and progression of hip OA, to optimise and automate methods for (imaging) analysis, and to develop a personalised prediction model for hip OA. PARTICIPANTS: World COACH aimed to include participants of prospective cohort studies with ≥200 participants, that have hip imaging data available from at least 2 time points at least 4 years apart. All individual participant data, including clinical data, imaging (data), biochemical markers, questionnaires and genetic data, were collected and pooled into a single, individual-level database. FINDINGS TO DATE: World COACH currently consists of 9 cohorts, with 38 021 participants aged 18-80 years at baseline. Overall, 71% of the participants were women and mean baseline age was 65.3±8.6 years. Over 34 000 participants had baseline pelvic radiographs available, and over 22 000 had an additional pelvic radiograph after 8-12 years of follow-up. Even longer radiographic follow-up (15-25 years) is available for over 6000 of these participants. FUTURE PLANS: The World COACH consortium offers unique opportunities for studies on the relationship between determinants/risk factors and the development or progression of hip OA, by using harmonised data on clinical findings, imaging, biomarkers, genetics and lifestyle. This provides a unique opportunity to develop a personalised hip OA risk prediction model and to optimise methods for imaging analysis of the hip.

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.

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.

ObjectiveAdults with radiographic knee OA (rKOA) are at increased risk of mortality and walking difficulty may modify this relation. Little is known about specific aspects of walking difficulty that increase mortality risk. We investigated the association of walking speed (objective measure of walking difficulty) with mortality and examined the threshold that best discriminated this risk in adults with rKOA.MethodsParticipants with rKOA from the Johnston County Osteoarthritis Project (JoCoOA, longitudinal population-based cohort), Osteoarthritis Initiative and Multicenter Osteoarthritis Study (OAI and MOST, cohorts of individuals with or at high risk of knee OA) were included. Baseline speed was measured via 2.4-meter (m) walk test (short-distance) in JoCoOA and 20-m walk test (standard-distance) in OAI and MOST. To examine the association of walking speed with mortality risk over 9 years, hazard ratios (HR) and 95% confidence intervals (CI) were calculated from Cox regression models adjusted for potential confounders. A Maximal Likelihood Ratio Chi-square Approach was utilized to identify an optimal threshold of walking speed predictive of mortality.ResultsDeaths after 9 years of follow-up occurred in 23.3% (290/1244) of JoCoOA and 5.9% (249/4215) of OAI + MOST. Walking 0.2 m/s slower during short- and standard-distance walk tests was associated with 23% (aHR [95%CI]; 1.23 [1.10, 1.39]) and 25% (1.25 [1.09, 1.43]) higher mortality risk, respectively. Walking

BackgroundThe role of intra-articular mineralization in osteoarthritis (OA) is unclear. Its understanding may potentially advance our knowledge of knee OA pathogenesis. We describe and assess the reliability of a novel computed tomography (CT) scoring system, the Boston University Calcium Knee Score (BUCKS) for evaluating intra-articular mineralization.MethodsWe included subjects from the most recent study visit of the Multicenter Osteoarthritis Study (MOST) Study, a NIH-funded longitudinal cohort of community-dwelling older adults with or at risk of knee OA. All subjects underwent CT of bilateral knees. Each knee was scored at 28 scored locations (14 for cartilage, 6 for menisci, 6 for ligaments, 1 for joint capsule, and 1 popliteal-tibial vessels). A single musculoskeletal radiologist scored cartilage and meniscus subregions, as well as vascular calcifications assigning to each a score ranging from 0 to 3. The joint capsule, medial and lateral posterior meniscal roots, anterior cruciate ligament (ACL)/posterior cruciate ligament (PCL) and 2 collateral ligaments [medial collateral ligament (MCL)/lateral collateral ligament (LCL)] were each scored 0 or 1 for absence or presence of mineralization. To assess reliability, 31 subject CTs were reread 12 weeks later by the same reader and by a second reader and agreement was evaluated using a weighted kappa.ResultsThe intra-reader reliability ranged from 0.92 for ligaments to 1.0 for joint capsule. The inter-reader reliability ranged from 0.94 for cartilage and ligaments, to 1.0 for joint capsule.ConclusionBUCKS demonstrated excellent reliability and is a potentially useful CT-based tool for studying the role of calcium crystals in knee OA.

BackgroundPatients with knee osteoarthritis may undergo total knee replacement too early or may delay or underuse this procedure. We quantified these categories of total knee replacement utilization in 2 cohorts of participants with knee osteoarthritis and investigated factors associated with each category.MethodsData were pooled from 2 multicenter cohort studies that collected demographic, patient-reported, radiographic, clinical examination, and total knee replacement utilization information longitudinally on 8,002 participants who had or were at risk for knee osteoarthritis and were followed for up to 8 years. Validated total knee replacement appropriateness criteria were longitudinally applied to classify participants as either potentially appropriate or likely inappropriate for total knee replacement. Participants were further classified on the basis of total knee replacement utilization into 3 categories: timely (indicating that the patient had total knee replacement within 2 years after the procedure had become potentially appropriate), potentially appropriate but knee not replaced (indicating that the knee had remained unreplaced for >2 years after the procedure had become potentially appropriate), and premature (indicating that the procedure was likely inappropriate but had been performed). Utilization rates were calculated, and factors associated with each category were identified.ResultsAmong 8,002 participants, 3,417 knees fulfilled our inclusion and exclusion criteria and were classified into 1 of 3 utilization categories as follows: 290 knees (8% of the total and 9% of the knees for which replacement was potentially appropriate) were classified as "timely", 2,833 knees (83% of the total and 91% of those for which replacement was potentially appropriate) were classified as "potentially appropriate but not replaced", and 294 knees (comprising 9% of the total and 26% of the 1,114 total knee replacements performed) were considered to be "likely inappropriate" yet underwent total knee replacement and were classified as "premature". Of the knees that were potentially appropriate but were not replaced, 1,204 (42.5%) had severe symptoms. Compared with the patients who underwent timely total knee replacement, the likelihood of being classified as potentially appropriate but not undergoing total knee replacement was greater for black participants and the likelihood of having premature total knee replacement was lower among participants with a body mass index of >25 kg/m and those with depression.ConclusionsIn 2 multicenter cohorts of patients with knee osteoarthritis, we observed substantial numbers of patients who had premature total knee replacement as well as of patients for whom total knee replacement was potentially appropriate but had not been performed >2 years after it had become potentially appropriate. Further understanding of these observations is needed, especially among the latter group.Clinical relevanceUndergoing total knee replacement too early may result in little or no benefit while exposing the patient to the risks of a major operation, whereas waiting too long may cause limitations in physical activity that in turn increase the risk of additional disability and chronic disease; however, little is known about timing of this surgery. We quantified the extent of premature, timely, and delayed use, and found a high prevalence of both premature and delayed use.

OBJECTIVE:Knee osteoarthritis (OA) is a risk factor for a decline in gait speed. Daily walking reduces the risk of developing slow gait speed and future persistent functional limitation. However, the protective role of walking intensity is unclear. We investigated the association of substituting time spent not walking, with walking at light and moderate-to-vigorous intensities for incident slow gait over 2-years, among people with or at high risk of knee OA. METHOD:We used baseline and 2-year follow-up data from the Multicenter Osteoarthritis (MOST) study (n = 1731) and the Osteoarthritis Initiative (OAI, n = 1925). Daily walking intensity was objectively assessed using accelerometer-enabled devices, and classified as; not walking (100 steps/min). We defined slow gait during a 20-m walk, as 100 steps/min) may be best recommended in order to reduce the risk of developing critical slow gait speed among people with, or at high risk of knee OA.

ObjectivePopulation-based osteoarthritis (OA) cohorts provide vital data on risk factors and outcomes of OA, however the methods to define OA vary between cohorts. We aimed to provide recommendations for combining knee and hip OA data in extant and future population cohort studies, in order to facilitate informative individual participant level analyses.MethodInternational OA experts met to make recommendations on: 1) defining OA by X-ray and/or pain; 2) compare The National Health and Nutrition Examination Survey (NHANES)-type OA pain questions; 3) the comparability of the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) scale to NHANES-type OA pain questions; 4) the best radiographic scoring method; 5) the usefulness of other OA outcome measures. Key issues were explored using new analyses in two population-based OA cohorts (Multicenter Osteoarthritis Study; MOST and Osteoarthritis Initiative OAI).ResultsOA should be defined by both symptoms and radiographs, with symptoms alone as a secondary definition. Kellgren and Lawrence (K/L) grade ≥2 should be used to define radiographic OA (ROA). The variable wording of pain questions can result in varying prevalence between 41.0% and 75.4%, however questions where the time anchor is similar have high sensitivity and specificity (91.2% and 89.9% respectively). A threshold of 3 on a 0-20 scale (95% CI 2.1, 3.9) in the WOMAC pain subscale demonstrated equivalence with the preferred NHANES-type question.ConclusionThis research provides recommendations, based on expert agreement, for harmonising and combining OA data in existing and future population-based cohorts.

OBJECTIVE:To determine the relationship of meniscal damage to magnetic resonance imaging (MRI) features of compartment-specific patellofemoral joint (PFJ) osteoarthritis (OA) at baseline and 2 years later. METHOD:Individuals from a prospective cohort of individuals aged 50-79 with or at risk of knee OA were included. At the 60-month and 84-month study visit, Whole-Organ MRI Score (WORMS) was used to assess meniscal tears and extrusions as well as cartilage damage and bone marrow lesions (BMLs) in the medial and lateral patella and trochlea. Worsening of structural features was defined as any increase in WORMS score from 60 to 84 months. Logistic regression was used to determine the cross-sectional and longitudinal relation of meniscus damage to features of compartment-specific PFJ OA. RESULTS:Relative to knees without lateral meniscal pathology at baseline, those with grades 3-4 lateral meniscal tear and extrusion had greater risk of worsening of cartilage damage in the lateral PFJ 2 years later (Risk ratio: 1.7 [95% CI: 1.1-2.7) and (1.7 [1.2-2.5]), respectively. Relative to those without medial meniscal pathology at baseline, those with grades 1-2 (0.6 [0.4-0.9]) and 3-4 (0.7 [0.5-1.0]) medial meniscal tears had lower risk of worsening of BMLs in the medial PFJ 2 years later. CONCLUSION:Meniscal tear and extrusion are associated with increased risk of medial and lateral PFJ OA and more severe meniscal pathology is associated with worsening of PFJ OA 2 years later. Lateral meniscal pathology appears to be more detrimental to the lateral PFJ.

ObjectiveAmong high risk individuals, whether knee lesions in tissues involved in osteoarthritis (OA) can improve prediction of knee OA is unclear. We hypothesized that models predicting (1) incident osteophytes and (2) incident osteophytes and joint space narrowing can be improved by including symptoms or function, and further improved by lesion status.DesignIn Osteoarthritis Initiative (OAI) participants with normal knee X-rays, we assessed cartilage damage, bone marrow lesions (BMLs), and menisci. Cox proportional hazards models were used to develop risk prediction models for risk of each outcome. Nested models (increasingly larger baseline covariable sets) were compared using likelihood ratio tests and Schwarz Bayesian Information Criterion (SBC). Model discrimination used receiver operating characteristic (ROC) curves and area under the curve (AUC).ResultsIn 841 participants [age 59.6, body mass index (BMI) 26.7, 55.9% women] over up to 7 years follow-up, each larger set improved prediction (+hand OA, injury, surgery, activities; +symptoms/function). Prediction was further improved by including cartilage damage both compartments, BMLs both compartments, meniscal tear, meniscal extrusion, sum of lesion types, number of subregions with cartilage damage, number of subregions with BMLs, and (concurrently) subregion number with cartilage damage, subregion number with BMLs, and meniscal tear. AUCs were ≥0.80 for both outcomes for number of subregions with cartilage damage and the combined model.ConclusionsAmong persons at higher risk for knee OA with normal X-rays, MRI tissue lesions improved prediction of mild as well as moderate disease. These findings support that disease onset is likely occurring during the "high-risk" period and encourage a reorientation of approach.

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.

ObjectivesTo investigate changes in cartilage damage and bone marrow lesions (BMLs) on MRI in the patellofemoral and tibiofemoral joints (TFJs) over 7 years.MethodsThe Multicenter Osteoarthritis (MOST) Study is a cohort study of persons aged 50-79 years at baseline with or at high risk for knee osteoarthritis (OA). Knees were eligible for the current study if they had knee MRI (1.0T) assessed for cartilage damage and BMLs at the baseline and 84-month visits. Knees were categorized as having MRI-detected structural damage (cartilage and BMLs) isolated to the patellofemoral joint (PFJ), isolated to the TFJ, mixed or no damage at baseline and 84-months. We determined the changes in PFJ and TFJ structural damage over 7 years and used logistic regression to assess the relation of baseline compartment distribution to incident isolated PFJ, isolated TFJ and mixed damage.ResultsAmong 339 knees that had full-thickness cartilage loss isolated to the PFJ or TFJ at baseline, only 68 (20.1%) developed full-thickness cartilage loss in the other compartment while 271 (79.9%) continued to only have the initial compartment affected. Compared to knees without full-thickness cartilage damage (n = 582), those with isolated TFJ and PFJ full-thickness cartilage damage had 2.7 (1.5, 4.9) and 5.8 (3.6, 9.6) times the odds of incident mixed full-thickness cartilage damage, respectively. Similar results were seen when using other definitions of MRI-defined structural damage.ConclusionsMost knees with structural damage at baseline do not develop it in the other compartment. Knees that develop mixed structural damage are more likely to start with it isolated to the PFJ.

UnlabelledTwo comorbidity indices were adapted for use in the FREEDOM trial and significantly correlated with the number of medications and impaired health status at baseline. The indices have applications for the analysis of clinical trial data and would allow for the appropriate adjustment of comorbidities when evaluating clinical trial outcomes.IntroductionThe purpose of this study is to adapt two published comorbidity indices for use with the FREEDOM clinical trial evaluating postmenopausal women with osteoporosis.MethodsFREEDOM enrolled women aged 60-90 years with a bone mineral density T-score

ObjectivesThe purpose of this study was to assess the concurrent validity and sensitivity to change of three knee osteoarthritis (OA) grading scales. The Kellgren-Lawrence (KL) and the Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) grading scales are well-established. The third scale, the compartmental grading scale for OA (CG) is a novel scale which grades JSN, femoral osteophytes, tibial erosion and subluxation to create a total score.MethodsOne sample of 72 posteroanterior (PA) fixed-flexion radiographs displaying mild to moderate knee OA was selected from the Multicenter Osteoarthritis Study (MOST) to study validity. A second sample of 75 radiograph pairs, which showed an increase in OA severity over 30 months, was selected to study sensitivity to change. The three radiographic grading scales were applied to each radiograph in both samples. Spearman's rank correlation coefficients were used to correlate the radiographic grades and the change in grades over 30 months with a Whole-organ Magnetic Resonance Imaging Score (WORMS)-based composite score which included five articular features of knee OA.ResultsCorrelations between the KL, OARSI JSN and CG grading scales and the magnetic resonance image (MRI)-based score were 0.836, 0.840 and 0.773 (P < 0.0001) respectively while correlations between change in the radiographic grading scales and change in the MRI-based score were 0.501, 0.525 and 0.492 (P < 0.0001).ConclusionsAll three radiographic grading scales showed high validity and are suitable to assess knee OA severity. They showed moderate sensitivity to change; therefore caution should be taken when using ordinal radiographic grading scales to monitor knee OA over time.

Background: Debilitating pain associated with knee osteoarthritis (OA) often leads patients to seek and complete total knee arthroplasty (TKA). To date, few studies have evaluated the relation of functional impairment to the risk of TKA, despite the fact that OA is associated with functional impairment. Questions/purposes: The purpose of our study was to (1) evaluate whether function as measured by WOMAC physical function subscale was associated with undergoing TKA; and (2) whether any such association varied by sex. Methods: The National Institutes of Health-funded Multicenter Osteoarthritis Study (MOST) is an observational cohort study of persons aged 50 to 79 years with or at high risk of symptomatic knee OA who were recruited from the community. All eligible subjects with complete data were included in this analysis. Our study population sample consisted of 2946 patients with 5796 knees; 1776 (60%) of patients were women. We performed a repeated-measures analysis using baseline WOMAC physical function score to predict the risk of TKA from baseline to 30 months and WOMAC score at 30 months to predict risk of incident TKA from 30 months to 60 months. We used generalized estimating equations to account for the correlation between two knees within an individual and across the two periods. We calculated relative risk (RR) of TKA over 30 months by WOMAC function using a score of 0 to 5 as the referent in multiple binomial regressions with log link. Results: Those with the greatest functional impairment (WOMAC scores 40–68; 62 TKAs in 462 knee periods) had 15.5 times (95% confidence interval [CI], 7.6–31.8; 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.

BackgroundVitamin K-dependent (VKD) proteins, including the mineralization inhibitor matrix-gla protein (MGP), are found in joint tissues including cartilage and bone. Previous studies suggest low vitamin K status is associated with higher osteoarthritis (OA) prevalence and incidence.ObjectiveTo clarify what joint tissues vitamin K is relevant to in OA, we investigated the cross-sectional and longitudinal association between vitamin K status and knee OA structural features measured using magnetic resonance imaging (MRI).MethodsPlasma phylloquinone (PK, vitamin K1) and dephosphorylated-uncarboxylated MGP ((dp)ucMGP) were measured in 791 older community-dwelling adults who had bilateral knee MRIs (mean ± SD age = 74 ± 3 y; 67% female). The adjusted odds ratios (and 95% confidence intervals) [OR (95%CI)] for presence and progression of knee OA features according to vitamin K status were calculated using marginal models with generalized estimating equations (GEEs), adjusted for age, sex, body mass index (BMI), triglycerides and other pertinent confounders.ResultsLongitudinally, participants with very low plasma PK (

ObjectiveTo compare cross-sectional and longitudinal side-differences in thigh muscle anatomical cross-sectional areas (ACSAs), muscle strength, and specific strength (strength/ACSA), between knees with early radiographic change vs knees without radiographic knee osteoarthritis (RKOA), in the same person.Design55 (of 4796) Osteoarthritis Initiative (OAI) participants fulfilled the inclusion criteria of early RKOA in one limb (definite tibiofemoral osteophytes; no radiographic joint space narrowing [JSN]) vs no RKOA (no osteophyte; no JSN) in the contralateral limb. ACSAs of the thigh muscles and quadriceps heads were determined using axial MRIs at 33%/30% femoral length (distal to proximal). Isometric extensor and flexor muscle strength were measured (Good Strength Chair). Baseline quadriceps ACSA and extensor (specific) strength represented the primary analytic focus, and 2-year changes of quadriceps ACSAs the secondary focus.ResultsNo statistically significant side-differences in quadriceps (or other thigh muscle) ACSAs, muscle strength, or specific strength were observed between early RKOA vs contralateral limbs without RKOA (P ≥ 0.44), neither in men nor in women. The 2-year reduction in quadriceps ACSA in limbs with early RKOA was -0.9 ± 6% (mean ± standard deviation) vs -0.5 ± 6% in limbs without RKOA (statistical difference P = 0.85).ConclusionOur results do not provide evidence that early unilateral radiographic changes, i.e., presence of osteophytes, are associated with cross-sectional or longitudinal differences in quadriceps muscle status compared with contralateral knees without RKOA. At the stage of early unilateral RKOA there thus appears to be no clinical need for countervailing a potential dys-balance in quadriceps ACSAs and strength between both knees.

ObjectiveKnee replacement (KR) represents a clinically important endpoint of knee osteoarthritis (KOA). Here we examine the 4-year trajectory of femoro-tibial cartilage thickness loss prior to KR vs non-replaced controls.MethodsA nested case-control study was performed in Osteoarthritis Initiative (OAI) participants: Cases with KR between 12 and 60 month (M) follow-up were each matched with one control (without KR through 60M) by age, sex, and baseline radiographic stage. Femoro-tibial cartilage thickness was measured quantitatively using magnetic resonance imaging (MRI) at the annual visit prior to KR occurrence (T0), and at 1-4 years prior to T0 (T-1 to T-4). Cartilage loss between cases and controls was compared using paired t-tests and conditional logistic regression.ResultsOne hundred and eighty-nine knees of 164 OAI participants [55% women; age 64 ± 8.7; body mass index (BMI) 29 ± 4.5] had KR and longitudinal cartilage data. Comparison of annualized slopes of change across all time points revealed greater loss in the central medial tibia (primary outcome) in KRs than in controls [94 ± 137 vs 55 ± 104 μm; P = 0.0017 (paired t); odds ratio (OR) 1.36 (95% confidence interval (CI): 1.08-1.70)]. The discrimination was stronger for T-2 → T0 [OR 1.61 (1.33-1.95), n = 127] than for T-1 → T0, and was not statistically significant for intervals prior to T-2 [i.e., T-4 → T-2, OR 0.97 (0.67-1.41), n = 60]. Results were similar for total medial femoro-tibial cartilage loss (secondary outcome), and when adjusting for pain and BMI.ConclusionsIn knees with subsequent replacement, cartilage loss accelerates in the 2 years, and particularly in the year prior to surgery, compared with controls. Whether slowing this cartilage loss can delay KR remains to be determined.

Background: To examine if different rates of total knee replacement (TKR) in two similar cohorts with symptomatic knee osteoarthritis (OA) were associated with different functional impact of disease. Methods. Subjects from the Multicenter Osteoarthritis St

ObjectiveTo determine the predictive value of unicompartimental joint space narrowing (JSN) for MRI-based cartilage thickness loss in the narrowed and the non-narrowed femorotibial compartment.Methods922 knees from 922 Osteoarthritis Initiative (OAI) participants (62.2 ± 9.0 years, 61% females) with radiographic OA (158 without JSN [noJSN], 175 with lateral JSN [latJSN], 589 with medial JSN [medJSN]) were analyzed using 3 T MRI. One-year cartilage thickness change was determined in the lateral (LFTC) and medial femorotibial compartment (MFTC), and in femorotibial subregions. The probability of subsequent cartilage loss was calculated using predefined thresholds. The predictive value of JSN for the probability and magnitude of cartilage loss was compared between latJSN, medJSN and noJSN knees using Fisher's exact and Mann-Whitney-U tests.ResultsThe probability of cartilage loss was greater in the narrowed compartment of latJSN/medJSN knees (34.9%/32.4%) than in noJSN knees (13.3%/12.7%, P ≤ 6.4 × 10(-6)) and so was the magnitude of cartilage thickness change (P ≤ 8.2 × 10(-6)). No significant differences were observed between the narrowed compartments of latJSN vs. medJSN knees (probability: P = 0.58, magnitude: P = 0.19) or between the non-narrowed compartment of latJSN/medJSN vs. noJSN knees (probability: P ≥ 0.35, magnitude: P = ≥0.23). These results were confirmed by the location-independent ordered value (OV) analyses of femorotibial subregions.ConclusionThe predictive value of latJSN for lateral compartment cartilage loss was comparable to that of medJSN for medial compartment cartilage loss, whereas cartilage loss in the non-narrowed compartment was similar to that in noJSN knees. These findings provide important clues to predicting progression of knee OA, and in tailoring inclusion criteria for clinical trials.

ObjectiveWe evaluated the association of parity to both risk of knee replacement (KR) and knee osteoarthritis (OA).DesignThe NIH-funded Multicenter Osteoarthritis Study (MOST) is a longitudinal observational study of persons age 50-79 years with either symptomatic knee OA or at elevated risk of disease. Baseline and 30-month knee radiographic OA (ROA) was defined as Kellgren/Lawrence (K/L) grade ≥2 or KR. Women were grouped based by number of births: 0; 1 (reference group); 2; 3; 4; and 5 or more. We examined the relation of parity to the incidence over 30 months of ROA and KR using a Poisson regression model. Generalized estimating equations (GEE) were used to control for correlation between two knees within a subject. We adjusted for age, BMI, race, education, occupation, baseline estrogen use, clinical site, injury, and for KR analyses WOMAC pain and use of pain medication.ResultsAmong 1618 women who reported parity information, mean age was 62.6 years, mean BMI 30.7 kg/m(2), mean WOMAC pain subscale score 3.7 at baseline. There were 115 KRs and 134 cases of incident knee ROA over 30 months. The relative risk of incident KR was 2.7 times as high (95% CI: 1.0, 7.3) and relative risk of incident knee ROA was 2.6 times as high (95% CI: 1.2, 5.3) among women with five to 12 children compared with those with one birth.ConclusionParity in women at risk for OA is associated with both incident ROA and KR, particularly for those with more than four children.

ObjectiveMinimum radiographic joint space width (mJSW) represents the Food and Drug Administration (FDA) standard for demonstrating structural therapeutic benefits for knee osteoarthritis (KOA), but only shows moderate responsiveness (sensitivity to change). We directly compare the responsiveness of magnetic resonance imaging (MRI)-based cartilage thickness and JSW measures from fixed-flexion radiography (FFR) and explore the correlation of region-matched changes between both methods.MethodsNine hundred and sixty-seven knees of Osteoarthritis Initiative participants with radiographic KOA were studied: 445 over 1 year with coronal FLASH MRI and FFR, and 375/522 over 1/2 years with sagittal DESS MRI and FFR. Standardized response means (SRM) of cartilage thickness and mJSW were compared using the sign-test.ResultsWith FLASH MRI, SRM was -0.28 for medial femorotibial compartment (MFTC) cartilage loss vs -0.15 for mJSW, and -0.32 vs -0.22 for the most sensitive MRI subregion (central MFTC) vs the most sensitive fixed-location JSW(x = 0.25). With DESS MRI, 1-year SRM was -0.34 for MFTC vs -0.22 for mJSW and -0.44 vs -0.28 for central MFTC vs JSW(x = 0.225). Over 2 years, the SRM was significantly greater for MFTC than for mJSW (-0.43 vs -0.31, P = 0.017) and for central MFTC than for JSW(x = 0.225) (-0.51 vs -0.44, P < 0.001). Correlations between changes in spatially matched MRI subregions and fixed-location JSW were not consistently higher (r = 0.10-0.51) than those between non-matched locations (r = 0.15-0.50).ConclusionsMRI displays greater responsiveness in KOA than JSW FFR-based JSW, with the greatest SRM observed in the central medial femorotibial compartment. Fixed-location radiographic measures appear not capable of determining the spatial distribution of femorotibial cartilage loss.

ObjectiveTo compare unbiased estimates of short- vs long-term cartilage loss in osteoarthritic knees.Method441 knees [216 Kellgren Lawrence (KL) grade 2, 225 KL grade 3] from participants of the Osteoarthritis Initiative were studied over a 4-year period. Femorotibial cartilage thickness was determined using 3 T double echo steady state magnetic resonance imaging, the readers being blinded to time points. Because common measurement time points bias correlations, short-term change (year-1 to year-2: Y1 → Y2) was compared with long-term change (baseline to year-4: BL → Y4), and initial (BL → Y1) with subsequent (Y2 → Y4) observation periods.ResultsThe mean femorotibial cartilage thickness change (standardized response mean) was -1.2%/-0.8% (-0.42/-0.28) over 1 (BL → Y1/Y1 → Y2), -2.1%/-2.5% (-0.56/-0.55) over 2 (BL → Y2/Y2 → Y4), -3.3% (-0.63) over 3 (Y1 → Y4), and -4.5% (-0.78) over 4 years. Spearman correlations were 0.33 for Y1 → Y2 vs BL → Y4, and 0.17 for BL → Y1 vs Y2 → Y4 change. Percent agreement between knees showing progression during Y1 → Y2 vs BL → Y4 was 59%, and 64% for BL → Y1 vs Y2 → Y4. The area under the receiver operating characteristic curve was 0.66 for using Y1 → Y2 to predict BL → Y4, and 0.59 for using BL → Y1 to predict Y2 → Y4 change.ConclusionWeak to moderate correlations and agreement were observed between individual short- vs long-term cartilage loss, and between initial and subsequent observation periods. Hence, longer observation periods are recommended to achieve robust results on cartilage loss in individual knees. At cohort and subcohort level (e.g., KLG3 vs KLG2 knees), the mean cartilage loss increased almost linearly with the length of the observation period and was constant throughout the study.

ObjectiveAs cartilage loss and bone marrow lesions (BMLs) are associated with knee joint pain and structural worsening, this study assessed whether non-invasive estimates of articular contact stress may longitudinally predict risk for worsening of knee cartilage morphology and BMLs.DesignThis was a longitudinal cohort study of adults aged 50-79 years with risk factors for knee osteoarthritis. Baseline and follow-up measures included whole-organ magnetic resonance imaging score (WORMS) classification of knee cartilage morphology and BMLs. Tibiofemoral geometry was manually segmented on baseline magnetic resonance imaging (MRI), and three-dimensional (3D) tibiofemoral point clouds were registered into subject-specific loaded apposition using fixed-flexion knee radiographs. Discrete element analysis (DEA) was used to estimate mean and peak contact stresses for the medial and lateral compartments. The association of baseline contact stress with worsening cartilage and BMLs in the same subregion over 30 months was assessed using conditional logistic regression.ResultsSubjects (N = 38, 60.5% female) had a mean ± standard deviation (SD) age and body mass index (BMI) of 63.5 ± 8.4 years and 30.5 ± 3.7 kg/m2 respectively. Elevated mean articular contact stress at baseline was associated with worsening cartilage morphology and worsening BMLs by 30 months, with odds ratio (OR) [95% confidence interval (CI)] of 4.0 (2.5, 6.4) and 6.6 (2.7, 16.5) respectively. Peak contact stress also was significantly associated with worsening cartilage morphology and BMLs {1.9 (1.5, 2.3) and 2.3 (1.5, 3.6)}(all P < 0.0001).ConclusionsDetection of higher contact stress 30 months prior to structural worsening suggests an etiological role for mechanical loading. Estimation of articular contact stress with DEA is an efficient and accurate means of predicting subregion-specific knee joint worsening and may be useful in guiding prognosis and treatment.

ObjectiveStrong associations between radiographic features of knee osteoarthritis (OA) and pain have been demonstrated in persons with unilateral knee symptoms. This study was undertaken to compare radiographic and magnetic resonance imaging (MRI) features of knee OA and assess their ability to discriminate between painful and nonpainful knees in persons with unilateral symptoms.MethodsThe study population included 283 individuals ages 70-79 years with unilateral knee pain who were enrolled in the Health, Aging, and Body Composition Study, a study of weight-related diseases and mobility. Radiographs of both knees were read for Kellgren/Lawrence (K/L) grade and individual radiographic features, and 1.5T MRIs were assessed using the Whole-Organ Magnetic Resonance Imaging Score. The association between structural features and pain was assessed using a within-person case-control design and conditional logistic regression. Receiver operating characteristic (ROC) analysis was then used to test the discriminatory performance of structural features.ResultsIn conditional logistic analyses, knee pain was significantly associated with both radiographic features (any joint space narrowing grade ≥ 1) (odds ratio 3.20 [95% confidence interval 1.79-5.71]) and MRI features (any cartilage defect scored ≥ 2) (odds ratio 3.67 [95% confidence interval 1.49-9.04]). However, in most subjects, MRI revealed osteophytes and cartilage and bone marrow lesions in both knees, and using ROC analysis, no individual structural feature discriminated well between painful and nonpainful knees. The best-performing MRI feature (synovitis/effusion) was not significantly more informative than K/L grade ≥ 2 (P = 0.42).ConclusionIn persons with unilateral knee pain, MRI and radiographic features were associated with knee pain, confirming that structural abnormalities in the knee have an important role in the etiology of pain. However, no single MRI or radiographic finding performed well in discriminating between painful and nonpainful knees. Further work is needed to examine how structural and nonstructural factors influence knee pain.

Many falls occur among older adults with no traditional risk factors. We examined potential independent effects of lifestyle on fall risk. Not smoking and going outdoors frequently or infrequently were independently associated with more falls, indicating lifestyle-related behavioral and environmental risk factors are important causes of falls in older women.Physical and lifestyle risk factors for falls and population attributable risks (PAR) were examined.We conducted a 4-year prospective study of 8,378 community-dwelling women (mean age = 71 years, SD = 3) enrolled in the Study of Osteoporotic Fractures. Data on number of falls were self-reported every 4 months. Fall rates were calculated (# falls/woman-years). Poisson regression was used to estimate relative risks (RR).Physical risk factors (p ≤ 0.05 for all) included tall height (RR = 0.89 per 5 in.), dizziness (RR = 1.16), fear of falling (RR = 1.20), self-reported health decline (RR = 1.19), difficulty with Instrumental Activities of Daily Living (IADLs) (RR = 1.12, per item), fast usual-paced walking speed (RR = 1.18, per 2 SD), and use of antidepressants (RR = 1.20), benzodiazepines (RR = 1.11), or anticonvulsants (RR = 1.62). Protective physical factors (p ≤ 0.05 for all) included good visual acuity (RR = 0.87, per 2 SD) and good balance (RR = 0.85 vs. poor). Lifestyle predicted fewer falls including current smoking (RR = 0.76), going outdoors at least twice weekly but not more than once a day (RR = 0.89 and vs. twice daily). High physical activity was associated with more falls but only among IADL impaired women. Five potentially modifiable physical risk factors had PAR ≥ 5%.Fall interventions addressing modifiable physical risk factors with PAR ≥ 5% while considering environmental/behavioral risk factors are indicated.

Vertebral fractures in older women signal an increased risk of additional osteoporotic fractures. To identify risk factors for first vertebral fractures, we studied 5822 women greater than or equal to65 years of age who had no fracture on baseline radiographs of the spine. Several modifiable risk factors increased an older woman's risk of developing a first vertebral fracture, and women with multiple risk factors and low BMD had the highest risk. Risk factors and low BMD should be useful to help focus efforts to prevent these fractures. Introduction: Vertebral fractures are a common cause of back pain and disability and signal an increased risk of additional osteoporotic fractures in older women. Little is known about the risk factors for the first occurrence of a vertebral fracture. Materials and Methods: To identify risk factors for a first vertebral fracture, we studied 5822 women greater than or equal to65 years of age from the Study of Osteoporotic Fractures who had no fracture on baseline radiographs of the spine. We measured potential risk factors and BMD of the wrist and calcaneus at baseline and BMD of the spine and hip halfway through follow-up. Fractures were assessed by standard methods from spine radiographs obtained at baseline and follow-up an average of 3.7 years later. Results and Conclusions: In multivariable analyses, older age, previous nonspine fracture, low BMD at all sites, a low body mass index (BMI), current smoking, low milk consumption during pregnancy, low levels of daily physical activity, having a fall, and regular use of aluminum-containing antacids independently increased the risk of a first vertebral fracture. Women using estrogen and those who engaged in recreational physical activity had a decreased risk. The effects of low BMI, smoking, use of estrogen and antacids, and previous fracture were partially mediated by BMD. Women in the lower third of wrist BMD with five or more risk factors had a 12-fold greater risk than women in the highest third of BMD who had zero to three risk factors. The 27% of women at highest risk suffered 60% of the incident fractures. In conclusion, several modifiable risk factors and BMD independently increase an older woman's risk of developing a first vertebral fracture. The combination of risk factors and BMD should be useful for focusing efforts to prevent vertebral fractures.