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.

Cartilage contact characteristics of the knee during gait in individuals with obesity.

Obesity increases the risk of knee osteoarthritis (OA). Knee joint contact characteristics have been thought to provide insights into the pathogenesis of knee OA; however, the cartilage contact characteristics in individuals with obesity have not been fully described. We conducted cartilage-to-cartilage contact analyses through high-precision fluoroscopy imaging with subject-specific magnetic resonance cartilage models. Twenty-five individuals with obesity were recruited for this study, and previously published data consisted of eight nonobese individuals who were used as the comparator group. In both groups, knees were imaged by a dual fluoroscopic imaging system during treadmill walking, and the tibiofemoral cartilage contact locations were analyzed and described on the tibial plateau in the medial-lateral (ML) and anterior-posterior (AP) directions and on femoral condyle surfaces using contact angles in the sagittal plane and deviation angles in a plane perpendicular to the sagittal plane. On the medial tibial plateau, the ML contact locations in the individuals with obesity were located more medially than in the nonobese group throughout the stance phase. The medial plateau AP contact locations in individuals with obesity showed a different pattern compared with the nonobese group. The ML contact excursions on the medial plateau in the individuals with obesity were larger than in the nonobese group. These findings suggest that obesity affects the contact location mainly in the medial compartment, which explains, in part, the high prevalence of medial knee OA in the obese population.

Knee osteoarthritis risk in non-industrial societies undergoing an energy balance transition: evidence from the indigenous Tarahumara of Mexico.

Non-industrial societies with low energy balance levels are expected to be less vulnerable than industrial societies to diseases associated with obesity including knee osteoarthritis. However, as non-industrial societies undergo rapid lifestyle changes that promote positive energy balance, individuals whose metabolisms are adapted to energetic scarcity are encountering greater energy abundance, increasing their propensity to accumulate abdominal adipose tissue and thus potentially their sensitivity to obesity-related diseases. OBJECTIVES: Here, we propose that knee osteoarthritis is one such disease for which susceptibility is amplified by this energy balance transition. METHODS: Support for our hypothesis comes from comparisons of knee radiographs, knee pain and anthropometry among men aged ≥40 years in two populations: Tarahumara subsistence farmers in Mexico undergoing the energy balance transition and urban Americans from Framingham, Massachusetts. RESULTS: We show that despite having markedly lower obesity levels than the Americans, the Tarahumara appear predisposed to accrue greater abdominal adiposity (ie, larger abdomens) for a given body weight, and are more vulnerable to radiographic and symptomatic knee osteoarthritis at lower levels of body mass index. Also, proportionate increases in abdomen size in the two groups are associated with greater increases in radiographic knee osteoarthritis risk among the Tarahumara than the Americans, implying that the abdominal adipose tissue of the Tarahumara is a more potent stimulus for knee degeneration. CONCLUSIONS: Heightened vulnerability to knee osteoarthritis among non-industrial societies experiencing rapid lifestyle changes is a concern that warrants further investigation since such groups represent a large but understudied fraction of the global population.

Weight loss changed gait kinematics in individuals with obesity and knee pain.

BACKGROUND: Obesity is a mechanical risk factor for osteoarthritis. In individuals with obesity, knee joint pain is prevalent. Weight loss reduces joint loads, and therefore potentially delays disease progression; however, how the knee joint responds to weight loss in individuals with obesity and knee pain is not clear. RESEARCH QUESTION: To assess the effect of weight loss on knee joint kinematics during gait in individuals with obesity and knee pain. METHODS: We recruited individuals with obesity (BMI ≥ 35) and knee pain who were participating in a weight loss program which included bariatric surgery or medical management. At baseline and 1 year follow-up, participants walked on a treadmill, and their knee joint kinematics were assessed using a dual-fluoroscopic imaging system and subject-specific magnetic resonance imaging knee joint models. Gait changes were represented by change in range of tibiofemoral motion, i.e., excursions in flexion-extension, adduction-abduction, internal-external rotation, anterior-posterior translation, medial-lateral translation, and superior-inferior translation during gait. RESULTS: Twelve individuals with obesity and knee pain completed the gait analysis at baseline and 1 year follow-up. Participants lost on average 10.4% (standard deviation: 17.2%) of their baseline body weight. Reduction in body weight was associated with increased range of flexion-extension (r = -0.75, p < 0.01) and decreased range of adduction-abduction (r = 0.60, p = 0.04) during gait. The reduction in body weight was also associated with self-reported pain decrease (r = 0.62, p = 0.04); however, the change in pain was not significantly associated with kinematic changes. SIGNIFICANCE: Weight loss was associated with improved gait kinematics in the sagittal and frontal planes. The change in gait pattern in individuals with obesity and knee pain was not associated with the change in pain given a reduction in body weight.

Brief Report: Leg Length Inequality and Hip Osteoarthritis in the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative.

OBJECTIVE: Studies suggest that persons with a leg length inequality (LLI) of ≥2 cm have an increased risk of developing knee osteoarthritis (OA) in that limb. The present study was undertaken to examine whether LLI also confers an increased risk of hip OA. METHODS: Using long limb radiographs from subjects in the Multicenter Arthritis Study (MOST) and the Osteoarthritis Initiative (OAI), we measured LLI and scored hip radiographs that were obtained at baseline and 3-5-year follow-up. The associations of LLI of ≥1 cm and LLI of ≥2 cm with radiographic hip OA were examined cross-sectionally and longitudinally, assessing risk in shorter limbs and longer limbs compared to limbs from subjects with no LLI. We carried out logistic regression analyses with generalized estimating equations and adjusted for age, sex, body mass index, height, and cohort of origin. RESULTS: There were 1,966 subjects from the MOST and 2,627 subjects from the OAI. Twelve percent had LLI of ≥1 cm and 1% had LLI of ≥2 cm. For LLI ≥1 cm, the adjusted odds ratio for prevalent hip OA in the shorter leg was 1.47 (95% confidence interval [95% CI] 1.07-2.02) and for LLI ≥2 cm, it was 2.15 (95% CI 0.87-5.34). For LLI ≥1 cm, the odds of incident hip OA in the shorter leg were 1.39 (95% CI 0.81-2.39) while for LLI ≥2 cm, they were 4.20 (95% CI 1.26-14.03). We found no increased risk of hip OA in longer limbs. CONCLUSION: Our findings suggest that, as with knee OA, legs that are at least 2 cm shorter than the contralateral leg are at increased risk of hip OA.

Metabolic Syndrome, Its Components, and Knee Osteoarthritis: The Framingham Osteoarthritis Study.

OBJECTIVE: Previous studies have suggested that metabolic syndrome is associated with osteoarthritis (OA). However, analyses have often not included adjustment for body mass index (BMI) and have not addressed whether levels of individual metabolic syndrome components are related to OA. This study was undertaken to examine the relationship of metabolic syndrome and its components with radiographic and symptomatic knee OA. METHODS: Framingham Study subjects were assessed for OA in 1992-1995 and again in 2002-2005. Near the baseline visit, subjects had components of metabolic syndrome assessed. We defined incident radiographic OA as present when a knee without radiographic OA at baseline had a Kellgren/Lawrence grade of ≥2 at follow-up, and defined incident symptomatic OA as present when a knee developed the new combination of radiographic OA and knee pain. After excluding knees with prevalent OA at baseline, we tested the relationship of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria and its components with the risk of incident radiographic OA and symptomatic OA before and after adjusting for BMI using the risk ratio from a binary regression with generalized estimating equations. RESULTS: A total of 991 subjects (55.1% women) with a mean age of 54.2 years were studied, and 26.7% of men and 22.9% of women had metabolic syndrome. Metabolic syndrome and many of its components were associated with both incident radiographic OA and symptomatic OA, but after adjustment for BMI, almost all of these associations became weak and nonsignificant. An association of high blood pressure, especially diastolic pressure, with OA outcomes persisted in both men and women. CONCLUSION: After adjustment for BMI, neither metabolic syndrome nor its components were associated with incident OA. There may be an association between OA and high blood pressure that needs further study.

Improved Financial Capability Can Reduce Material Hardship among Mothers.

This study draws on the theoretical framework of financial capability in investigating whether financial access (that is, availability of financial products and services) and financial knowledge (that is, understanding of basic financial concepts) can influence the risk of material hardship. Authors examine the possibility of direct associations as well as of indirect ones in which financial management (that is, individual financial behaviors) serves as a mediator. The probability sample of mothers with young children born in Oklahoma during 2007 (N = 2,529) was selected from Oklahoma birth certificates. Results from structural equation modeling analyses show that financial access is positively associated with financial management (p < 0.001) but that financial knowledge is not; both financial access (p < 0.001) and financial management (p < 0.001) are negatively correlated with material hardship. Similar results are obtained from analyses with a subsample of low-income mothers. Findings suggest that financial capability, particularly the financial access component, is critical for improving financial management and reducing the risk of material hardship among mothers with young children, including low-income mothers. Efforts to promote financial capability offer social workers an important strategy for improving their clients' economic well-being.

Effects of child development accounts on early social-emotional development: an experimental test.

IMPORTANCE: This study, based on Oklahoma's statewide Child Development Accounts (CDAs) program, presents findings from the first experimental test of the hypothesis that creating lifelong savings accounts for children at birth promotes their long-term well-being. OBJECTIVE: To examine the effects of CDAs, an innovative social policy to encourage lifelong saving and asset building for long-term development, on parent-reported social-emotional development in early childhood. DESIGN, SETTING, AND PARTICIPANTS: A statewide randomized experiment of CDAs was conducted in 2008, drawing a probability sample of 7328 children from all infants born in two 3-month periods in Oklahoma (April 1 through June 30 and August 1 through October 31, 2007). After agreeing to participate in the experiment, caregivers of 2704 infants completed a baseline survey and were randomly assigned to treatment (n = 1358) and control groups (n = 1346). Approximately 84% of participants completed a follow-up survey in the spring of 2011. INTERVENTIONS: The intervention offered CDAs, built on the existing Oklahoma 529 college-savings plan, to treatment participants. It also provided additional financial incentives and information. MAIN OUTCOMES AND MEASURES: The primary outcome-child social-emotional development-is measured by scores from a 17-item version of the Ages and Stages Questionnaire: Social-Emotional. Caregivers completed it in the 3-year follow-up survey. Lower scores indicate better functioning. RESULTS: The CDAs have positive effects on social-emotional development for children at approximately age 4 years. The nonweighted treatment-control difference is -1.56 (90% CI, -2.87 to -0.22; P = .06), but the weighted difference is nonsignificant. The effects appear to be greater for disadvantaged subsamples, such as low-income households (weighted mean difference, -2.21; 90% CI, -4.01 to -0.42; P = .04). CONCLUSIONS AND RELEVANCE: As a complement to other early education and health interventions, CDAs may improve social-emotional development in early childhood. Their effects may be explained as a mediating process that influences parents. Child Development Accounts may influence parental attitudes, behaviors, expectations, and involvement; in turn, these may affect child development.

Relation of hand enthesophytes with knee enthesopathy: is osteoarthritis related to a systemic enthesopathy?

OBJECTIVE: Enthesopathy has been reported as a feature of osteoarthritis (OA) in the distal interphalangeal (DIP) joints. We previously reported that central bone marrow lesions (BML) on magnetic resonance imaging (MRI) scans are associated with OA. In this study, we evaluated whether hand and knee enthesopathy were related. METHODS: We studied knee and hand radiographs of subjects from the Framingham Osteoarthritis Study. Subjects seen in 2002-2005 had bilateral posteroanterior hand radiographs, weight-bearing knee radiographs, and knee MRI scans. Hand radiographs were read for enthesophytes at the juxtaarticular nonsynovial areas of metacarpophalangeal (MCP), proximal interphalangeal (PIP), and DIP joints, and midshafts of the phalanges. We selected 100 cases of knees with central BML and 100 matched controls. Conditional logistic regression was used to assess associations. RESULTS: Subjects with enthesophytes of at least 1 score ≥ 2 at DIP, PIP, and/or MCP were not more likely to have central knee BML (OR 0.49, 95% CI 0.17-1.40) than those without enthesophytes. Similarly, having at least 1 score ≥ 2 on the shafts was not significantly associated with having a central knee BML (OR 0.59, 95% CI 0.23-1.51). Adjustment for the presence of diabetes mellitus did not affect these results, but there was an increased prevalence of diabetes in those with hand enthesophytes (OR 3.09, 95% 1.29-7.40, enthesophyte score ≥ 2). CONCLUSION: We found no increase in the prevalence of hand enthesophytes among persons with central knee BML on their knee MRI scans. This provides evidence against a systemic enthesopathic disorder in association with knee OA.

Quadriceps weakness, patella alta, and structural features of patellofemoral osteoarthritis.

OBJECTIVE: To determine the relationship between quadriceps weakness and cartilage damage and bone marrow lesions (BMLs) in the patellofemoral joint (PFJ) and if this relationship is modified by patella alta. METHODS: The Multicenter Osteoarthritis Study is a cohort study of persons ages 50-79 years with or at risk of knee osteoarthritis. Concentric knee extensor strength was measured using an isokinetic dynamometer. Patella alta was measured using the Insall-Salvati ratio (ISR) on the lateral radiograph, and cartilage damage and BMLs were graded on magnetic resonance imaging in the PFJ. We determined the association between quadriceps weakness with cartilage damage and BMLs in the PFJ among knees with (ISR ≥1.2) and without (ISR <1.2) patella alta using multiple binomial regression. RESULTS: A total of 807 knees were studied (mean age 62 years, body mass index 30 kg/m(2) , ISR 1.10) and 64% were from women. Compared with the knees in the highest strength tertile, those in the lowest had 10.2% (95% confidence interval [95% CI] 3, 18), 9.1% (95% CI 2, 16), and 7.1% (95% CI 1, 13) higher prevalence of lateral PFJ cartilage damage, medial PFJ cartilage damage, and lateral PFJ BMLs, respectively. The association between quadriceps weakness with cartilage damage and BMLs was not different between knees with and without patella alta in the lateral PFJ. CONCLUSION: Quadriceps weakness was associated with PFJ cartilage damage and BMLs. While both patella alta and quadriceps weakness were associated with PFJ damage, the combination of the two was not associated with more damage than either of these factors alone.

Prevalence, incidence and progression of hand osteoarthritis in the general population: the Framingham Osteoarthritis Study.

OBJECTIVES: To describe the prevalence and longitudinal course of radiographic, erosive and symptomatic hand osteoarthritis (HOA) in the general population. METHODS: Framingham osteoarthritis (OA) study participants obtained bilateral hand radiographs at baseline and 9-year follow-up. The authors defined radiographic HOA at joint level as Kellgren-Lawrence grade (KLG)≥2, erosive HOA as KLG≥2 plus erosion and symptomatic HOA as KLG≥2 plus pain/aching/stiffness. Presence of HOA at individual level was defined as ≥1 affected joint. The prevalence was age-standardised (US 2000 Population 40-84 years). RESULTS: Mean (SD) baseline age was 58.9 (9.9) years (56.5% women). The age-standardised prevalence of HOA was only modestly higher in women (44.2%) than men (37.7%), whereas the age-standardised prevalence of erosive and symptomatic OA was much higher in women (9.9% vs 3.3%, and 15.9% vs 8.2%). The crude incidence of HOA over 9-year follow-up was similar in women (34.6%) and men (33.7%), whereas the majority of those women (96.4%) and men (91.4%) with HOA at baseline showed progression during follow-up. Incident metacarpophalangeal and wrist OA were rare, but occurred more frequently and from an earlier age in men than women. Development of erosive disease occurred mainly in those with non-erosive HOA at baseline (as opposed to those without HOA), and was more frequent in women (17.3%) than men (9.6%). CONCLUSIONS: The usual female predominance of prevalent and incident HOA was less clear for radiographic HOA than for symptomatic and erosive HOA. With an ageing population, the impact of HOA will further increase.

Consistency of knee pain and risk of knee replacement: the Multicenter Osteoarthritis Study.

OBJECTIVE: To examine whether the consistency or persistence of knee pain, in addition to its severity, predicts incident total knee replacement (TKR). METHODS: The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of persons aged 50 to 79 years with symptomatic knee osteoarthritis or at high risk of disease. Subjects were queried about the presence of knee pain on most days of the previous 30 days (i.e., frequent knee pain; FKP) at 2 timepoints: a telephone screen followed by a clinic visit (median separation 4 weeks). We defined a knee as having "consistent pain" if the subject answered positively to the FKP question at both timepoints, "inconsistent pain" if FKP was positive at only one timepoint, or as "no FKP" if negative at both. We examined the association between consistent FKP and risk of TKR using multiple binomial regression with generalized estimating equations. RESULTS: In 3026 persons (mean age 63 yrs, mean body mass index 30.4), 2979 knees (50%) had no FKP at baseline, 1279 knees (21.5%) had inconsistent FKP, and 1696 knees (28.5%) had consistent FKP. Risk of TKR over 30 months was 0.8%, 2.6%, and 8.8% for knees with no, inconsistent, and consistent FKP, respectively. Relative risks of TKR over 30 months were 1.2 (95% CI 0.6-2.3) and 2.3 (95% CI 1.2-4.4) for knees with inconsistent and consistent FKP, compared with those without FKP. This association was consistent across each level of pain severity on the Western Ontario and McMaster Universities Osteoarthritis Index. CONCLUSION: Consistency of frequent knee pain is associated with an increased risk of TKR independently of knee pain severity.

Quadriceps strength and the risk of cartilage loss and symptom progression in knee osteoarthritis.

OBJECTIVE: To determine the effect of quadriceps strength in individuals with knee osteoarthritis (OA) on loss of cartilage at the tibiofemoral and patellofemoral joints (assessed by magnetic resonance imaging [MRI]) and on knee pain and function. METHODS: We studied 265 subjects (154 men and 111 women, mean+/-SD age 67+/-9 years) who met the American College of Rheumatology criteria for symptomatic knee OA and who were participating in a prospective, 30-month natural history study of knee OA. Quadriceps strength was measured at baseline, isokinetically, during concentric knee extension. MRI of the knee at baseline and at 15 and 30 months was used to assess cartilage loss at the tibiofemoral and patellofemoral joints, with medial and lateral compartments assessed separately. At baseline and at followup visits, knee pain was assessed using a visual analog scale, and physical function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index. RESULTS: There was no association between quadriceps strength and cartilage loss at the tibiofemoral joint. Results were similar in malaligned knees. However, greater quadriceps strength was protective against cartilage loss at the lateral compartment of the patellofemoral joint (for highest versus lowest tertile of strength, odds ratio 0.4 [95% confidence interval 0.2, 0.9]). Those with greater quadriceps strength had less knee pain and better physical function over followup (P<0.001). CONCLUSION: Greater quadriceps strength had no influence on cartilage loss at the tibiofemoral joint, including in malaligned knees. We report for the first time that greater quadriceps strength protected against cartilage loss at the lateral compartment of the patellofemoral joint, a finding that requires confirmation. Subjects with greater quadriceps strength also had less knee pain and better physical function over followup.

Incidental meniscal findings on knee MRI in middle-aged and elderly persons.

BACKGROUND: Magnetic resonance imaging (MRI) of the knee is often performed in patients who have knee symptoms of unclear cause. When meniscal tears are found, it is commonly assumed that the symptoms are attributable to them. However, there is a paucity of data regarding the prevalence of meniscal damage in the general population and the association of meniscal tears with knee symptoms and with radiographic evidence of osteoarthritis. METHODS: We studied persons from Framingham, Massachusetts, who were drawn from census-tract data and random-digit telephone dialing. Subjects were 50 to 90 years of age and ambulatory; selection was not made on the basis of knee or other joint problems. We assessed the integrity of the menisci in the right knee on 1.5-tesla MRI scans obtained from 991 subjects (57% of whom were women). Symptoms involving the right knee were evaluated by questionnaire. RESULTS: The prevalence of a meniscal tear or of meniscal destruction in the right knee as detected on MRI ranged from 19% (95% confidence interval [CI], 15 to 24) among women 50 to 59 years of age to 56% (95% CI, 46 to 66) among men 70 to 90 years of age; prevalences were not materially lower when subjects who had had previous knee surgery were excluded. Among persons with radiographic evidence of osteoarthritis (Kellgren-Lawrence grade 2 or higher, on a scale of 0 to 4, with higher numbers indicating more definite signs of osteoarthritis), the prevalence of a meniscal tear was 63% among those with knee pain, aching, or stiffness on most days and 60% among those without these symptoms. The corresponding prevalences among persons without radiographic evidence of osteoarthritis were 32% and 23%. Sixty-one percent of the subjects who had meniscal tears in their knees had not had any pain, aching, or stiffness during the previous month. CONCLUSIONS: Incidental meniscal findings on MRI of the knee are common in the general population and increase with increasing age.

A new approach yields high rates of radiographic progression in knee osteoarthritis.

OBJECTIVE: Progression of knee osteoarthritis (OA) has typically been assessed in the medial tibiofemoral (TF) compartment on the anteroposterior (AP) or posteroanterior (PA) view. We propose a new approach using multiple views and compartments that is likely to be more sensitive to change and reveals progression throughout the knee. METHODS: We tested our approach in the Multicenter Osteoarthritis Study, a study of persons with OA or at high risk of disease. At baseline and 30 months, subjects provided PA (fixed flexion without fluoro) and lateral weight-bearing knee radiographs. Paired radiographs were read by 2 readers who scored joint space (JS) using a 0-3 atlas-based scale. When JS narrowed but narrowing did not reach a full grade on the scale, readers used half-grades. Change was scored in medial and lateral TF compartments on both PA and lateral views and in the patellofemoral (PF) joint on lateral view. A knee showed progression when there was at least a half-grade worsening in JS width in any compartment at followup. Disagreements were adjudicated by a panel of 3 readers. To validate progression, we tested definitions for TF progression to see if malalignment on long-limb radiographs at baseline (>or=3 degrees malaligned in any direction with nonmalaligned knees being reference) increased risk of progression. A valid definition of progression would show that malalignment strongly predicted progression. RESULTS: We studied 842 knees with either Kellgren-Lawrence grade>or=2 or PF OA at baseline in 606 subjects (age range 50-79 yrs, mean 63.9 yrs; 66.6% women). Mean body mass index was 31.9, and 32.8% of knees had frequent knee pain at baseline. Of these, 500 knees (59.4%) showed progression. Of the 500, 75 (15%) had progression only in the PF joint, while the remainder had progression in the TF joint. Malalignment increased the risk of overall progression in TF joint and increased the risk of half-grade progression, suggesting that half-grade progression had validity. CONCLUSION: PA and lateral views obtained in persons at high risk of OA progression can produce a cumulative incidence of progression above 50% at 30 months. Keys to increasing the yield include imaging PF and lateral compartments, using semiquantitative scales designed to detect change, and examining more than one radiographic view.

Correlation of the development of knee pain with enlarging bone marrow lesions on magnetic resonance imaging.

OBJECTIVE: Results of cross-sectional studies have suggested that bone marrow lesions (BMLs) visualized on magnetic resonance imaging (MRI) are related to knee pain, but no longitudinal studies have been done. This study was undertaken to determine whether enlarging BMLs are associated with new knee pain. METHODS: Subjects ages 50-79 years with knee osteoarthritis (OA) or at high risk of knee OA were asked twice at baseline about the presence of knee pain, aching, or stiffness (classified as frequent knee pain) on most days; absence of knee pain was the baseline eligibility criterion. At 15 months' followup, subjects were again queried twice about frequent knee pain. A case knee was defined as absence of knee pain at baseline but presence of knee pain both times at followup. Controls were selected randomly from among knees with absence of pain at baseline. All MR images were scored for volume of BMLs in the medial, lateral, and patellofemoral compartments. We focused on the maximal change in BML score among the knee compartments from baseline to 15 months. Multiple logistic regression, with adjustments for demographic and clinical variables, was used to assess whether an increased BML score is predictive of the development of knee pain. RESULTS: Among case knees, 54 of 110 (49.1%) showed an increase in BML score within a compartment, whereas only 59 of 220 control knees (26.8%) showed an increase (P < 0.001 by chi-square test). A BML score increase of at least 2 units was much more common in case knees than in control knees (27.5% versus 8.6%; adjusted odds ratio 3.2, 95% confidence interval 1.5-6.8). Among case knees with increased BMLs, most already had BMLs at baseline, with enlarging BMLs at followup, but among the subset of knees with no BMLs at baseline, new BMLs were more common in case knees (11 [32.4%] of 34) than in control knees (9 [10.8%] of 83). CONCLUSION: Development of knee pain is associated with an increase in BMLs as revealed on MRI.

Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis.

OBJECTIVE: To examine the relationship between longitudinal fluctuations in synovitis with change in pain and cartilage in knee osteoarthritis. METHODS: Study subjects were patients 45 years of age and older with symptomatic knee osteoarthritis from the Boston Osteoarthritis of the Knee Study. Baseline and follow-up assessments at 15 and 30 months included knee magnetic resonance imaging (MRI), BMI and pain assessment (VAS) over the last week. Synovitis was scored at 3 locations (infrapatellar fat pad, suprapatellar and intercondylar regions) using a semiquantitative scale (0-3) at all 3 time points on MRI. Scores at each site were added to give a summary synovitis score (0-9). RESULTS: We assessed 270 subjects whose mean (SD) age was 66.7 (9.2) years, BMI 31.5 (5.7) kg/m(2); 42% were female. There was no correlation of baseline synovitis with baseline pain score (r = 0.09, p = 0.17). The change in summary synovitis score was correlated with the change in pain (r = 0.21, p = 0.0003). An increase of one unit in summary synovitis score resulted in a 3.15-mm increase in VAS pain score (0-100 scale). Effusion change was not associated with pain change. Of the 3 locations for synovitis, changes in the infrapatellar fat pad were most strongly related to pain change. Despite cartilage loss occurring in over 50% of knees, synovitis was not associated with cartilage loss in either tibiofemoral or patellofemoral compartment. CONCLUSIONS: Change in synovitis was correlated with change in knee pain, but not loss of cartilage. Treatment of pain in knee osteoarthritis (OA) needs to consider treatment of synovitis.

Effect of recreational physical activities on the development of knee osteoarthritis in older adults of different weights: the Framingham Study.

OBJECTIVE: To evaluate the long-term effect of recreational exercise on the development of knee osteoarthritis (OA) in a community-based cohort of older adults, many of whom were overweight or obese. METHODS: Subjects were asked about recreational activities including walking or jogging for exercise and working up a sweat, and were asked to compare their activity levels with others. Subjects were then asked about knee pain and weight-bearing anteroposterior and lateral knee radiographs were obtained. Approximately 9 years later, subjects were reexamined for OA. Radiographs were read for OA features in both tibiofemoral and patellofemoral compartments and were scored for tibiofemoral joint space narrowing. To evaluate incident OA, we excluded knees with OA at baseline for all analyses and focused on 3 knee-specific outcomes: incident radiographic OA, symptomatic OA, and tibiofemoral joint space loss. After adjusting for age, sex, body mass index (BMI), knee injury history, and correlation between knees, we evaluated the association of each recreational activity with OA development. RESULTS: A total of 1,279 subjects underwent both baseline and followup examinations (mean age at baseline 53.2 years). Neither recreational walking, jogging, frequent working up a sweat, nor high activity levels relative to peers were associated with a decrease or increase in risk of OA. Joint space loss was also unaffected by activity. Persons with BMI above the median (27.7 kg/m(2) for men and 25.7 kg/m(2) for women; mean BMI >30 kg/m(2) for both) had no increases in risk of OA by different type of activity. CONCLUSION: Among middle-aged and elderly persons without knee OA, many of whom were overweight, recreational exercise neither protects against nor increases risk of knee OA.

Low levels of vitamin D and worsening of knee osteoarthritis: results of two longitudinal studies.

OBJECTIVE: To confirm reports that 25-hydroxyvitamin D (25[OH]D) deficiency is associated with an increased risk of joint space narrowing or cartilage loss in osteoarthritis (OA). METHODS: We measured 25(OH)D levels in subjects from 2 longitudinal cohort studies, the Framingham Osteoarthritis Study and the Boston Osteoarthritis of the Knee Study (BOKS). In the first, weight-bearing anteroposterior (AP) and lateral knee radiographs were obtained on subjects in 1993-1994 and again in 2002-2005 (mean interval 9 years); blood was drawn for measurement of vitamin D status in 1996-2000. In the second, subjects with symptomatic knee OA participating in a natural history study had fluoroscopically positioned semiflexed posteroanterior (PA) and lateral radiography of both knees and magnetic resonance imaging (MRI) of the more symptomatic knee performed at baseline and at 15 and 30 months. Blood was drawn at all visits, and the baseline specimen was used when available. In both studies, we defined radiographic worsening based on joint space loss in the tibiofemoral joint on either AP/PA or lateral weight-bearing views, using a semiquantitative scale (worsening defined as increase by > or =1 on a 0-3 scale). In the BOKS, we evaluated cartilage loss semiquantitatively, using the Whole-Organ Magnetic Resonance Imaging Score. In both studies, 25(OH)D levels were measured by radioimmunoassay. Analyses focused on whether vitamin D levels, defined in tertiles or as deficient (25[OH]D <20 ng/ml) versus nondeficient, predicted worsening of OA. Logistic regression analysis adjusted for age, body mass index, sex, and baseline OA level was used. RESULTS: The 715 subjects in the Framingham Study had a mean 25(OH)D level of 20 ng/ml at baseline, and 20.3% of the knees showed worsening, during the course of the study, with most knees having had no evidence of OA at baseline. The 277 subjects with OA in the BOKS had a mean 25(OH)D level of 20 ng/ml at baseline with 23.6% of knees showing radiographic worsening. We found no association of baseline 25(OH)D levels with radiographic worsening in either cohort, and confidence limits in the analyses of vitamin D deficiency were narrow, suggesting that results were not based on insufficient power. In fact, the risk of worsening was slightly, but not significantly, lower in persons with low levels of vitamin D than in persons with higher levels. In the BOKS, vitamin D levels were unrelated to cartilage loss seen on MRI. CONCLUSION: The findings indicate that vitamin D status is unrelated to the risk of joint space or cartilage loss in knee OA.

The relationship between cartilage loss on magnetic resonance imaging and radiographic progression in men and women with knee osteoarthritis.

OBJECTIVE: To determine the relationship between radiographic progression of joint space narrowing and cartilage loss on magnetic resonance imaging (MRI) in patients with symptomatic knee osteoarthritis (OA), and to investigate the location of MRI-based cartilage loss in the knee and its relation to radiographic progression. METHODS: Two hundred twenty-four men and women (mean age 66 years) were studied. Radiographs and MRI of the more symptomatic knee were obtained at baseline and at 15- and 30-month followup. Radiographs of the knee (with weight-bearing) were read for joint space narrowing (scale 0-3), with progression defined as any worsening in score. We used a semiquantitative method to score cartilage morphology in all 5 regions of the tibiofemoral joint, and defined cartilage loss as an increase in score (scale 0-4) at any region. We examined the relationship between progression of joint space narrowing on radiographic images and cartilage loss on MRI, using a generalized estimating equation proportional odds logistic regression, adjusted for baseline cartilage score, age, body mass index, and sex. The medial and lateral compartments were analyzed separately. RESULTS: In the medial compartment, 104 knees (46%) had cartilage loss detected by MRI. The adjusted odds ratio was 3.7 (95% confidence interval 2.2-6.3) for radiographic progression being predictive of cartilage loss on MRI. However, there was still a substantial proportion of knees (80 of 189 [42%]) with cartilage loss visible on MRI when no radiographic progression was apparent. Cartilage loss occurred frequently in the central regions of the femur and tibia as well as the posterior femur region, but radiographic progression was less likely to be observed when posterior femur regions showed cartilage loss. Radiographic progression appeared specific (91%) but not sensitive (23%) for cartilage loss. Overall findings were similar for the lateral compartment. CONCLUSION: While our results provide longitudinal evidence that radiographic progression of joint space narrowing is predictive of cartilage loss assessed on MRI, radiography is not a sensitive measure, and if used alone, will miss a substantial proportion of knees with cartilage loss.