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1.  Measures of Knee Function 
Arthritis care & research  2011;63(0 11):S208-S228.
PMCID: PMC4336550  PMID: 22588746
2.  Does Clinically Important Change in Function After Knee Replacement Guarantee Good Absolute Function? The Multicenter Osteoarthritis Study 
The Journal of rheumatology  2013;41(1):60-64.
Poor functional outcomes post knee replacement are common, but estimates of its prevalence vary, likely in part because of differences in methods used to assess function. The agreement between improvement in function and absolute good levels of function after knee replacement has not been evaluated. We evaluated the attainment of improvement in function and absolute good function after total knee replacement (TKR) and the agreement between these measures.
Using data from The Multicenter Osteoarthritis (MOST) Study, we determined the prevalence of achieving a minimal clinically important improvement (MCII, ≥ 14.2/68 point improvement) and Patient Acceptable Symptom State (PASS, ≤ 22/68 post-TKR score) on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function subscale at least 6 months after knee replacement. We also assessed the frequency of co-occurrence of the 2 outcomes, and the prevalence according to pre-knee replacement functional status.
We included 228 subjects who had a knee replacement during followup (mean age 65 yrs, mean body mass index 33.4,73% female). Seventy-one percent attained the PASS for function after knee replacement, while only 44% attained the MCII. Of the subjects who met the MCII, 93% also attained the PASS; however, of subjects who did not meet the MCII, 54% still achieved a PASS. Baseline functional status was associated with attainment of each MCII and PASS.
There was only partial overlap between attainment of a good level of function and actually improving by an acceptable amount. Subjects were more likely to attain an acceptable level of function than to achieve a clinically important amount of improvement post knee replacement.
PMCID: PMC3914207  PMID: 24293582
3.  The association of parity with osteoarthritis and knee replacement in the Multicenter Osteoarthritis Study 
We evaluated the association of parity to both risk of knee replacement (KR) and knee osteoarthritis (OA).
The NIH-funded Multicenter Osteoarthritis Study (MOST) is a longitudinal observational study of persons age 50 to 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 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.
Among 1618 women who reported parity information, mean age was 62.6 years, mean BMI 30.7 kg/m2, 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 5–12 children compared with those with one birth.
Parity in women at risk for OA is associated with both incident ROA and KR, particularly for those with more than 4 children.
PMCID: PMC3855897  PMID: 24029601
parity; knee; osteoarthritis; joint replacement
5.  The Diagnostic Performance of Anterior Knee Pain and Activity-related Pain in Identifying Knees with Structural Damage in the Patellofemoral Joint: The Multicenter Osteoarthritis Study 
The Journal of rheumatology  2014;41(8):1695-1702.
To determine the diagnostic test performance of location of pain and activity-related pain in identifying knees with patellofemoral joint (PFJ) structural damage.
The Multicenter Osteoarthritis Study is a US National Institutes of Health-funded cohort study of older adults with or at risk of knee osteoarthritis. Subjects identified painful areas around the knee on a knee pain map and the Western Ontario and McMaster Universities Osteoarthritis Index was used to assess pain with stairs and walking on level ground. Cartilage damage and bone marrow lesions were assessed from knee magnetic resonance imaging. We determined the sensitivity, specificity, positive and negative predictive values for presence of anterior knee pain (AKP), pain with stairs, absence of pain while walking on level ground, and combinations of tests in discriminating knees with isolated PFJ structural damage from those with isolated tibiofemoral joint (TFJ) or no structural damage. Knees with mixed PFJ/TFJ damage were removed from our analyses because of the inability to determine which compartment was causing pain.
There were 407 knees that met our inclusion criteria. “Any” AKP had a sensitivity of 60% and specificity of 53%; and if AKP was the only area of pain, the sensitivity dropped to 27% but specificity rose to 81%. Absence of moderate pain with walking on level ground had the greatest sensitivity (93%) but poor specificity (13%). The combination of “isolated” AKP and moderate pain with stairs had poor sensitivity (9%) but the greatest specificity (97%) of strategies tested.
Commonly used questions purported to identify knees with PFJ structural damage do not identify this condition with great accuracy.
PMCID: PMC4182011  PMID: 24931959
6.  Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study 
Annals of the rheumatic diseases  2010;70(5):805-811.
To introduce a comprehensive and reliable scoring system for the assessment of whole-knee joint synovitis based on contrast-enhanced (CE) MRI.
Multicenter Osteoarthritis Study (MOST) is a cohort study of people with, or at high risk of, knee osteoarthritis (OA). Subjects are an unselected subset of MOST who volunteered for CE-MRI. Synovitis was assessed at 11 sites of the joint. Synovial thickness was scored semiquantitatively: grade 0 (<2 mm), grade 1 (2–4 mm) and grade 2 (>4 mm) at each site. Two musculoskeletal radiologists performed the readings and inter- and intrareader reliability was evaluated. Whole-knee synovitis was assessed by summing the scores from all sites. The association of Western Ontario and McMaster Osteoarthritis Index pain score with this summed score and with the maximum synovitis grade for each site was assessed.
400 subjects were included (mean age 58.8±7.0 years, body mass index 29.5±4.9 kg/m2, 46% women). For individual sites, intrareader reliability (weighted κ) was 0.67–1.00 for reader 1 and 0.60–1.00 for reader 2. Inter-reader agreement (κ) was 0.67–0.92. For the summed synovitis scores, intrareader reliability (intraclass correlation coefficient (ICC)) was 0.98 and 0.96 for each reader and inter-reader agreement (ICC) was 0.94. Moderate to severe synovitis in the parapatellar subregion was associated with the higher maximum pain score (adjusted OR (95% CI), 2.8 (1.4 to 5.4) and 3.1 (1.2 to 7.9), respectively).
A comprehensive semiquantitative scoring system for the assessment of whole-knee synovitis is proposed. It is reliable and identifies knees with pain, and thus is a potentially powerful tool for synovitis assessment in epidemiological OA studies.
PMCID: PMC4180232  PMID: 21187293
7.  MRI-based three-dimensional bone shape of the knee predicts onset of knee osteoarthritis: Data from the Osteoarthritis Initiative 
Arthritis and rheumatism  2013;65(8):2048-2058.
To examine whether MRI-based 3D bone shape predicts the onset of radiographic knee osteoarthritis (OA).
We conducted a case-control study within the Osteoarthritis Initiative by identifying knees that developed incident tibiofemoral radiographic knee OA (case knees) over follow-up, and matching them to two random control knees. Using knee MRI's, we used active appearance modeling of the femur, tibia and patella and linear discriminant analysis to identify vectors that best classified knees having OA vs. not. Vectors were scaled such that -1 and +1 represented the mean non-OA and mean OA shapes, respectively. We examined the relation of 3D bone shape to incident OA (new onset Kellgren and Lawrence (KL) grade ≥2) occurring 12 months later using conditional logistic regression.
178 case knees (incident OA) were matched to 353 control knees. The whole joint (i.e., tibia, femur, and patella) 3D bone shape vector had the strongest magnitude of effect, with knees in the highest tertile having 3.0 times higher likelihood of developing incident radiographic knee OA 12 months later compared with those in the lowest tertile (95% CI 1.8-5.0, p<0.0001). The associations were even stronger among knees that showed completely normal radiographs before incidence (KL grade 0) (OR 12.5, 95% CI 4.0-39.3). Bone shape at baseline, often several years before incidence, predicted later OA.
MRI-based 3D bone shape predicted the later onset of radiographic OA. Further study is warranted to determine whether such methods can detect treatment effects in trials and provide pathophysiologic insight into OA development.
PMCID: PMC3729737  PMID: 23650083
8.  The ACR20 and defining a threshold for response in rheumatic diseases: too much of a good thing 
In the past 20 years great progress has been made in the development of multidimensional outcome measures (such as the Disease Activity Score and ACR20) to evaluate treatments in rheumatoid arthritis, a process disseminated throughout rheumatic diseases. These outcome measures have standardized the assessment of outcomes in trials, making it possible to evaluate and compare the efficacy of treatments. The methodologic advances have included the selection of pre-existing outcome measures that detected change in a sensitive fashion (in rheumatoid arthritis, this was the Core Set Measures). These measures were then combined into a single multidimensional outcome measure and such outcome measures have been widely adopted in trials and endorsed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) and regulatory agencies. The secular improvement in treatment for patients with rheumatoid arthritis has been facilitated in part by these major methodologic advancements. The one element of this effort that has not optimized measurement of outcomes nor made it easier to detect the effect of treatments is the dichotomization of continuous measures of response, creating responders and non-responder definitions (for example, ACR20 responders; EULAR good responders). Dichotomizing response sacrifices statistical power and eliminates variability in response. Future methodologic work will need to focus on improving multidimensional outcome measurement without arbitrarily characterizing some patients as responders while labeling others as non-responders.
PMCID: PMC3978644  PMID: 24387346
9.  The association between meniscal damage of the posterior horns and localized posterior synovitis detected on T1-weighted contrast-enhanced MRI—the MOST study 
Synovitis is thought to be a secondary phenomenon in the osteoarthritis (OA) process and the menisci might be triggers of localized synovitis. The aim was to assess the cross-sectional associations of posterior horn meniscal damage with perimeniscal synovitis, and with synovitis posterior to the posterior cruciate ligament (PCL) using contrast enhanced (CE) MRI.
The Multicenter Osteoarthritis (MOST) Study is a longitudinal observational study of subjects with or at risk for knee OA. Subjects are a subset of MOST who were examined with 1.5 T CE MRI and had semiquantitative synovitis (scored from 0–2 at 11 locations) and meniscal readings (scored with WORMS from 0–4 ) available. Logistic regression was used to assess the association of posterior meniscal damage and perimeniscal synovitis in the same compartment, and between posterior meniscal damage and synovitis posterior to the PCL.
Three hundred and seventy seven knees were included (mean age 61.1 years ± 6.9, mean BMI 29.6 ± 4.9, 44.3% women). The odds for ipsi-compartmental perimeniscal synovitis were increased for knees with medial posterior horn meniscal damage (adjusted odds ratio [aOR] 2.5, 95% confidence intervals [95% CI] 1.3,4.8), but not for lateral damage (aOR 1.7, 95% CI 0.4,6.6). No positive associations were found for meniscal damage and presence of synovitis posterior to the PCL (aOR 0.9, 95% CI 0.6,1.5).
Meniscal damage of the posterior horns is associated with ipsi-compartmental perimensical synovitis. No associations were found for posterior horn meniscal damage with synovitis posterior to the PCL, which suggests that synovitis posterior to the PCL is likely to be triggered by different pathomechanisms.
PMCID: PMC3640766  PMID: 23270763
Osteoarthritis; Magnetic resonance imaging; Synovitis; Meniscal damage
10.  Physical activity, alignment and knee osteoarthritis: Data from MOST and the OAI 
To determine the effect of physical activity on knee osteoarthritis (OA) development in persons without knee injury and according to knee alignment
We combined data from MOST and OAI, studies of persons with or at high risk of OA. Subjects had long limb and repeated posteroanterior knee radiographs and completed the physical activity survey for the elderly (PASE). We studied persons without radiographic OA and excluded knees with major injury and without long limb films. We followed subjects 30 months (in MOST) and 48 months (in OAI) for one of two incident outcomes: 1. symptomatic tibiofemoral OA (radiographic OA and knee pain), or 2. tibiofemoral narrowing. ‘Active’ persons were those with PASE score in the highest quartile by gender. We examined risk of OA in active group using logistic regression adjusting for age, gender, BMI, WOMAC pain score, Kellgren and Lawrence grade (0 or 1), and study of origin. We also analyzed knees from malaligned and neutrally aligned limbs.
The combined sample comprised 2073 subjects (3542 knees) with mean age 61 years. The cumulative incidence of symptomatic tibiofemoral OA was 1.12% in the active group vs. 1.82% in the others (OR among active group 0.6, 95% CI 0.3, 1.3). Joint space narrowing occurred in 3.41% of knees in the active group vs. 4.04% in the others (OR among active group 0.9 (95% CI 0.5, 1.5)). Results did not differ by alignment status.
Physical activity in the highest quartile did not affect the risk of developing OA.
PMCID: PMC3648587  PMID: 23523851
physical activity; knee osteoarthritis; alignment; radiography
11.  Breaking the Law of Valgus: the surprising and unexplained prevalence of medial patellofemoral cartilage damage 
Annals of the rheumatic diseases  2012;71(11):1827-1832.
To compare the prevalence of medial and lateral patellofemoral (PF) cartilage damage in three large osteoarthritis (OA) studies and determine the relationship of this damage to varus, neutral, and valgus knee alignment.
In the Boston OA of the Knee (BOKS), Framingham OA (FOA), and Multicenter OA (MOST) studies, MRIs were read for cartilage morphology at the medial and lateral patella and trochlea femoris using Whole-Organ MRI Scores (WORMS). WORMS scores ≥ 2 (any cartilage defect), ≥ 3 (areas of partial thickness loss), ≥ 4 (diffuse partial thickness loss), and ≥ 5 (extensive full thickness loss) were all variously considered as thresholds to identify damage that may indicate OA. Full-limb radiographs were measured for mechanical alignment, and varus (< −2°), neutral (−2° to 2°), and valgus (> 2°) knees were identified.
The prevalence of medial PF cartilage damage exceeded that of lateral damage in all three OA studies and according to nearly every threshold. Only among severely involved knees (WORMS ≥ 4 or ≥ 5) did the prevalence of lateral PF cartilage damage approximate that of medial damage. The high prevalence of medial PF damage persisted in all strata of knee alignment. Even among knees with valgus malalignment, the prevalence of lateral PF cartilage damage equaled or surpassed that of medial PF damage only when the threshold was specific to severely involved knees.
Medial PF cartilage damage is at least as prevalent among older adults as lateral PF cartilage damage.
PMCID: PMC4011177  PMID: 22534825
Osteoarthritis; Knee; Patellofemoral Joint; Prevalence; Articular Cartilage
12.  Comparing the functional impact of knee replacements in two cohorts 
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.
Subjects from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI), persons with or at high risk of OA, had knee radiographs, completed Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) surveys and had TKRs confirmed at each visit. At each visit, subjects were defined as having symptomatic OA (SxOA) if ≥ one knee had pain and radiographic OA or if they had a TKR. WOMAC function scores at each visit were compared by analysis of covariance adjusting for age, sex, body mass index, race, site, depression, comorbidity, painful leg joints and knees affected. Post-TKR function scores were imputed to estimate scores that would have been present without TKR.
Subjects with SxOA (n > 750 in MOST and in OAI) had a mean age 66 to 67 years; most were women and were White. Subjects were followed 4–5 years. Among those with SxOA, more TKRs were done in MOST (35%) than OAI (19%). Adjusted mean WOMAC function (0–68, 68 = worst) improved from 26.9 to 21.9 in MOST and from 24.5 to 22.0 in OAI (difference between MOST and OAI in change in WOMAC function, p = .01). Estimates of function without TKRs showed function would not have changed in MOST (23.2 at baseline to 22.4).
Functional status of subjects with knee OA in MOST improved more than in OAI, probably because of higher rates of TKRs. The decline suggests that TKR diminishes the functional impact of OA in the community.
PMCID: PMC4016673  PMID: 24885404
Total knee replacement; Function; Epidemiology
13.  Using magnetic resonance imaging to determine the compartmental prevalence of knee joint structural damage 
To describe the prevalence of magnetic resonance imaging (MRI) detected structural damage in the patellofemoral joint (PFJ) and tibiofemoral (TFJ) in a population-based cohort. A secondary aim was to evaluate the patterns of compartmental involvement in knees with pain, between men and women, and in different age and body mass index (BMI) categories.
We studied 970 knees, one knee per subject, from the Framingham Osteoarthritis Study, a population-based cohort study of persons 51–92 years old. Cartilage damage and bone marrow lesions (BMLs) were assessed using the Whole Organ Magnetic Resonance Imaging Score (WORMS). The prevalence of isolated PFJ, isolated TFJ, and mixed structural damage was determined using the following definitions: any cartilage damage, full thickness cartilage loss, any BML, and the combination of full thickness cartilage loss with any BML.
The mean age and body mass index was 63.4 years and 28.6 m/kg2, respectively; 57% were female. Isolated PFJ damage occurred in 15–20% of knees and isolated TFJ damage occurred in 8–17% of knees depending on the definition used. The prevalence of isolated PFJ damage was greater than isolated TFJ damage using all definitions except the any BML definition. This pattern was similar between genders and among age and BMI categories. In those with knee pain, isolated PFJ was at least as common as TFJ damage depending on the definition used.
Using MRI to assess knee joint structural damage, isolated PFJ damage was at least as common as, if not more common than, isolated TFJ damage.
PMCID: PMC3638815  PMID: 23428598
osteoarthritis; patellofemoral; magnetic resonance imaging
15.  Walking to meet physical activity guidelines in knee osteoarthritis: Is 10,000 steps enough? 
To study if step goals (e.g. walking 10,000 steps/day) approximate meeting 2008 Physical Activity Guidelines for Americans among adults with or at high risk of knee OA.
Cross-sectional observational cohort
People with or at high risk of knee OA
Main Outcome Measures
Objective physical activity data were collected over 7 consecutive days from people with or at high risk of knee (OA) participating in the Multicenter Osteoarthritis Study. Using activity monitor data, we determined the proportion that 1) walked ≥10,000 steps/day, 2) met the 2008 Physical Activity Guidelines, and 3) achieved both recommendations.
Of 1788 subjects studied (age 67 ± 8 yrs, BMI 31 ± 6 kg/m2, 60% women), 16.7% of men and 12.6% of women walked ≥10,000 steps/day, while 6% of men and 5% of women met the 2008 Physical Activity Guidelines for Americans. Of those walking ≥10,000 steps/day, 16.7% and 26.7% of men and women also met the 2008 Physical Activity Guidelines.
Among this sample of older adults with or at high risk of knee OA, walking ≥10,000 steps/day did not translate into meeting public health guidelines. These findings highlight the disparity between number of steps/day believed to be needed and recommended time-intensity guidelines to achieve positive health benefits.
PMCID: PMC3608824  PMID: 23228625
Physical Activity; knee osteoarthritis; pedometer; Public Health Guidelines; Walking
To assess the diagnostic performance of signal changes in Hoffa's fat pad (HFP) assessed on non-contrast-enhanced (CE) MRI in detecting synovitis, and the association of pain with signal changes in Hoffa’s fat pad on non-CE MRI and peripatellar synovial thickness on CE MRI.
The Multicenter Osteoarthritis (MOST) Study is an observational study of individuals who have or are at high risk for knee OA. All subjects with available non-CE and CE MRIs were included. Signal changes in HFP were scored from 0 to 3 in 2 regions using non-CE MRI. Synovial thickness was scored from 0 to 2 on CE MRI in 5 peripatellar regions. Sensitivity, specificity and accuracy of HFP signal changes were calculated considering synovial thickness on CE MRI as the reference standard. We used logistic regression to assess the associations of HFP changes (non-CE MRI) and synovial thickness (CE MRI) with pain from walking up or down stairs, after adjusting for potential confounders.
A total of 393 subjects were included. Sensitivity of infrapatellar and intercondylar signal changes in HFP was high (71% and 88%), but specificity was low (55% and 30%). No significant associations were found between HFP changes on non-CE MRI and pain. Grade 2 synovial thickness assessed on CE MRI was significantly associated with pain after adjustments for potential confounders.
Signal changes in HFP detected on non-CE MRI are a sensitive but non-specific surrogate for the assessment of synovitis. CE MRI identifies associations with pain better than non-CE MRI.
PMCID: PMC3578385  PMID: 23277189
Knee osteoarthritis; synovitis; magnetic resonance imaging; knee pain
17.  Prevalent cartilage damage and cartilage loss over time are associated with incident bone marrow lesions in the tibiofemoral compartments: the MOST Study 
To assess the association of prevalent cartilage damage and cartilage loss over time with incident bone marrow lesions (BMLs) in the same subregion of the tibiofemoral compartments as detected on magnetic resonance imaging (MRI).
The Multicenter Osteoarthritis Study is an observational study of individuals with or at risk for knee osteoarthritis (OA). Subjects whose baseline and 30-month follow-up MRIs were read for findings of OA were included. MRI was performed with a 1.0T extremity system. Tibiofemoral compartments were divided into 10 subregions. Cartilage morphology was scored from 0 to 6 and BMLs were scored from 0 to 3. Prevalent cartilage damage and cartilage loss over time were considered predictors of incident BMLs. Associations were assessed using logistic regression, with adjustments for potential confounders.
Medially, incident BMLs were associated with baseline cartilage damage (adjusted odds ratio (OR) 3.9 [95% CI 3.0, 5.1]), incident cartilage loss (7.3 [95% CI 5.0, 10.7]) and progression of cartilage loss (7.6 [95% CI 5.1, 11.3]) Laterally, incident BMLs were associated with baseline cartilage damage (4.1 [95% CI 2.6, 6.3]), incident cartilage loss (6.0 [95% CI 3.1, 11.8]), and progression of cartilage loss (11.9 [95% CI 6.2, 23.0]).
Prevalent cartilage damage and cartilage loss over time are strongly associated with incident BMLs in the same subregion, supporting the significance of the close interrelation of the osteochondral unit in the progression of knee OA.
PMCID: PMC3556203  PMID: 23178289
Bone marrow; cartilage; knee; osteoarthritis; magnetic resonance imaging
18.  Valgus Malalignment is a Risk Factor for Lateral Knee Osteoarthritis Incidence and Progression: Findings from MOST and the Osteoarthritis Initiative 
Arthritis and rheumatism  2013;65(2):355-362.
We studied the effect of valgus malalignment on knee osteoarthritis (OA) incidence and progression.
We measured mechanical axis from long limb radiographs from the MOST Study and the Osteoarthritis Initiative (OAI) to define valgus limbs (>1° valgus) and examined the effect of valgus vs. neutral (neither varus nor valgus) on OA structural outcomes. Posteroanterior x-rays and knee MRIs were obtained in subjects at the time of the long limb x-ray and at follow-up examinations. Lateral progression was defined by an increase in joint space narrowing (on a semiquantitative scale) and incidence as new lateral narrowing in knees without x-ray OA. We defined lateral cartilage damage and progressive meniscal damage when WORMS (MOST) or BLOKS (OAI) scores for cartilage or meniscus increased at follow-up. We used logistic regression with adjustment for age, sex, BMI and Kellgren and Lawrence grade and used GEE to evaluate the effect of valgus vs. neutral alignment on disease outcomes.
We studied 5046 knees (881 valgus) from MOST and 5953 knees (1235 valgus) from OAI. In both studies, all strata of valgus malalignment including 1.1 to 3° valgus were associated with an increased risk of lateral disease progression. In knees without radiographic OA, valgus alignment above 3° was associated with incidence (for example in MOST, adjOR = 2.7 (95% 1.1, 6.8)). Valgus 3° or more was also associated with cartilage damage on MRI in knees without OA (for example in OAI, adjOR = 5.9 (95% CI, 1.3, 30.3)). We found a strong relation of valgus with progressive lateral meniscal damage.
Valgus malalignment increases the risk of knee OA x-ray progression, incidence and of lateral cartilage damage. It may cause these effects, in part, by increasing the risk of meniscal damage.
PMCID: PMC3558618  PMID: 23203672
19.  Do radiographic disease and pain account for why people with or at high risk of knee osteoarthritis do not meet Physical Activity Guidelines? 
Arthritis and rheumatism  2013;65(1):139-147.
Knee Osteoarthritis (OA) and pain are assumed to be barriers for meeting physical activity guidelines, but this has not been formally evaluated. The purpose of this study was to determine the proportion of people with and without knee OA and knee pain who met recommended physical activity levels through walking.
Cross-sectional analysis of community dwelling adults who have or who are at high risk of knee OA from The Multicenter Osteoarthritis Study. Participants wore a StepWatch activity monitor to record steps/day over 7 days. The proportion that met the recommended physical activity levels was determined as those accumulating ≥150 minutes/week at ≥100 steps/minute in bouts lasting ≥10 minutes. These proportions were also determined for those with and without knee OA, as classified by radiograph, and by severity of knee pain.
Of the 1788 study participants (age 67 sd 8 yrs, BMI 31 sd 6 kg/m2, 60% female), lower overall percentages of participants with radiographic knee OA and knee pain met recommended physical activity levels. However, these differences were not statistically significant between those with and without knee OA; 7.3% and 10.1% of men (p=0.34), and 6.3% and 7.8% of women (p=0.51), respectively, met recommended physical activity levels. Similarly, for those with moderate/severe pain versus no pain, 12.9% and 10.9% of men (p=0.74) and 6.7% and 11.0% (p=0.40) of women met recommended physical activity levels.
Disease and pain have little impact on achieving recommended physical activity levels among people with or at high risk of knee OA.
PMCID: PMC3535507  PMID: 23124774
20.  Osteoarthritis as a disease of mechanics 
Mechanics means relating to or caused by movement or physical forces. In this paper, I shall contend that OA is almost always caused by increased physical forces causing damage to a joint. While examples of joint injury causing osteoarthritis are numerous, I shall contend that most or almost all osteoarthritis is caused in part by mechanically induced injury to joint tissues. Further, once joint pathology has developed, as is the case for almost all clinical osteoarthritis, pathomechanics overwhelms all other factors in causing disease progression. Treatments which correct the pathomechanics have long lasting favorable effects on pain and joint function compared with treatments that suppress inflammation which have only temporary effects. I shall lastly contend that the mechanically induced joint injury leads to variable inflammatory responses but that the role of this inflammation in worsening structural damage in an already osteoarthritic joint has not yet been proven.
PMCID: PMC3538894  PMID: 23041436
osteoarthritis; biomechanics; inflammation
21.  Co-Localization of non-cartilaginous articular pathology increases risk of cartilage loss in the tibiofemoral joint - the MOST Study 
Annals of the rheumatic diseases  2012;72(6):10.1136/annrheumdis-2012-201810.
To assess risk of cartilage loss in the tibiofemoral joint in relation to baseline damage severity, and to analyze the association of nearby pathologic findings on the risk of subsequent cartilage loss.
The Multicenter Osteoarthritis (MOST) Study is a longitudinal study of individuals with or at high risk for knee osteoarthritis. Magnetic resonance imaging (MRI) examinations were assessed according to the Whole Organ Magnetic Resonance Imaging Score (WORMS). Included were all knees with available baseline and 30 months MRIs. Ordinal logistic regression was used to estimate risk of cartilage loss in each subregion in relation to the number of associated articular features including bone marrow lesions, meniscal damage and extrusion and also in regard to baseline damage severity, respectively.
13524 subregions of 1365 knees were included. 3777 (27.9%) subregions exhibited prevalent cartilage damage at baseline and 1119 (8.3%) subregions showed cartilage loss at 30-month follow-up. Risk of cartilage loss was increased for subregions with associated features (ORs 2.53, 95% confidence interval [CI] 2.03-3.15 for one, 4.32 95% CI 3.42-5.47 for two and 5.30 95% CI 3.95-7.12 for three associated features; p for trend <0.0001). Subregions with prevalent cartilage damage showed increased risk for further cartilage loss compared to subregions with intact cartilage at baseline with small superficial defects exhibiting highest risk.
Risk of cartilage loss is increased for subregions with associated pathology and further increased when more than one type of associated feature is present. In addition, prevalent cartilage damage increases risk for subsequent cartilage loss.
PMCID: PMC3871211  PMID: 22956600
magnetic resonance imaging; osteoarthritis; risk factors; cartilage loss; meniscal damage; mensical extrusion; bone marrow lesions
22.  Prevalence, incidence and progression of hand osteoarthritis in the general population: the Framingham Osteoarthritis Study 
Annals of the rheumatic diseases  2011;70(9):10.1136/ard.2011.150078.
To describe the prevalence and longitudinal course of radiographic, erosive and symptomatic hand osteoarthritis (HOA) in the general population.
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).
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%).
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.
PMCID: PMC3867970  PMID: 21622766
23.  Predictive validity of within-grade scoring of longitudinal changes of MRI-based cartilage morphology and bone marrow lesion assessment in the tibio-femoral joint - the MOST Study 
In order to increase sensitivity to detect longitudinal change, recording of within-grade changes was introduced for cartilage morphology and bone marrow lesion (BML) assessment in semiquantitative magnetic resonance imaging (MRI) scoring of knee osteoarthritis. The aim of this study was to examine the validity provided by within-grade scoring.
The Multicenter Osteoarthritis (MOST) Study is a longitudinal study of subjects with or at risk of knee osteoarthritis. Baseline and 30 months MRIs were read according to the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) system including within-grade changes for cartilage and BMLs. We tested the validity of within-grade changes by whether the 30 month changes in cartilage and bone marrow lesion assessment were predicted by baseline ipsi-compartmental meniscal damage and malalignment, factors known to affect cartilage loss and bone marrow lesions, using ordinal logistic regression.
1867 knees (from 1411 participants) were included. Severe medial meniscal damage predicted partial grade (aOR 4.4, 95%CI 2.2,8.7) but not ≥ full grade (aOR 1.3, 95%CI 0.8,2.2) worsening of cartilage loss and predicted both, partial grade (aOR 9.6, 95%CI 3.6,25.1) and ≥ full grade (aOR 5.1, 95%CI 3.2,8.2) worsening of BMLs. Severe, but not moderate, malalignment predicted ipsicompartmental within-grade (medial cartilage damage: aOR 5.5, 95%CI 2.6,11.6; medial worsening of BMLs: aOR 4.9, 95%CI 2.0,12.3) but not full grade worsening of BMLs and cartilage damage.
Within-grade changes in semiquantitative MRI assessment of cartilage and bone marrow lesions are valid and their use may increase the sensitivity of semiquantitative readings in detecting longitudinal changes in these structures.
PMCID: PMC3863692  PMID: 22846715
osteoarthritis; MRI; semiquantitative scoring; WORMS; within grade; validity
24.  The Role of Varus and Valgus Alignment in the Initial Development of Knee Cartilage Damage by MRI: the MOST Study 
Annals of the rheumatic diseases  2012;72(2):10.1136/annrheumdis-2011-201070.
Varus and valgus alignment are associated with progression of knee osteoarthritis, but their role in incident disease is less certain. Radiographic measures of incident knee osteoarthritis may be capturing early progression rather than disease development. We tested the hypothesis: in knees with normal cartilage morphology by MRI, varus is associated with incident medial cartilage damage and valgus with incident lateral damage.
In MOST, a prospective study of persons at risk for or with knee osteoarthritis, baseline full-limb x-rays and baseline and 30-month MRIs were acquired. In knees with normal baseline cartilage morphology in all tibiofemoral subregions, we used logistic regression with GEE to examine the association between alignment and incident cartilage damage adjusting for age, gender, BMI, laxity, meniscal tear, and extrusion.
Of 1881 knees, 293 from 256 persons met criteria. Varus vs. non-varus was associated with incident medial damage (adjusted OR 3.59, 95% CI: 1.59, 8.10), as was varus vs. neutral, with evidence of a dose effect (adjusted OR 1.38/1° varus, 95% CI: 1.19, 1.59). Findings held even excluding knees with medial meniscal damage. Valgus was not associated with incident lateral damage. Varus and valgus were associated with a reduced risk of incident lateral and medial damage, respectively.
In knees with normal cartilage morphology, varus was associated with incident cartilage damage in the medial compartment, and varus and valgus with a reduced risk of incident damage in the less loaded compartment. These results support that varus increases the risk for initial development of knee osteoarthritis.
PMCID: PMC3845483  PMID: 22550314
25.  The association between erosive hand osteoarthritis and subchondral bone attrition of the knee: the Framingham Osteoarthritis Study 
Annals of the rheumatic diseases  2012;71(10):1698-1701.
To examine whether erosive hand osteoarthritis (OA) is associated with knee subchondral bone attrition (SBA) and systemic bone mineral density (BMD).
Associations of MRI-defined knee SBA with radiographic erosive hand OA were evaluated in 1253 Framingham participants using logistic regression with generalised estimating equations. We also examined the association between the number of erosive OA finger joints and SBA adjusted for the number of non-erosive OA finger joints. Associations between erosive hand OA and femoral neck BMD were explored in 2236 participants with linear regression. Analyses were adjusted for age, sex and body mass index.
Participants with erosive hand OA had increased odds of knee SBA (OR=1.60, 95% CI 1.07 to 2.38). The relation between the number of erosive OA finger joints and SBA became non-significant when adjusted for the number of non-erosive OA joints as a proxy for the burden of disease. There was a non-significant trend towards higher BMD in erosive hand OA compared with participants without hand OA.
Erosive hand OA was associated with knee SBA, but the relation might be best explained by a heightened burden of disease. No significant relation of erosive hand OA with BMD was found.
PMCID: PMC3653622  PMID: 22730369

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