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author:("negi, yuhina")
1.  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
2.  Increased Risk of Recurrent Gout Attacks with Hospitalization 
The American journal of medicine  2013;126(12):10.1016/j.amjmed.2013.06.026.
While anecdotal evidence suggests that risk of recurrent gout attack increases with hospitalization, no study has formally tested this hypothesis.
We conducted an online case-crossover study of individuals with gout. We obtained information on gout attacks over a one-year period, including: onset date, symptoms and signs, medications, and exposure to potential risk factors, including hospitalization, during the 2-day hazard period prior to each gout attack. The same exposure information was also obtained over 2-day intercritical gout control periods. We performed conditional logistic regression to examine the relationship of hospitalization with recurrent gout attacks and whether such a relationship was modified by concomitant use of anti-gout medications.
Of 724 participants (mean age 54.5 years, 78.5% male), 35 hospitalizations occurred during either a hazard or control period. The adjusted odds of gout attacks was increased 4-fold with hospitalization (OR 4.05, 95% confidence interval: 1.78–9.19) compared with no hospitalization. The effect of hospitalization tended to attenuate with use of allopurinol, colchicine, or NSAIDs, but not statistically significantly.
Our study confirmed that the risk of gout attacks increases among gout patients during hospitalization. Appropriate measures should be considered for prevention of gout attacks during hospitalization for patients with pre-existing gout.
PMCID: PMC3838663  PMID: 24054179
4.  New classification criteria for gout: a framework for progress 
Rheumatology (Oxford, England)  2013;52(10):1748-1753.
The definitive classification or diagnosis of gout normally relies upon the identification of MSU crystals in SF or from tophi. Where microscopic examination of SF is not available or is impractical, the best approach may differ depending upon the context. For many types of research, clinical classification criteria are necessary. The increasing prevalence of gout, advances in therapeutics and the development of international research collaborations to understand the impact, mechanisms and optimal treatment of this condition emphasize the need for accurate and uniform classification criteria for gout. Five clinical classification criteria for gout currently exist. However, none of the currently available criteria has been adequately validated. An international project is currently under way to develop new validated gout classification criteria. These criteria will be an essential step forward to advance the research agenda in the modern era of gout management.
PMCID: PMC4047282  PMID: 23611919
gout; classification; urate; research
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.  The Epidemiology and Impact of Pain in Osteoarthritis 
Osteoarthritis is the most common form of arthritis and a leading cause of disability worldwide, largely due to pain, the primary symptom of the disease. The pain experience in knee osteoarthritis in particular is well-recognized as typically transitioning from intermittent weight-bearing pain to a more persistent, chronic pain. Methods to validly assess pain in osteoarthritis studies have been developed to address the complex nature of the pain experience. The etiology of pain in osteoarthritis is recognized to be multifactorial, with both intra-articular and extra-articular risk factors. Nonetheless, greater insights are needed into pain mechanisms in osteoarthritis to enable rational mechanism-based management of pain. Consequences of pain related to osteoarthritis contribute to a substantial socioeconomic burden.
PMCID: PMC3753584  PMID: 23973124
osteoarthritis; pain; risk factors
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.  Rheumatoid Arthritis Disease Activity Measures: American College of Rheumatology Recommendations for Use in Clinical Practice 
Arthritis care & research  2012;64(5):640-647.
Although the systematic measurement of disease activity facilitates clinical decision making in rheumatoid arthritis (RA), no recommendations currently exist on which measures should be applied in clinical practice in the US. The American College of Rheumatology (ACR) convened a Working Group (WG) to comprehensively evaluate the validity, feasibility, and acceptability of available RA disease activity measures and derive recommendations for their use in clinical practice.
The Rheumatoid Arthritis Clinical Disease Activity Measures Working Group conducted a systematic review of the literature to identify RA disease activity measures. Using exclusion criteria, input from an Expert Advisory Panel (EAP), and psychometric analysis, a list of potential measures was created. A survey was administered to rheumatologists soliciting input. The WG used these survey results in conjunction with the psychometric analyses to derive final recommendations.
Systematic review of the literature resulted in identification of 63 RA disease activity measures. Application of exclusion criteria and ratings by the EAP narrowed the list to 14 measures for further evaluation. Practicing rheumatologists rated 9 of these 14 measures as most useful and feasible. From these 9 measures, the WG selected 6 with the best psychometric properties for inclusion in the final set of ACR-recommended RA disease activity measures.
We recommend the Clinical Disease Activity Index, Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein), Patient Activity Scale (PAS), PAS-II, Routine Assessment of Patient Index Data with 3 measures, and Simplified Disease Activity Index because they are accurate reflections of disease activity; are sensitive to change; discriminate well between low, moderate, and high disease activity states; have remission criteria; and are feasible to perform in clinical settings.
PMCID: PMC4028066  PMID: 22473918
9.  Trajectories of Gait Speed Predict Mortality in Well-Functioning Older Adults: The Health, Aging and Body Composition Study 
Although gait speed slows with age, the rate of slowing varies greatly. To date, little is known about the trajectories of gait speed, their correlates, and their risk for mortality in older adults.
Gait speed during a 20-m walk was measured for a period of 8 years in initially well-functioning men and women aged 70–79 years participating in the Health, Aging and Body Composition study. We described the trajectories of gait speed and examined their correlates using a group-based mixture model. Also risk associated with different gait speed trajectories on all-cause mortality was estimated using a Cox-proportional hazard model.
Of 2,364 participants (mean age, 73.5±2.9 years; 52% women), we identified three gait speed trajectories: slow (n = 637), moderate (n = 1,209), and fast decline (n = 518). Those with fast decline slowed 0.030 m/s per year or 2.4% per year from baseline to the last follow-up visit. Women, blacks, and participants who were obese, had limited knee extensor strength, and had low physical activity were more likely to have fast decline than their counterparts. Participants with fast decline in gait speed had a 90% greater risk of mortality than those with slow decline.
Despite being well-functioning at baseline, a quarter of older adults experienced fast decline in gait speed, which was associated with an increased risk of mortality.
PMCID: PMC3593620  PMID: 23051974
Gait speed; Older adults; Mortality.
10.  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
11.  Epidemiology of OA 
Osteoarthritis (OA) is the most common form of arthritis in the US, and a leading cause of disability. It is typically defined in epidemiologic studies on the basis of radiographic findings and consideration of symptoms. Its incidence and prevalence are rising, likely related to the aging of the population and increasing obesity. Risk factors for OA include a number of person-level factors, such as age, sex, obesity, and genetics, as well as joint-specific factors that are likely reflective of abnormal loading of the joints. A number of methodologic challenges exist in studying OA that can hamper our ability to identify pertinent relationships.
PMCID: PMC3545412  PMID: 23312408
Osteoarthritis; epidemiology; risk factors; pain
12.  Assistive Walking Device Use and Knee Osteoarthritis: the Health, Aging, and Body Composition Study (Health ABC Study) 
To identify factors that predicted incident use of assistive walking devices (AWDs) and to explore whether AWD use was associated with changes in osteoarthritis of the knee.
Prospective cohort study.
2,639 elderly men and women in the Health ABC (Health, Aging and Body Composition). Study followed for incident use of AWDs, including a subset of 874 with prevalent knee pain.
Main Outcome Measures
Incident use of AWDs, mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores and frequency of joint space narrowing on knee radiographs over a three year time period.
AWD use was initiated by 9% of the entire Health ABC cohort and 12% of the knee pain subset. Factors that predicted use in both groups were age ≥73 [entire cohort: OR 2.07 (95% CI 1.43, 3.01); knee pain subset: OR 1.87 (95% CI 1.16, 3.03)], black race [entire cohort: OR 2.95 (95% CI 2.09, 4.16); knee pain subset: OR 3.21 (95% CI 2.01, 5.11)] and lower balance ratios [entire cohort: OR 3.18 (95% CI 2.21, 4.59); knee pain subset: OR 3.77 (95% CI 2.34, 6.07)]. Mean WOMAC pain scores decreased slightly over time in both AWD and non-AWD users. 20% of non-AWD users and 28% of AWD users had radiographic progression in joint space narrowing of the tibiofemoral joint in at least one knee. 14% of non-AWD users and 12% of AWD users had radiographic progression in joint space narrowing in the patellofemoral joint in at least one knee.
Assistive walking devices are frequently used by elderly men and women. Knee pain and balance problems are significant reasons why elderly individuals initiate use of an assistive walking device. In an exploratory analysis, there was no consistent relationship between use or nonuse of an AWD and WOMAC pain scores or knee joint space narrowing progression. Further studies of the relationship of use of AWDs to changes in knee osteoarthritis are needed.
PMCID: PMC3557749  PMID: 23041146
AWDs; Balance; Knee pain
13.  Purine-rich foods intake and recurrent gout attacks 
Annals of the rheumatic diseases  2012;71(9):1448-1453.
To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients.
The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods.
This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine.
The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.
PMCID: PMC3889483  PMID: 22648933
14.  Tophus measurement as an outcome measure for clinical trials of chronic gout: progress and research priorities 
The Journal of rheumatology  2011;38(7):10.3899/jrheum.110272.
Despite the recognition that tophus regression is an important outcome measure in clinical trials of chronic gout, there is no agreed method of tophus measurement. A number of methods have been used in clinical trials of chronic gout, from simple physical measurement techniques to complex advanced imaging methods. This paper summarises the methods of tophus measurement that have been used and discusses the properties of these methods. Physical measurement using Vernier calipers fulfils most aspects of the Outcomes Measures in Rheumatology (OMERACT) filter. Rigorous testing of the complex methods, particularly with respect to reliability and sensitivity to change is needed, to determine the appropriate use of these methods. Further information is also required regarding which method of physical measurement is best for use in future clinical trials. The need to develop and test a patient reported measure of tophus burden is also highlighted.
PMCID: PMC3882031  PMID: 21724716
15.  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
16.  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
17.  Patient-reported Outcomes in Chronic Gout: A Report from OMERACT 10 
The Journal of rheumatology  2011;38(7):10.3899/jrheum.110271.
To summarize the endorsement of measures of patient-reported outcome (PRO) domains in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10).
During the OMERACT 10 gout workshop, validation data were presented for key PRO domains including pain [pain by visual analog scale (VAS)], patient global (patient global VAS), activity limitation [Health Assessment Questionnaire-Disability Index (HAQ-DI)], and a disease-specific measure, the Gout Assessment Questionnaire version 2.0 (GAQ v2.0). Data were presented on all 3 aspects of the OMERACT filters of truth, discrimination, and feasibility. One PRO, health-related quality of life measurement with the Medical Outcomes Study Short-form 36 (SF-36), was previously endorsed at OMERACT 9.
One measure for each of the 3 PRO of pain, patient global, and activity limitation was endorsed by > 70% of the OMERACT delegates to have appropriate validation data. Specifically, pain measurement by VAS was endorsed by 85%, patient global assessment by VAS by 73%, and activity limitation by HAQ-DI by 71%. GAQ v2.0 received 30% vote and was not endorsed due to several concerns including low internal consistency and lack of familiarity with the measure. More validation studies are needed for this measure.
With the endorsement of one measure each for pain, patient global, SF-36, and activity limitation, all 4 PRO for chronic gout have been endorsed. Future validation studies are needed for the disease-specific measure, GAQ v2.0. Validation for PRO for acute gout will be the focus of the next validation exercise for the OMERACT gout group.
PMCID: PMC3850171  PMID: 21724715
18.  Cherry Consumption and the Risk of Recurrent Gout Attacks 
Arthritis and rheumatism  2012;64(12):4004-4011.
To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout.
We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression.
Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42).
These findings suggest that cherry intake is associated with a lower risk of gout attacks.
PMCID: PMC3510330  PMID: 23023818
Cherry; gout; case-crossover study
19.  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
22.  Defining Physiologically “Normal” Vitamin D in African Americans 
Vitamin D levels ≥30 ng/ml are commonly considered “normal” based upon maximal suppression of intact parathyroid hormone (iPTH); however, this has recently been challenged and the optimal 25(OH)D level among non-Caucasians is unclear. We evaluated the cross-sectional relationship between serum 25(OH)D and iPTH in a sample of Caucasian and African American adults.
We used baseline serum samples of participants from the Multicenter Osteoarthritis Study (MOST) for this analysis, and used three methods to model the relationship between 25(OH)D and iPTH: ordinary least squares regression (OLS), segmented regression, and Helmert contrasts.
Among Caucasians (n=1,258), 25(OH)D and iPTH ranged from 4-51 ng/ml and 2-120 pg/ml and from 3-32 ng/ml and 3-119 pg/ml in African Americans (n=423). We observed different thresholds between African Americans and Caucasians using each analytic technique. Using 25(OH)D as a categorical variable in OLS, iPTH was statistically higher at lower 25(OH)D categories than the 24-32 ng/ml referent group among Caucasians. However, in African Americans, the mean iPTH was only significantly higher at 25(OH)D levels below 15 ng/ml. Using segmented regression, iPTH appeared to stabilize at a lower 25(OH)D level in African Americans (19-23 ng/ml) compared to in Caucasians (>32 ng/ml). Helmert contrasts also revealed a lower threshold in African Americans than Caucasians.
Among MOST participants, the 25(OH)D thresholds at which no further change in iPTH was observed was approximately 20 ng/ml in African Americans versus approximately 30 ng/ml in Caucasians, suggesting optimal vitamin D levels in Caucasians may not be applicable to African Americans.
PMCID: PMC3677509  PMID: 22189572
vitamin D; parathyroid hormone; racial differences; African American; thresholds; osteoporosis
23.  When it hurts, a positive attitude may help: The association of positive affect with daily walking in knee OA: the MOST Study 
Arthritis care & research  2012;64(9):1312-1319.
While depressive symptoms and knee pain are independently known to impede daily walking in older adults, it is unknown whether positive affect promotes daily walking. This study investigated this association among adults with knee osteoarthritis (OA) and examined whether knee pain modified this association.
Cross-sectional analysis of the Multicenter Osteoarthritis Study. We included 1018 participants (mean age 63.1 ± 7.8 years, 60% female) who had radiographic knee OA and had worn a StepWatch monitor to record steps/day. High- and low- positive affect, and depressive symptoms were based on the Center for Epidemiologic Studies-Depression Scale. Knee pain was categorized as present in respondents who reported pain on most days at both a clinic visit and a telephone screen.
Compared to respondents with low positive affect (27% of respondents), those with high positive affect (63%) walked similar steps/day while those with depressive symptoms (10%) walked less (adjusted beta coefficients = −32.6 [−458.9, 393.8] and −579.1 [−1274.9, 116.7], respectively). There was a statistically significant interaction of positive affect by knee pain (p= 0.0045). Among respondents with knee pain (39%), those with high positive affect walked significantly more steps/day (711.0 [55.1, 1366.9]) than those with low positive affect.
High positive affect was associated with more daily walking among adults with painful knee OA. Positive affect may be an important psychological factor to consider to promote physical activity among people with painful knee OA.
PMCID: PMC3410957  PMID: 22504854
Physical Activity; Positive Affect; Depressive Symptoms; Knee Pain; Walking
24.  Vitamin K Deficiency Is Associated with Incident Knee Osteoarthritis 
The American journal of medicine  2013;126(3):243-248.
Osteoarthritis is the most common form of arthritis, with knee osteoarthritis being the leading cause of lower extremity disability among older adults in the US. There are no treatments available to prevent the structural pathology of osteoarthritis. Because of vitamin K’s role in regulating skeletal mineralization, it has potential to be a preventative option for osteoarthritis. We therefore examined the relation of vitamin K to new-onset radiographic knee osteoarthritis and early osteoarthritis changes on magnetic resonance imaging (MRI).
Subjects from the Multicenter Osteoarthritis (MOST) Study had knee radiographs and MRI scans obtained at baseline and 30 months later, and plasma phylloquinone (vitamin K) measured at baseline. We examined the relationship of subclinical vitamin K deficiency to incident radiographic knee osteoarthritis and MRI-based cartilage lesions and osteophytes, respectively, using log binomial regression with generalized estimating equations, adjusting for potential confounders.
Among 1180 participants (62% women, mean age 62 ± 8 years, mean body mass index 30.1 ± 5.1 kg/m2), subclinical vitamin K deficiency was associated with incident radiographic knee osteoarthritis (risk ratio [RR] 1.56; 95% confidence interval [CI], 1.08–2.25) and cartilage lesions (RR 2.39; 95% CI, 1.05–5.40) compared with no deficiency, but not with osteophytes (RR 2.35; 95% CI, 0.54–10.13). Subclinically vitamin K-deficient subjects were more likely to develop osteoarthritis in one or both knees than neither knee (RR 1.33; 95% CI, 1.01–1.75 and RR 2.12; 95% CI, 1.06-4.24, respectively).
In the first such longitudinal study, subclinical vitamin K deficiency was associated with increased risk of developing radiographic knee osteoarthritis and MRI-based cartilage lesions. Further study of vitamin K is warranted given its therapeutic/prophylactic potential for osteoarthritis.
PMCID: PMC3641753  PMID: 23410565
Incident knee osteoarthritis; MRI cartilage abnormalities; Vitamin K
25.  Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region 
Annals of the rheumatic diseases  2012;72(3):427-436.
Chronic widespread pain (CWP) is a common disorder affecting ~10% of the general population and has an estimated heritability of 48-52%. In the first large-scale genome-wide association study (GWAS) meta-analysis, we aimed to identify common genetic variants associated with CWP.
We conducted a GWAS meta-analysis in 1,308 female CWP cases and 5,791 controls of European descent, and replicated the effects of the genetic variants with suggestive evidence for association in 1,480 CWP cases and 7,989 controls (P<1×10−5). Subsequently, we studied gene expression levels of the nearest genes in two chronic inflammatory pain mouse models, and examined 92 genetic variants previously described associated with pain.
The minor C-allele of rs13361160 on chromosome 5p15.2, located upstream of CCT5 and downstream of FAM173B, was found to be associated with a 30% higher risk of CWP (MAF=43%; OR=1.30, 95%CI=1.19-1.42, P=1.2×10−8). Combined with the replication, we observed a slightly attenuated OR of 1.17 (95%CI=1.10-1.24, P=4.7×10−7) with moderate heterogeneity (I2=28.4%). However, in a sensitivity analysis that only allowed studies with joint-specific pain, the combined association was genome-wide significant (OR=1.23, 95%CI=1.14-1.32, P=3.4×10−8, I2=0%). Expression levels of Cct5 and Fam173b in mice with inflammatory pain were higher in the lumbar spinal cord, not in the lumbar dorsal root ganglions, compared to mice without pain. None of the 92 genetic variants previously described were significantly associated with pain (P>7.7×10−4).
We identified a common genetic variant on chromosome 5p15.2 associated with joint-specific CWP in humans. This work suggests that CCT5 and FAM173B are promising targets in the regulation of pain.
PMCID: PMC3691951  PMID: 22956598
Gene Polymorphism; Fibromyalgia/Pain Syndromes; Epidemiology

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