Biomedical subjects

D T Felson

Publications and source records attributed to D T Felson.

At least 19 recordsLinked to original sources

PubMed2006

Cigarette smoking and the risk for cartilage loss and knee pain in men with knee osteoarthritis.

OBJECTIVE: To examine the effects of smoking on cartilage loss and pain at the knee in individuals with knee osteoarthritis. METHODS: 159 men with symptomatic knee osteoarthritis who participated in a 30-month, prospective, natural history study of knee osteoarthritis were examined. The more symptomatic knee was imaged using magnetic resonance imaging (MRI) at baseline, and again at 15 and 30 months of follow-up. Cartilage was scored using the Whole-Organ MRI Score semiquantitative method at the medial and lateral tibiofemoral joints and at the patellofemoral joint. At baseline and follow-up visits, the severity of knee pain was assessed using a Visual Analogue Scale pain score (0-100 mm). RESULTS: Among the 159 men, 19 (12%) were current smokers at baseline. Current smokers were younger (mean (standard deviation (SD)) age 62 (9) v 69 (9) years) and leaner (mean (SD) body mass index (BMI): 28.9 (3.2) v 31.3 (4.8) kg/m(2)) than men who were not current smokers. When adjusted for age, BMI and baseline cartilage scores, men who were current smokers were found to have an increased risk for cartilage loss at the medial tibiofemoral joint (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.0 to 5.4) and the patellofemoral joint (OR 2.5, 95% CI 1.1 to 5.7). Current smokers also had higher adjusted pain scores at baseline (60.5 v 45.0, p<0.05) and at follow-up (59.4 v 44.3, p<0.05) than men who were not current smokers. CONCLUSIONS: Men with knee osteoarthritis who smoke sustain greater cartilage loss and have more severe knee pain than men who do not smoke.

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PubMed2006

Urinary pentosidine does not predict cartilage loss among subjects with symptomatic knee OA: the BOKS Study.

OBJECTIVE: Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major changes in the extracellular matrix of cartilage is the age-related accumulation of advanced glycation end products (AGEs). Pentosidine, an AGE crosslink, is one of the few characterized AGEs and is considered an adequate marker for the many AGEs that are formed in vivo. We used data from a longitudinal observation study to determine if urinary pentosidine could serve as a marker to predict cartilage loss. METHODS: We conducted a prospective analysis of data from the Boston Osteoarthritis of the Knee Study (BOKS); a completed natural history study of knee OA. All subjects in the study met American College of Rheumatology (ACR) criteria for knee OA. Knee magnetic resonance (MR) images were scored for cartilage in 14 plates of the knee using the Whole Organ Magnetic Resonance Imaging Score (WORMS) semiquantitative grading scheme. Within the BOKS population, a nested sample of 127 subjects (39% of the whole sample) who had both baseline pentosidine and longitudinal magnetic resonance imaging (MRI) measurements (MRIs performed at baseline and 30 months later) was assessed. Urinary pentosidine was assayed and normalized to creatinine to account for differences in urine concentrations. We analyzed the data using three different methods to assess if baseline measures of pentosidine predicted subsequent cartilage loss on MRI. These were (1) analysis 1: logistic regression with the outcome cartilage loss in any plate; (2) analysis 2: proportional odds model where the outcome was defined as 0=no cartilage loss, 1=cartilage loss in one plate, 2=cartilage loss in two plates, and 3=cartilage loss in at least three plates; and (3) analysis 3: Poisson regression with the outcome the number of plates with cartilage loss. All analyses were adjusted for age, sex and Body Mass Index (BMI). RESULTS: At baseline the mean (standard deviation) age was 67 (9) years and 54% were male. The results for the three analytic steps are as follows: Analysis 1: the odds ratio for cartilage loss is 1.01 (95% confidence interval (CI) 0.93-1.09) with 1 unit increase in pentosidine. Analysis 2: the odds ratio for more cartilage loss is 0.99 (95% CI 0.92-1.06) with 1 unit increase in pentosidine. Analysis 3: the relative number of plates with cartilage loss decreased was 1.00 (95% CI 0.95-1.03) with a 1 unit increase in pentosidine. CONCLUSION: Urinary pentosidine does not predict knee cartilage loss. Previous studies have suggested that local content within cartilage of AGEs is elevated in persons at high risk for progression. Our data suggest that these changes are not measurable systemically. Alternatively, urinary pentosidine levels reflect cartilage degradation in all joints (thus whole body cartilage breakdown) and may therefore not relate to OA severity in a single knee joint.

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PubMed2006

The ratio of medial to lateral tibial plateau bone mineral density and compartment-specific tibiofemoral osteoarthritis.

INTRODUCTION: Bone is thought to play an important role in osteoarthritis (OA) pathophysiology. Our aim was to look at specific features of OA and their relation to the ratio of medial:lateral tibial plateau bone mineral density (M:L BMD Ratio). METHODS: We examined our research question in the Framingham OA Study Cohort. All participants had BMDs and weight-bearing plain radiographs of the knees (2002-2005). M:L BMD Ratios were calculated using BMD from medial and lateral regions in the tibial plateau. Knee x-rays were read for osteophytes (OSTs), joint space narrowing (JSN), and sclerosis (Osteoarthritis Research Society International (OARSI) scoring system). Knees were classified as having medial and/or lateral JSN if they had JSN >or=1 in the medial and/or lateral tibiofemoral compartments, respectively. Medial and/or lateral OSTs were defined as medial and/or lateral tibial and/or femoral OSTs >or=2, respectively. Medial sclerosis and lateral sclerosis were defined as medial and lateral tibial sclerosis >or=1, respectively. We performed a logistic regression with medial JSN as the outcome and with M:L BMD Ratio groups as predictor variables, using the median group as the referent. Analyses were adjusted for age, sex, and body mass index (BMI). Generalized estimating equations were used to adjust for correlation between knees. Identical analyses were performed with medial OSTs, medial sclerosis, lateral JSN, lateral OSTs, and lateral sclerosis as the outcomes. RESULTS: Mean age of 1612 subjects (3048 knees) was 63.9 (Standard Deviation (SD)+/-8.9), 56% were women, and mean BMI was 28.5 (SD+/-5.5). M:L BMD Ratio was positively associated with medial JSN (P for linear trend <0.0001) and negatively associated with lateral JSN (P for linear trend <0.0001). The relations of the ratio with medial and lateral OSTs were j-shaped with P for quadratic trends <0.0001. There were also strong associations between M:L BMD Ratio and compartment-specific sclerosis (P for linear trends <0.0001) with most knees with medial and lateral sclerosis being in the highest and lowest M:L BMD Ratio groups, respectively. CONCLUSION: In summary, the extremes of the M:L BMD Ratio are strongly associated with individual radiographic features of OA. These findings add to existing evidence supporting the importance of understanding bone in OA pathophysiology.

Absorptiometry, Photon↗

PubMed2006

Examining a whole-organ magnetic resonance imaging scoring system for osteoarthritis of the knee using Rasch analysis.

OBJECTIVE: The ability to reliably quantify all the structural abnormalities in osteoarthritis (OA) of the knee is a long-standing goal of OA research. On December 5 and 6, 2002, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society, International held a Workshop for Consensus on Osteoarthritis Imaging in Bethesda, MD, with the aim of providing a state-of-the-art review of imaging outcome measures for OA of the knee. As part of the Workshop, data from previous clinical trials and epidemiological studies of OA were analysed with respect to the metrological properties of the measurement methods used. The following report outlines the results of analyses aimed at evaluating the internal construct validity of a whole-organ, ordinal (semi-quantitative) magnetic resonance imaging score (WORMS) using Rasch analysis. The fit of data to the Rasch model offers a measure of the validity of summing different items into a subscale score and the degree to which this score behaves as a unidimensional, interval level measurement tool. METHODS: The Rasch model was applied in two OA studies. The first was a clinical cohort comprising OA knee subjects entering a clinical trial; study entry criteria included patients with at least moderate pain, radiographic osteophytes and a minimum of 1.5mm tibiofemoral joint-space width. The second cohort was from the Boston Osteoarthritis Knee Study, an observational cohort of subjects with symptomatic knee OA with pain on most days and a definite osteophyte in either the tibiofemoral or patellofemoral joints. Baseline WORMS scores from both studies were used for the Rasch analysis, performed with RUMM 2020 software. RESULTS: There was a substantial proportion of subjects in both study populations with zero scores in several of the subscales of WORMS. Few of the subscales met the requirements of the Rasch measurement model when summated across all sites, and summations of some postulated compartmentally based sites also failed to fit the Rasch model. The existing scoring categories also required rescoring at many sites. CONCLUSION: There remain important issues in constructing outcome measurements that summate different features across multiple anatomical sites. The whole-organ scoring system evaluated here is no exception. Resolving these issues will improve the ability of imaging studies to assess complex pathological structural change.

Adult↗

PubMed2006

High signal in knee osteophytes is not associated with knee pain.

OBJECTIVE: Our understanding of the local source of pain in osteoarthritis (OA) remains unclear. We undertook this study to determine if the presence of high-signal osteophytes on magnetic resonance imaging (MRI) was associated with pain presence, location or severity. METHODS: Subjects were chosen from the Boston Osteoarthritis of the Knee Study, a natural history study of symptomatic knee OA. Assessments included knee MRI, pain assessments and information on weight and height. Osteophyte signal was defined as areas of increased signal intensity in the osteophyte on fat-suppressed T2 weighted images, and graded in the joint margins where osteophyte size is graded. All patients were evaluated with the frequent knee symptoms question for pain presence, the Western Ontario McMasters Osteoarthritis Index (WOMAC) for pain severity, and location of self-reported pain was recorded as present or absent based on locations identified on a standardized diagram. The osteophyte signal measures anywhere within one given knee were summed, creating an osteophyte signal aggregate. Logistic regression was conducted with quartile of osteophyte signal aggregate as the independent predictor and frequent knee symptom question as the dependent outcome. Association between quartile of osteophyte signal aggregate and pain severity on WOMAC was assessed using a linear regression. Logistic regression was used to evaluate the association between compartment-specific high-signal osteophytes aggregates (independent variable) and compartment-specific knee pain (dependent variable). Analyses were adjusted for gender, body mass index (BMI), and age. RESULTS: Two hundred and seventeen subjects were included in this analysis. They were predominantly male and 75% of subjects had radiographic tibio-femoral (TF) OA, and the remainder had patello-femoral (PF) radiographic OA. We did not find any association of high-signal osteophytes with presence of pain, pain severity or self-reported pain location. CONCLUSION: High-signal osteophytes detected on MRI are not associated with the presence of pain, pain severity or the self-reported location of pain.

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PubMed2006

Abdominal aortic calcification and exostoses at the hand and lumbar spine: the Framingham Study.

Bony proliferation (exostoses) and vascular calcification are common in elderly men and women, but it is unclear whether they have a common etiology. Lateral lumbar and hand radiographs were obtained (1967-1970) in 777 men and 1,241 women (mean age 59, range 47-80 years) from the Framingham Heart Study. Each group of hand exostoses, specifically apiostoses (tufting), enthesophytes, and osteophytes, was graded on a scale of 0-3 (absent to severe) and summed across phalanges of digits 2-5. Anterior lumbar osteophytes were assessed in intervertebral spaces T12-L5 and abdominal aortic calcification (AAC) at lumbar segments L1-L4. Information on age, sex, body mass index, smoking, alcohol consumption, physical activity, systolic blood pressure, total cholesterol level, diabetes, and estrogen replacement therapy in women was obtained at the time of radiography and adjusted for in multivariate analyses. We used multivariable logistic regression models to assess the relationship between AAC (dependent variable) and exostoses for each sex. Multivariable adjusted logistic regression revealed a significant association between increased anterior lumbar osteophytes and prevalent AAC in men [odds ratio (OR) = 1.20, 95% confidence interval (CI) 1.1-1.3 per unit increase in osteophytes] and in women (OR = 1.25, 95% CI 1.1-1.4). There also was an inverse association between enthesophytes and AAC in women only (OR = 0.82, 95% CI 0.73-0.92). Apiostoses were weakly associated with AAC in men only. Hand osteophytes were not associated with AAC. In conclusion, in this cross-sectional study, anterior lumbar osteophytes and AAC occurred in the same individuals after adjustment for age and other covariates. In general, hand exostoses were not associated with aortic calcification.

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PubMed2006

The association of meniscal pathologic changes with cartilage loss in symptomatic knee osteoarthritis.

OBJECTIVE: To explore the role of meniscal tears and meniscal malposition as risk factors for subsequent cartilage loss in subjects with symptomatic osteoarthritis (OA). METHODS: Study subjects were patients with symptomatic knee OA from the Boston Osteoarthritis of the Knee Study. Baseline assessments included knee magnetic resonance imaging (MRI) with followup MRI at 15 and 30 months. Cartilage and meniscal damage were scored on MRI in the medial and lateral tibiofemoral joints using the semiquantitative whole-organ magnetic resonance imaging score. Tibiofemoral cartilage was scored on MR images of all 5 plates of each tibiofemoral joint, and the meniscal position was measured using eFilm Workstation software. A proportional odds logistic regression model with generalized estimating equations was used to assess the effect of each predictor (meniscal position factor and meniscal damage as dichotomous predictors in each model) on cartilage loss in each of the 5 plates within a compartment. Models were adjusted for age, body mass index (BMI), tibial width, and sex. RESULTS: We assessed 257 subjects whose mean +/- SD age was 66.6 +/- 9.2 years and BMI was 31.5 +/- 5.7 kg/m2; 42% of subjects were female, and 77% of knees had a Kellgren/Lawrence radiographic severity grade > or = 2. In the medial tibiofemoral joint, each measure of meniscal malposition was associated with an increased risk of cartilage loss. There was also a strong association between meniscal damage and cartilage loss. Since meniscal coverage and meniscal height diminished with subluxation, less coverage and reduced height also increased the risk of cartilage loss. CONCLUSION: This study highlights the importance of an intact and functioning meniscus in patients with symptomatic knee OA, since the findings demonstrate that loss of this function has important consequences for cartilage loss.

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PubMed2006

Lack of association between chondrocalcinosis and increased risk of cartilage loss in knees with osteoarthritis: results of two prospective longitudinal magnetic resonance imaging studies.

OBJECTIVE: To evaluate the relationship between chondrocalcinosis and the progression of knee osteoarthritis (OA) using longitudinal magnetic resonance imaging (MRI) assessments. METHODS: Longitudinal knee MRIs were obtained in the Boston OA Knee Study (BOKS) and in the Health, Aging and Body Composition (Health ABC) Study. Chondrocalcinosis was determined as present or absent on baseline knee radiographs. Cartilage morphology was graded on paired longitudinal MRIs using the Whole-Organ Magnetic Resonance Imaging Score in 5 cartilage subregions of each of the medial and lateral tibiofemoral joints. Cartilage loss in a subregion was defined as an increase in the cartilage score of > or = 1 (0-4 scale). The risk for change in the number of subregions with cartilage loss was assessed using Poisson regression, with generalized estimating equations to account for correlations. Analyses were adjusted for age, sex, body mass index, baseline cartilage score, and presence of damaged menisci. RESULTS: In BOKS, 23 of the 265 included knees (9%) had chondrocalcinosis. In Health ABC, 373 knees were included, of which 69 knees (18.5%) had chondrocalcinosis. In BOKS, knees with chondrocalcinosis had a lower risk of cartilage loss compared with knees without chondrocalcinosis (adjusted risk ratio [RR] 0.4, 95% confidence interval [95% CI] 0.2-0.7) (P = 0.002), and there was no difference in risk in Health ABC (adjusted RR 0.9, 95% CI 0.6-1.5) (P = 0.7). Stratification by intact versus damaged menisci produced similar results within each cohort. CONCLUSION: In knees with OA, the presence of chondrocalcinosis was not associated with increased cartilage loss. These findings do not support the hypothesis that chondrocalcinosis worsens OA progression.

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PubMed2006

Change in joint space width: hyaline articular cartilage loss or alteration in meniscus?

OBJECTIVE: To explore the relative contribution of hyaline cartilage morphologic features and the meniscus to the radiographic joint space. METHODS: The Boston Osteoarthritis of the Knee Study is a natural history study of symptomatic knee osteoarthritis (OA). Baseline and 30-month followup assessments included knee magnetic resonance imaging (MRI) and fluoroscopically positioned weight-bearing knee radiographs. Cartilage and meniscal degeneration were scored on MRI in the medial and lateral tibiofemoral joints using a semiquantitative grading system. Meniscal position was measured to the nearest millimeter. The dependent variable was joint space narrowing (JSN) on the plain radiograph (possible range 0-3). The predictor variables were MRI cartilage score, meniscal degeneration, and meniscal position measures. We first conducted a cross-sectional analysis using multivariate regression to determine the relative contribution of meniscal factors and cartilage morphologic features to JSN, adjusting for body mass index (BMI), age, and sex. The same approach was used for change in JSN and change in predictor variables. RESULTS: We evaluated 264 study participants with knee OA (mean age 66.7 years, 59% men, mean BMI 31.4 kg/m(2)). The results from the models demonstrated that meniscal position and meniscal degeneration each contributed to prediction of JSN, in addition to the contribution by cartilage morphologic features. For change in medial joint space, both change in meniscal position and change in articular cartilage score contributed substantially to narrowing of the joint space. CONCLUSION: The meniscus (both its position and degeneration) accounts for a substantial proportion of the variance explained in JSN, and the change in meniscal position accounts for a substantial proportion of change in JSN.

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PubMed2005

Trapeziometacarpal subluxation predisposes to incident trapeziometacarpal osteoarthritis (OA): the Framingham Study.

OBJECTIVE: Osteoarthritis (OA) of the thumb carpo-metacarpal joint is a common condition that can lead to substantial pain, instability, deformity, and loss of motion. It has been hypothesized that instability of the trapeziometacarpal joint combined with strenuous use can potentially lead to OA. However, as yet there have been no longitudinal evaluations to determine if this hypothesis is true. We examined the relation of radial subluxation to the risk of radiographic OA at trapeziometacarpal joint. METHODS: We conducted a nested case-control study. We restricted our evaluation of cases to subjects with no radiographic trapeziometacarpal OA at baseline (1967). We defined incident trapeziometacarpal OA as the development of a modified Kellgren and Lawrence grade>or=2 in that joint at a later examination (1992-1993). Radial subluxation of the base of the first metacarpal off the trapezium and the amount of the base of the first metacarpal covering the articulating surface of the trapezium were measured using a digital calculation caliper. We examined the relation of gender-specific quartile groups of radial subluxation to the risk of trapeziometacarpal OA using a conditional logistic regression model. RESULTS: We assessed 203 men and 431 women. After adjusting for age, handedness, number of other joints with OA, and grip strength, the odds ratios for the risk of trapeziometacarpal OA in men were 1.0, 1.8, 2.7, and 3.1 from the lowest quartile of radial subluxation to the highest quartile, respectively (P for trend=0.015). There was no significant relationship between radial subluxation quartiles and incident trapeziometacarpal OA in women. CONCLUSION: This study provides evidence that radial subluxation predisposes to subsequent OA of the trapeziometacarpal joint in men.

Adult↗

PubMed2004

Osteophytes and progression of knee osteoarthritis.

OBJECTIVES: Osteophytes are thought to stabilize an osteoarthritic joint, thereby preventing structural progression. Meagre longitudinal data suggest, however, that they are associated with an increased risk of structural progression. Our objective was to evaluate the effect of osteophyte size on radiographic progression in osteoarthritis (OA). METHODS: Using data from a natural history study of persons with symptomatic knee OA, we obtained fluoroscopically positioned postero-anterior (PA) radiographs at baseline, 15 and 30 months. Using an atlas, osteophyte size was scored on a scale of 0-3 at each of four sites on the PA film and, for each knee, both compartment-specific (i.e. medial; lateral) and overall osteophyte scores were computed. Progression was defined as an increase over follow-up in medial or lateral joint space narrowing, based on a semiquantitative grading. Mechanical alignment was assessed using long limb films at the 15 month examination. Logistic regression was used to evaluate the relation of osteophyte size with progression, adjusting for age, gender and body mass index, and with and without adjustment for alignment. RESULTS: Of 270 subjects who had 470 eligible knees with follow-up, 104 (22%) knees showed progression. Overall, osteophyte score modestly increased the risk of progression [odds ratio (OR) per S.D. increase of osteophyte score=1.4 (95% CI 1.1, 1.8, P=0.02)], but this effect weakened and became non-significant after adjustment for limb alignment (OR=1.3). Compartment osteophyte score was strongly associated with malalignment to the side of the osteophyte (e.g. medial osteophyte and varus). Compartment-specific osteophyte score markedly increased the risk of ipsilateral progression (e.g. medial osteophytes --> medial progression) [OR per S.D.=1.9 (95% CI 1.5, 2.5, P<0.001)] and decreased the risk of contralateral progression [OR per S.D.= 0.6 (95% CI 0.5, 0.8, P=0.002)], but these associations diminished when we adjusted for limb alignment (OR=1.5 and 0.7 respectively). CONCLUSIONS: Large osteophytes do not affect the risk of structural progression. They are strongly associated with malalignment to the side of the osteophyte, and any relation they have with progression is partly explained by the association of malalignment with progression.

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PubMed2004

Patient preferences for treatment of rheumatoid arthritis.

OBJECTIVE: To elicit treatment preferences of patients with rheumatoid arthritis (RA) for disease modifying antirheumatic drugs (DMARDs) with varying risk profiles. METHODS: Patient values for 16 DMARD characteristics were ascertained using published data about side effects, effectiveness, and cost. Patient preferences were determined by Adaptive Conjoint Analysis, an interactive computer program that predicts preferences by asking patients to make trade-offs between specific treatment characteristics. Simulations were run to derive preferences for four drugs: methotrexate, gold, leflunomide, and etanercept, under different risk-benefit scenarios. Infliximab was not included because it is given with methotrexate, and we did not include preferences for combination therapy. Based on each patient's expressed preferences, and the characteristics of the treatments available at the time of the study, the option that best fitted each patient's perspective was identified. RESULTS: 120 patients (mean age 70 years) were interviewed. For the base case scenario (which assumed the maximum benefits reported in the literature, a low probability of adverse effects, and low equal monthly "co-pays" (out of pocket costs)), 95% of the respondents preferred etanercept over the other treatment options. When all four options were described as being equally effective, 88% continued to prefer etanercept owing to its safer short term adverse effect profile. Increasing etanercept's co-pay to $30.00 decreased the percentage of patients preferring this option to 80%. CONCLUSIONS: In this study, older patients with RA, when asked to consider trade-offs between specific risk and benefits, preferred etanercept over other treatment options. Preference for etanercept is explained by older patients' risk aversion for drug toxicity.

Adult↗

PubMed2004

Prevalence of foot and ankle conditions in a multiethnic community sample of older adults.

The prevalence of foot and ankle disorders was determined in a community-based, multiethnic (non-Hispanic White, African American, and Puerto Rican) random sample of 784 community-dwelling adults aged 65 or more years in 2001-2002 in Springfield, Massachusetts. Overall, the five most common conditions were toenail disorders (74.9%), lesser toe deformities (60.0%), corns and calluses (58.2%), bunions (37.1%), and signs of fungal infection, cracks/fissures, or maceration between toes (36.3%); 30.9% had some tenderness to palpation of the foot or ankle, and 14.9% had ankle joint pain on most days in the past 4 weeks. Toenail conditions, fungal symptoms, and ulcers or lacerations were more common in men, while bunions and corns and calluses were more common in women (p < 0.001). Significant racial/ethnic differences, independent of education or gender, were found for the prevalence of most toe deformities and flat feet, as well as for corns and calluses, fungal signs, edema, ankle joint pain, tenderness to palpation, and sensory loss. Foot and ankle disorders are common in these older adults. Examination of their prevalence in different segments of the community may inform future studies to determine etiology and means of prevention.

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PubMed2004

A genome scan for joint-specific hand osteoarthritis susceptibility: The Framingham Study.

OBJECTIVE: Studies investigating hand osteoarthritis (OA) as a single entity have not shown strong linkage of the disease with any chromosomal sites. We undertook this study to test our hypothesis that phenotypes of hand OA may show stronger linkage than has been shown for overall hand OA. METHODS: We performed a factor analysis on measures of hand OA to determine patterns of disease. Using the joint regions identified by this analysis, we performed a genome-wide linkage analysis for OA susceptibility loci using 426 original cohort members and 790 offspring cohort members in 267 pedigrees. Radiographic OA features evaluated included the Kellgren/Lawrence score, osteophytes, and joint space narrowing. Prior to linkage analysis, standardized residuals were computed from regression analysis of each phenotype on age. This was performed separately for each sex and cohort. The variance component model (GeneHunter) was then applied to the normalized scores of the residuals of both sexes and cohorts. RESULTS: There was evidence suggestive of linkage (logarithm of odds [LOD] score >1.5) at 16 sites. Four of these sites had LOD scores >3.0. Two of these sites (identified in the full sample) included a linkage region for OA of the distal interphalangeal (DIP) joint on chromosome 7 (155 cM; LOD score 3.06) and a linkage region for OA of the first carpometacarpal (CMC) joint on chromosome 15 (81 cM; LOD score 6.25). The other 2 sites (identified in women) included a linkage region for OA of the DIP joint on chromosome 1 (202 cM; LOD score 3.03) and a linkage region for OA of the first CMC joint on chromosome 20 (4 cM; LOD score 3.74). CONCLUSION: These data suggest that several chromosomes contain hand OA susceptibility genes and that a joint-specific approach may be more rewarding than a global approach to the genetics of hand OA. Further investigation of these regions is warranted using finer maps and other populations.

Chromosome Mapping↗

PubMed2003

Symmetry and clustering of symptomatic hand osteoarthritis in elderly men and women: the Framingham Study.

OBJECTIVE: While symmetry and clustering of radiographic hand osteoarthritis (OA) have been described in middle-aged women, these have not been studied in elderly individuals and similar investigations are lacking for symptomatic hand OA. The goal of this study was to study patterns of joint involvement in symptomatic hand OA among elderly Caucasian men and women. METHODS: Using data from the Framingham Osteoarthritis Study, we defined a joint as having symptomatic OA if it had symptoms and radiographic OA (Kellgren and Lawrence grade > or =2). We assessed clustering of symptomatic OA using a chi(2)-test and evaluated the interrelationship of occurrence of symptomatic OA among different joints with generalized estimating equations. RESULTS: Of 976 subjects (age 71-99 yr, 36% men) examined, symptomatic OA more often affected multiple hand joints in an individual than would be expected by chance (P<0.001). The presence of symptomatic OA at a particular joint was strongly associated with symptomatic OA in the same joint of the opposite hand, followed by other joints in the same row of the same hand, and then other joints in the same ray of the same hand. The symmetrical pattern of symptomatic OA was more apparent in women than in men. CONCLUSION: Our study demonstrates that symptomatic OA often affects multiple hand joints, and is more likely to cluster by row than by ray. The disease also occurs in a remarkably symmetrical pattern, especially in women.

Age Distribution↗

PubMed2002

Genome scan for quantity of hand osteoarthritis: the Framingham Study.

OBJECTIVE: To search for markers linked to quantity of radiographic hand osteoarthritis (OA) in the Framingham Heart Study. METHODS: The sample included 684 original cohort members and 793 offspring in 296 pedigrees. Radiographic OA features evaluated included the Kellgren/Lawrence (K/L) score, osteophytes, and joint space narrowing (0-3 scale). Four quantitative phenotypes were computed from these measurements: sum of K/L scores across hand joints, sum of osteophyte scores, sum of joint space narrowing scores, and proportion of affected joints. Prior to linkage analysis, these phenotypes were adjusted for age using a linear regression analysis from which standardized residuals were computed. The regression analysis was performed separately for each sex and each generation. The variance component model (SOLAR) was then applied to the normalized scores of the residuals. RESULTS: The average age was 62 years for the original cohort and 54 years for the offspring. Fifty percent of the original cohort and 30% of their offspring had at least 1 affected joint (K/L score >or=2). Heritability ranged from 28% (proportion of joints affected with OA) to 34% (sum of K/L scores). Eight chromosomal regions indicated suggestive linkage (multipoint logarithm of odds [LOD] score >1.5) for at least 1 phenotype; LOD scores were highest for joint space narrowing, with a multipoint LOD score = 2.96 on chromosome 1p at D1S1665. Chromosomes 7, 9, 13, and 19 indicated consistent LOD score elevation for multiple OA phenotypes. CONCLUSION: There are several chromosomes that may harbor OA susceptibility genes. Further investigation of these regions using larger studies and finer maps will be important to confirm linkage.

Adult↗

PubMed2001

Bone mineral density and verbal memory impairment: Third National Health and Nutrition Examination Survey.

Previous studies have examined the relation of endogenous estrogen levels or estrogen replacement therapy to the risk of poor cognitive function, but results have been inconclusive. Bone mineral density has been proposed as a marker for cumulative estrogen exposure. The authors studied the relation of bone mineral density to the prevalence of verbal memory impairment among 4,304 elderly subjects in the Third National Health and Nutrition Examination Survey (1988-1994). Bone mineral density was measured in five regions of the proximal femur with dual-energy x-ray absorptiometry. Verbal memory was assessed using delayed recall of a three-item word list and a six-item story. Verbal memory impairment was defined as a combined score of <4. The prevalence of verbal memory impairment for each increasing bone mineral density quintile at the femoral neck was 8.35, 5.74, 5.22, 5.00, and 3.38% in women and 11.54, 7.27, 8.47, 6.29, and 5.89% in men, respectively. With adjustment for age, sex, and other covariates, the prevalence ratios of verbal memory impairment for each increased bone mineral density quintile were 1.00, 0.64, 0.65, 0.55, and 0.44, respectively (p for trend < 0.001). These results suggest that bone mineral density in the elderly is associated with verbal memory impairment. The mechanisms underlying this relation are not understood, but cumulative exposure to estrogen may play a role.

Absorptiometry, Photon↗

PubMed2001

The role of knee alignment in disease progression and functional decline in knee osteoarthritis.

CONTEXT: Knee osteoarthritis (OA) is a leading cause of disability in older persons. Few risk factors for disease progression or functional decline have been identified. Hip-knee-ankle alignment influences load distribution at the knee; varus and valgus alignment increase medial and lateral load, respectively. OBJECTIVE: To test the hypotheses that (1) varus alignment increases risk of medial knee OA progression during the subsequent 18 months, (2) valgus alignment increases risk of subsequent lateral knee OA progression, (3) greater severity of malalignment is associated with greater subsequent loss of joint space, and (4) greater burden of malalignment is associated with greater subsequent decline in physical function. DESIGN AND SETTING: Prospective longitudinal cohort study conducted March 1997 to March 2000 at an academic medical center in Chicago, Ill. PARTICIPANTS: A total of 237 persons recruited from the community with primary knee OA, defined by presence of definite tibiofemoral osteophytes and at least some difficulty with knee-requiring activity; 230 (97%) completed the study. MAIN OUTCOME MEASURES: Progression of OA, defined as a 1-grade increase in severity of joint space narrowing on semiflexed, fluoroscopically confirmed knee radiographs; change in narrowest joint space width; and change in physical function between baseline and 18 months, compared by knee alignment at baseline. RESULTS: Varus alignment at baseline was associated with a 4-fold increase in the odds of medial progression, adjusting for age, sex, and body mass index (adjusted odds ratio [OR], 4.09; 95% confidence interval [CI], 2.20-7.62). Valgus alignment at baseline was associated with a nearly 5-fold increase in the odds of lateral progression (adjusted OR, 4.89; 95% CI, 2.13-11.20). Severity of varus correlated with greater medial joint space loss during the subsequent 18 months (R = 0.52; 95% CI, 0.40-0.62 in dominant knees), and severity of valgus correlated with greater subsequent lateral joint space loss (R = 0.35; 95% CI, 0.21-0.47 in dominant knees). Having alignment of more than 5 degrees (in either direction) in both knees at baseline was associated with significantly greater functional deterioration during the 18 months than having alignment of 5 degrees or less in both knees, after adjusting for age, sex, body mass index, and pain. CONCLUSION: This is, to our knowledge, the first demonstration that in primary knee OA varus alignment increases risk of medial OA progression, that valgus alignment increases risk of lateral OA progression, that burden of malalignment predicts decline in physical function, and that these effects can be detected after as little as 18 months of observation.

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