David T. Felson

Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II.

OBJECTIVE To provide a single source for the best available estimates of the US prevalence of and number of individuals affected by osteoarthritis, polymyalgia rheumatica and giant cell arteritis, gout, fibromyalgia, and carpal tunnel syndrome, as well as the symptoms of neck and back pain. A companion article (part I) addresses additional conditions. METHODS The National Arthritis Data Workgroup reviewed published analyses from available national surveys, such as the National Health and Nutrition Examination Survey and the National Health Interview Survey. Because data based on national population samples are unavailable for most specific rheumatic conditions, we derived estimates from published studies of smaller, defined populations. For specific conditions, the best available prevalence estimates were applied to the corresponding 2005 US population estimates from the Census Bureau, to estimate the number affected with each condition. RESULTS We estimated that among US adults, nearly 27 million have clinical osteoarthritis (up from the estimate of 21 million for 1995), 711,000 have polymyalgia rheumatica, 228,000 have giant cell arteritis, up to 3.0 million have had self-reported gout in the past year (up from the estimate of 2.1 million for 1995), 5.0 million have fibromyalgia, 4-10 million have carpal tunnel syndrome, 59 million have had low back pain in the past 3 months, and 30.1 million have had neck pain in the past 3 months. CONCLUSION Estimates for many specific rheumatic conditions rely on a few, small studies of uncertain generalizability to the US population. This report provides the best available prevalence estimates for the US, but for most specific conditions more studies generalizable to the US or addressing understudied populations are needed.

Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States

OBJECTIVE To provide a single source for the best available estimates of the national prevalence of arthritis in general and of selected musculoskeletal disorders (osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, the spondylarthropathies, systemic lupus erythematosus, scleroderma, polymyalgia rheumatica/giant cell arteritis, gout, fibromyalgia, and low back pain). METHODS The National Arthritis Data Workgroup reviewed data from available surveys, such as the National Health and Nutrition Examination Survey series. For overall national estimates, we used surveys based on representative samples. Because data based on national population samples are unavailable for most specific musculoskeletal conditions, we derived data from various smaller survey samples from defined populations. Prevalence estimates from these surveys were linked to 1990 US Bureau of the Census population data to calculate national estimates. We also estimated the expected frequency of arthritis in the year 2020. RESULTS Current national estimates are provided, with important caveats regarding their interpretation, for self-reported arthritis and selected conditions. An estimated 15% (40 million) of Americans had some form of arthritis in 1995. By the year 2020, an estimated 18.2% (59.4 million) will be affected. CONCLUSION Given the limitations of the data on which they are based, this report provides the best available prevalence estimates for arthritis and other rheumatic conditions overall, and for selected musculoskeletal disorders, in the US population.

2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative

Objective The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease—this being the appropriate current paradigm underlying the disease construct ‘RA’. Results In the new criteria set, classification as ‘definite RA’ is based on the confirmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). Conclusion This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct ‘RA’.

The effects of specific medical conditions on the functional limitations of elders in the Framingham Study.

OBJECTIVES The purpose of this study was to identify associations between specific medical conditions in the elderly and limitations in functional tasks; to compare risks of disability across medical conditions, controlling for age, sex, and comorbidity; and to determine the proportion of disability attributable to each condition. METHODS The subjects were 709 noninstitutionalized men and 1060 women of the Framingham Study cohort (mean age 73.7 +/- 6.3 years). Ten medical conditions were identified for study: knee osteoarthritis, hip fracture, diabetes, stroke, heart disease, intermittent claudication, congestive heart failure, chronic obstructive pulmonary disease, depressive symptomatology, and cognitive impairment. Adjusted odds ratios were calculated for dependence on human assistance in seven functional activities. RESULTS Stroke was significantly associated with functional limitations in all seven tasks; depressive symptomatology and hip fracture were associated with limitations in five tasks; and knee osteoarthritis, heart disease, congestive heart failure, and chronic obstructive pulmonary disease, were associated with limitations in four tasks each. CONCLUSIONS In general, stroke, depressive symptomatology, hip fracture, knee osteoarthritis, and heart disease account for more physical disability in noninstitutionalized elderly men and women than other diseases.

Obesity and Knee Osteoarthritis: The Framingham Study

STUDY OBJECTIVE To determine whether obesity preceded knee osteoarthritis and was thus a possible cause. DESIGN Cohort study with weight and other important variables measured in 1948 to 1951 (mean age of subjects, 37 years) and knee arthritis evaluated in 1983 to 1985 (mean age of subjects, 73 years). SETTING Population-based participants; a subset (n = 1420) of the Framingham Heart Study cohort. METHODS For those subjects in the Framingham Study having knee radiographs taken as part of the 18th biennial examination (1983 to 1985), we examined Metropolitan Relative Weight, a measure of weight adjusted for height at the onset of the study (1948 to 1951). Relative risks were computed as the cumulative incidence rate of radiographic knee osteoarthritis in the heaviest weight groups at examination 1 divided by the cumulative rate in the lightest 60% weight groups at examination 1. Relative risks were adjusted for age, physical activity level, and uric acid level. RESULTS In 1983 to 1985, 468 subjects (33%) had radiographic knee osteoarthritis. For men, the risk of knee osteoarthritis was increased in those in the heaviest quintile of weight at examination 1 compared with those in the lightest three quintiles (age-adjusted relative risk, 1.51; 95% confidence interval [CI], 1.14 to 1.98); risk was not increased for those in the second heaviest quintile (relative risk, 1.0). The association between weight and knee osteoarthritis was stronger in women than in men; for women in the most overweight quintile at examination 1, relative risk was 2.07 (95% CI, 1.67 to 2.55), and for those in the second heaviest group, relative risk was 1.44 (95% CI, 1.11 to 1.86). This link between obesity and subsequent osteoarthritis persisted after controlling for serum uric acid level and physical activity level, and was strongest for persons with severest radiographic disease. Obesity at examination 1 was associated with the risk of developing both symptomatic and asymptomatic osteoarthritis. CONCLUSIONS These results and other corroborative cross-sectional data show that obesity or as yet unknown factors associated with obesity cause knee osteoarthritis.

Weight Loss Reduces the Risk for Symptomatic Knee Osteoarthritis in Women: The Framingham Study

OBJECTIVE To evaluate the effect of weight loss in preventing symptomatic knee osteoarthritis in women. DESIGN Cohort analytic study. SETTING The Framingham Study, based on a sample of a defined population. PATIENTS Women who participated in the Framingham Knee Osteoarthritis Study (1983 to 1985): Sixty-four out of 796 women studied had recent-onset symptomatic knee osteoarthritis (knee symptoms plus radiographically confirmed osteoarthritis) were compared with women without disease. MEASUREMENTS Recalled date of symptom onset was used as the incident date of disease. Historical weight was defined as baseline body mass index up to 12 years before symptom onset. Change in body mass index was assessed at several intervals before the current examination. Odds ratios assessing the association between weight change and knee osteoarthritis were adjusted for age, baseline body mass index, history of previous knee injury, habitual physical activity level, occupational physical labor, smoking status, and attained education. RESULTS Weight change significantly affected the risk for the development of knee osteoarthritis. For example, a decrease in body mass index of 2 units or more (weight loss, approximately 5,1 kg) over the 10 years before the current examination decreased the odds for developing osteoarthritis by over 50% (odds ratio, 0.46; 95% Cl, 0.24 to 0.86; P = 0.02). Among those women with a high risk for osteoarthritis due to elevated baseline body mass index (greater than or equal to 25), weight loss also decreased the risk (for 2 units of body mass index, odds ratio, 0.41; P = 0.02). Weight gain was associated with a slightly increased risk for osteoarthritis, which was not statistically significant. CONCLUSION Weight loss reduces the risk for symptomatic knee osteoarthritis in women.

The association of bone marrow lesions with pain in knee osteoarthritis.

Knee osteoarthritis affects 11% to 15% of the U.S. population 65 years of age or older (1) and is a leading cause of disability in the elderly. The major source of disability and care seeking for patients with osteoarthritis is pain in the knee (2). The cause of knee pain in patients with osteoarthritis is unclear. Osteoarthritis has been considered a disease whose characteristic pathologic feature is loss of hyaline articular cartilage, but that tissue contains no pain fibers. Pain fibers are present in several other structures, however, that are often affected by pathologic processes in knee osteoarthritis, including the joint capsule, ligaments in and around the knee joint, the outer third of the meniscus, and possibly the synovium (although for this last tissue, evidence is conflicting [3, 4]). In addition, bone in the periosteum and bone marrow is richly innervated with nociceptive fibers and represents a potential source of pain in patients with knee osteoarthritis. In athletes and younger adults who do not have osteoarthritis, traumatic knee injuries produce high-signal lesions in the medullary space extending to subcortical bone according to T2-weighted magnetic resonance imaging (MRI). These lesions are thought to represent contusions within the bone marrow and have been correlated with the occurrence of pain in athletes (5). Bone marrow lesions that are similar in appearance to those contusions have been noted (6) in patients with knee osteoarthritis, but their association with the occurrence of pain in this disease is unknown. The treatment of pain in osteoarthritis has been frustrating, in part because the target of therapy is unclear. Creamer and colleagues (7) injected intra-articular anesthetic into joints and found that only 6 of 10 persons with painful osteoarthritis had pain relief. This suggests that in some patients, pain originates from extraarticular, noncapsular sources, one of the most likely of which is bone. If pain in some patients does emanate from bone, this finding would have important therapeutic implications and suggests that for these patients, anti-inflammatory treatments targeted at synovitis or intra-articular drainage to relieve capsular distention would be ineffective. We sought to evaluate whether persons with knee pain and osteoarthritis were more often affected by bone marrow lesions than similarly aged persons without knee pain, many of whom also had radiographic knee osteoarthritis. We tested whether pain in the knee was associated with the presence of bone marrow lesions after adjustment for the severity of radiographic osteoarthritis. In addition, among persons with symptomatic knee osteoarthritis, we evaluated whether the severity of their pain was associated with the presence of these lesions. Methods Patient Selection The minimum age for entry into the study was 45 years for men and 50 years for women. The entry age for women was chosen to lessen the chance of inadvertently obtaining radiographs in pregnant women. Male participants were drawn from the Veterans Health Study (VHS), a prospective observational study of health outcomes in 2425 veterans (8). Participants in the VHS were recruited from all men receiving ambulatory care between August 1993 and March 1996 at four Veterans Administration system facilities in the Boston area. Veterans who indicated that they could not read, were identified as unable to answer questions by an accompanying proxy, were disoriented, or did not complete the screening questionnaire were ineligible. A random sample of eligible respondents was contacted by telephone and recruited for the VHS. Of the 4137 patients who were telephoned, 2425 (59%) participated in the VHS. Participant age ranged from 22 to 91 years (mean, 62.4 years). The VHS was designed to be representative of users of ambulatory care in the Veterans Administration system. Compared with all utilizers of the Veterans Administration health care system, the sample underrepresented patients with less education or limitations in literacy or cognitive functioning. Patients in the VHS had lower functional status scores on the physical and mental health components of the Short Form-36 survey (a measure of health status) and had more comorbid conditions (8) than do men 45 years of age or older in the general U.S. population. Male participants were also drawn separately from Veteran Affairs clinics and from the community. Female participants were drawn from clinics at Boston Medical Center and the Veterans Affairs Medical Center; from advertisements in local newspapers; and from a study of women veterans, the Veterans Administration Womens Health Project (n = 719), that was designed to describe the health status of female veterans using ambulatory health care services. The human studies committee and the institutional review board approved protocols. Informed consent was obtained from all participants. All participants were surveyed about knee symptoms. They were asked two questions: Do you have pain, aching, or stiffness in one or both knees on most days? and Has a doctor ever told you that you have knee arthritis? For persons interested in participating in our study of knee pain and osteoarthritis, we conducted a follow-up interview in which those who answered yes to both questions were asked about other types of arthritis that could cause knee symptoms. If no other forms of arthritis were identified in the interview, the person was eligible for recruitment as a participant with knee pain (which we characterize here as knee symptoms). Figure 1 is a flow diagram of the source of participants. Of our male participants, 151 came from the Veterans Health Study, 76 came from Veterans Administration ambulatory clinics, and 8 came from the community. Of our female participants, 18 came from the Veterans Administration Womens Health Project, 9 came from ambulatory clinics, and 89 came from the community. Figure 1. Sources of study participants. We recruited participants from the VHS and the Veterans Administration Womens Health Project without knee pain from among those who answered no to both of the above screening questions (Figure 1). We also asked participants to evaluate the severity of pain in each knee, which they scored by using a 100-mm visual analogue scale (generating a score of 0 [no pain] to 100 [most severe pain possible]). Participants also filled out the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) questionnaire (9), a validated instrument that assesses knee pain and disability during various activities; we analyzed their WOMAC pain subscale score. Radiographic Evaluation All participants underwent weight-bearing posteroanterior radiography by using the protocol of Buckland-Wright (10 and weight-bearing skyline [9] and weight-bearing lateral radiography (11). For the posteroanterior view, the knee was positioned and radiographed under fluoroscopy so that the anterior and posterior medial tibial plateaus were superimposed; this was done to optimize measurement of joint space. Radiographs were read for the presence of definite osteophytes and other features by one radiologist using an atlas. If a definite osteophyte was present in a knee (including the patella) on any one of the three views, the knee was characterized as having osteoarthritis regardless of whether the participant experienced symptoms. This definition of radiographic disease has been recommended by other investigators (22). On the basis of responses to the screening questions, we defined a knee as symptomatic if the participant stated that he or she had pain or aching in that knee on most days. This definition of symptomatic osteoarthritis meets American College of Rheumatology criteria (12). We identified too few symptomatic persons without a radiographic osteophyte to include them as a separate study group (n = 4) and therefore excluded them; we also excluded 16 participants without knee pain whose radiographs showed no osteophytes. Kellgren and Lawrence grades have been developed for the anteroposterior (posteroanterior) view. We therefore assigned Kellgren and Lawrence grades (0 to 4) on this view only. In addition, we read posteroanterior, skyline, and lateral radiographic views and scored them for individual radiographic featuresosteophytes (scale of 0 to 3), joint space narrowing (scale of 0 to 3), cysts (scale of 0 to 1), and sclerosis (scale of 0 to 3)by using the Framingham Osteoarthritis Study atlas (13). The reproducibility of readings of these features and of the Kellgren and Lawrence scale is reported elsewhere (14). Magnetic Resonance Imaging Each person with knee pain underwent MRI of the more symptomatic knee. For persons without knee pain, the dominant knee was selected for imaging. All studies were performed on a General Electric Signa 1.5-Tesla MRI system (GE Medical Systems, Milwaukee, Wisconsin) using a phased-array knee coil. A positioning device for the ankle and knee was used to ensure uniformity between patients. Coronal, sagittal, and axial images were obtained in each participant. Coronal spin-echo fat-saturated proton-density and T2-weighted fat-saturated images (repetition time, 2200 ms; echo time, 20/80 ms) with a slice thickness of 3 mm, a 1-mm interslice gap, 1 excitation, a field of view of 11 to 12 cm, and a matrix of 256 128 pixels were obtained. To evaluate bone marrow lesions on MRI, we used coronal spin-echo T2-weighted fat-saturated images. Each femur and tibia was divided into medial, central, and lateral quadrants, resulting in six potential sites of lesions in each knee. We defined bone marrow lesions as discrete areas of increased signal adjacent to the subcortical bone in either the femur or the tibia, and we scored each bone marrow lesion from 0 to 3 on the basis of lesion size (Figure 2). Lesions with a score of at least 1 were considered definite bone marrow lesions, and lesions with a score of at least 2 were considered larg

Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study.

BACKGROUND Dermatomyositis and polymyositis are associated with cancer, but previous nationwide studies have not had sufficient cases to test the association between myositis and specific cancer types. Our aim was to investigate the risk of specific cancer types in individuals with dermatomyositis and polymyositis. METHODS We did a pooled analysis of published national data from Sweden, Denmark, and Finland. All patients with dermatomyositis and polymyositis (> or =15 years old) were identified by discharge diagnosis from the Swedish National Board of Health (1964-83), Danish Hospital Discharge Registry (1977-89), and Finnish National Board of Health (1969-85). Personal details were matched to national cancer registries, to identify all cases of cancer up to 1987 in Sweden, 1995 in Denmark, and 1997 in Finland, and to national death registries for the same periods. We calculated standardised incidence ratios (SIR) for individual cancer sites for dermatomyositis and polymyositis separately, using national cancer rates by country, sex, age, and date. FINDINGS We identified 618 cases of dermatomyositis, of whom 198 had cancer. 115 of the 198 developed cancer after diagnosis of dermatomyositis. This disease was strongly associated with malignant disease (SIR 3.0, 95% CI 2.5-3.6), particularly ovarian (10.5, 6.1-18.1), lung (5.9, 3.7-9.2), pancreatic (3.8, 1.6-9.0), stomach (3.5, 1.7-7.3), and colorectal (2.5, 1.4-4.4) cancers, and non-Hodgkin lymphoma (3.6, 1.2-11.1). 137 of the 914 cases of polymyositis had cancer, which developed after diagnosis of polymyositis in 95. Polymyositis was associated with a raised risk of non-Hodgkin lymphoma (3.7, 1.7-8.2), and lung (2.8, 1.8-4.4) and bladder cancers (2.4, 1.3-4.7). In both dermatomyositis and polymyositis, risk of malignant disease was highest at time of myositis diagnosis. INTERPRETATION Our results provide evidence that dermatomyositis is strongly associated with a wide range of cancers. The overall risk of malignant disease is also modestly increased among patients with polymyositis, with an excess for some cancers.

American College of Rheumatology/European League Against Rheumatism Provisional Definition of Remission in Rheumatoid Arthritis for Clinical Trials

OBJECTIVE Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a definition. METHODS A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecified analyses from RA clinical trials. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to define remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate definitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analyzed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes. RESULTS Survey results for the definition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (e.g., tender and swollen joint counts, C-reactive protein [CRP] level, and global assessments on a 0-10 scale). Analyses suggested the need to include a patient-reported measure. Examination of 2-year followup data suggested that many candidate definitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score-based measures of remission did not predict good radiographic outcomes as well as the other candidate definitions did. Given these and other considerations, we propose that a patients RA can be defined as being in remission based on one of two definitions: (a) when scores on the tender joint count, swollen joint count, CRP (in mg/dl), and patient global assessment (0-10 scale) are all ≤ 1, or (b) when the score on the Simplified Disease Activity Index is ≤ 3.3. CONCLUSION We propose two new definitions of remission, both of which can be uniformly applied and widely used in RA clinical trials. We recommend that one of these be selected as an outcome measure in each trial and that the results on both be reported for each trial.

Hip fracture and the use of estrogens in postmenopausal women. The Framingham Study.

Abstract To assess the effect of postmenopausal use of estrogens on the subsequent risk of hip fracture, we performed a retrospective cohort study of 2873 women in the Framingham Heart Study. Information obtained at routine biennial examinations about the use of estrogens, body weight, age at menopause, smoking, and alcohol consumption was used to evaluate the risk of hip fracture among postmenopausal women who received estrogens. Hip fractures occurred in 179 postmenopausal women, at a rate that increased exponentially after the age of 50. The risk of fracture was inversely related to weight at all ages. The relative risk of hip fracture in subjects who had taken estrogens at any time was 0.65 after adjustment for age and weight (95 percent confidence interval, 0.44 to 0.98). The adjusted relative risk in women who had taken estrogens within the previous two years was further reduced, to 0.34 (95 percent confidence interval, 0.12 to 0.98). Taking estrogens within four years of menopause also protected ag...