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PubMed2000

Linkage analysis of candidate genes as susceptibility loci for osteoarthritis-suggestive linkage of COL9A1 to female hip osteoarthritis.

OBJECTIVE: To examine 11 candidate genes as susceptibility loci for osteoarthritis (OA). METHODS: A total of 481 families have been ascertained in which at least two siblings have had joint replacement surgery of the hip, or knee, or hip and knee for idiopathic OA. Each candidate gene was targeted using one or more intragenic or closely linked microsatellite marker. The linkage data were analysed unstratified and following stratification by sex and by joint replaced (hip or knee). RESULTS: The analyses revealed suggestive linkage of the type IX collagen gene COL9A1 (6q12-q13) to a subset of 132 families that contained affected females who were concordant for hip OA (female-hip) with a P-value of 0.00053 and logarithm of the odds (LOD) score of 2.33 [corrected P-value of 0. 0016, corrected LOD score of 1.85]. CONCLUSIONS: COL9A1 may therefore be a susceptibility locus for female hip OA. In addition, there was weak evidence of linkage to HLA/COL11A2 (6p21.3) in female hip OA with a corrected P-value of 0.016.

Arthroplasty, Replacement↗
PubMed2004

The IPSO study: ibuprofen, paracetamol study in osteoarthritis. A randomised comparative clinical study comparing the efficacy and safety of ibuprofen and paracetamol analgesic treatment of osteoarthritis of the knee or hip.

OBJECTIVE: To compare the analgesic efficacy of single and multiple doses of ibuprofen with that of paracetamol in patients with knee or hip osteoarthritis (IPSO study). METHOD: 222 patients were randomised in a double blind, multicentre study-156 (70%) had a painful knee joint and 66 (30%) a painful hip joint. The main efficacy criterion was pain intensity assessment after a single dose (ibuprofen 400 mg, paracetamol 1000 mg). Functional disability assessment and patient global assessment were carried out over 14 days. RESULTS: The sum of the pain intensity difference over 6 hours after the first administration was significantly higher (p = 0.046) in the ibuprofen group than in the paracetamol group. Over 14 days pain intensity decreased from the first day and was significantly lower in the ibuprofen group than in the paracetamol group (p<0.05). The functional disability of the patient was assessed using the WOMAC; the ibuprofen group improved significantly over 2 weeks compared with the paracetamol group for each of the subscales: stiffness (p<0.002), pain (p<0.001), physical function (p<0.002). The drugs were equally safe. CONCLUSION: The IPSO study shows that for the treatment of osteoarthritic pain, ibuprofen 400 mg at a single and multiple dose (1200 mg/day) for 14 days is more effective than paracetamol, either as a single dose of 1000 mg or a multiple dose (3000 mg/day). Because ibuprofen and paracetamol have similar tolerability, this study indicates that the efficacy/tolerability ratio of ibuprofen is better than that of paracetamol in this indication over 14 days.

Acetaminophen↗
PubMed1997

Genetic influences in end-stage osteoarthritis. Sibling risks of hip and knee replacement for idiopathic osteoarthritis.

From a prospective, cross-sectional survey of 402 patients who had a total hip (THR) or a total knee (TKR) replacement for idiopathic osteoarthritis (OA) at a major centre, we determined the prevalence of these replacements for idiopathic OA in their 1171 siblings and 376 spouses. Using spouses as controls, the relative risk of THR in siblings was 1.86 (95% CI 0.93 to 3.69). The relative risk for TKR in siblings v spouses was 4.8 (95 % CI 0.64 to 36.4) whereas the risk for the combined outcome measure of THR or TKR was 2.32 (95% CI 1.22 to 4.43) when siblings and spouses over 64 years of age were compared. Using a threshold liability model (Falconer), the heritability of end-stage OA of the hip was estimated at 27%. The increased risks of joint replacement for severe, idiopathic OA which we found in siblings suggest that genetic influences are important in end-stage OA of the hip and knee.

Adult↗
PubMed2001

Responsiveness of the WOMAC osteoarthritis index as compared with the SF-36 in patients with osteoarthritis of the legs undergoing a comprehensive rehabilitation intervention.

OBJECTIVE: To compare the responsiveness of the condition-specific Western Ontario and McMaster Universities osteoarthritis (OA) index (WOMAC) and the generic Short Form-36 (SF-36) in patients with OA of the legs undergoing a comprehensive inpatient rehabilitation intervention. METHODS: A prospective follow up study of consecutively referred inpatients of a rehabilitation clinic was made. The patients included fulfilled the American College of Rheumatology criteria for knee or hip OA and underwent both passive and, particularly, active physical therapy for three to four weeks. Responsiveness assessment was performed using the standardised response mean (SRM), effect size, and Guyatt's responsiveness statistic between admission and discharge (end of rehabilitation) and then again between admission and three months later. For pain and function the SRMs were stratified by sex and OA joint. Effects were tested by the t test and SRMs of different scales were compared by the jack knife test. RESULTS: At the three month follow up, complete data were obtained for 223 patients. In general, the three responsiveness statistics showed a similar order of responsiveness. For both instruments, the pain scales were more responsive than the function scales. The responsiveness of the pain scale of both instruments was comparable (SRM=0.723 for WOMAC and SRM=0.528 for SF-36 at the end of rehabilitation; SRM=0.377 for WOMAC and SRM=0.468 for SF-36 at the three month follow up). In the measurement of function, the WOMAC was significantly more responsive than the SF-36 (SRMs, end of rehabilitation: 0.628 v 0.249; three month follow up: 0.235 v -0.001). Responsiveness tended to be higher in women and in knee OA than in men and hip OA. CONCLUSIONS: Both instruments, the WOMAC and the SF-36, capture improvement in pain in patients undergoing comprehensive inpatient rehabilitation intervention. Functional improvement can be detected better by the WOMAC than by the SF-36. All the other scales of both instruments were more weakly responsive.

Adult↗
PubMed1998

Diclofenac/misoprostol compared with diclofenac in the treatment of osteoarthritis of the knee or hip: a randomized, placebo controlled trial. Arthrotec Osteoarthritis Study Group.

OBJECTIVE: Gastric (GU) and duodenal ulcers (DU) are common adverse effects of nonsteroidal anti-inflammatory drugs (NSAID). Endoscopically diagnosed upper gastrointestinal (GI) ulceration occurs in about 24% of longterm NSAID users. Coadministration of misoprostol with the NSAID reduces the incidence of NSAID induced GU and DU and their complications. However, compliance is limited by the different dosing regimens of misoprostol and NSAID and GI symptoms associated with misoprostol at its recommended q.i.d. dose. We compared the efficacy, safety, and incidence of endoscopic upper GI ulceration associated with the administration of 2 combinations of diclofenac (50 or 75 mg) and misoprostol 200 microg (D50/M200 t.i.d., D75/M200 b.i.d.), diclofenac 75 mg b.i.d., and placebo in a 6 week, randomized, double blind study in patients with osteoarthritis (OA) of the knee or hip. METHODS: A total of 572 patients with symptomatic OA of the knee or hip and history of GU, DU. or 10 or more erosions were randomized to receive D50/M200 t.i.d., D75/M200 b.i.d., diclofenac 75 mg b.i.d., or placebo for 6 weeks. Arthritis assessments were performed at baseline, 2, and 6 weeks, and upper GI endoscopies at baseline and end of treatment. RESULTS: All active treatment groups were significantly better than placebo, at all visits, in improving OA symptoms. There were no significant differences in arthritis efficacy between the diclofenac/ misoprostol combinations and diclofenac. However, endoscopically diagnosed GU and/or DU were significantly less frequent in patients receiving D50/M200 t.i.d. (8%), D75/M200 b.i.d. (7%), and placebo (4%) compared to diclofenac 75 mg b.i.d. (17%). Adverse events were not different between the active treatment groups, except for higher incidences of flatulence with D75/M200 and diarrhea with D50/M200. CONCLUSION: Diclofenac 50 mg/misoprostol 200 microg t.i.d. and diclofenac 75 mg/misoprostol 200 microg b.i.d. are as efficacious as diclofenac 75 mg b.i.d. in the treatment of OA, but are associated with a significantly lower incidence of gastric and/or duodenal ulcers.

Adult↗
PubMedDate not supplied

Rofecoxib, a new cyclooxygenase 2 inhibitor, shows sustained efficacy, comparable with other nonsteroidal anti-inflammatory drugs: a 6-week and a 1-year trial in patients with osteoarthritis. Osteoarthritis Studies Group.

INTRODUCTION: Rofecoxib, a cyclooxygenase 2 inhibitor (sometimes known as a specific cyclooxygenase 2 inhibitor or Coxib), is used in osteoarthritis (OA). Published information indicates rofecoxib's improved gastrointestinal safety profile over nonselective nonsteroidal anti-inflammatory agents (NSAIDs). OBJECTIVE: To evaluate the efficacy and safety of rofecoxib in treating OA in 2 studies. METHODS: Two randomized, double-blind, parallel-group studies in patients with OA of the knee or hip were conducted using identical entry criteria and end points. A 6-week placebo-controlled trial in 736 patients compared 12.5 and 25 mg of rofecoxib once daily with 800 mg of ibuprofen 3 times daily, and a 1-year study compared 12.5 and 25 mg of rofecoxib once daily with 50 mg of diclofenac 3 times daily in 693 patients. RESULTS: Rofecoxib, at 12.5 and 25 mg, demonstrated efficacy clinically comparable with ibuprofen, assessed by 3 primary end points according to predefined comparability criteria. Both rofecoxib doses and ibuprofen provided significantly greater efficacy than placebo on all primary end points at 6 weeks. Both rofecoxib doses and diclofenac showed similar efficacy over 1 year. All treatments were well tolerated. CONCLUSIONS: Rofecoxib is effective in treating OA with once-daily dosing for 6 weeks and 1 year. Rofecoxib was generally safe and well-tolerated in OA patients for 6 weeks and 1 year. Arch Fam Med. 2000;9:1124-1134

Adult↗
PubMed1998

Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology.

OBJECTIVE: To determine which kind of cell death occurs in cartilage from patients with osteoarthritis (OA). METHODS: Seven normal and 16 OA cartilage samples were collected at autopsy or during joint replacement surgery, respectively. A piece of cartilage was cryopreserved until histologic studies were done. The rest of the cartilage was used to isolate chondrocytes. Apoptotic chondrocytes were analyzed by light and fluorescence microscopy using nuclear 4',6-diamidino-2-phenylindole dihydrochloride stain. Apoptotic chondrocytes were quantified by fluorescence-activated cell sorter (FACS) analysis. The TUNEL technique was used to study histologic apoptosis in situ. Superficial cartilage was processed for ultrastructural study by electron microscopy. RESULTS: OA chondrocytes displayed nuclear and cytoplasmic changes consistent with apoptotic cell death. FACS analysis showed that the OA cartilage had a higher proportion of apoptotic chondrocytes than did normal tissue (51% versus 11%; P < 0.01). In situ study of DNA fragmentation in the cartilage showed that apoptotic cells were located in the superficial and middle zones. Ultrastructural analysis of the superficial OA cartilage revealed some empty lacunae, lysosomal-like structures, matrix vesicle-like structures, fragmented chondrocytes, and nuclear condensation. CONCLUSION: Chondrocytes in OA cartilage demonstrated morphologic changes that are characteristic features of apoptosis. This mechanism of cell death plays an important role in the pathogenesis of OA and could be targeted for new treatment strategies.

Aged↗
PubMed1999

Diacerhein treatment reduces the severity of osteoarthritis in the canine cruciate-deficiency model of osteoarthritis.

OBJECTIVE: To determine if diacerhein protects against the early stages of joint damage in a canine model of osteoarthritis (OA). METHODS: OA was induced in 20 adult mongrel dogs by transection of the anterior cruciate ligament of the left knee. Beginning the day after surgery, dogs in the active treatment group were dosed twice a day with capsules of diacerhein, providing a total daily dose of 40 mg/kg, for 32 weeks. Dogs in the control group received placebo capsules on the same schedule. Pathology in the unstable knee was assessed arthroscopically 16 weeks after surgery and by direct observation when the dogs were killed 32 weeks after surgery. The severity of gross joint pathology was recorded, and samples of the medial femoral condyle cartilage and the synovial tissue adjacent to the central portion of the medial meniscus were collected for histologic evaluation. Water content and uronic acid concentration of the articular cartilage from the femoral condyle were determined, and collagenolytic activity in extracts of cartilage pooled from the medial and lateral tibial plateaus was assayed against 14C-labeled collagen fibers. RESULTS: Diacerhein treatment slowed the progression of OA, as measured by grading of gross changes in the unstable knee at arthroscopy 16 weeks after cruciate ligament transection (P = 0.04) and at the time the animals were killed, 32 weeks after surgery (P = 0.05). However, 32 weeks after ACL transection, the mean proteoglycan concentration and water content of the OA cartilage and the level of collagenolytic activity in extracts of the cartilage were not significantly different in the diacerhein treatment group than in the placebo treatment group. CONCLUSION: Diacerhein treatment significantly reduced the severity of morphologic changes of OA compared with placebo. These findings support the view that diacerhein may be a disease-modifying drug for OA.

Animals↗
PubMed2001

Comparison of the prevalence of knee osteoarthritis between the elderly Chinese population in Beijing and whites in the United States: The Beijing Osteoarthritis Study.

OBJECTIVE: To estimate the prevalence of radiographic and symptomatic knee osteoarthritis (OA) in a population-based sample of elderly subjects in Beijing, China and compare it with that reported in the Framingham (Massachusetts) OA Study. METHODS: We recruited a sample of persons age > or = 60, using door-to-door enumeration in randomly selected neighborhoods in Beijing. Subjects completed a home interview including questions on knee symptoms and a hospital examination including knee radiographs obtained during weight bearing. The protocol was identical to that used in the Framingham OA Study. A reader read intermingled Beijing and Framingham Study films to ensure high reliability. We defined a subject as having radiographic knee OA when the Kellgren/Lawrence grade was > or = 2 in at least 1 knee. Symptomatic knee OA was recorded as present when knee pain was reported and the symptomatic knee had radiographic OA. We estimated the prevalence of these entities in elderly subjects in Beijing and compared it with OA prevalence in Framingham, using an age-standardized prevalence ratio. RESULTS: Of 2,180 age-eligible Beijing subjects contacted, knee radiographs were obtained in 1,787 (82.0%). The prevalence of radiographic knee OA was 42.8% in women and 21.5% in men. Symptomatic knee OA occurred in 15.0% of women and 5.6% of men. Compared with women of the same age in Framingham, women in Beijing had a higher prevalence of radiographic knee OA (prevalence ratio 1.45, 95% confidence interval 1.31-1.60) and of symptomatic knee OA (prevalence ratio 1.43, 95% confidence interval 1.16-1.75). The prevalence of knee OA in Chinese men was similar to that in their white US counterparts (for radiographic OA, prevalence ratio 0.90; for symptomatic OA, prevalence ratio 1.02). CONCLUSION: Using identical methods and definitions to evaluate the prevalence of OA across populations, we found, surprisingly, that older Chinese women have a higher prevalence of knee OA than women in Framingham, Massachusetts. The prevalence in men was comparable. Possible explanations for these differences range from genetic differences to heavy physical activity among Chinese.

Age Distribution↗
PubMed2002

Very low prevalence of hip osteoarthritis among Chinese elderly in Beijing, China, compared with whites in the United States: the Beijing osteoarthritis study.

OBJECTIVE: To compare the prevalence of osteoarthritis (OA) of the hip among elderly persons in China and the US. METHODS: We recruited a population-based sample of 1,506 persons (82% of those enumerated) ages > or = 60 years living in Beijing, China. Subjects answered questions about joint symptoms and underwent radiography of the pelvis. Radiographs of the Beijing subjects were intermingled with hip radiographs of white women ages > or = 65 years from the Study of Osteoporotic Fractures (SOF) and white men and women ages 60-74 years from the First National Health and Nutrition Examination Survey (NHANES-I) and were then interpreted. Radiographic hip OA was defined as the presence of 1 of the following 3 findings in either hip: minimum joint space of < or = 1.5 mm, definite osteophytes and joint space narrowing, or > or = 3 radiographic features of OA. Symptomatic hip OA was defined as both radiographic OA and hip pain. RESULTS: The crude prevalence of radiographic hip OA in Chinese ages 60-89 years was 0.9% in women and 1.1% in men; it did not increase with age. Chinese women had a lower age-standardized prevalence of radiographic hip OA compared with white women in the SOF (age-standardized prevalence ratio 0.07) and the NHANES-I (prevalence ratio 0.22). Chinese men had a lower prevalence of radiographic hip OA compared with white men of the same age in the NHANES-I (prevalence ratio 0.19). There were no cases of symptomatic hip OA in the Chinese men and only 1 case in the Chinese women; 35 cases were expected in both sexes. CONCLUSION: This is the first population-based study of hip OA in China to use standardized radiographic methods and definitions. We found that hip OA was 80-90% less frequent than in white persons in the US. Identification of the genetic and environmental factors that underlie these differences may help elucidate the etiology and prevention of hip OA.

Aged↗
PubMed2003

Lower prevalence of hand osteoarthritis among Chinese subjects in Beijing compared with white subjects in the United States: the Beijing Osteoarthritis Study.

OBJECTIVE: Fewer Chinese subjects in Beijing have hip osteoarthritis (OA) compared with whites in the United States, but as many or more Chinese subjects have knee OA. If these differences are due to a systemic predilection for disease, then the prevalence of hand OA, the best indicator of generalized disease, should be different in China. The goals of this study were to estimate the prevalence of hand OA among elderly Chinese in Beijing, and to compare it with that among elderly whites in the United States. METHODS: We recruited a random sample of Beijing residents ages > or =60 years. Subjects answered questions on joint symptoms and provided posteroanterior radiographs of the hand. The protocol was identical to that used in the Framingham, Massachusetts OA Study. The hand radiographs from the Beijing OA Study were read intermingled with films from the Framingham OA Study. We defined a hand joint as having radiographic OA if it had a Kellgren and Lawrence grade >/=2. Symptomatic OA was present when both radiographic OA and self-reported pain were present in the same joint. We classified a subject as having radiographic or symptomatic hand OA if at least 1 hand joint had radiographic or symptomatic OA. We estimated the prevalence of hand OA in elderly subjects in Beijing and compared it with the prevalence of hand OA in elderly subjects from Framingham, using an age-standardized prevalence ratio. RESULTS: We obtained both symptom information and hand radiographs from 2,525 subjects. Despite the older age of the group, only 44.5% of men and 47.0% of women had radiographic hand OA. Symptomatic hand OA occurred in 3.0% of men and 5.8% of women. Compared with white men in Framingham, the Beijing Chinese men had a much lower prevalence of radiographic hand OA (age-adjusted prevalence ratio 0.64, 95% confidence interval [95% CI] 0.58-0.70) and symptomatic hand OA (age-adjusted prevalence ratio 0.25, 95% CI 0.16-0.34). The proportion of multiple hand joints affected by OA in Chinese men was also significantly lower than in white men. A similar magnitude of difference was also observed in the women. However, prevalence of symptomatic OA at the metacarpophalangeal (MCP) joints in Chinese men and prevalence of radiographic OA at the MCP joints in Chinese women were similar to those in their white counterparts in Framingham. CONCLUSION: Elderly Chinese subjects in Beijing had a much lower prevalence of hand OA than did elderly whites in Framingham, Massachusetts. Coupled with the exceedingly low prevalence of hip OA in China, these results may suggest that the overall predilection for OA is less among subjects in China than among whites in the United States.

Aged↗
PubMed1986

Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association.

For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. Comparison diagnoses included rheumatoid arthritis and other painful conditions of the knee, exclusive of referred or para-articular pain. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms.

Adult↗
PubMed1987

The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study.

To investigate the prevalence of osteoarthritis (OA) of the knee in elderly subjects, we studied the Framingham Heart Study cohort, a population-based group. During the eighteenth biennial examination, we evaluated the cohort members for OA of the knee by use of medical history, physical examination, and anteroposterior (standing) radiograph of the knees. Radiographs were obtained on 1,424 of the 1,805 subjects (79%). Their ages ranged from 63-94 years (mean 73). Radiographs were read by a radiologist who specializes in bone and joint radiology, and were graded 0-4 according to the scale described by Kellgren and Lawrence. OA was defined as grade 2 changes (definite osteophytes), or higher, in either knee. Radiographic evidence of OA increased with age, from 27% in subjects younger than age 70, to 44% in subjects age 80 or older. There was a slightly higher prevalence of radiographic changes of OA in women than in men (34% versus 31%); however, there was a significantly higher proportion of women with symptomatic disease (11% of all women versus 7% of all men; P = 0.003). The age-associated increase in OA was almost entirely the result of the marked age-associated increase in the incidence of OA in the women studied. This study extends current knowledge about OA of the knee to include elderly subjects, and shows that the prevalence of knee OA increases with age throughout the elderly years.

Age Factors↗
PubMed2004

Association of radiographic hand osteoarthritis with radiographic knee osteoarthritis after meniscectomy.

OBJECTIVE: To evaluate the association between radiographic hand osteoarthritis (OA), a disease with marked heredity, and radiographic knee OA in patients treated with meniscectomy. METHODS: We retrospectively identified 170 patients (mean age 54 years [range 33-87 years], 23% women) who had undergone isolated meniscectomy an average of 20 years earlier (range 17-22 years). Patients with cruciate ligament injury were excluded. All subjects were examined by standardized knee and hand radiography. Individual joints were considered to have OA when displaying radiographic features corresponding to a Kellgren/Lawrence (K/L) grade > or =2. Hand OA was considered present if at least 1 of the following criteria was fulfilled: the presence of radiographic OA (K/L grade > or =2) in at least 1 interphalangeal joint in each hand symmetrically, or in at least 2 distal or proximal interphalangeal joints in the same hand in a pattern consistent with primary OA (in the same row or ray), or in the first carpometacarpal joint bilaterally. The association between radiographic hand OA and radiographic knee OA was evaluated using logistic regression. RESULTS: Radiographic hand OA was present in 57 patients (34%) and radiographic knee OA was identified in 105 patients (62%), within 94 index knees (55%) and 47 contralateral knees (28%). In a multivariate model, radiographic hand OA was associated with an increased likelihood of radiographic OA in the index knee (odds ratio [OR] 3.0, 95% confidence interval [95% CI] 1.2-7.5) and in the nonoperated contralateral knee (OR 3.5, 95% CI 1.0-12.2). CONCLUSION: The presence of radiographic hand OA is associated with an increased frequency of radiographic knee OA after meniscectomy. This finding confirms and extends that of a single previous study showing an interaction between hereditary and environmental risk factors for OA, a common and genetically complex disease. Accordingly, the development of OA following a meniscal tear and the resulting meniscal surgery should not be regarded to be of secondary origin only.

Arthroscopy↗
PubMed2004

Association of squatting with increased prevalence of radiographic tibiofemoral knee osteoarthritis: the Beijing Osteoarthritis Study.

OBJECTIVE: To examine the association between squatting, a common daily posture in China, and the prevalence of radiographic osteoarthritis (OA) in different knee compartments among Chinese subjects from Beijing, and to estimate how much of the difference in prevalence of knee OA between Chinese subjects in Beijing and white subjects in Framingham, Massachusetts is accounted for by the impact of squatting. METHODS: We recruited a random sample of Beijing residents age > or =60 years. Subjects answered questions on joint symptoms, and knee radiographs were obtained. Subjects were also asked to recall the average amount of time spent squatting each day at age 25 years. Radiographic films (weight-bearing anteroposterior and skyline views) were read for Kellgren/Lawrence (K/L) grade and individual radiographic features. Medial disease was defined when radiographs showed a K/L grade of > or =2 at the tibiofemoral joint and a medial joint space narrowing score of > or =1, and lateral disease was assessed in a comparable manner in the lateral compartments. We examined the association of squatting with the prevalence of tibiofemoral OA as well as with the prevalence of patellofemoral knee OA, while adjusting for age and other potential confounding factors. We used the same approach to assess the relationship between squatting and tibiofemoral OA in the medial compartment and in the lateral compartment. Finally, we estimated the impact of squatting at age 25 on the difference in prevalence of knee OA between Chinese subjects in Beijing and white subjects in the Framingham OA Study. RESULTS: Squatting was very common among the Chinese subjects: approximately 40% of men and approximately 68% of women reported squatting > or =1 hour per day at age 25. The prevalence of tibiofemoral OA increased as the time spent squatting at age 25 increased in both the men and the women. Compared with subjects who squatted <30 minutes per day at age 25, the multivariable-adjusted prevalence odds ratios of tibiofemoral OA were 1.1 for time spent squatting of 30-59 minutes/day, 1.0 for 60-119 minutes/day, 1.7 for 120-179 minutes/day, and 2.0 for > or =120 minutes/day among the men (P for trend = 0.074), and the respective odds ratios among the women were 1.4, 1.3, 1.2, and 2.4 (P for trend = 0.077). A weaker association with patellofemoral OA was found. Prolonged squatting in daily life was more strongly associated with medial knee OA than with lateral disease in the men, but had a similar effect on both knee compartments in the women. After adjusting for the impact of squatting, the age-adjusted difference in prevalence of tibiofemoral OA was reduced from an excess of 14.4% to 9.5% in the Chinese women, but the difference in prevalence of tibiofemoral OA in the Chinese men increased after adjustment for age and squatting, from 2.9% lower to 7.0% lower as compared with their white counterparts. CONCLUSION: Prolonged squatting is a strong risk factor for tibiofemoral knee OA among elderly Chinese subjects in Beijing, and accounts for a substantial proportion of the difference in prevalence of tibiofemoral OA between Chinese subjects in Beijing and white subjects in Framingham.

Aged↗
PubMed2004

Proteomic surveillance of autoimmunity in osteoarthritis: identification of triosephosphate isomerase as an autoantigen in patients with osteoarthritis.

OBJECTIVE: Autoimmunity to proteins, such as type II collagen and cartilage intermediate layer protein, that are produced by chondrocytes has been reported in patients with osteoarthritis (OA) as well as in patients with rheumatoid arthritis (RA). However, it remains to be determined whether the overall specificities of the autoimmunity differ between OA and RA patients. This study sought to clarify the differences by applying proteomic surveillance for the detection of autoantigens comprehensively. METHODS: Serum samples were obtained from 20 patients with OA, 20 patients with RA, and 20 healthy volunteers. Human chondrocyte proteins were separated from the sera by 2-dimensional electrophoresis, and antigenic protein spots were detected by Western blotting. The antigenic proteins were then identified by mass fingerprinting. The antigenicity of the identified proteins was confirmed and the prevalence of the autoantibodies in the OA, RA, and other disease groups was determined with the use of recombinant proteins. In addition, autoepitopes were mapped on the antigens. RESULTS: Nineteen protein spots were recognized only by the OA sera, but not by the RA sera. One of these proteins was identified as triosephosphate isomerase (TPI). IgG-type anti-TPI autoantibodies were detected in 24.7% of the serum samples and 24.1% of the synovial fluid samples from the patients with OA, whereas <6% of the RA and systemic lupus erythematosus samples were positive for anti-TPI. In addition, multiple autoepitopes were identified on TPI. CONCLUSION: The overall profile of autoimmunity in OA differs from that in RA, which may reflect the OA-specific pathologic role of autoimmunity. The autoantibody to TPI, detected predominantly in the OA samples and produced by the antigen-driven mechanism, has the potential to be used as a diagnostic marker for OA.

Adult↗
PubMed2004

Quadriceps weakness and its relationship to tibiofemoral and patellofemoral knee osteoarthritis in Chinese: the Beijing osteoarthritis study.

OBJECTIVE: Weakness has been documented as a feature of tibiofemoral knee osteoarthritis (OA) and may cause disease in this compartment by shock absorption during impulse loading at heel strike, when the patellofemoral joint is not engaged. Our objective was to determine the association of muscle weakness with compartment-specific knee OA, to evaluate sex-specific differences in this relationship, and to determine, by evaluating asymptomatic individuals with OA, whether symptoms may produce the weakness seen in OA. METHODS: This cross-sectional study involved 2,472 subjects (1,475 women and 997 men) ages 60 years or older from 4 central districts of Beijing, China. For all subjects, a skyline view of each knee and an anteroposterior (AP) or posteroanterior (PA) radiograph of both knees were obtained during weight bearing. Radiographs were read by one reader for Kellgren/Lawrence (K/L) grade, joint space narrowing (JSN), and osteophytes. We defined a subject as having tibiofemoral OA when the K/L grade was > or =2 on AP/PA view, patellofemoral OA on skyline view when the osteophyte score was > or =2 (or when the JSN score was > or =2 and the osteophyte score was > or =1), and mixed OA when the knee had both patellofemoral and tibiofemoral radiographic OA. Strength was measured isometrically for each leg separately, and knee pain was evaluated by questionnaire. RESULTS: In women, quadriceps weakness was associated with tibiofemoral OA (odds ratio [OR] 0.7, 95% confidence interval [95% CI] 0.4-1.0), patellofemoral OA (OR 0.6, 95% CI 0.4-0.9), and mixed OA (OR 0.4, 95% CI 0.3-0.6). In men, weakness was associated with mixed OA (OR 0.5, 95% CI 0.3-0.8), and the ORs suggesting an association of patellofemoral OA with weakness were the same as those in women, although in men this trend did not reach statistical significance (P = 0.12). In men, isolated tibiofemoral disease was not associated with weakness; however, the sample size in this analysis was limited. When subjects with knee symptoms were excluded, the relationship of quadriceps weakness to OA was attenuated, with only the relationship between muscle weakness and mixed OA remaining significant. CONCLUSION: There is a relationship between quadriceps weakness and knee OA in all compartments, with the strongest association in mixed disease. Pain may contribute to some of this weakness.

Aged↗
PubMed2005

Knee height, knee pain, and knee osteoarthritis: the Beijing Osteoarthritis Study.

OBJECTIVE: Few risk factors for knee osteoarthritis (OA) are appreciated, and the discordance between symptoms and the severity of structural disease has not been explained. Knee height contributes to moments around the knee. The longer the leg, the more torque is present. Although this would suggest that having long legs would be related to the occurrence of knee OA and pain, this issue has not been studied. Our aim was to explore the association between knee height, knee pain, and knee OA. METHODS: We recruited a random sample of Beijing residents ages 60 years and older. Subjects answered questions about joint symptoms, and radiographs of their knees were obtained. A knee joint with a Kellgren/Lawrence grade of >/=2 was defined as having radiographic OA. Patellofemoral OA was defined as being present when grade >/=1 osteophytes or grade >/=1 joint space narrowing was observed on skyline views of the patella or anterior femur. Subjects were considered to have symptomatic OA when both radiographic OA and self-reported pain were present in the same joint. Knee height was measured on the right leg using a sliding broad-blade caliper; the subject was seated, and the subject's feet were bare. We used logistic regression analyses to assess whether knee height was associated with prevalent radiographic and symptomatic OA. We then assessed whether knee height was associated with knee symptoms independently of structural change. RESULTS: A total of 1,006 men (mean +/- SD age 68.4 +/- 6.4 years) and 1,500 women (mean +/- SD age 67.5 +/- 6.1 years) participated in this study. Higher knee height was associated with an increasing prevalence of both radiographic and symptomatic OA, especially among women. For radiographic OA, the magnitude of association was similar for the patellofemoral and tibiofemoral compartments. Among women with knee pain, higher knee height was associated with more severe knee pain (P = 0.0004 for the highest quartile versus the lowest quartile of knee height) independently of the severity of radiographic OA. CONCLUSION: Knee height is associated with prevalent radiographic and symptomatic knee OA. It may also play an important role in knee symptoms. This study highlights the importance of mechanical forces in the determination of OA and knee symptoms.

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