Clearwater Osteoarthritis Study Research Articles

Pain in knee osteoarthritis is associated with variation in the neurokinin 1/substance P receptor (TACR1) gene

Substance P (SP) is a pain- and inflammation-related neuropeptide which preferentially binds to the neurokinin receptor 1 (NK1 ). SP and NK1 receptors have been implicated in joint pain, inflammation and damage in animal models and human studies of osteoarthritis (OA). The aim of this study was to test if genetic variation at the neurokinin 1 receptor gene (TACR1) is associated with pain in individuals with radiographic knee OA. Participants from the Genetics of OA and Lifestyle study were used for the discovery group (n=1615). Genotype data for six SNPs selected to cover most variation in the TACR1 gene were used to test for an association with symptomatic OA. Replication analysis was performed using data from the Chingford 1000 Women Study, Hertfordshire Cohort Study, Tasmanian Older Adult Cohort Study and the Clearwater OA Study. In total, n=1715 symptomatic OA and n=735 asymptomatic OA individuals were analysed. Out of six SNPs tested in the TACR1 gene, one (rs11688000) showed a nominally significant association with a decreased risk of symptomatic OA in the discovery cohort. This was then replicated in four additional cohorts. After adjusting for age, gender, body mass index and radiographic severity, the G (minor) allele at rs11688000 was associated with a decreased risk of symptomatic OA compared to asymptomatic OA cases (p=9.90×10-4 , OR=0.79 95% 0.68-0.90 after meta-analysis). This study supports a contribution from the TACR1 gene in human OA pain, supporting further investigation of this gene's function in OA. This study contributes to the knowledge of the genetics of painful osteoarthritis, a condition which affects millions of individuals worldwide. Specifically, a contribution from the TACR1 gene to modulating pain sensitivity in osteoarthritis is suggested.

Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain

To assess the genetic association of pain in patients with knee osteoarthritis (OA) and those with multiple regional pain with the R1150W variant in the α-subunit of the voltage-gated sodium channel Na(V)1.7. Knee OA patients from 2 UK cohorts (1,411 from the Genetics of Osteoarthritis and Lifestyle study and 267 from the Hertfordshire Cohort Study; 74% with symptomatic OA) with Western Ontario and McMaster Universities OA Index (WOMAC) pain scores were genotyped for rs6746030 (encoding the R1150W change). One hundred seventy-six knee OA patients (53% symptomatic) from the Clearwater Osteoarthritis Study were also tested. A total of 4,295 samples (both affected and unaffected OA) from all 3 studies with data on multiple regional pain were tested. Fixed-effects meta-analyses were carried out with the WOMAC, symptomatic OA (adjusting for radiographic severity), and multiple regional pain as outcomes. No association with the WOMAC was seen in the UK cohorts. Overall, the meta-analysis of WOMAC yielded a summary statistic of β = 0.47 (95% confidence interval [95% CI] 0.04, 0.89; P = 0.030) for the variant allele. The meta-analysis of symptomatic versus asymptomatic OA did not demonstrate an association with rs6746030 (odds ratio [OR] 0.90 [95% CI 0.71, 1.15], P = 0.38). The meta-analysis of multiple regional pain resulted in a significant OR of 1.40 (95% CI 1.08, 1.80; P = 0.0085). No interstudy heterogeneity was seen for any of the analyses. We find evidence that the R1150W amino acid change in the Na(V)1.7 α-chain is associated with multiple regional pain. This variant is confirmed to be involved in genetic susceptibility to pain, but it does not appear to have a major role in OA-specific pain.

Job-Related Osteoarthritis of the Knee, Foot, Hand, and Cervical Spine

To assess the influence of occupational exposures on risk of site-specific radiographic osteoarthritis (OA) of the knee, hand, foot, and cervical spine. Using a cross-sectional design, data collected from men and women aged 40 years and older participating in the Clearwater Osteoarthritis Study were analyzed (n = 3436). Subjects' occupational exposures were queried using the study intake form, including stair climbing, standing on a rigid surface, squatting, and jolting. Physical examinations including radiographs of the knee, hand, foot, and cervical spine were conducted. The Kellgren and Lawrence ordinal scale was used to determine evidence of radiographic OA. Both the unadjusted and adjusted odds ratios (ORs) for men and women indicated that age and body mass index were associated with OA. There were no other significant odds ratios for the cervical spine. Among men, there were significant associations with knee OA for stair climbing and jolting of the legs and with foot OA with stair climbing. Among women, there was a significant association between standing on a rigid surface and knee OA. For hand OA in women, there was a significant association for jolting of the hands. Although the association with stair climbing was found in other investigations for knee OA, it was also associated with foot OA in this study. In addition, the jolting feature was seen in only one other study for men (knees) and novel for women (hands).

Site specific osteoarthritis and the index to ring finger length ratio

To quantify the relationship between the index to ring finger length ratio second digit:fourth digit(2D:4D) and radiographic osteoarthritis (OA) of the knee. Data from the Clearwater Osteoarthritis Study (COS) were analyzed. We selected a random sample of 236 subjects with knee OA (Kellgren-Lawrence scores >or=2) and compared their finger length ratio pattern with a random sample of 242 controls. Finger length measurements were recorded from digitized hand radiographs. Subjects were classified into three groups: type 1 (index finger longer than ring finger), type 2 (fingers of equal length) and type 3 (index finger shorter than ring finger). Using a case-control design, we calculated odds ratios (OR). The type 3 finger pattern was significantly associated with knee OA (OR 2.59, 95% confidence interval (CI) 1.54-4.37). Women demonstrated a stronger association of visual type 3 finger pattern and knee OA (OR 4.40, 95% CI 2.62-7.38) compared to men (OR 2.59, 95% CI 1.34-5.00). The type 3 finger length pattern is associated, to a statistically significant degree, with OA of the knee. The type 3 finger length pattern (ring finger longer than index finger) appears to be an indicator of OA predisposition. Consideration of this pattern in clinical assessments may be an added aid as clinicians screen patients for OA risk.

Radiographic cervical spine osteoarthritis progression rates: a longitudinal assessment

Relative to other sites, the cervical spine has received little attention in the osteoarthritis (OA) literature. Using data from a longitudinal study, we provide age-specific progression rates of radiographic cervical spine OA, by gender. Data from cohort subjects (ages 40+) from the Clearwater Osteoarthritis Study were analyzed (N = 707). All study subjects' demonstrated radiographic cervical spine OA at baseline (2+). Lateral cervical spine radiographs were taken biennially. The study outcome was radiographic disease progression. A grade increase of 1, or more, by the Lawrence and Kellgren ordinal scale was considered progression. Incidence rates were calculated as per 100 person-years of observation. We show that the progression rates for cervical spine OA increase with age. For all ages combined, men demonstrated higher rates of progression compared with women. However, among subjects in their forties and fifties, women were more likely to experience worsening of their disease when compared with men. Progression rates were similar for men and women in their sixties (8.2 and 8.0, respectively). Among subjects in their seventies, men demonstrated a significantly higher rate of progression compared with women (12.5 and 8.6, respectively). As the baby-boomer population continues to increase, cervical spine OA progression assessment can be a useful tool for health-care resource planning. Cervical spine OA research offers an abundance of opportunities. Instability as a precursor to the development of cervical spine OA warrants further research. Epidemiological studies addressing demographic differences (e.g., gender, age) in the incidence of cervical spine OA will contribute to the current knowledge base.

VITAMIN SUPPLEMENTS AND RADIOGRAPHIC KNEE OSTEOARTHRITIS: THE CLEARWATER OSTEOARTHRITIS STUDY

Objective: To evaluate the association between vitamin supplements and the incidence and progression of radiographic knee osteoarthritis (OA). Study Design: Prospective cohort. Methods: Men and women aged 40 years and older (N = 2239) participating in the community-based Clearwater Osteoarthritis Study (1988–current) with biennial, sequential radiographs. The Lawrence & Kellgren ordinal scale was used to determine evidence of the study outcome, radiographic knee OA, and progression of radiographic knee OA. The study exposure was baseline history of self-reported vitamin supplement usage. Results: Individuals without baseline knee OA who self-reported vitamin supplement usage were 12% less likely to develop knee OA than were those individuals who self-reported no vitamin supplement usage (RR = 0.88; 95% C.I. 0.86–0.89). Those with baseline knee OA who self-reported vitamin supplement usage were 7% less likely to experience knee OA progression than were those individuals who self-reported no vitamin supplement usage (RR = 0.93; 95% C.I. 0.87–0.99). Conclusion: After consideration of BMI, gender, age, history of knee trauma, exercise and vitamin supplement usage prior to study baseline, these findings suggest that vitamin supplement usage may play a protective role in knee OA. Vitamin supplements may be a cost-effective strategy to reduce the incidence and/or slow the progression of knee OA. As many approved OA drugs are accompanied by adverse side effects, the role of vitamin supplements in the development and progression of knee OA warrants further investigation.

The association of BMI and knee pain among persons with radiographic knee osteoarthritis: A cross-sectional study

BackgroundMany people with radiographic knee osteoarthritis (RKOA) do not present with pain. It is suspected that such persons tend toward lower body mass index (BMI). The purpose of the study was to explore the relationship between BMI and knee pain among persons with RKOA.MethodsSubjects in the Clearwater Osteoarthritis Study with RKOA (N = 576) were classified as reporting knee pain (Pain) or no knee pain (No Pain). WHO-classified BMI categories were compared by pain status. Odds ratios were calculated for the four elevated BMI groups, with the normal BMI group as the reference group. Elevated BMI was the risk factor, and knee pain status was the outcome factor.ResultsPain subjects presented with a higher mean BMI (30.4 kg/m2) compared with No Pain subjects (27.5 kg/m2) (p < 0.0001). Unadjusted and adjusted odds ratios demonstrated a positive association between BMI group and pain for each successive elevated BMI category. Adjusted odds ratios ranged from 1.6 for the Pre-obese group (p < 0.05) to 7.5 for the Obese III group (p < 0.0001).ConclusionAmong subjects with RKOA, those presenting with an elevated BMI had a greater likelihood of knee pain compared to subjects with a normal BMI, and this chance rose with each successive elevated BMI category. As BMI is a modifiable risk factor, longitudinal research is needed to confirm these findings and elucidate the mechanisms underlying this relationship.

HEIGHT AND RADIOGRAPHIC OSTEOARTHRITIS: AN EPIDEMIOLOGIC ASSESSMENT — SHORT COMMUNICATION

Purpose: To epidemiologically assess the gender-specific relationship between height and radiographic osteoarthritis (OA) of the knee, hand, foot, and cervical spine. Methods: Data collected from men (N = 1090) and women (N = 2441) aged 40 years and older participating in the Clearwater Osteoarthritis Study (1988–current) were used (N = 3531). Physical exams including radiographs were conducted. The Kellgren and Lawrence ordinal scale was used to determine evidence of radiographic OA. Results: There is a modest, albeit consistent, increase in OA prevalence among shorter-stature study subjects at all four sites in women and at two sites in men (hands and cervical spine). Our adjusted findings suggest that shorter stature is a risk factor for OA for the hands, feet, and cervical spine, with odds ratios varying between 1.25 and 1.82. After adjusting for body mass index and age, this relationship maintained statistical significance among women for hand OA. (OR = 1.57; p = 0.0001) and feet OA (OR = 1.41; p - value = 0.009). Curiously, no significant association was indicated between height and knee OA for either gender. Conclusions: Shorter stature appears to be associated with an elevated risk of OA, but particularly so for women. Future epidemiologic studies examining this relationship can offer insight into skeletal growth and development knowledge, thus further elucidating the etiology of OA.

340 THE INFLUENCE OF LIFETIME HIP JOINT FORCE ON THE RISK OF SELF-REPORTED HIP OSTEOARTHRITIS: A NEW METHOD TO QUANTIFY PHYSICAL ACTIVITY

wear and secondary osteoarthritis. The investigation of this relationship using epidemiologic data can enhance our understanding of the underlying biologic mechanisms which may be at play. We sought to quantify the association between site-specific radiographic osteoarthritis (ROA) and self-reported diabetes. Methods: Site-specific OA status was radiographically-confirmed among subjects drawn from the Clearwater Osteoarthritis Study (COS) (N=3438). The COS is a 25-year longitudinal cohort begun in 1988 to investigate risk factors for the incidence and progression of OA among men and women ages 40 years and older. Biennial physical exams including site-specific radiographs were conducted. The Kellgren & Lawrence ordinal scale was used to determine radiological evidence of the study outcome, ROA. Results: After adjusting for age, gender and body mass index (BMI), subjects who self-reported a history of diabetes were 40% more likely to have hand OA (OR=1.4; 95% C.I. 1.1−1.6; p-value <0.002) than were those without diabetes. Likewise, those subjects with diabetes were 20% more likely to have foot OA, although this was not statistically significant (OR=1.2; 95% C.I. = 0.98−1.5; p-value 0.08).

Positive Hindfoot Valgus and Osteoarthritis of the First Metatarsophalangeal Joint

The aim of this retrospective cohort study was to evaluate the association between increased hindfoot valgus and the subsequent development of osteoarthritis of the first metatarsophalangeal (MTP) joint. Specifically, our hypothesis was that among individuals free from first MTP joint osteoarthritis, those who have positive hindfoot valgus are more likely to develop first MTP joint osteoarthritis than are those individuals with normal hindfoot alignment. Our sample consisted of 1592 men and women, 40 years of age or older, participating in the Clearwater Osteoarthritis Study (1988 to 2001). Biennial physical examinations, including serial radiographs, were conducted. The Kellgren and Lawrence ordinal scale was used to determine radiographic evidence (grades 2+) of the study outcomes and incidence of first MTP joint osteoarthritis. Standing hindfoot valgus was assessed visually by a registered nurse, with a hindfoot valgus measurement of more than 5 degrees classified as a positive hindfoot valgus. Individuals with hindfoot valgus were 23% more likely to subsequently develop first MTP joint osteoarthritis than were those without hindfoot malalignment (risk ratio = 1.23; p-value < 0.006). This risk estimate reflects the potential influence of age, gender, and body mass index. Our data suggest that hindfoot valgus may increase the risk of developing foot osteoarthritis. The association of hindfoot valgus with first MTP joint osteoarthritis in this epidemiological assessment is supportive of the mechanical theory for the development of osteoarthritis. The authors speculate that future, related studies may determine that osteoarthritis prevention strategies can be broadened to include individuals with positive hindfoot valgus.

The association of radiographic foot osteoarthritis and radiographic osteoarthritis at other sites

To quantify the association between radiographic foot osteoarthritis (OA) and radiographic OA at four joints: second distal interphalangeal (DIP), third proximal interphalangeal (PIP), first carpometacarpal (CMC), and the knee. Data collected for the Clearwater Osteoarthritis Study (COS) were analyzed (N=3436). The study outcome was first metatarso-phalangeal joint (first MTP) OA status. The predictor variables were second DIP, third PIP, first CMC, and knee OA. The Kellgren and Lawrence scale determined OA status. The strength of the association between foot OA and other sites was further explored by unilateral and bilateral categories. For both genders, we found a significant, positive relationship between grade 2+ foot OA and second DIP, third PIP, first CMC, and knee OA. This relationship maintained its significance after adjustment for age, body mass index, and occupational history. Adjusted odds ratios ranged from 3.2 for the second DIP joint (P<0.0001) to 3.7 for the knee joint (P<0.0001). Relative to unilateral joint disease, co-existing bilateral disease yielded a significantly elevated risk for foot OA for all joints examined. While other studies have not specifically examined co-occurrence with foot OA, our findings are consistent with results from related studies. There is a dearth of studies exploring foot OA. Our findings support the theory of a systemic etiology involved in the development of OA. Future epidemiological studies that further distinguish the relationship between OA at differing sites will provide an enhanced ability to describe the respective influences of mechanical and systemic factors in the development of this disease.

Smoking and osteoarthritis: Is there an association? The Clearwater Osteoarthritis Study

Objective To evaluate the association between cigarette smoking and the subsequent development of osteoarthritis (OA) at four separate sites: knee, hand, foot and cervical spine.Methods This cohort study examined 2505 men and women aged 40 years and older participating in the longitudinal Clearwater Osteoarthritis Study (1988–current). Biennial physical exams, including serial radiographs, as well as historical information, were collected. The Lawrence and Kellgren ordinal scale was used to determine radiological evidence of the study outcome, OA. Self-reported history of smoking behavior was used to determine the study exposure. Smoking was classified using four approaches: (1) ever/never, (2) former/never, (3) current/never, and (4) dose.Results Among the individuals at study entry, radiologically confirmed incident OA was detected during the follow-up period at four sites: knee (32%), hand (49%), foot (28%), and cervical spine (52%). Approximately 11% were self-reported current smokers. Unadjusted analyses indicated that individuals classified as current smokers demonstrated significant levels of protection from OA at all four sites investigated. However, adjusted point estimates ranging from 0.60–1.48 were suggestive of no association between smoking and the development of OA at any of the four sites investigated.Conclusion Based upon the findings of this prospective study, smoking does not appear to convey a clinically significant level of protection against the development of radiologically-confirmed OA. While these findings corroborate previous studies indicating no association between smoking and OA, anecdotal evidence warrants investigation into the role that cigarette smoking may play in the symptomatology of OA. Copyright 2003 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.

History of acute knee injury and osteoarthritis of the knee: a prospective epidemiological assessment: The Clearwater Osteoarthritis Study

Objective To evaluate the association between acute joint injury to the knee and knee osteoarthritis (OA).Design Prospective cohort. Sample size=1,436. Men and women aged 40 years and older participating in the population-based Clearwater Osteoarthritis Study (1988–current) with biennial physical exams including serial radiographs. Radiologically confirmed knee OA=27%; self-reported knee injury=11%. Lawrence and Kellgren ordinal scale was used to determine radiological evidence of the study outcome, knee OA. Self-reported history of knee injury was used to determine the study exposure.ResultsIndividuals with a history of knee injury were 7.4 (95% C.I. 5.9–9.4) times as likely to develop knee OA than were those individuals who did not have a history of knee injury.Conclusion Acute knee joint injury appears to be a risk factor for the development of knee OA. Prevention strategies for OA should be targeted to those individuals with a history of acute knee injury. Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.