Does mild cognitive impairment affect the occurrence of radiographic knee osteoarthritis? A 3-year follow-up in the ROAD study.
ABSTRACT: To determine whether mild cognitive impairment (MCI) increases the risk of occurrence or progression of radiographic knee osteoarthritis (KOA) in a general population.Population-based cohort study.Residents in mountain and seaside areas of Wakayama Prefecture, Japan.1690 participants (596 men, 1094 women; mean age 65.2 years old) were enrolled from the large-scale cohort for the Research on Osteoarthritis (OA)/osteoporosis Against Disability (ROAD) study initiated in 2005 to investigate epidemiological features of OA in Japan. Of these, 1384 individuals (81.9%; 466 men, 918 women) completed the second survey including knee radiography 3 years later.Radiographic KOA was defined as Kellgren-Lawrence (KL) grade ? 2 using paired x-ray films. Incidence of KOA during follow-up defined on radiographs as KL grade ?2, progression of KOA defined as a higher KL grade (either knee) at follow-up compared with baseline. MCI defined as a summary mini-mental state examination (MMSE) score ?23. Associations between MCI and incidence or progression of KOA were analysed.The annual cumulative incidence of KOA was 3.3%; for progression of OA it was 8.0%. On logistic regression analysis adjusted for age, gender, regional differences, body mass index, grip strength (worse side), smoking, alcohol consumption, regular exercise and history of knee injury, baseline MMSE summary score was significantly associated with the incidence of KOA (+1 MMSE score; OR 0.83, p=0.010). Baseline MCI was also significantly associated with the incidence of KOA (vs non-occurrence of KOA; OR 4.90, p=0.027). There was no significant association between MMSE scores, the presence of MCI and progression of KOA (+1 MMSE score; OR 0.96, p=0.232; vs non-progression of KOA; OR 1.38, p=0.416).MCI significantly increases the risk of incident radiographic KOA, but not the progression of KOA.
Project description:Within the interleukin-1 (IL-1) cytokine family, IL-1 receptor antagonist (IL1RN) gene variants have been associated with radiological severity of knee osteoarthritis (OA) in cross-sectional studies. The present study tested the relation between IL1RN gene variants and progression of knee OA assessed radiographically by change in Kellgren-Lawrence (KL) score over time.1153 Caucasian adults (age range: 44-89) from the Johnson County Osteoarthritis Project were evaluated for unequivocal radiographic evidence of knee OA at baseline, defined as KL score ?2, and were re-examined after 4-11 years for radiographic changes typical of OA progression. IL1RN gene variants were tested for association with OA progression and for potential interaction with body mass index (BMI). Other IL-1 gene variations were tested for association with OA progression as a secondary objective.Of 154 subjects with OA at baseline, 88 showed progression at follow-up. Seven IL1RN single nucleotide polymorphisms (SNPs) and one IL-1 receptor SNP were associated with progression. Four IL1RN haplotypes, each occurring in >5% of this population, showed different relationships with progression, including one (rs315931/rs4251961/rs2637988/rs3181052/rs1794066/rs419598/rs380092/rs579543/rs315952/rs9005/rs315943/rs1374281; ACAGATACTGCC) associated with increased progression [odds ratio (OR) 1.91 (95%CI 1.16-3.15); P = 0.012]. Haplotypes associated with progression by KL score were also associated with categorical change in joint space narrowing. BMI was associated with OA progression in subjects carrying a specific IL1RN haplotype, but not in subjects without that haplotype.A significantly greater likelihood of radiological progression of knee OA was associated with a commonly occurring IL1RN haplotype that could be tagged by three IL1RN SNPs (rs419598, rs9005, rs315943). Interactions were also observed between IL1RN gene variants and BMI relative to OA progression. This suggests that IL1RN gene markers may be useful in stratifying patients for medical management and drug development.
Project description:Diabetes has been proposed as a factor involved in the pathogenesis of osteoarthritis (OA). Currently, there is a lack of research evaluating the prospective impact of diabetes on OA structural outcomes. In this study, we assessed the effects of medication-treated diabetes on incidence and progression of knee OA. We analysed longitudinal data from the multi-center, longitudinal, prospective observational Osteoarthritis Initiative (OAI) study. The main outcomes were radiographic OA incidence (development of Kellgren-Lawrence grade 2 with joint space narrowing, JSN) and progression (increase in semiquantitative JSN or a new knee replacement). For the study of incidence, we selected participants with KL <2 or /KL?=?2 without JSN at baseline (incidence sample). To evaluate progression, we selected participants with baseline JSN <3 (progression sample). We used generalized estimating equations (GEE) logistic regression with adjustment for potential confounders to evaluate the effects of medication-treated diabetes on knee OA incidence and progression. We studied 3725 knees (3498 non-diabetic and 228 diabetic) in the incidence sample and 3594 knees (3335 non-diabetic and 259 diabetic) in the progression sample. Medication-treated diabetes did not have an effect on knee OA incidence (odds ratio, OR 0.53, 95% confidence interval, CI 0.23-1.5). There was an independent association between medication-treated diabetes and reduced progression of knee OA [OR 0.66, 95% CI (0.44-0.98)]. Medication-treated diabetes has no effect on knee OA incidence but reduces knee OA progression. The role of diabetes and anti-diabetic drugs in knee OA progression needs further exploration.
Project description:Little is known about the temporal evolution of pain severity in persons with knee osteoarthritis (OA). We sought to describe the pain trajectory over 6 years in a cohort of subjects with radiographic, symptomatic knee OA.We used data from the Osteoarthritis Initiative (OAI), a multi-center, longitudinal study of subjects with diagnosed radiographic evidence of knee OA. Pain was assessed at baseline and annually for 6 years. Our analysis cohort included subjects with symptomatic knee OA at baseline, defined as baseline Kellgren-Lawrence (KL) score ?2 with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score >0. We used group-based trajectory modeling to identify distinct patterns of pain progression over a 6-year follow-up. Factors examined included sex, race, education, comorbidities, age, body mass index (BMI), alignment, KL grade, and depression.We used data from 1753 OAI participants with symptomatic knee OA. Mean baseline WOMAC pain score was 26.5 (0-100, 100=worst) with standard deviation (SD) 19. Group-based trajectory modeling identified five distinct pain trajectories; baseline pain scores for each ranged from 15 to 62. None of the trajectories exhibited substantial worsening. One fifth of subjects in the two trajectories with the greatest pain underwent total knee replacement (TKR) over follow-up. Higher KL grade, obesity, depression, medical comorbidities, female sex, non-white race, lower education, and younger age were associated with trajectories characterized by greater pain.We found that knee pain changes little, on average, over 6 years in most subjects. These observations suggest knee OA is characterized by persistent rather than inexorably worsening symptoms.
Project description:<h4>Background</h4>Cartilage morphometry based on magnetic resonance images (MRIs) is an emerging outcome measure for clinical trials among patients with knee osteoarthritis (KOA). However, current methods for cartilage morphometry take many hours per knee and require extensive training on the use of the associated software. In this study we tested the feasibility, reliability, and construct validity of a novel osteoarthritis cartilage damage quantification method (Cartilage Damage Index [CDI]) that utilizes informative locations on knee MRIs.<h4>Methods</h4>We selected 102 knee MRIs from the Osteoarthritis Initiative that represented a range of KOA structural severity (Kellgren Lawrence [KL] Grade 0 - 4). We tested the intra- and inter-tester reliability of the CDI and compared the CDI scores against different measures of severity (radiographic joint space narrowing [JSN] grade, KL score, joint space width [JSW]) and static knee alignment, both cross-sectionally and longitudinally.<h4>Results</h4>Determination of the CDI took on average14.4 minutes (s.d. 2.1) per knee pair (baseline and follow-up of one knee). Repeatability was good (intra- and inter-tester reliability: intraclass correlation coefficient >0.86). The mean CDI scores related to all four measures of osteoarthritis severity (JSN grade, KL score, JSW, and knee alignment; all p values < 0.05). Baseline JSN grade and knee alignment also predicted subsequent 24-month longitudinal change in the CDI (p trends <0.05). During 24 months, knees with worsening in JSN or KL grade (i.e. progressors) had greater change in CDI score.<h4>Conclusions</h4>The CDI is a novel knee cartilage quantification method that is rapid, reliable, and has construct validity for assessment of medial tibiofemoral osteoarthritis structural severity and its progression. It has the potential to addresses the barriers inherent to studies requiring assessment of cartilage damage on large numbers of knees, and as a biomarker for knee osteoarthritis progression.
Project description:Objective:To determine if people with incident accelerated knee osteoarthritis (AKOA) were more likely to receive a pharmacological treatment or arthroscopic knee surgery than those with typical knee osteoarthritis (KOA) or no KOA. Methods:We conducted a nested cohort study using data from baseline and the first 8 years of the Osteoarthritis Initiative. Eligible participants had no radiographic KOA at baseline (Kellgren-Lawrence [KL] < 2). We classified three groups using KL grades: 1) AKOA: knee progressed to advanced-stage KOA (KL 3/4) in 4 years or less, 2) typical KOA: knee increased in KL grade by 8 years (excluding AKOA), and 3) No KOA: no change in KL grade by 8 years. The outcome was self-reported arthroscopic knee surgery or a pharmacological treatment option: nonsteroidal anti-inflammatory drugs (NSAIDs), hyaluronic acid injections, intra-articular corticosteroid injections, or prescription analgesics. Between-group differences in therapeutic use were evaluated with Chi-square tests. Results:Adults who developed AKOA (n = 92) were more likely to report arthroscopic knee surgery (AKOA: 32%, KOA [n = 380]: 8%, no KOA [n = 875]: 3%; P < 0.001), hyaluronic acid injections (AKOA: 10%, KOA: 4%, no KOA: 1%; P < 0.001), intra-articular corticosteroid injections (AKOA: 30%, KOA: 7%, no KOA: 4%; P < 0.001), and NSAID use (over the counter: AKOA: 65%, KOA: 48%, and no KOA: 46%; P = 0.003; prescription: AKOA: 61%, KOA: 43%, no KOA: 41%; P = 0.002). Conclusion:Adults with AKOA are more likely to receive pharmacological treatment or arthroscopic knee surgery than their peers. Adults with AKOA are an important patient population that is understudied in clinical research despite their use of greater health care resources.
Project description:INTRODUCTION: Osteoarthritis (OA) is considered to be a multifactorial and polygenic disease and diagnosis is mainly clinical and radiological. Correlation between radiographic data and clinical status has been reported. However, very few studies, especially in Caucasian people, describe the association between the Kellgren and Lawrence OA grading scale (KL) and genetic alterations to better understand OA etiopathogenesis and susceptibility. In order to update the knee OA grading, in this study we assessed the associations between KL grade, clinical features such as American Knee Society Score (AKSS), age, and polymorphisms in the principal osteoarthritis susceptibility (OS) genes in Sicilian individuals. METHODS: In 66 Sicilian individuals affected by primary knee OA, the clinical and radiographic evaluation was performed using 2 sub-scores of AKSS (knee score (KS) and function score (FS)) and KL. The patients were also classified according to age. Online Mendelian Inheritance in Man (OMIM) and Database of Single Nucleotide Polymorphisms (dbSNP) Short Genetic Variations databases were used to select gene regions containing the following polymorphisms to analyze: FRZB rs288326 and rs7775, MATN3 rs77245812, ASPN D14 repeats, PTHR2 rs76758470, GDF5 rs143383 and DVWA rs11718863. Patient genotypes were obtained using Sanger DNA sequencing analysis. RESULTS: In our cohort of patients a statistical association between the variables analyzed was reported in all associations tested (KL versus KS, FS and age). We observed that a mild to severe OA radiographic grade is related to severe clinical conditions and loss of articular function and that the severity of symptoms increases with age. Concerning the genotyping analysis, our results revealed a significant statistical association between KL grading and GDF5 rs143383 and DVWA rs11718863 genetic alterations. The latter was also associated with a more severe radiographic grade, displaying its predictive role as OA marker progression. Statistically significant association between clinical, radiographic and genetic signs observed, suggests extending the actual grading of knee OA based mainly on X-ray features. CONCLUSIONS: This work represents a multidisciplinary and translational medicine approach to study OA where clinical, radiological, and OS5 and OS6 SNPs evaluation could contribute to better define grading and progression of OA and to the development of new therapies.
Project description:To explore the association of baseline trabecular bone structure with incident tibiofemoral (TF) osteoarthritis (OA) and with increase in joint space narrowing (JSN) score.The Multicenter Osteoarthritis Study (MOST) includes subjects with or at risk for knee OA. Knee radiographs were scored for Kellgren-Lawrence (KL) grade and JSN at baseline, 30, 60 and 84 months. Knees (KL ? 1) at baseline were assessed for incident OA (KL ? 2) and increases in JSN score. For each knee image at baseline, a variance orientation transform method (VOT) was applied to subchondral tibial bone regions of medial and lateral compartments. Seventeen fractal parameters were calculated per region. Associations of each parameter with OA incidence and with medial and lateral JSN increases were explored using logistic regression. Analyses were stratified by digitized film (DF) vs computer radiography (CR) and adjusted for confounders.Of 894 knees with CR and 1158 knees with DF, 195 (22%) and 303 (26%) developed incident OA. Higher medial bone roughness was associated with increased odds of OA incidence at 60 and 84 months and also, medial and lateral JSN increases (primarily vertical). Lower medial and lateral anisotropy was associated with increased odds of medial and lateral JSN increase. Compared to DF, CR had more associations and also, similar results at overlapping scales.Baseline trabecular bone texture was associated with incident radiographic OA and increase of JSN scores independently of risk factors for knee OA. Higher roughness and lower anisotropy were associated with increased odds for radiographic OA change.
Project description:Background To investigate the frequency of pain among subjects with advanced radiographic knee osteoarthritis (OA) defined as Kellgren–Lawrence (KL) grade 4 and clinical features associated with pain. Methods Subjects from the Hallym Aging Study (HAS), the Korean National Health and Nutrition Examination Survey (KNHANES), and the Osteoarthritis Initiative (OAI) were included. Participants were asked knee-specific questions regarding the presence of knee pain. Clinical characteristics associated with the presence of pain were evaluated with multivariable logistic regression analysis. Results The study population consisted of 504, 10,152 and 4796 subjects from HAS, KNHANES, and OAI, respectively. KL grade 4 OA was identified in 9.3, 7.6, and 11.5% of subjects, while pain was absent in 23.5, 31.2, and 5.9% of subjects in KL grade 4 knee OA, respectively. After multivariable analysis, female gender showed a significant association with pain in the KNHANES group, while in the OAI group, younger age did. Advanced knee OA patients without pain did not differ from non-OA subjects in most items of SF-12 in both Korean and OAI subjects. Total WOMAC score was not significantly different between non-OA and advanced knee OA subjects without pain in the OAI. Conclusions Our study showed that a considerable number of subjects with KL grade 4 OA did not report pain. In patients whose pain arises from causes other than structural damage of the joint, therapeutic decision based on knee X-ray would lead to suboptimal result. In addition, treatment options focusing solely on cartilage engineering, should be viewed with caution.
Project description:BACKGROUND:Prior research on accelerated knee osteoarthritis (AKOA) was primarily confined to the Osteoarthritis Initiative, which was enriched with people with risk factors for knee osteoarthritis (KOA). It is unclear how often AKOA develops in a community-based cohort and whether we can replicate prior findings from the Osteoarthritis Initiative in another cohort. Hence, we determined the incidence and characteristics of AKOA among women in the Chingford Study, which is a prospective community-based cohort. METHODS:The Chingford Study had 1003 women with quinquennial knee radiographs over 15?years. We divided the 15-year observation period into three consecutive 5-year phases. Within each 5-year phase, we selected 3 groups of participants among women who started a phase without KOA (Kellgren-Lawrence [KL]?<?2): 1) incident AKOA developed KL grade???3, 2) typical KOA increased radiographic scoring (excluding AKOA), and 3) no KOA had the same KL grade over time. Study staff recorded each participant's age, body mass index (BMI), and blood pressure at baseline, 5-year, and 10-year study visits. We used multinomial logistic regression models to test the association between groups (outcome) and age, BMI, and blood pressure at the start of each phase. The cumulative incidences and odds ratios (OR) from each phase were pooled using a fixed-effect meta-analysis model. RESULTS:The person-based cumulative incidence of AKOA was 3.9% over 5 years (pooled estimate across the three 5-year phases). Among incident cases of KOA, AKOA represented ~?15% of women with incident KOA. Women with AKOA were older than those with typical (OR?=?1.56, 95%CI?=?1.16-2.11) or no KOA (OR?=?1.84, 95%CI?=?1.40-2.43). Women with AKOA had a greater BMI than those without KOA (OR?=?1.52, 95%CI?=?1.17-1.97). We observed no association between group and blood pressure. CONCLUSIONS:In a community-based cohort, >?1 in 7 women with incident KOA had AKOA. Like the Osteoarthritis Initiative, people with AKOA were more likely to have greater age and BMI.