Genomic heterozygosity is associated with a lower risk of osteoarthritis.

BACKGROUND: Genomic heterozygosity has been shown to confer a health advantage in humans and play a protective role in complex diseases. Given osteoarthritis (OA) is a highly polygenic disease, we set out to determine if an association exists between OA and genomic heterozygosity. RESULTS: End-stage knee and hip OA patients and healthy controls were recruited from the Newfoundland and Labrador (NL) population. The Arthritis Research UK Osteoarthritis Genetics (arcOGEN) consortium database was utilized as a replication cohort. DNA was extracted from blood samples and genotyped. Individual rates of observed heterozygosity (HetRate) and heterozygosity excess (HetExcess) relative to the expected were mathematically derived, and standardized to a z-score. Logistic regression modeling was used to examine the association between OA and HetRate or HetExcess. A total of 559 knee and hip OA patients (mean age 66.5 years, body mass index (BMI) 33.7 kg/m2, and 55% females) and 118 healthy controls (mean age 56.4 years, BMI 29.5 kg/m2, and 59% female) were included in the NL cohort analysis. We found that OA had an inverse relationship with HetRate and HetExcess with odds ratios of 0.64 (95% CI: 0.45-0.91) and 0.65 (95% CI: 0.45-0.93) per standard deviation (SD), respectively. The arcOGEN data included 2,019 end-stage knee and hip OA patients and 2,029 healthy controls, validating our findings with HetRate and HetExcess odds ratios of 0.60 (95% CI: 0.56-0.64) and 0.44 (95% CI: 0.40-0.47) per SD, respectively. CONCLUSIONS: Our results are the first to clearly show evidence, from two separate cohorts, that reduced genomic heterozygosity confers a risk for the future development of OA.

Obesity and the risk of multiple or severe frequent knee pain episodes: a 4-year follow-up of the ELSA-Brasil MSK cohort.

BACKGROUND/OBJECTIVE: Knee pain is an important health problem due to its high prevalence, negative impact on daily activities and quality of life, and societal burden. While the link between excess weight and knee pain has been well-documented in the literature, many studies are limited to patients with osteoarthritis or use cross-sectional data. This longitudinal study investigated whether overweight and obesity were associated with the frequency and severity of frequent knee pain (FKP) episodes over 4 years in civil servants enrolled in the ELSA-Brasil MSK cohort. METHODS: Knee pain was assessed during baseline face-to-face interviews (2012-2014) and four yearly telephone follow-ups (2015-2019). Disabling FKP episodes or those of moderate to very severe intensity were classified as severe. Multinomial logistic regression models adjusted for confounders were used to test for associations in two participant groups: those with knee pain at baseline (prognosis cohort) and those without knee pain (incidence cohort). RESULTS: A total of 2644 participants were included: 54.2% female, mean age 55.8 (SD 8.8) years. In the incidence cohort (n = 1896), obesity increased the risk of one (OR: 1.63; 95% CI 1.13-2.37) and multiple FKP episodes (OR: 2.61; 95% CI 1.71-3.97), as well as the risk of non-severe (OR: 1.72; 95% CI 1.04-2.84) and severe FKP episodes (OR: 2.10; 95% CI 1.50-2.95). In the prognosis cohort (n = 748), obesity increased the risk of multiple (OR: 2.54; 95% CI 1.60-4.05) and severe FKP episodes (OR: 2.31; 95% CI 1.49-3.59). Overweight presented the same trends but fell short of significance. CONCLUSIONS: These results provide further support that overweight and obesity are important contributors to the incidence and worsening of FKP, and that weight management must be prioritized in multidisciplinary knee pain prevention and treatment programs to reduce the burden of musculoskeletal disorders.

Prognostic model to predict the incidence of radiographic knee osteoarthritis.

OBJECTIVE: Early diagnosis of knee osteoarthritis (KOA) in asymptomatic stages is essential for the timely management of patients using preventative strategies. We develop and validate a prognostic model useful for predicting the incidence of radiographic KOA (rKOA) in non-radiographic osteoarthritic subjects and stratify individuals at high risk of developing the disease. METHODS: Subjects without radiographic signs of KOA according to the Kellgren and Lawrence (KL) classification scale (KL=0 in both knees) were enrolled in the OA initiative (OAI) cohort and the Prospective Cohort of A Coruña (PROCOAC). Prognostic models were developed to predict rKOA incidence during a 96-month follow-up period among OAI participants based on clinical variables and serum levels of the candidate protein biomarkers APOA1, APOA4, ZA2G and A2AP. The predictive capability of the biomarkers was assessed based on area under the curve (AUC), and internal validation was performed to correct for overfitting. A nomogram was plotted based on the regression parameters. Model performance was externally validated in the PROCOAC. RESULTS: 282 participants from the OAI were included in the development dataset. The model built with demographic, anthropometric and clinical data (age, sex, body mass index and WOMAC pain score) showed an AUC=0.702 for predicting rKOA incidence during the follow-up. The inclusion of ZA2G, A2AP and APOA1 data significantly improved the model's sensitivity and predictive performance (AUC=0.831). The simplest model, including only clinical covariates and ZA2G and A2AP serum levels, achieved an AUC=0.826. Both models were internally cross-validated. Predictive performance was externally validated in an independent dataset of 100 individuals from the PROCOAC (AUC=0.713). CONCLUSION: A novel prognostic model based on common clinical variables and protein biomarkers was developed and externally validated to predict rKOA incidence over a 96-month period in individuals without any radiographic signs of disease. The resulting nomogram is a useful tool for stratifying high-risk populations and could potentially lead to personalised medicine strategies for treating OA.

Constructing a clinical radiographic knee osteoarthritis database using artificial intelligence tools with limited human labor: A proof of principle.

OBJECTIVE: To create a scalable and feasible retrospective consecutive knee osteoarthritis (OA) radiographic database with limited human labor using commercial and custom-built artificial intelligence (AI) tools. METHODS: We applied four AI tools, two commercially available and two custom-built tools, to analyze 6 years of clinical consecutive knee radiographs from patients aged 35-79 at the University of Copenhagen Hospital, Bispebjerg-Frederiksberg Hospital, Denmark. The tools provided Kellgren-Lawrence (KL) grades, joint space widths, patella osteophyte detection, radiographic view detection, knee joint implant detection, and radiographic marker detection. RESULTS: In total, 25,778 knee radiographs from 8575 patients were included in the database after excluding inapplicable radiographs, and 92.5% of the knees had a complete OA dataset. Using the four AI tools, we saved about 800 hours of radiologist reading time and only manually reviewed 16.0% of the images in the database. CONCLUSIONS: This study shows that clinical knee OA databases can be built using AI with limited human reading time for uniform grading and measurements. The concept is scalable temporally and across geographic regions and could help diversify further OA research by efficiently including radiographic knee OA data from different populations globally. We can prevent data dredging and overfitting OA theories on existing trite cohorts by including various gene pools and continuous expansion of new clinical cohorts. Furthermore, the suggested tools and applied approaches provide an ability to retest previous hypotheses and test new hypotheses on real-life clinical data with current disease prevalence and trends.

Mitonuclear epistasis involving TP63 and haplogroup Uk: Risk of rapid progression of knee OA in patients from the OAI.

OBJECTIVE: To investigate genetic interactions between mitochondrial deoxyribonucleic acid (mtDNA) haplogroups and nuclear single nucleotide polymorphisms (nSNPs) to analyze their impact on the development of the rapid progression of knee osteoarthritis (OA). DESIGN: A total of 1095 subjects from the Osteoarthritis Initiative, with a follow-up time of at least 48-months, were included. Appropriate statistical approaches were performed, including generalized estimating equations adjusting for age, gender, body mass index, contralateral knee OA, Western Ontario and McMaster Universities Osteoarthritis Index pain, previous injury in target knee and the presence of the mtDNA variant m.16519C. Additional genomic data consisted in the genotyping of Caucasian mtDNA haplogroups and eight nSNPs previously associated with the risk of knee OA in robust genome-wide association studies. RESULTS: The simultaneous presence of the G allele of rs12107036 at TP63 and the haplogroup Uk significantly increases the risk of a rapid progression of knee OA (odds ratio = 1.670; 95% confidence interval [CI]: 1.031-2.706; adjusted p-value = 0.027). The assessment of the population attributable fraction showed that the highest proportion of rapid progressors was under the simultaneous presence of the G allele of rs12107036 and the haplogroup Uk (23.4%) (95%CI: 7.89-38.9; p-value < 0.05). The area under the curve of the cross-validation model (0.730) was very similar to the obtained for the predictive model (0.735). A nomogram was constructed to help clinicians to perform clinical trials or epidemiologic studies. CONCLUSIONS: This study demonstrates the existence of a mitonuclear epistasis in OA, providing new mechanisms by which nuclear and mitochondrial variation influence the susceptibility to develop different OA phenotypes.

Assessing the association of epigenetic age acceleration with osteoarthritis in the Multicenter Osteoarthritis Study (MOST).

PURPOSE: Advancing age is one of the strongest risk factors for osteoarthritis (OA). DNA methylation-based measures of epigenetic age acceleration may provide insights into mechanisms underlying OA. METHODS: We analyzed data from the Multicenter Osteoarthritis Study in a subset of 671 participants ages 45-69 years with no or mild radiographic knee OA. DNA methylation was assessed with the Illumina Infinium MethylationEPIC 850K array. We calculated predicted epigenetic age according to Hannum, Horvath, PhenoAge, and GrimAge epigenetic clocks, then regressed epigenetic age on chronological age to obtain the residuals. Associations between the residuals and knee, hand, and multi-joint OA were assessed using logistic regression, adjusted for chronological age, sex, clinical site, smoking status, and race. RESULTS: Twenty-three percent met criteria for radiographic hand OA, 25% met criteria for radiographic knee OA, and 8% met criteria for multi-joint OA. Mean chronological age (SD) was 58.4 (6.7) years. Mean predicted epigenetic age (SD) according to Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks was 64.9 (6.4), 68.6 (5.9), 50.5 (7.7), and 67.0 (6.2), respectively. Horvath epigenetic age acceleration was not associated with an increased odds of hand OA, odds ratio (95% confidence intervals) = 1.03 (0.99-1.08), with similar findings for knee and multi-joint OA. We found similar magnitudes of associations for Hannum epigenetic age, PhenoAge, and GrimAge acceleration compared to Horvath epigenetic age acceleration. CONCLUSIONS: Epigenetic age acceleration as measured by various well-validated epigenetic clocks based on DNA methylation was not associated with increased risk of knee, hand, or multi-joint OA independent of chronological age.

Plasma Cartilage Acidic Protein 1 Measured by ELISA Is Associated With the Progression to Total Joint Replacement in Postmenopausal Women.

OBJECTIVE: To investigate the association of plasma cartilage acidic protein 1 (CRTAC1), a novel biochemical marker of osteoarthritis (OA), and total joint replacement (TJR) in postmenopausal women. METHODS: The association of plasma CRTAC1 with the incidence of TJR was investigated in a prospective cohort including 478 postmenopausal women. A total of 38 women underwent a TJR for OA during a median follow-up of 18 years. Every one of the TJR cases were age- and BMI (kg/m2)-matched with 2 controls with no TJR from the same cohort. Plasma CRTAC1 was measured before TJR. The association between CRTAC1 and TJR incidence was investigated by conditional logistic regression. RESULTS: Increased CRTAC1 was associated with a higher risk of TJR with an odds ratio (OR) of 1.80 (95% CI 1.11-2.92) for 1 SD increase, which remained significant after adjusting for Western Ontario and McMaster Universities Osteoarthritis Index, knee OA baseline severity (Kellgren-Lawrence grade), hip OA, and hip bone mineral density. Urinary crosslinked C-telopeptide of type II collagen (CTX-II) was also associated with a higher risk of TJR with an adjusted OR of 1.83 (95% CI 1.11-3.00). When CRTAC1 and CTX-II were included in the same model, both markers were significantly associated with TJR with similar ORs. CONCLUSION: CRTAC1 is a new risk indicator of TJR for OA in postmenopausal women. Combined with knee and hip OA and CTX-II, it may help to identify subjects at risk for TJR.

Urinary incontinence in middle-aged and older women with hip and knee osteoarthritis: An outpatient study of frequency and risk factors.

AIMS: To investigate the frequency and the factors associated with urinary incontinence (UI) in a sample of middle-aged and older women with lower limb osteoarthritis (OA). METHODS: Women aged 50 years or older with clinical hip/knee OA diagnoses were recruited for this cross-sectional study. Self-reported UI and type, sociodemographic characteristics, medical conditions, physical activity level, anthropometric and body composition measurements, muscle strength, and physical function were assessed. Uni and multivariable logistic regression were used to investigate the factors associated with UI. RESULTS: Among 100 middle-aged and older women (mean 67.27 ± 8.77 SD years), 67% reported UI. In the UI group, 33% reported stress UI, 36% reported urgency UI, and 31% reported mixed UI. In the univariate analysis, age, level of physical activity, pulmonary disease, number of medications, body mass index (BMI), number of deliveries, and activity limitation were significantly associated with UI. In the multivariable analysis, older age (60-69 years OR: 4.91, 95% CI: 1.25-19.36; ≥70 years OR: 8.06, 95% CI: 1.96-33.22), compared to 50-59 years, morbid obesity (OR: 14.10, 95% CI: 1.36-146.48), compared to BMI < 30 kg/m2 , and activity limitation (OR: 5.31, 95% CI: 1.61-17.54), assessed as short physical performance battery ≤8, remained significantly associated with UI. CONCLUSIONS: UI was highly frequent among middle-aged and older women with hip/knee OA. Older age, activity limitation, and morbid obesity were independently associated with UI. Interventions targeting physical function and weight management must be considered to prevent and treat UI in this population.

Increased Risk of New-Onset Rheumatoid Arthritis Among Osteoarthritis Patients Received Total Knee Arthroplasty: a global federated health network analysis.

Background: Complications of total knee arthroplasty (TKA) had been widely discussed. However, whether TKA influence risk of rheumatoid arthritis (RA) in osteoarthritis patients remained uncertain. We intend to evaluate the risk of RA in osteoarthritis patients underwent TKA. Methods: In this retrospective cohort study, data was retrieved from the US collaborative networks in TriNetX research network. Within the study period between 2005 and 2017, osteoarthritis patients underwent TKA were enrolled as case cohort whereas osteoarthritis patients never underwent TKA were enrolled as control cohort. Covariates were matched via propensity score matching. Risk of RA in TKA patients were valuated under various follow-up time and sensitivity models. Results: Under 1-year, 3-year and 5-year of follow-up, TKA patients were associated with significantly elevated risk of RA, especially under 1-year follow-up (HR=1.74; 95% CI, 1.39-2.18). Subgroup analysis demonstrated a significant increase in the risk of RA following TKA in the female subgroup (HR=1.42; 95% CI, 1.24-1.63), the subgroup aged 18-64 years (HR=1.48; 95% CI, 1.11-1.97), and the subgroup aged greater than 65 years old (HR=1.38; 95% CI, 1.21-1.58) based on 5-year follow-up. Conclusion: Clinicians should be concerned about uncharted association between TKA and RA reported our current study. Additional prospective studies and in-depth mechanistic inquiries were warranted to determine the causation.

Causal relationship between sarcopenia with osteoarthritis and the mediating role of obesity: a univariate, multivariate, two-step Mendelian randomization study.

BACKGROUND: Recent genetic evidence supports a causal role for sarcopenia in osteoarthritis, which may be mediated by the occurrence of obesity or changes in circulating inflammatory protein levels. Here, we leveraged publicly available genome-wide association study data to investigate the intrinsic causal relationship between sarcopenia, obesity, circulating inflammatory protein levels, and osteoarthritis. METHODS: In this study, we used Mendelian randomization analyses to explore the causal relationship between sarcopenia phenotypes (Appendicular lean mass [ALM], Low hand-grip strength [LHG], and usual walking pace [UWP]) and osteoarthritis (Knee osteoarthritis [KOA], and Hip osteoarthritis [HOA]). Univariable Mendelian randomization (UVMR) analyses were performed using the inverse variance weighted (IVW) method, MR-Egger, weighted median method, simple mode, and weighted mode, with the IVW method being the primary analytical technique. Subsequently, the independent causal effects of sarcopenia phenotype on osteoarthritis were investigated using multivariate Mendelian randomization (MVMR) analysis. To further explore the mechanisms involved, obesity and circulating inflammatory proteins were introduced as the mediator variables, and a two-step Mendelian randomization analysis was used to explore the mediating effects of obesity and circulating inflammatory proteins between ALM and KOA as well as the mediating proportions. RESULTS: UVMR analysis showed a causal relationship between ALM, LHG, UWP and KOA [(OR = 1.151, 95% CI: 1.087-1.218, P = 1.19 × 10-6, PFDR = 7.14 × 10-6) (OR = 1.215, 95% CI: 1.004-1.470; P = 0.046, PFDR = 0.055) (OR = 0.503, 95% CI: 0.292-0.867; P = 0.013, PFDR = 0.027)], and a causal relationship between ALM, UWP and HOA [(OR = 1.181, 95% CI: 1.103-1.265, P = 2.05 × 10-6, PFDR = 6.15 × 10-6) (OR = 0.438, 95% CI: 0.226-0.849, P = 0.014, PFDR = 0.022)]. In the MVMR analyses adjusting for confounders (body mass index, insomnia, sedentary behavior, and bone density), causal relationships were observed between ALM, LHG, UWP and KOA [(ALM: OR = 1.323, 95%CI: 1.224- 1.431, P = 2.07 × 10-12), (LHG: OR = 1.161, 95%CI: 1.044- 1.292, P = 0.006), (UWP: OR = 0.511, 95%CI: 0.290- 0.899, P = 0.020)], and between ALM and HOA (ALM: OR = 1.245, 95%CI: 1.149- 1.348, P = 7.65 × 10-8). In a two-step MR analysis, obesity was identified to play a potential mediating role in ALM and KOA (proportion mediated: 5.9%). CONCLUSIONS: The results of this study suggest that decreased appendicular lean mass, grip strength, and walking speed increase the risk of KOA and decreased appendicular lean mass increases the risk of HOA in patients with sarcopenia in a European population. Obesity plays a mediator role in the occurrence of KOA due to appendicular lean body mass reduction.

Incidence of knee and hip joint replacement associated with cumulative exposure to physical factors at work.

BACKGROUND: Knee osteoarthritis (OA) has been quite consistently associated with high physical workload and specific physical factors at work, while for hip OA, fewer studies are available, which still indicate possible associations with heavy lifting and physical workload. The objective of the study was to assess the association between exposure to workplace physical factors and incidence of knee and hip arthroplasty, as markers of severe OA in these joints. METHODS: The study population was composed of employees 25-60 years who participated in the Turin 2011 census. For each job held since 1995, exposure to physical factors was assigned to individuals in the cohort through a Job-Exposure Matrix constructed from the Italian O*NET database. Using Poisson regression models, the incidence of knee and hip arthroplasty for OA, identified through hospitalizations from 2012 to 2018, was examined in relation to cumulative exposure to 7 different physical hazards and a composite indicator of physical workload constructed from 17 physical factors (Ergo-Index). RESULTS: The risk of knee OA was significantly increased in the highest cumulative exposure quartile of physical workload (incidence rate ratio = 1.98, 95% confidence interval: 1.24-3.16) and of all single hazards examined, compared to the lowest quartile, with significant trends in risk with increasing exposure. In contrast, no association was found with hip OA, whose relative risks were close to or below one in all higher-exposure quartiles of physical workload and of each single hazard. CONCLUSIONS: Our results indicate that exposure to physical hazards at work increases the likelihood of developing knee OA, but not hip OA.

Causal analysis of body composition measurements in osteoarthritis knee: a two-sample mendelian randomization study.

BACKGROUND: To analyse the causal associations of different physical measures with osteoarthritis knee (KOA). METHODS: Exposure factors (weight, body mass index (BMI), body fat percentage, waist circumference, hip circumference, waist-hip ratio (WHR), and basal metabolic rate (BMR)), and outcome factor KOA were analyzed by inverse-variance weighted (IVW) method, along with heterogeneity test, sensitivity and pleiotropy analyses. Meta-analysis was used to combine the effect values of IVW methods in different data sources. RESULTS: Weight, BMI, body fat percentage, waist circumference, hip circumference and BMR analyses showed causal association with increased KOA risk, while WHR analysis indicated a reduction of the incidence of KOA. P-value for all the results was less than 0.05 and F-value large than 20. All results were negative for heterogeneity tests and sensitivity analyses, and there was pleiotropy in weight and BMR. Meta-analysis results showed that the results of Odds Ratios (95% Confidence Intervals) for Weight (1.43(1.35-1.51)), BMI (1.40(1.10-1.78)), body fat percentage (1.56(1.44-1.68)), waist circumference (1.40(1.10-1.78)), hip circumference (1.37(1.30-1.44)), WHR (0.86(0.71-1.04)) and BMR (1.36(1.27-1.46) were consistent with the ones by Mendelian randomization analyses. CONCLUSIONS: Body fat percentage may be a better indicator of KOA than BMI. In addition, weight and BMR may have a causal effect in KOA, but WHR does not have a causal relationship. BMI, body fat percentage, waist circumference, and hip circumference has a causal effect on KOA.

Phenotypes of osteoarthritis-related knee pain and their transition over time: data from the osteoarthritis initiative.

BACKGROUND: Identification of knee osteoarthritis (OA) pain phenotypes, their transition patterns, and risk factors for worse phenotypes, may guide prognosis and targeted treatment; however, few studies have described them. We aimed to investigate different pain phenotypes, their transition patterns, and potential risk factors for worse pain phenotypes. METHODS: Utilizing data from the Osteoarthritis Initiative (OAI), pain severity was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. We identified the activity-related pain phenotypes and estimated the transition probabilities of pain phenotypes from baseline to the 24-month using latent transition analysis. We examined the risk factors at baseline with the 24-month pain phenotypes and the transition of pain phenotypes. RESULTS: In 4796 participants, we identified four distinct knee pain phenotypes at both baseline and 24-month follow-up: no pain, mild pain during activity (Mild P-A), mild pain during both rest and activity (Mild P-R-A), and moderate pain during both rest and activity (Mod P-R-A). 82.9% knees with no pain at baseline stayed the same at 24-month follow-up, 17.1% progressed to worse pain phenotypes. Among "Mild P-A" at baseline, 32.0% converted to no-pain, 12.8% progressed to "Mild P-R-A", and 53.2% remained. Approximately 46.1% of "Mild P-R-A" and 54.5% of "Mod P-R-A" at baseline experienced remission by 24-month. Female, non-whites, participants with higher depression score, higher body mass index (BMI), higher Kellgren and Lawrence (KL) grade, and knee injury history were more likely to be in the worse pain phenotypes, while participants aged 65 years or older and with higher education were less likely to be in worse pain phenotypes at 24-month follow-up visit. Risk factors for greater transition probability to worse pain phenotypes at 24-month included being female, non-whites, participants with higher depression score, higher BMI, and higher KL grade. CONCLUSIONS: We identified four distinct knee pain phenotypes. While the pain phenotypes remained stable in the majority of knees over 24 months period, substantial proportion of knees switched to different pain phenotypes. Several socio-demographics as well as radiographic lesions at baseline are associated with worse pain phenotypes at 24-month follow-up visit and transition of pain phenotypes.

Clinical phenotypes of comorbidities in end-stage knee osteoarthritis: a cluster analysis.

OBJECTIVES: Comorbidities, as components of these heterogeneous features, often coexist with knee osteoarthritis, and are particularly prevalent in end-stage knee osteoarthritis. Here, we attempted to identify the different clinical phenotypes of comorbidities in patients with end-stage knee osteoarthritis by cluster analysis. METHODS: A total of 421 inpatients diagnosed with end-stage knee osteoarthritis who underwent inpatient surgery were included in this cross-sectional study. 23 demographic, comorbidity, inflammatory immune and evaluation scale variables were collected. Systematic clustering after factor analysis and separate two-step cluster analysis were performed for individual comorbidity variables and all variables, respectively, to objectively identify the different clinical phenotypes of the study patients. RESULTS: Four clusters were finally identified. Cluster 1 had the largest proportion of obese patients (93.8%) and hypertension was common (71.2%). Almost all patients in cluster 2 were depressed (95.8%) and anxiety disorders (94.7%). Cluster 3 combined patients with isolated end-stage knee osteoarthritis and a few comorbidities. Cluster 4 had the highest proportion of patients with rheumatoid arthritis (58.8%). CONCLUSIONS: Patients with end-stage knee osteoarthritis may be classified into four different clinical phenotypes: "isolated end-stage knee osteoarthritis"; "obesity + hypertension"; "depression + anxiety"; and "rheumatoid arthritis", which may help guide individualized patient care and treatment strategies.

Radiographic knee osteoarthritis severity has no impact on fall risk: the locomotive syndrome and health outcomes in the aizu cohort study (LOHAS): a cross-sectional study.

BACKGROUND: To investigate factors that have an impact on the risk of falls and determine whether radiographic knee osteoarthritis (KOA) is a factor involved in falls independent of knee pain, psychological factors, and physical function. METHODS: A cross-sectional analysis was conducted on 1083 subjects for the 2009 Locomotive Syndrome and Health Outcomes in the Aizu Cohort Study (LOHAS). A logistic regression analysis was performed to examine the relationship between radiographic KOA and fall history. RESULTS: Fall history was significantly associated with the severity of knee pain. Compared to subjects with no knee pain, the odds ratio (OR) was 1.53 times higher in the subjects with mild knee pain (95% confidence interval [CI]: 1.04-2.25), 1.69 times higher in those with moderate knee pain (95%CI: 1.03-2.79), and 2.98 times higher in those with severe knee pain (95%CI: 1.67-5.30). In subjects with depression, the OR was 1.91 (95%CI: 1.25-2.92), and in those with decreased mobility, the OR was 1.70 (95%CI: 1.08-2.69). Age, gender, knee crepitus, BMI, OLST, and sleeping pill use were not significantly associated with fall risk. In a multivariate analysis, radiographic KOA severity was not significantly associated with fall risk (OR 0.81, 95%CI 0.44-1.50 in mild OA; OR 1.10, 95%CI 0.57-2.14 in severe OA). CONCLUSION: Knee pain, decreased mobility, and depression, but not the radiographic KOA severity, were significantly associated with a fall risk. Regardless of the individual's radiographic KOA severity, the risk of falls may be reduced by treating his/her knee pain, mobility problems, and/or psychological factors.

Association of physical activity trajectories over 8 years and risk of knee replacement: data from the osteoarthritis initiative.

BACKGROUND: To identify physical activity (PA) trajectories in adults with or at risk of knee osteoarthritis and to evaluate the association of PA trajectories with incident knee replacement (KR). METHODS: This study used data from the Osteoarthritis Initiative. The Physical Activity Scale for the Elderly and the KR were assessed annually from baseline to 9 years. Individuals were included if they did not undergo KR surgery at baseline and had data on PA at ≥ 1 visit before KR. Latent class growth mixture Modeling was used to identify the optimal trajectories of PA before KR. Log-binomial regression models were used to assess the association between PA trajectories and the risk of KR. Data analyses were conducted in all individuals and those with radiographic osteoarthritis (ROA) and significant knee pain (Western Ontario and McMaster Osteoarthritis Index pain score of ≥ 5 on a 0-20 scale) at baseline, respectively. RESULTS: Of 4731 participants (mean age 61.1 years, 58.5% female), four distinct and slightly declined PA trajectories were identified. Compared to individuals with a "Low" PA trajectory, those with "Medium-low", "Medium-high", or "High" PA trajectories were not significantly associated with the risk of KR (risk ratios: 0.97-1.19, all p > 0.05). Similar PA trajectories and associations with the risk of KR were observed in the subgroups of individuals with radiographic osteoarthritis and those with significant knee pain at baseline, respectively. CONCLUSION: In participants with or at risk of knee osteoarthritis, PA slightly declines over time and may play no role in the risk of KR.

Association between Dietary total antioxidant capacity and knee osteoarthritis: a case-control study in the Iranian Population.

AIM: Knee osteoarthritis (KOA) is a prevalent chronic condition associated with significant pain, disability, and healthcare costs, particularly among the elderly population. Despite the considerable burden of KOA, effective treatment options for managing the condition's underlying causes remain limited. This case-control study aims to investigate the relationship between dietary total antioxidant capacity (DTAC) and knee osteoarthritis. METHODS: This case-control study was conducted on 105 patients with confirmed KOA and 210 controls. KOA was diagnosed based on the American College of Rheumatology criteria. Dietary total antioxidant capacity (DTAC) was calculated based on the ferric-reducing antioxidant power method. RESULTS: The mean age and BMI of the participants were 53.6 ± 8.8 years old and 27.3 ± 2.7 kg/m2, respectively. The study participant's DTAC score ranged from 3.56 to 25.32 with a mean and SD of 12.46 ± 5.12. In the crude model, individuals in the highest quartile of DTAC score had 71% lower odds of having knee osteoarthritis compared to those in the first quartile (OR: 0.29, 95%CI: 0.15 to 0.58, P-trend < 0.001). These associations remained significant after adjustment for potential confounders including age, sex, energy intake, family history of osteoarthritis, vitamin D and calcium use, physical activity level, cigarette smoking and BMI. Although the odds of having knee osteoarthritis decreased with increasing quartiles of DTAC in both sexes, this relationship was stronger among males than females. CONCLUSION: The results of this study showed that there was an inverse correlation between DTAC and KOA among the Iranian patients with KOA.

Regional disparities, age-related changes and sex-related differences in knee osteoarthritis.

BACKGROUND: The objective of the study is to analyse the regions, age and sex differences in the incidence of knee osteoarthritis (KOA). METHODS: Data were extracted from the global burden of diseases (GBD) 2019 study, including incidence, years lived with disability (YLD), disability-adjusted life-years (DALYs) and risk factors. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in age standardized rate (ASR) of KOA. Paired t-test, paired Wilcoxon signed-rank test and spearman correlation were performed to analyze the association of sex disparity in KOA and socio-demographic index (SDI). RESULTS: There were significant regional differences in the incidence of knee osteoarthritis. In 2019, South Korea had the highest incidence of knee osteoarthritis (474.85,95%UI:413.34-539.64) and Thailand had the highest increase in incidence of knee osteoarthritis (EAPC = 0.56, 95%CI = 0.54-0.58). Notably, higher incidence, YLD and DALYs of knee osteoarthritis were associated with areas with a high socio-demographic index (r = 0.336, p < 0.001; r = 0.324, p < 0.001; r = 0.324, p < 0.001). In terms of age differences, the greatest increase in the incidence of knee osteoarthritis was between the 35-39 and 40-44 age groups. (EAPC = 0.52, 95%CI = 0.40-0.63; 0.47, 95%CI = 0.36-0.58). In addition, there were significant sex differences in the disease burden of knee osteoarthritis (P < 0.001). CONCLUSIONS: The incidence of knee osteoarthritis is significantly different with regions, age and sex.

Contralateral knee osteoarthritis is a risk factor for ipsilateral knee osteoarthritis progressing: a case control study.

BACKGROUND: Knee osteoarthritis (KOA) is a highly disabling disease, and studying its progression is crucial. However, it is still unclear whether the progression of ipsilateral knee osteoarthritis is influenced by contralateral knee osteoarthritis. METHODS: Data were collected from the OAI database and divided into two study cohorts (right/left KOA cohort). Each cohort had a target knee (right/left knee) and was further divided into two groups (exposure/control group). The demographic data of both cohorts were balanced at baseline by propensity score matching (PSM), and the data included rating scale and radiographic and clinical data. After checking for balance in the matched variables, we then compared the differences between the two groups in each cohort. Our primary focus was on the minimum joint space width (mJSW) of the target knee, which was measured four years after baseline. The secondary outcome was the arthroplasty rate of the target knee within nine years. RESULTS: In this study, a total of 678 participants were enrolled and matched. After 1:1 PSM of the baseline demographic data, 98 participants in the right KOA cohort (RKOAC) were successfully matched, and 117 participants in the left KOA cohort (LKOAC) were successfully matched. Furthermore, the standardized mean difference (SMD) of the matched variables in both cohorts was less than 0.25. After analyzing the outcome metrics, we found that the target knee had a significantly lower mJSW in the fourth year after baseline and a significantly greater arthroplasty rate within nine years in the exposed group than in the control group. RKOAC: mJSW (exposure: 2.6(1.1 ~ 3.6) vs. control: 3.3(2.0 ~ 4.2), P < 0.05), arthroplasty rate (exposure: 14(14.3%) vs. control: 4(4.1%), P < 0.05); LKOAC: mJSW (exposure: 3.1(2 ~ 3.9) vs. control: 3.4(2.6 ~ 4.2), P < 0.05), arthroplasty rate (exposure: 16(13.7%) vs. control: 7(6%), P < 0.05). CONCLUSIONS: Patients with knee osteoarthritis experienced greater progression of osteoarthritis when the contralateral knee was also affected.

Eligibility for knee arthroplasty is associated with increased risk of acquired hallux valgus - a Mendelian randomized study.

OBJECTIVE: Clinically, it has been found that patients undergoing knee replacement have a high incidence of concomitant hallux valgus. In this study, we analyzed whether patients with osteoarthritis who underwent surgery and those patient who did not have surgery had an increased risk of hallux valgus by Mendelian randomization and performed reverse causal analysis. DESIGN: Genomewide association study (GWAS) data for osteoarthritis, categorized by knee arthritis with joint replacement, knee arthritis without joint replacement, hip arthritis with joint replacement, and hip arthritis without joint replacement.And acquired hallux valgus were downloaded for Mendelian randomized studies. MR analysis was performed using inverse variance-weighted (IVW), weighted median, and MR-Egger methods. MR-egger regression, MR pleiotropic residuals and outliers (MR-presso), and Cochran's Q statistical methods were used to evaluate heterogeneity and pleiotropy. RESULTS: The IVW results indicate that, compared to healthy individuals, patients who meet the criteria for knee osteoarthritis joint replacement surgery have a significantly higher risk of acquired hallux valgus. There were no significant causal relationships found for the remaining results. No significant heterogeneity or multiplicity was observed in all the Mr analyses. CONCLUSION: Our study supports the increased risk of acquired hallux valgus in patients eligible for knee replacement. There is necessary for clinicians to be concerned about the hallux valgus status of patients undergoing knee arthroplasty.