Risk Of Knee Osteoarthritis Research Articles

Mendelian randomization analysis of female reproductive factors on osteoarthritis.

Epidemiology shows women have a higher incidence of osteoarthritis (OA) than men. However, there is not enough evidence to suggest a direct correlation between female reproductive factors and OA. Therefore, this study will employ Mendelian randomization (MR) analysis to investigate whether there is a causal relationship between the 2. This study used a 2-sample MR analysis with single nucleotide polymorphisms significantly associated with female reproductive factors as instrumental variables (IV). We used inverse variance weighted (IVW), MR-Egger regression, weighted median method to infer a causal relationship between female reproductive factors and OA, Cochran Q heterogeneity test by IVW and MR-Egger method, MR PRESSO method and IVW-radial method to detect outliers, MR_pleiotropy_test function and MR PRESSO method for multivariate validity test, and calculation of F-value was used to assess the presence of weak IVs. Finally, the stability of the findings was assessed using the leave-one-out method. Our research shows that there is no reliable causal relationship between an increase in Age at menarche (years) (AAM) and Age at menopause (years) (AM) and OA, that an increase in Age first had sexual intercourse (years) (AFS) is associated with a decreased risk of knee OA and/or hip OA and hand OA, that an increase in Age at first live birth (years) (AFB) is associated with a decreased risk of knee OA and/or hip OA and knee OA, and that an increase in Number of live births (NOB) is associated with an increased risk of knee OA and/or hip OA. This study provides genetic support for an increase in AFS as a reduced knee OA and/or hip OA and hand OA risk factor, an increase in AFB as a reduced knee OA and/or hip OA and knee OA risk factor, and an increase in NOB as an increased knee OA and/or hip OA risk factor. Further studies are needed to elucidate the potential mechanisms underlying the causal associations between AFS, AFB, and NOB and site-specific OA.

"Association of vitamin D blood deficiency and the rs731236 polymorphism vitamin D receptor with primary knee osteoarthritis in subjects from Mexico".

Vitamin D deficiency is a public health problem worldwide. Some studies have associated serum vitamin D deficiency with knee osteoarthritis. Additionally, some vitamin D receptor polymorphisms have been linked to knee osteoarthritis. This study analyzed the associations among the rs731236 polymorphism of the vitamin D receptor, blood levels of vitamin D and primary knee osteoarthritis in a population from northern Mexico.A case‒control study was conducted from November 2023 to June 2024 with 449 unrelated participants. The vitamin D concentration in the blood was measured semiquantitatively. The presence of vitamin D receptor gene polymorphism genotypes (rs731236) was determined via the rhAmpTM SNP Assay methodology. We used the chi-square test to compare the groups and odds ratios with confidence intervals to calculate risk.In the presence of vitamin D deficiency, subjects showed a 1.5-fold increased risk of primary knee osteoarthritis (59.5%; p = 0.001). Notably, this association remained significant for subjects carrying the AA and AG genotypes and in a dominant model (60.0%, p = 0.023; 61.1%, p = 0.008 and 59.0%, p = 0.042, respectively), after including a multivariate association model.Our study identified a high prevalence of Vitamin D deficiency among individuals with primary knee osteoarthritis. This study suggests a potential association between deficient levels of vitamin D and primary KOA in carriers of the AA and AG rs731236 genotypes. Key Points • We observed a significant 1.5-fold increased risk of primary knee osteoarthritis in the presence of vitamin D deficiency. • Vitamin D deficiency is significantly associated with primary knee osteoarthritis in carriers of AA and AG genotypes of rs73123.

Viral infections of the central nervous system increase the risk of knee osteoarthritis: a two-sample mendelian randomization study

ObjectiveOsteoarthritis (OA) represents a condition under the influence of central nervous system (CNS) regulatory mechanisms. This investigation aims to examine the causal association between viral infections of the central nervous system (VICNS) and inflammatory diseases of the central nervous system (IDCNS) and knee osteoarthritis (KOA) at the genetic level.MethodsIn this investigation, VICNS and IDCNS were considered as primary exposure variables, while KOA served as the primary outcome. Employing a two-sample mendelian randomization (MR) approach, we conducted an analysis utilizing summary data derived from genome-wide association studies (GWAS). The GWAS summary data pertaining to VICNS and IDCNS were procured from the Finnish consortium, whereas the IEU OpenGWAS database furnished the requisite data for KOA. To ensure the robustness of our genetic causal assessment, a comprehensive array of sensitivity analyses was undertaken, encompassing evaluations of heterogeneity, horizontal pleiotropy, outlier identification, leave-one-out analyses, and assessment of the normal distribution.ResultsThe results of the MR analyses revealed a suggestive positive genetic causal relationship between VICNS and KOA (P = 0.012, odds ratio [OR] with a 95% confidence interval [CI] of 1.033 [1.007–1.059]). Conversely, the MR analyses did not indicate any evidence of genetic causation between IDCNS and KOA (P = 0.575, OR 95% CI = 0.986 [0.940–1.035]). Importantly, the genetic causal assessment of the exposure and outcome variables did not demonstrate any indications of heterogeneity, horizontal pleiotropy, or outliers. Furthermore, this assessment remained robust against the influence of individual single nucleotide polymorphisms (SNPs) and exhibited adherence to a normal distribution.ConclusionThe result of this study has elucidated a suggestive positive genetic causal link between the VICNS and KOA. However, no such genetic causal relationship was observed between the IDCNS and KOA. These findings substantiate the genetic underpinnings supporting the association between the CNS and OA.

Socioeconomic Factors and Risk of Knee Osteoarthritis: A Case-Control Study

Background: The risk factor for knee osteoarthritis (knee OA) is multifactorial. Socioeconomic status is a risk factor that is commonly underreported. The study aims to find the relationship between socio-economic factors and knee OA, and the influence of these on gender. Methods: This is a case-control study conducted at Orthopaedic Hospital Wamakko, Sokoto, North-Western Nigeria between January 2022 and December 2022. Adult patients aged >40 years with knee OA were included in the study. The data was collected via participants’ interviews through a self-administered questionnaire. The risk factors for knee OA under consideration were occupation, educational level, and monthly income. Data were analysed using the SPSS version 23. The significant level was set at less than 5%. Results: There were a total of 372 patients in the study, with 124 cases and 248 controls in a ratio of 1:2. The average age was 53.7±10.8 (range 40 to 88 years). There were 165(44.4%) males and 207(55.6%) females. For occupation, 201(53.7%) were unemployed, 60(16%) on business, 61(16.3%) were civil servants and 50(13.4%) worked as farmers. For education, 250(66.8%) had non-formal education, and 122(32.6%) had formal education. Most patients (237/57.8%) were high-income earners and 135 (41.7%) were low-income earners. The knee OA prevalence was 13.17% for males and 20.16% for females. In the case group, the majority were unemployed with 63 (50.8%) patients and the least were farmers with only 16 (12.9%). Non-formal education was the most common educational level among the cases with 89(71.8%), and low-income earners are also more common with 74(59.7%) compared with high-income earners with 61 (40.3%). There was a statistically significance result between socioeconomic status and knee OA (OR=0.334, CI=0.214-0.521, and P<0.0001). The odd ratio (OR) for low-income earners among females is 2.238 (CI=1.878-2.666) and p value<0.0001. The OR for non-formal education in low-income earners is 2.332 (CI=1.466-3.709) and p value<0.0001. Conclusion: Low-income level was the most important predictor of knee OA in the study, and the female gender has the lowest income with higher knee OA risk and ....

The impact of different types of physical activity on the risk of knee osteoarthritis: A Mendelian randomization study

BackgroundWe aim to evaluate the causal relationship between different types of physical activity and the risk of knee osteoarthritis (KOA) through a two-sample Mendelian randomization study. MethodsWe performed a two-sample Mendelian randomization analysis using publicly available Genome-wide association study associated with physical activity (460 376 individuals) and KOA (403 124 individuals). Two-sample Mendelian randomization analyses were performed to investigate the effects of exposure traits on KOA risk. ResultsIn this Mendelian randomization analysis, we investigated the impact of different types of physical activity on the risk of KOA. Light do-it-yourself and walking for pleasure demonstrated a protective effect on the risk of KOA (P = 8.19 × 10−4 and P = 4.24 × 10−6, respectively). No statistically significant differences were observed for heavy do-it-yourself, strenuous sports, other exercises or physical inactivity. ConclusionThis study has revealed that engaging in light do-it-yourself activities and walking may serve as potential protective factors against KOA. These findings underscore the significance of introducing such activities into public health strategies designed for the prevention and management of KOA. Additional research is warranted to reveal the underlying mechanisms further.

Causal Association between Saturated Fatty Acid Foods and Osteoarthritis and Identification of Potential Targets

Background: Numerous studies suggest a link between the consumption of foods rich in saturated fatty acids and the development of osteoarthritis. However, the causal relationships are still unclear. Moreover, the complex pathogenesis poses challenges in developing targeted drugs and identifying biomarkers. Objective: To investigate the potential causal association between the consumption of foods in saturated fatty acids and osteoarthritis, as well as to identify potential therapeutic targets and biomarkers using colocalization analysis. Methods: A two-sample Mendelian randomization (MR) analysis based on publicly available genome-wide association studies was employed to infer the causal relationship. The effect estimates were calculated using the random-effects inverse-variance-weighted method. Bayesian colocalization analysis was conducted to identify potential therapeutic targets and metabolic products. Results: Cheese intake per standard deviation increase causally reduced the risks of knee osteoarthritis (OR = 0.605; 95% CI, 0.479-0.764; p < 0.001), osteoarthritis of the hip or knee (OR = 0.676; 95% CI, 0.553-0.826; p < 0.001), and osteoarthritis self-reported (OR = 0.720; 95% CI, 0.521-0.995; p = 0.047). Cheesy biscuits intake per standard deviation increase causally reduced the risks of knee osteoarthritis (OR = 0.485; 95% CI, 0.239-0.987; p = 0.046), osteoarthritis of the hip or knee (OR = 0.535; 95% CI, 0.315-0.909; p = 0.021). Pork intake per standard deviation increase causally reduced the level of basophil (OR = 0.738; 95% CI,0.579-0.941; p = 0.014); each standard deviation increase in mutton intake reduced the level of CRP (OR = 0.763; 95% CI. 0.594-0.979; p = 0.034), each additional standard deviation of whole milk intake reduced the level of CRP (OR = 0.079; 95% CI, 0.008-0.737; p = 0.026), and each additional standard deviation of fried potato intake reduced the level of the neutrophil count (OR = 0.944; 95% CI, 0.892-0.999; p = 0.048). Three single nucleotide polymorphisms (SNPs), namely rs143384, rs66989638, and rs8053839, associated with knee or hip osteoarthritis, as well as one SNP (rs112635299) associated with osteoarthritis metabolism, were identified through colocalization analysis. Conclusions: This two sample MR analysis found a causal negative association between foods containing saturated fatty acids and both osteoarthritis and biomarkers. Colocalization analysis identified three potential drug targets and one metabolite that could serve as a diagnostic marker.

Development and validation of a three-dimensional nomogram prediction model for knee osteoarthritis in middle-aged population

ObjectivesThis study aims to identify predictors of knee osteoarthritis (KOA) risk in middle-aged population, construct and validate a nomogram for KOA in this demographic.MethodsFrom June to December 2020, we conducted a cross-sectional survey on 5,527 middle-aged individuals from Changsha and Zhangjiajie cities in Hunan Province, selected using a stratified multi-stage random sampling method. Data collection involved a structured questionnaire encompassing general demographic, physical condition, and lifestyle behaviors dimensions. The dataset was randomly split into a training set (n = 3868) and a validation set (n = 1659) at a 7:3 ratio via computerized randomization. We analyzed the prevalence of self-reported KOA and identified its influencing factors using logistic regression. A nomogram was constructed based on these "three-dimensional" factors. Subsequent validation was conducted, and the nomogram's performance was further evaluated through ROC curves, C-index, Hosmer–Lemeshow test, and calibration curves.ResultsThe self-reported prevalence of KOA in the middle-aged population was 11.4% (632/5527). The risk factor with the greatest impact is: diagnosed with osteoporosis(95% CI 2.269–3.568, OR = 2.845), followed by age between 51 to 60 years (95% CI 2.176–3.151, OR = 2.619), diagnosed with hypertension(95% CI 1.633–2.499, OR = 2.02), diagnosed with diabetes (OR = 1.689), ethnic Han Chinese (OR = 1.673), exercise according to physical condition (OR = 1.643), pay attention to keeping the knee joint warm (OR = 1.535), eating habits are mainly light vegetables (OR = 1.374), male gender (OR = 1.343), drink occasionally in small amounts (OR = 1.286); a higher level of education (OR = 0.477) and frequently or always apply an external or plaster to relieve symptoms after knee discomfort (OR = 0.377; OR = 0.385) are protective factors.The C-index of the training set model was 0.8107 (95% CI: 0.8102–0.8111), with a statistically significant area under the ROC curve (AUC = 0.818), and the calibration curve showed a good fit. The C-index for the validation set was 0.8124 (95% CI: 0.8109–0.8140), with an AUC of 0.812. The Hosmer–Lemeshow test resulted in a P-value of 0.46 (P ≥ 0.05)indicating good calibration of the model.ConclusionThe three dimensions nomogram generated in this study was a valid and easy-to-use tool for assessing the risk of KOA in middle-aged population, and helped healthcare professionals to screen the high-risk population.

Neighborhood Disadvantage and Knee Osteoarthritis Pain: Do Sleep and Catastrophizing Play a Role?

The objective was to examine potential pathways linking neighborhood disadvantage to pain severity in individuals with knee pain consistent with or at risk for knee osteoarthritis (KOA). The current investigation is a cross-sectional analysis. Data were collected from 140 middle-aged to older non-Hispanic White and non-Hispanic Black adults from the Understanding Pain and Limitations in Osteoarthritic Disease Study 2 (UPLOAD-2). Relationships among neighborhood disadvantage, sleep efficiency, pain catastrophizing, and pain severity were assessed. Neighborhood disadvantage was quantified using the Area Deprivation Index, and actigraphy data were used to assess sleep efficiency. The Coping Strategies Questionnaire-Revised catastrophizing subscale and the Western Ontario and McMaster Universities Osteoarthritis Index pain severity scale were used to assess pain catastrophizing and pain severity, respectively. A serial mediation model assessed the neighborhood-sleep-catastrophizing-pain pathway, as well as the neighborhood-sleep-pain and the neighborhood-catastrophizing-pain pathways. Greater neighborhood disadvantage was associated with worse sleep efficiency, ultimately contributing to greater pain severity. Although neither neighborhood disadvantage nor sleep efficiency were associated with pain catastrophizing, pain catastrophizing itself was associated with greater KOA pain. Neighborhood disadvantage impacts KOA pain outcomes through sleep efficiency but not pain catastrophizing, thereby highlighting environmental aspects that impact sleep as potential targets for intervention.

Causal effects of circulating inflammatory proteins on knee and hip osteoarthritis: A two sample Mendelian randomization study.

Numerous circulating proteins are linked to the presence or severity of joint inflammation. However, traditional studies could not explain whether these protein biomarkers are proximate to disease progression. We conducted a study to explore the causal effects of 91 circulating inflammation-related proteins (CIPs) on knee osteoarthritis (KOA) and hip osteoarthritis (HOA), using two-sample Mendelian randomization (MR). The primary analysis utilized the inverse variance weighted (IVW) method, augmented by complementary approaches including weighted median, weighted mode, simple median, MR-Egger, and MR-PRESSO analysis. Sensitivity analysis validated the robustness of the results and ensured the absence of heterogeneity and horizontal pleiotropy. We identified 2 CIPs with a causal effect on KOA, including CXCL9 (OR = 1.249, 95% CI = 1.046-1.492, P = 0.014) and TNF-β (OR = 1.105, 95% CI = 1.014-1.204, P = 0.023). Additionally, 3 CIPs were found to have a causal effect on HOA, including CXCL6 (OR = 1.058, 95% CI = 1.004-1.116, P = 0.035), RANKL (OR = 1.067, 95% CI = 1.002-1.137, P = 0.044), and VEGFA (OR = 1.072, 95% CI = 1.008-1.140, P = 0.027). In the current study, our findings indicated that CXCL9 and TNF-β had the potential to influence the risk of KOA, while CXCL6, RANKL, and VEGFA could impact the risk of HOA. These discoveries underscored the significance of these proteins as potential targets for intervention in the prevention and treatment of KOA and HOA. Key Points •We presented genetic evidence supporting a causal link between circulating inflammatory proteins associated with joint inflammation using MR methods. •5 CIPs have demonstrated promotive effects on the occurrence of KOA and HOA.

The impact of coffee consumption on osteoarthritis: insights from NHANES and Mendelian randomization analysis.

Osteoarthritis (OA) is a prevalent degenerative joint condition, and emerging evidence suggests that dietary factors, such as coffee consumption, may influence its risk. However, the relationship between coffee consumption and the risk of developing OA remains ambiguous. This study aims to explore the association between coffee intake and OA complemented by Mendelian randomization (MR) to infer causality. We analyzed data from 32,439 participants across 10 NHANES cycles (1999-2018), including 3,676 individuals diagnosed with OA. Osteoarthritis was diagnosed through a structured questionnaire, while coffee consumption was assessed via 24-h dietary recalls. Participants were categorized based on reported coffee intake: 0 cups, <2 cups, 2-4 cups, and >4 cups per day. We employed weighted multivariable logistic regression to examine associations between coffee consumption and OA by using data from the NHANES 1999-2018, adjusting for various covariates. Subsequently, a MR analysis was conducted using genetic variants as instrumental variables to infer causal relationships, with multiple methods including inverse-variance weighted (IVW) analysis, MR-Egger regression, and weighted median techniques to assess the robustness, heterogeneity, and potential pleiotropy of our findings. Our regression models indicated an increased risk of OA with rising coffee consumption, with significant associations noted particularly for those consuming more than 4 cups daily (OR = 1.19, 95% CI: 1.00-1.41, p = 0.049). In MR analysis, coffee intake was causally linked to OA types, demonstrating increased risk for knee OA (KOA: OR = 1.60, 95% CI: 1.08-2.35, p = 0.018), hip OA (HOA: OR = 1.85, 95% CI: 1.06-3.25, p = 0.031), and combined KOA and HOA (KHOA: OR = 1.66, 95% CI: 1.18-2.33, p = 0.003). Sensitivity analyses confirmed the stability of results across multiple evaluation methods. Our findings highlight a significant association between coffee consumption and an increased risk of OA, suggesting that higher intake levels may contribute to OA morbidity. These results warrant further exploration into the underlying biological mechanisms and implications for dietary guidelines in populations at risk for OA.

Association of sarcopenia and its prognostic value in symptomatic knee osteoarthritis among older people in China: the first longitudinal evidence from CHARLS

BackgroundSarcopenia and knee osteoarthritis (KOA) are two common musculoskeletal disorders, often coexisting in aged population and potentially influencing each other. However, the underlying relationship between two conditions remains unclear and controversial. To fill this knowledge gap, we aimed to investigate the longitudinal association among the older Chinese population.MethodsData were attracted from 2 waves of the China Health and Retirement Longitudinal Study (CHARLS), and 6212 individuals aged ≥ 60 years were included. Sarcopenia status was defined by the Asian Working Group for Sarcopenia 2019 criteria. Multivariate logistic regression and generalized estimation equation models were applied to estimate the impact of sarcopenia on KOA. A prognostic nomogram was developed through train-test cross-validation.ResultsAt baseline in CHARLS 2015, the prevalence of symptomatic KOA was 12.7% (792/6212) in total population, 9% (270/2996) in no-sarcopenia group, 17.5% (286/1638) in possible sarcopenia group, and 15.0% (236/1578) in sarcopenia group. Over a 3-year follow-up, 4980 respondents were included, with incident KOA cases identified as 56 (2.2%), 38 (3.0%), and 43 (3.6%) in no-sarcopenia, possible sarcopenia, and sarcopenia groups, respectively. Sarcopenia was significantly associated with increased new-onset KOA compared to no-sarcopenia peers in the fully adjusted model (OR: 1.91, 95% CI: 1.15–3.18), whereas this association was non-significant for possible sarcopenia. In females, low muscle mass alone significantly increased the incident risk of KOA (OR: 2.58, 95% CI: 1.05–6.49). The final prognostic model and nomogram, including sarcopenia status, age, gender, body mass index, self-reported health status, comorbidities, history of falls and physical activity, had a considerable discrimination (AUC = 0.744, C-index = 0.660). The calibration curve indicated significant agreement between predicted and actual observations. Decision curve analysis revealed net benefits for clinical intervention at a probability threshold of 1–17%.ConclusionsSarcopenia was associated with a higher incident risk of symptomatic KOA, wherein low muscle mass may play an important role. The inferior prognosis of sarcopenia in KOA needs more attention in clinical practice.

Effects of hypothetical low versus moderate-to-high intensity weight management regimens on knee replacements.

This study aimed to investigate the efficacy of a hypothetical biennial weight management regimen in reducing the necessity for knee replacement (KR) surgery among middle-aged and older adults with or at a higher risk for knee osteoarthritis (OA). Data from the Osteoarthritis Initiative cohort in the US, comprising community-dwelling adults aged 45-79 years at high risk for or with symptomatic knee OA who underwent baseline assessments from September 2008 to December 2010 were used. Subsequent evaluations were conducted at 12, 24, and 96 months. A hypothetical biennial weight management regimen, ranging from low to moderate-to-high intensity, was employed as the exposure, whereas the incidence of KR during follow-up was the outcome. This study, using a targeted learning approach to estimate hypothetical weight management regimens adjusted for time-varying confounding and attrition due to loss to follow-up, revealed that a 7.5% reduction in body mass index (high-intensity) resulted in a notable decrease in KR rates, from 5.93% [95% confidence interval (CI), 5.64-6.21] in the baseline maintenance regimen (low-intensity) to 3.60% (95% CI, 2.70-4.50) in the high-intensity regimen. In conclusion, a hypothetical weight management regimen significantly reduces the need for KR surgery in adults with knee OA.

Causal relationship of salt intake with osteoarthritis: A Mendelian randomization analysis.

Recent studies have demonstrated a correlation between salt intake (SI) and various diseases. However, it remains uncertain whether the relationship between SI (including salt added to food and sodium levels in urine) and benign osteoarthritis is causal. To investigate this, we conducted a 2-sample Mendelian randomization (MR) analysis to estimate the causal impact of SI on osteoarthritis (OA). A genome-wide association study of salt added to food and sodium in urine was used as the exposure, while hip osteoarthritis, knee osteoarthritis, and rheumatoid arthritis were defined as the outcomes. Inverse variance weighting (IVW) was used to calculate causal estimates, and sensitivity analyses were performed using methods including weighted mode, weighted median, MR-Egger, and Bayesian weighted MR. All statistical analyses were conducted using R software. Our results, primarily based on the IVW method, support the existence of a causal relationship between salt added to food and knee osteoarthritis (KOA). Specifically, salt added to food was associated with a decreased risk of KOA (OR = 1.248, P = .024, 95% CI: 1.030-1.512). This study is the first MR investigation exploring the causal relationship between salt added to food and KOA, potentially providing new insights and a theoretical basis for the prevention and treatment of KOA in the future.

Prevalence and risk factors of knee osteoarthritis: a cross-sectional survey in Nanjing, China.

Knee osteoarthritis (KOA) presents a significant public health challenge due to its hazards and increasingly severe trends. Addressing this challenge requires targeted investigation into the prevalence and identification of risk factors for KOA across different regions, especially in populous and vast China. Therefore, a cross-sectional survey was conducted in Nanjing, China, with the aim of investigating the prevalence and risk factors of KOA among individuals aged 50 and above. A total of 1,045 subjects were selected using the stratified random sampling method and diagnosed with KOA based on the diagnostic criteria established by the Chinese Medical Association. Data on 14 potential risk factors were collected through a self-designed questionnaire and standardized on-site tests. The association between KOA and these risk factors was explored using t-tests, Chi-square tests, and logistic regression analysis. The prevalence of KOA among the subjects was 23.64%. Multiple logistic regression models indicated that the risk of KOA was significantly higher among women (OR: 5.34, 95% CI: 3.13-9.11), subjects aged 60-69 (OR: 1.83, 95% CI: 1.25-2.69) and over 70 (OR: 2.87, 95% CI: 1.80-4.59), individuals with high school education and above (OR:2.22, 95% CI: 1.37-3.60), those with flatfoot (OR: 1.74, 95% CI: 1.10-2.74), and subjects classified as overweight (OR: 1.91, 95% CI: 1.21-3.04) and obese (OR: 4.63, 95% CI: 2.18-9.85) based on their BMI status. Additionally, the models identified weight (OR: 1.04, 95% CI: 1.01-1.08), 30-s chair stand performance (OR: 0.94, 95% CI: 0.91-0.97), and single-leg stand performance (OR: 0.96, 95% CI: 0.93-0.99) as independent risk factors for KOA. The prevalence of KOA is remarkable in Nanjing city. The risk factors for KOA include women, older age, higher education, flatfoot, increased weight and BMI, as well as poor performance in 30-s chair stand and single-leg stand tests.

Associations between less knee kinematic variability and worse patient-reported outcomes following anterior cruciate ligament reconstruction

ABSTRACT Individuals with anterior cruciate ligament reconstruction (ACLR) exhibit less knee kinematic variability while walking than uninjured controls, associated with deleterious changes in cartilage composition linked to an increased risk for early knee osteoarthritis (KOA). It is unknown whether less knee kinematic variability is also associated with worse knee-related patient-reported outcomes (PROs) consistent with KOA development. This study examined associations between kinematic variability during gait and PROs in individuals post-ACLR. Gait kinematics and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were collected from 45 participants 6-months post-ACLR (67% Females; 21.45 ± 4.56 years). Overground gait biomechanics using 3D motion capture were collected, and knee kinematics were extracted for post-processing. Sample entropy (SampEn) was used to calculate knee kinematic variability. Pearson’s product-moment correlations were conducted to determine the associations between SampEn and KOOS sub-scores. Additionally, independent samples t-tests were performed to evaluate potential differences in SampEn outcomes between individuals with and without clinically relevant symptoms (defined in the introduction). Less sagittal plane kinematic variability is associated with greater pain (r = 0.37, p = 0.01) and symptoms (r = 0.32, p = 0.03). Symptomatic participants demonstrated less sagittal plane knee kinematic variability compared to asymptomatic participants (p = 0.01). The findings suggest less variable gait patterns 6-months post-ACLR may be linked to KOA-related symptoms.

Microbiome-Augmented Model for Predicting Knee Osteoarthritis Progression Based on Gut Microbiota and Kellgren-Lawrence Classification.

Knee osteoarthritis (OA) is a widespread chronic degenerative condition that mayexperience slow or rapid deterioration. The gut-joint axis represents a bidirectional relationshipinOA onset and progression. This study aimed to establish and validatea prediction model of knee OA disease progression. Thisprospective cohort investigation involved 296 patients diagnosed with knee OAusing X-ray and CT scans at Taizhou People's Hospital from January 2020 to January 2022. Fecal samples and general information were collected for gut microbiota analysis. Least absolute shrinkage and selection operator (LASSO) regression and various prediction models, including microbiome-augmented models, were employed for knee OA risk prediction.The models predicting Kellgren-Lawrence classification one year later were evaluated by accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC). A total of 270patients were involved in our study. After randomassignment, 214 patients belonged to the training set and 56 patients belonged to the test set.The final intestinal flora included in the analysis included the following 12species. Shannon index of patients with a Grade I Kellgren-Lawrence Classificationafter one year was lower than those with a Grade II/IIIafter one year (P=0.018). The best model was the microbiome-augmented model built by Light GBM (LGBM). The AUC of this model in the training set was 0.812 (0.754-0.870), the sensitivity was 0.804 (0.725-0.883), the specificity was 0.744 (0.664-0.823), the PPV was 0.722 (0.638-0.807), the NPV was 0.821 (0.748-0.894), and the accuracy was 0.771 (0.715-0.827). The AUC of this model in the testing set was 0.876 (0.781-0.972), the sensitivity was 0.759 (0.603-0.914), the specificity was 0.917 (0.806-1.000), the PPV was 0.917 (0.806-1.000), the NPV was 0.759 (0.603-0.914), and the accuracy was 0.830 (0.729-0.931). Conclusion: One year later, the microbiome-augmented model constructed by LGBM for knee OApatients based on general and gut microbiota data using the Kellgren-Lawrence classification demonstrated the highest performance. This approach could aid in identifying patients at risk of rapid disease progression, facilitating early intervention and personalized treatments. Furthermore, it offers a novel perspective on the gut-joint axis's role in OA.

Association between thyroid function and osteoarthritis: A population-based cohort study

ObjectivesPrevious genetic and animal studies indicated a causal role of thyroid hormones in osteoarthritis (OA), which has not been observed in the general population. We aimed to investigate whether thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were associated with hand, hip, or knee OA. MethodsParticipants from the Rotterdam Study with baseline TSH, FT4, and joint radiographs were included. We used multivariable regression models to investigate the association of thyroid function with the prevalence, severity, incidence, and progression of OA. We conducted stratified analyses by sex, age, body mass index (BMI) and weight-bearing physical activity. ResultsAmong 9054 participants included (mean age 65 years, 56.3% women), higher FT4 concentrations were associated with an increased risk of prevalent knee OA (OR 1.04 per pmol/L, 95% CI 1.01-1.06, corresponding to an OR of 1.62 across the reference range [i.e., 14pmol/L changes] of FT4) and more severe knee OA. There was a positive association between FT4 and overall progression of knee OA (OR 1.03 per pmol/L, 1.00-1.07). No association of TSH with hand, hip, or knee OA was identified. Stratified analysis revealed an association between FT4 and prevalent knee OA among individuals with BMI≥30 kg/m2 (OR 1.05 per pmol/L, 1.01-1.08) and those with high levels of weight-bearing physical activity (OR 1.05 per pmol/L, 1.01-1.10). ConclusionsOur study indicated that higher FT4 concentrations may increase the risk of knee OA. This association might be greater in individuals with extra joint loading, such as those with obesity.

Associations Between Body Mass Index, Gait Biomechanics, and In Vivo Cartilage Function After Exercise in Those With Anterior Cruciate Ligament Reconstruction

Background: Both high body mass index (BMI) and anterior cruciate ligament reconstruction (ACLR) independently influence knee osteoarthritis risk. Preliminary evidence shows the combination of these risk factors leads to poorer recovery and altered biomechanical outcomes after ACLR, but few studies have directly evaluated early changes in cartilage health between normal-BMI and high-BMI groups in this population. Purpose: To evaluate ultrasound-based measures of cartilage strain and compositional changes (via echo-intensity [EI]) in response to an incline walking stress test between normal-BMI and high-BMI individuals with ACLR. A secondary evaluation was conducted of associations between habitual walking biomechanics (ie, ground-reaction forces, sagittal knee kinetics and kinematics) and cartilage strain and EI outcomes. Study Design: Controlled laboratory study. Methods: Gait biomechanics and femoral trochlear ultrasound analyses were evaluated in 64 participants with ACLR who had normal BMI (BMI < 27.0; n = 40) and high BMI (BMI ≥ 27.0; n = 24). Ultrasound images were collected bilaterally before and after an incline treadmill walk, and medial and lateral trochlear strain and EI changes pre-post exercise were used to compare BMI groups and limbs. Gait outcomes included ground-reaction forces, peak sagittal plane knee moments, angles, and excursions and were used to determine associations with cartilage outcomes in the entire cohort. Results: High-BMI individuals with ACLR exhibited greater medial trochlear cartilage strain in the ACLR limb compared with normal-BMI individuals (approximately 6%; P < .01). In those with high BMI, the ACLR limb exhibited greater medial trochlear strain relative to non-ACLR limbs (approximately 4%; P < .05), but between-limb differences were not observed in the normal-BMI group (P > .05). Medial trochlear EI changes were greater bilaterally in those with high BMI compared with normal-BMI ACLR counterparts (approximately 10%; P < .01). Last, individuals who walked with greater peak knee flexion angles exhibited less medial cartilage strain (ΔR2 = 0.06; P = .025). Conclusion: The data suggested that high BMI affects cartilage functional properties after ACLR, whereas smaller knee flexion angles were associated with larger medial cartilage strain. Clinical Relevance: High-BMI individuals with ACLR may represent a subset of patients exhibiting earlier declines in cartilage functional integrity in response to loading, necessitating additional or more targeted interventions to mitigate disease development.

The association between ADAMTS14/rs4747096 gene polymorphism and some risk factors and knee osteoarthritis

Knee osteoarthritis (KOA) is an important cause of disability in the world and it denotes a public health defiance of the upcoming years.Aim To examine the connection between ADAMTS14 gene rs4747096 polymorphism and KOA and to assess risk factors associated with KOA.Methods A case control study was conducted on 158 patients with KOA and 120 controls with comparable age and sex randomly recruited from National Research Centre employees. All participants were subjected to full history taking, assessment of KOA severity using WOMAC scoring system, and thorough clinical examination. Blood sample was collected for detection of ADAMTS14/rs4747096 gene polymorphism.Results The frequency of ADAMTS14 gene rs4747096 genotypes among patients with KOA was 73.5% for AA, 25.7% for AG, and 0.7% for GG compared to controls 963%, 31.3%, and 5.6% respectively and the frequency of alleles among patients was 86.4% for A and 78.7% for G compared to controls (78.7% and 21.3% respectively, P < 0.05. The study found that the median levels of total WOMAC score and its domains were significantly higher among KOA patients than controls. The logistic regression analysis revealed that age ≥ 50 years, BMI ≥ 35, and long standing at work were predictive factors for KOA (P < 0.05). Regarding different genetic patterns, only the A recessive pattern of inheritance was found to be a predictive risk factor for KOA.Conclusion For ADAMTS14 rs4747096 genotype, the AA and AG genotypes significantly increased the risk of KOA. The recessive pattern of inheritance, older age, morbid obesity, and prolonged standing at work were the predictive risk factors for KOA. Further studies with larger sample size are encouraged to investigate the mechanism by which this genotype can affect the development of KOA.

Genetic association of gut microbiota with osteoarthritis: a multivariable Mendelian randomization study considering medication use.

Background. The interplay among human gut microbiota (GM) composition, osteoarthritis (OA) and OA-related medication use has been extensively discussed. However, to date, there has been no exploration of the genetic correlation among these three factors.Hypothesis/Gap. The potential causal link between GM and OA), and whether medications influence this relationship, remains unclear.Methods. We utilized bidirectional Mendelian randomization (MR) to explore the genetic associations between GM and OA. We leveraged genome-wide association study (GWAS) summary statistics from the MiBioGen and GO consortia, which provided data on GM taxa and OA cases, respectively. We identified outlier single-nucleotide polymorphisms using radial-MR and assessed causal associations using inverse variance weighting (IVW), weighted median and MR-Egger methods. Robust outcomes, consistent across these methods, were reported. We addressed potential biases through tests for horizontal pleiotropy and heterogeneity, supplemented by the Mendelian randomization pleiotropy residual sum and outlier method. Multivariable MR techniques were applied to adjust for OA medication use using UK Biobank data.Results. IVW estimates revealed a significant increase in hip OA risk for Gordonibacter and Eubacterium (brachy group) [odds ratio (OR): 1.09, 95% confidence interval (CI): 1.04-1.15, P=7.82E-04; OR: 1.09, 95% CI: 1.03-1.16, P=4.67E-03, respectively]. Conversely, Senegalimassilia, Slackia and Streptococcus exhibited protective effects (OR: 0.88, P=2.14E-02; OR: 0.88, P=3.33E-02; 0.91, P=4.29E-02). Sutterella increased the risk of knee OA (OR=1.15, 95% CI: 1.07-1.25, P=4.06E-04), while Haemophilus decreased it (OR=0.94, 95% CI: 0.88-1.00, P=4.26E-02). No significant heterogeneity or horizontal pleiotropy was observed in the results. Even after accounting for the potential confounding effect of medication, the results remained consistent. No reverse causation was detected.Conclusions. Our MR study reveals gut microbiome links to OA risk. Associations hold after adjusting for medication, indicating a potential causal connection between GM and OA.