Osteoarthritis In Men Research Articles

Increased alcohol intake is associated with radiographic severity of knee and hand osteoarthritis in men

Observational studies have shown controversial associations between alcohol intake and radiographic osteoarthritis (OA). This study investigated whether this association was causal using a Mendelian randomization (MR) study in a population-based cohort in Korean. The study enrolled 2429 subjects (1058 men, 1371 women) from the Dong-gu Study. X-rays of the hand and knee joints were scored using a semi-quantitative grading system to calculate the total score of the hand and knee joints. ALDH2 rs671 genotyping was performed by high-resolution melting analysis. MR instrumental variable analysis and observational multivariable regression analysis were used to estimate the association between genetically predicted alcohol intake and the radiographic severity of OA. Subjects with the G/G genotype had a higher current alcohol intake than those with the G/A and A/A genotypes in both men and women (all P < 0.001). Men with the G/G genotype had higher total knee (P < 0.001) and hand scores (P = 0.042) compared to those with the G/A and A/A genotypes after adjusting for age and body mass index, but not in women. In the observational multivariable regression analysis, each alcohol drink per day in men was associated with increased knee (P = 0.001) and hand joint scores (P = 0.013) after adjustment, but not in women. In our MR analysis, utilizing ALDH2 rs671 genotypes as instrumental variables for alcohol consumption, has shown a significant link between each additional daily alcohol drink and increased radiographic joint severity in men.

Association between Low Serum Creatinine Levels and Knee Osteoarthritis in Koreans without Renal Insufficiency.

This study aimed to investigate the correlation between serum creatinine levels and the presence and severity of radiographic knee osteoarthritis (OA) in individuals aged ≥50 years while adjusting for potential confounders. Cross-sectional data from the 2009-2011 Korea National Health and Nutrition Examination Survey comprising 3428 individuals aged ≥50 years were utilized. The Kellgren-Lawrence (K-L) grading scale was used to assess the radiographic presence and severity of knee OA. Logistic regression and receiver operating characteristic analyses were used to investigate the association between serum creatinine levels and the presence of knee OA, whereas ordinal regression was used to assess the impact of creatinine levels on knee OA severity. The presence of radiographic knee OA conferred by low serum creatinine levels was found to be significant in both sexes [odds ratio (OR), 0.118; 95% confidence interval (CI), 0.045-0.314, p<0.001 for men; OR, 0.148; 95% CI, 0.040-0.549, p=0.004 for women]. Low serum creatinine was significantly associated with knee OA-graded K-L severity in each sex-based group [β, -1.923; standard error, 0.478; p<0.001 for men and β, -1.532; SE, 0.575; p=0.008 for women]. Low serum creatinine level was associated with a higher presence of knee OA in both men and women, and was also linked to the severity of the disease. These findings suggest that the serum creatinine level may be a potential biomarker for assessing the presence and severity of knee OA.

The role of polymorphism of candidate genes in the development of knee osteoarthritis in men of the Central Chernozem region of Russia

Knee osteoarthritis (OA) is a disease resulting from the interaction of many local and systemic risk factors, among which an important role is played by genetic (hereditary) factors. This disease affects both men and women, but there are certain differences in the development and progression of the disease in different sexes.Aim: To study associations of polymorphic loci of candidate genes with the risk of developing knee ОА in the male population of the Central Chernozem region of Russia.Material and Methods. The study sample included 410 men (208 patients with knee OA and 202 controls). Ten polymorphic loci of candidate genes were genotyped: rs2820436 and rs2820443 LYPLAL1, rs3771501 TGFA, rs11177 GNL3, rs6976 GLT8D1, rs1060105 and rs56116847 SBNO1, rs6499244 NFAT5, rs34195470 WWP2, rs143384 GDF5. The study of associations of polymorphic genetic loci with the development of the disease was carried out by the method of logistic regression, taking into account covariates (age, BMI). The MB-MDR method was used to study intergenic interactions of polymorphisms associated with the disease.Results and Discussion. It was found that nine out of ten polymorphic loci of candidate genes (with the exception of rs6976 GLT8D1) are associated with the formation of knee OA in men in four models of interlocus interactions (pperm ≤ 0.024). The rs3771501 TGFA polymorphic locus (included in three of the four most significant models of gene-gene interactions) demonstrates the greatest contribution to the development of the disease in men. Independent effects of the studied polymorphic loci of candidate genes in the development of knee OA in men have not been identified (р &gt; 0,05).Conclusion. Polymorphic loci rs2820436 and rs2820443 LYPLAL1, rs3771501 TGFA, rs11177 GNL3, rs6976 GLT8D1, rs1060105 and rs56116847 SBNO1, rs6499244 NFAT5, rs34195470 WWP2, rs143384 GDF5 involved in the development of knee osteoarthritis in men in four models of intergenic interactions. Among the studied loci, rs3771501 of the TGFA gene has the greatest contribution to disease susceptibility.

The Association of Metabolic Syndrome and Obesity With Clinical Hip Osteoarthritis in the Study of Osteoporotic Fractures and the Osteoporotic Fractures in Men Study Cohorts.

Metabolic dysregulation frequently co-occurs with obesity, which has been shown to be a risk factor for lower extremity osteoarthritis (OA). We evaluated the association between metabolic syndrome (MetS), alone and in combination with obesity, and hip OA. In two parallel cross-sectional analyses, we studied 403 women from the Study of Osteoporotic Fractures (SOF) and 2354 men from the Osteoporotic Fractures in Men (MrOS) study. We used multivariable logistic regression to evaluate associations of obesity (body mass index ≥30 kg/m2 ) and/or MetS (three of five National Cholesterol Education Program Adult Treatment Panel III criteria) with clinical hip OA, defined as a modified Croft score of 2 or more or total hip replacement, and pain or limited range of motion. Our analysis adjusted for demographics. Approximately 3.5% of SOF women and 5.4% of MrOS men had clinical hip OA. Among women, obesity was not associated with hip OA, yet those with MetS had a 365% higher odds of hip OA (95% CI: 1.37-15.83). Among men, those who had obesity had a 115% higher odds of hip OA (95% CI: 1.39-3.32), yet MetS was not associated with hip OA. There was no interaction between MetS, obesity, and hip OA in either women or men. In women, but not in men, MetS was associated with hip OA. In men, but not in women, obesity was associated with hip OA. These findings suggest that mechanical effects of obesity may predominate in the pathogenesis of hip OA in men, whereas metabolic effects predominate in women.

The Association of Index-to-Ring Finger Ratio With Trapeziometacarpal Joint Osteoarthritis in an Elderly Korean Population.

Index-to-ring finger ratio (IRFR) has been reported to be associated with joint osteoarthritis (OA). We aimed to evaluate the association between IRFR and trapeziometacarpal joint (TMCJ) OA in an elderly Korean population. A population-based sample included 604 participants with a mean age of 74.8 years. IRFR was radiographically measured by the ratio of the length of the right second to fourth phalangeal bones ("phalangeal IRFR") and metacarpal bones ("metacarpal IRFR"), and was visually classified as either type 1 (index finger longer than or equal to ring finger) or type 2 (index finger shorter than ring finger). Odds ratios (ORs) for the presence of OA (Kellgren-Lawrence [KL] grade &gt; 1) and for severe OA (KL grade &gt; 2) were analyzed using logistic regression. The phalangeal IRFR averaged 91.3%, the metacarpal IRFR 116.7%, and 304 out of 604 participants (50.3%) had type 2 IRFR. We found TMCJ OA in 112 participants (18.5%), and severe TMCJ OA in 33 participants (5.5%). Presence of TMCJ OA was significantly associated with age (OR 1.04; 95% CI 1.01-1.06) and metacarpal IRFR (OR 0.94; 95% CI 0.88-0.99), and severe TMCJ OA with age (OR 1.08; 95% CI 1.03-1.12) and type 2 IRFR (OR 3.07; 95% CI 1.13-8.33). Radiographic IRFR, specifically metacarpal IRFR, was associated with the presence of TMCJ OA, and visual IRFR with severe TMCJ OA in both elderly Korean men and women. The results of this study suggest that IRFR might serve as an easily measurable biomarker to identify patients vulnerable to TMCJ OA.

Prevalence of osteoporosis in osteoarthritis: a systematic review and meta-analysis.

Data are contradictory regarding the relationship between osteoarthritis (OA) and osteoporosis (OP) with some studies showing the increased risk of OP in OA. The study was conducted to determine whether OP prevalence is increased in patients with OA, compared to age and sex-matched population. MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library (inception-2019) were searched for studies reporting the frequency, rate, prevalence, incidence, risk, or excess risk of OP in patients with OA compared to age and sex-matched population. Estimates were combined using a random effects model. Consistency was evaluated using the I2 statistic. Articles with fewer than 200 participants were excluded. Of 2772 articles, 49 had full article screening, and 8 articles met the inclusion criteria. Other articles reporting mean BMD and not OP were excluded. In women, 998 participants with OA were compared with 1903 controls. The pooled estimate of the odds ratio for prevalence of OP vs general matched population was not statistically different. In men, 136 participants with OA were compared with 682 controls. The results did not show a statistically significant difference in the frequency of OP in OA in men. According to the site of bone mineral density measurement, a higher prevalence of OP at lumbar spine was found in both men and women. The frequency of OP overall in participants with OA was not different, except for a higher prevalence of OP in lumbar spine in both men and women compared to the matched controls.

Association Between Prediabetes and Osteoarthritis: A Meta-Analysis.

Some studies have suggested that diabetes may be a risk factor for osteoarthritis. However, whether prediabetes is also associated with osteoarthritis has not been comprehensively examined. We performed a meta-analysis to evaluate the relationship between prediabetes and osteoarthritis. This meta-analysis included relevant observational studies from Medline, Embase, and Web of Science databases. A random-effect model after incorporation of the intra-study heterogeneity was selected to pool the results. Ten datasets from six observational studies were included, which involved 41 226 general adults and 10 785 (26.2%) of them were prediabetic. Pooled results showed that prediabetes was not independently associated with osteoarthritis [risk ratio (RR): 1.07, 95% confidence interval (CI): 1.00 to 1.14, p=0.06, I2=0%]. Sensitivity limited to studies with adjustment of age and body mass index showed consistent result (RR: 1.06, 95% CI: 0.99 to 1.14, p=0.09, I2=0%). Results of subgroup analyses showed that prediabetes was not associated with osteoarthritis in cross-sectional or cohort studies, in studies including Asian or non-Asian population, or in studies with different quality scores (p for subgroup difference>0.10). Besides, prediabetes was not associated with osteoarthritis in men or in women, in studies with prediabetes defined as impaired fasting glucose, impaired glucose tolerance, or HbA1c (approximately 39-46 mmol/mol). Moreover, prediabetes was not associated with overall osteoarthritis, and knee or hip osteoarthritis. Current evidence does not support that prediabetes is independently associated with osteoarthritis in adult population.

Association between circulating 25-hydroxyvitamin D concentrations and hip replacement for osteoarthritis: a prospective cohort study

BackgroundTo examine the association between circulating 25(OH)D concentrations and incidence of total hip replacement for osteoarthritis in a prospective cohort study.MethodsThis study examined a random sample of 2651 participants in the Melbourne Collaborative Cohort Study who had 25(OH)D concentrations measured from dried blood spots collected in 1990-1994. Participants who underwent total hip replacement for osteoarthritis between January 2001 and December 2018 were identified by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total hip replacement for osteoarthritis in relation to 25(OH)D concentrations, adjusted for confounders.ResultsEighty-six men and eighty-seven women had a total hip replacement for osteoarthritis. Compared with men in the lowest (1st) quartile of 25(OH)D concentration, the HR for total hip replacement was 2.32 (95% CI 1.05, 5.13) for those in the 2nd quartile, 2.77 (95% CI 1.28, 6.00) for those in the 3rd quartile, and 1.73 (95% CI 0.75, 4.02) for those in the highest quartile of 25(OH)D concentrations (p for trend 0.02). There was little evidence of an association in women.ConclusionsHigher circulating 25(OH)D concentrations were associated with an increased risk of total hip replacement for osteoarthritis in men but not in women. Although the underlying mechanism warrants further investigation, our findings highlight the need to determine the optimal levels of circulating 25(OH)D to reduce the risk of hip osteoarthritis.

Risk of Osteoarthritis is Positively Associated with Vitamin D Status, but Not Bone Mineral Density, in Older Adults in the United States

Objective We examined the risk of osteoarthritis (OA) according to vitamin D status and bone mineral density (BMD) using a cross-sectional nationally representative database. Methods National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2010 were used to assess the relationship between OA and vitamin D status in adults aged ≥40 years (n = 2934). NHANES data from 2005 to 2010 and 2013 to 2014 were analyzed to investigate the association between OA and BMD (n = 5949). Vitamin D status was categorized as serum 25-hydroxyvitamin D (25OHD) <20 ng/mL or ≥20 ng/mL. Bone health was classified according to T-score (normal, osteopenia, or osteoporosis) and BMD tertile. Risk of OA was assessed using logistic regression and adjusted for covariates. Results Participants with serum 25OHD <20 ng/mL had a 37% lower risk of OA (95% confidence interval (CI) [0.39–0.99], P = 0.046). When stratified by sex, the odds ratio for OA in men with lower vitamin D status was 0.35 (95% CI [0.15–0.81], P = 0.02). No association was found in women. The risk for OA did not differ according to BMD tertile or T-score classification. Conclusions The risk of OA is lower in older men with 25OHD less than 20 ng/mL but not in older women. Bone mineral density is not associated with OA risk in older adults in the United States.

Association of bone mineral density with the development of knee osteoarthritis in men and women: a cross-sectional study using the fourth and fifth Korea National Health and Nutrition Examination Surveys.

The purpose of this study was to evaluate the association of BMD in various body parts in conjunction with the presence or severity of radiographic knee osteoarthritis (KOA) in relation to sex. This study was a cross-sectional analysis using Korea National Health and Nutrition Examination Surveys. KOA was graded using the Kellgren-Lawrence (KL) grading system. Radiographic KOA was defined as a KL grade 2 or higher. The associations between KOA and BMD in certain body parts (femur, pelvis, lumbar, lower leg, and whole-body) were assessed. BMD was measured using dual-energy X-ray absorptiometry. The BMD of each body part was divided into quartiles and the relationship between KOA and BMD was examined according to sex. BMD did not show a significant tendency according to KL grade in either sex. In men, the severity of KL grade have a statistically significant relationship with total femur (R2 = 0.303, p < 0.05), femur neck (R2 = 0.257, p < 0.05), lumbar (R2 = 0.137, p < 0.05), and pelvis BMD (R2 = 0.185, p < 0.05). In women, total femur (R2 = 0.466, p < 0.05), lumbar (R2 = 0.316, p < 0.05), pelvis (R2 = 0.343, p < 0.05), and lower leg BMD (R2 = 0.133, p < 0.05) were associated with the severity of KL grade. When the BMD was divided into quartiles, lumbar (p < 0.05) and pelvis BMD (p < 0.05) in men had statistically significant association with knee OA as BMD decreased. In women, femur neck (p < 0.05) and lumbar BMD (p < 0.05) were significantly associated with knee OA as BMD increased. The relationship between BMD and OA severity varied according to sex. In women, there was a positive association between femur neck and lumbar BMD and OA, while BMD of the lumbar and pelvis in men was negatively correlated with OA. Cohort study, III.

Development and validation of a prediction model for incident hand osteoarthritis in the HUNT study

To develop and externally validate prediction models for incident hand osteoarthritis (OA) in a large population-based cohort of middle aged and older men and women. We included 17,153 men and 18,682 women from a population-based cohort, aged 35-70yearsat baseline (1995-1997). Incident hand OA were obtained from diagnostic codes in the Norwegian National Patient Register (1995-2018). We studied whether a range of self-reported and clinically measured predictors could predict hand OA, using the Area Under the receiver-operating Curve (AUC) from logistic regression. External validation of an existing prediction model for male hand OA was tested on discrimination in a sample of men. Bootstrapping was used to avoid overfitting. The model for men showed modest discriminatory ability (AUC=0.67, 95% CI 0.62-0.71). Adding a genetic risk score did not improve prediction. Similar discrimination was observed in the model for women (AUC=0.62, 95% CI 0.59-0.64). Prediction was not improved by adding a genetic risk score or hormonal and reproductive factors. Applying external validation, similar results were observed among men in HUNT (The Nord-Trøndelag Health Study) as in the developmental sample (AUC=0.62, 95% CI 0.57-0.65). We developed prediction models for incident hand OA in men and women. For women, the model included body mass index (BMI), heavy physical work, high physical activity and perceived poor health. The model showed moderate discrimination. For men, we have shown that a prediction model including BMI, education and information on sleep can predict incident hand OA in several populations with moderate discriminative ability.

Men and Women's Occupational Activities and the Risk of Developing Osteoarthritis of the Knee, Hip, or Hands: A Systematic Review and Recommendations for Future Research

ObjectiveTo systematically review the evidence for an increased risk of osteoarthritis in the hip, knee, hand, wrist, finger, ankle, foot, shoulder, neck, and spine related to diverse occupational activities of men and women and to examine dose‐response information related to the frequency, intensity, and duration of work exposures and the risk of osteoarthritis (OA).MethodsEstablished guidelines for systematic reviews in occupational health and safety studies were followed. MEDLINE, Embase, CINAHL, and Cochrane Library were searched from inception to December 2017. Studies were reviewed for relevance, quality was appraised, and data were extracted and synthesized.ResultsSixty‐nine studies from 23 countries yielded strong and moderate evidence for lifting, cumulative physical loads, full‐body vibration, and kneeling/squatting/bending as increasing the risks of developing OA in men and women. Strong and moderate evidence existed for no increased risk of OA related to sitting, standing, and walking (hip and knee OA), lifting and carrying (knee OA), climbing ladders (knee OA), driving (knee OA), and highly repetitive tasks (hand OA). Variability in dose‐response data resulted in an inability to synthesize these data.ConclusionEvidence points to the potential for OA occupational recommendations and practice considerations to be developed for women and men. However, research attention is needed to overcome deficits in the measurement and recall of specific work activities so that recommendations and practice considerations can provide the specificity needed to be adopted in workplaces.

Occupational load as a risk factor for clinically relevant base of thumb osteoarthritis

ObjectiveIt is postulated that increased load from pinch and grasp in occupational tasks increases the risk of thumb carpometacarpal (CMC1) osteoarthritis (OA). We sought to characterise the relationship between doctor-diagnosed...

The association of plasma fatty acids with hand and knee osteoarthritis: the NEO study

To investigate the association of postprandial and fasting plasma saturated fatty acid (SFAs), monounsaturated fatty acid (MUFAs) and polyunsaturated fatty acid (PUFAs) concentrations with hand and knee osteoarthritis (OA). In the population-based NEO study clinical hand and knee OA were defined by the ACR classification criteria. Structural knee OA was defined on MRI. Hand and knee pain was determined by Australian/Canadian Hand Osteoarthritis Index (AUSCAN) and KOOS, respectively. Plasma was sampled fasted and 150min after a standardized meal, and subsequently analysed using a nuclear magnetic resonance platform. Logistic regression analyses were used to investigate the association of total fatty acid, SFA, MUFA, total PUFA, omega-3 PUFA and omega-6 PUFA concentrations with clinical hand and knee OA, structural knee OA and hand and knee pain. Fatty acid concentrations were standardized (mean 0, SD 1). Analyses were stratified by sex and corrected for age, education, ethnicity and total body fat percentage. Of the 5,328 participants (mean age 56 years, 58% women) 7% was classified with hand OA, 10% with knee OA and 4% with concurrent hand and knee OA. In men, postprandial SFAs (OR (95% CI)) 1.23 (1.00; 1.50), total PUFAs 1.26 (1.00; 1.58) and omega-3 PUFAs 1.24 (1.01; 1.52) were associated with hand OA. SFAs and PUFAs were associated with structural, but not clinical knee OA. Association of fasting fatty acid concentrations were weaker than postprandial concentrations. Plasma postprandial SFA and PUFA levels were positively associated with clinical hand and structural knee OA in men, but not in women.

Modifiable factors associated with symptomatic knee osteoarthritis: The Murakami cohort study

ObjectivesModifiable risk factors for knee osteoarthritis (OA) have not been studied in detail. This study aimed to determine lifestyle-related modifiable factors of symptomatic knee osteoarthritis in an East Asian population. Study designThis 5-year cohort study involved 11,091 individuals (age range 40–72 years) living in the Murakami region of Niigata, Japan, who did not have a history of knee OA. At baseline, information on sociodemographic characteristics, body size, lifestyle, and living condition was obtained using a self-administered questionnaire. Main outcome measuresIncident symptomatic knee OA observed at hospitals and orthopaedic clinics in the five years to 2016. Clinical grades of knee OA were based on the Kellgren-Lawrence scale. P for trend was assessed to examine linear associations between predictors and the outcome in multiple logistic regression analysis. ResultsThe mean age of participants was 58.1 (SD 9.3) years. The number of cases of grade 2 or more incident knee OA was 429. In men, older age (P for trend < 0.0001), higher BMI (P for trend < 0.0001), higher METs score (P for trend = 0.0150), less smoking (P for trend = 0.0249), and lower green tea consumption (P for trend = 0.0437) were associated with incident knee OA. In women, older age (P for trend < 0.0001), higher BMI (P for trend < 0.0001), and alcohol consumption (P = 0.0153) were associated with incident knee OA. ConclusionsSeveral lifestyle-related factors were found to be associated with incident knee OA and exhibited sex-dependent differences. In particular, higher consumption of green tea was associated with a lower incidence of knee OA in men.

The different influence of high levels of physical activity on the incidence of knee OA in overweight and obese men and women-a gender specific analysis

To investigate the influence of physical activity on incidence of knee osteoarthritis (OA) in overweight and obese men and women. Data were extracted from the Osteoarthritis Initiative cohort on 1,667 participants without symptomatic knee OA at baseline. We used logistic regression and marginal effect models to estimate the effect of body mass index (BMI) and reported physical activity score, together with the interaction between them, on the development of radiographic knee OA, symptomatic knee OA and joint space narrowing (JSN) after 96-months. Men in the most active quartile had almost double the likelihood of knee OA, independent of OA definition [e.g., odds ratio (OR) 2.4 (95%CI: 1.2-4.5) for radiographic knee OA]. Interaction analyses showed statistically significant interactions between physical activity and BMI on developing knee OA (i) radiographic OA interaction(P=0.039), (ii) symptomatic OA interaction(P=0.022), (iii) JSN interactionP=0.012). The margin plots in men also demonstrated that the effect of physical activity on different measures of knee OA were modified by high levels of BMI. These effects were not mirrored in women where at all BMI levels, the level of reported physical activity did not influence likelihood of knee OA independent of OA definition. In overweight and obese men, there appears to be a threshold above which increasing levels of physical activity are associated with higher risk of knee OA. This is absent in women.

Vascular Pathology and Osteoarthritis: A Systematic Review.

Vascular pathology (changes in blood vessels) and osteoarthritis (OA) are both common chronic conditions associated with aging and obesity, but whether vascular pathology is a risk factor for OA is unclear. The aim of this study was to systematically review the evidence for an association between vascular pathology and risk of joint-specific OA. Scopus, Ovid Medline, and EMBASE were searched from inception to February 2019. MeSH terms and keywords were used to identify studies examining the association between vascular pathology and OA. Two reviewers independently extracted the data and assessed the methodological quality. Qualitative evidence synthesis was performed. Fifteen studies with high (n = 3), fair (n = 3), or low (n = 9) quality were included. Features of vascular pathology included atherosclerosis, vascular stiffness, and endothelial dysfunction in different vascular beds. There was evidence for an association between vascular pathology and risk of hand OA in women but not men, and between vascular pathology and risk of knee OA in both men and women. Only 2 studies examined hip OA showing no association between vascular pathology and risk of hip OA. There is evidence suggesting an association between vascular pathology and risk of hand and knee OA, with a potential causal relationship for knee OA. Based on the limited evidence, it is hard to conclude an association for hip OA. Further stronger evidence is needed to determine whether there is a causal relationship.

The association of plasma fatty acids levels with hand and knee osteoarthritis

Purpose: Obesity is one of the most important risk factors for osteoarthritis (OA). In addition to increased mechanical loading, systemic factors also likely play a role. Nutrient excess leading to obesity may result in lipotoxicity, with increased levels of circulating fatty acids. However, our knowledge about the effect of different fatty acids on OA is sparse. Therefore, we aimed to investigate the association of plasma saturated fatty acids (SFAs), monounsaturated fatty acid (MUFAs), polyunsaturated fatty acids (PUFAs), omega (n-)3 and n-6 PUFAs on clinically defined hand and knee OA. Since we are in a postprandial state most of the day, both fasting and postprandial samples after a standardized mixed meal were used for the association analyses. Methods: In the population-based Netherlands Epidemiology of Obesity (NEO) study, a total of 6,671 middle-aged participants were recruited from the greater area of Leiden. Clinical hand and knee OA were defined by the ACR clinical classification criteria. Blood samples were obtained after an overnight fast and 150 minutes after consumption of a standardized liquid mixed meal containing 600kCal, with 16% of energy (En%) derived from protein, 50 En% from carbohydrates and 34 En% from fat. EDTA-plasma samples were used for a high-throughput proton nuclear magnetic resonance (NMR) metabolomics platform (Nightingale Health Ltd., Helsinki, Finland) to quantify 159 lipid and metabolite measures. For the present analyses the concentrations of fasting and postprandial total fatty acids, SFAs, MUFAs, PUFAs, n-6 PUFAs and n-3 PUFAs in mmol/l were used. We excluded participants who reported to have inflammatory rheumatic disease or fibromyalgia, with missing physical examination, who were non-fasting at baseline, or reported using lipid-lowering medication. Logistic regression analyses were used to investigate the association between fatty acids and clinical OA phenotypes. All analyses were stratified by sex and corrected for age, education, ethnicity and total body fat percentage. Data are presented as odds ratios (OR) with 95% confidence intervals (CI). Results: In the current analysis 5,328 NEO participants were included, with a mean age of 56 years and 58% were women. Hand OA, knee OA and concurrent hand and knee OA were defined in 8%, 10% and 4%, respectively. After correction for possible confounders, SFA, total PUFA and omega-3 PUFA levels were positively associated with clinical hand OA in men, with OR (95% CI) of 1.26 (1.00 - 1.57), 1.35 (1.00 - 1.82) and 5.27 (1.07 - 25.96) respectively. In women, these associations were not found; however, although not significant, the OR of omega-3 PUFAs and hand OA was 2.49 (0.45 - 13.72). None of the postprandial fatty acid subtypes were statistically significantly associated with knee or concurrent hand and knee OA in both men and women. In comparison, although not significant, results from the analyses with fasting fatty acids showed similar albeit slightly dampened effect estimates. Conclusions: Quantitively measured plasma postprandial SFA and omega-3 PUFA levels were significantly associated with hand OA in men. In women no significant associations were found, however the estimated effect was comparable to the results in men. Intriguingly, although SFA and omega-3 PUFAs are deemed to have opposing effects on inflammation, both were positively associated with hand OA. No significant associations were found between fatty acids and knee and concurrent hand and knee OA. Future research is warranted to replicate the association and determine whether there is a causal role for plasma fatty acid levels in hand OA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Human OA model technologies: “Joint-on-a-chip”

Purpose: None of the currently available animal models is capable of capturing the full complexity of osteoarthritis in man. Organ-on-chip technology is an emerging field aiming at developing miniaturized humanized models for understanding organ function in health and disease. These micro-physiological systems are expected better predictive for human disease than animals and ultimately may reduce the need for animal testing. It is expected that these joint-on-chip models proof valuable in deciphering complex interactions between joint tissues in the initiation and progression of disease which cannot easily be studied in human. Methods: Various attempts are currently explored to engineer a human joint-on-chip. They have all in common that they rely on a multidisciplinary approach, requiring the input from typical engineering disciplines from diverse fields like microfluidics, polymer chemistry and processing and physics of fluids with life sciences. Results: In this session, I will highlight basic principles from organ-on-chip technologies. Together we will work on a set of minimal characteristics that would define a joint-on-chip. We will discuss the challenges that still need resolving. I will illustrate the session with examples from literature and our own work on recreating the human joint on a chip. Conclusions: While still in its infancy, the human joint-on-chip has the potential to advance our understanding of the human joint as an organ and increase our understanding of the complexity of osteoarthritis.

Hand and knee osteoarthritis are associated with reduced diameters in retinal vessels: the AGES-Reykjavik study.

To investigate the association between osteoarthritis (OA) and microvascular pathology, we examined the relationship between retinal microvascular caliber and osteoarthritis of the hand and knee in an elderly population. The AGES-Reykjavik is a population-based, multidisciplinary longitudinal cohort study of aging. Retinal vessel caliber, hand osteoarthritis and total knee joint replacements due to OA were examined in 4757 individuals (mean age 76 ± 5years; 57% female). Incident knee joint replacements during 5-year follow-up (n = 2961, mean age 75 ± 5years; 58% female) were also assessed. Logistic regression analysis, adjusting for age, sex, and body mass index, showed an association between narrow arteriolar caliber and hand OA, as well as knee replacement. After adjustment for other covariates, including statin therapy, this association was significant for both hand OA in men and women [OR 1.10(1.03-1.17), p < 0.01] (per unit standard deviation decrease in CRAE) and TKR prevalence [OR 1.15 (1.01-1.32), p = 0.04], especially for men [OR 1.22 (1.00-1.51) p = 0.04] and also for incident TKRs in men [OR 1.50 (1.07-2.10), p = 0.04]. Narrow venular caliber was associated with hand OA in women [OR 1.10 (1.01-1.21), p = 0.03]. Retinal arterial narrowing in hand and knee OA is present in males as well as females. Venular narrowing in hand OA in women was an unexpected finding and is in contrast with the venular widening usually observed in cardiovascular diseases.