Radiographic Knee Osteoarthritis Research Articles

Thigh muscle composition changes in knee osteoarthritis patients during weight loss: Sex-specific analysis using data from osteoarthritis initiative

ObjectivesSex of patients with knee osteoarthritis (KOA) may impact changes in thigh muscle composition during weight loss, the most well-known disease-modifying intervention. We investigated longitudinal sex-based changes in thigh muscle quality during weight loss in participants with KOA. MethodsUsing Osteoarthritis Initiative (OAI) cohort data, we included females and males with baseline radiographic KOA who experienced >5% reduction in BMI over four years. Using a previously validated deep-learning algorithm, we measured MRI-derived biomarkers of thigh muscles at baseline and year-4. Outcomes were the intra- and inter-muscular adipose tissue (Intra-MAT and Inter-MAT) and contractile percentage of thigh muscles between females and males. The analysis adjusted for potential confounders, such as demographics, risk factors, BMI change, physical activity, diet, and KOA status. ResultsA retrospective selection of available thigh MRIs from KOA participants who also had a 4-year weight loss (>5% of BMI) yielded a sample comprising 313 thighs (192 females and 121 males). Female and male participants exhibited a comparable degree of weight loss (females: -9.72±4.38, males: -8.83±3.64, P-value=0.060). However, the changes in thigh muscle quality were less beneficial for females compared to males, as shown by a less degree of longitudinal decrease in Intra-MAT (change difference,95%CI: 783.44 mm2/4-year, 505.70 to 1061.19, P-value<0.001) and longitudinal increase in contractile percentage (change difference,95%CI: -3.9%/4-year, -6.5 to -1.4, P-value=0.019). ConclusionsIn participants with KOA and 4-year weight loss, the longitudinal changes in thigh muscle quality were overall beneficial but to a less degree in females compared to males. Further research is warranted to investigate the underlying mechanisms and develop sex-specific interventions to optimize muscle quality during weight loss.

Diminished vibration perception and greater pressure pain sensitivity are associated with worse knee osteoarthritis outcomes across sex and race

ObjectiveTo examine associations of vibration sensitivity and pressure pain sensitivity with knee osteoarthritis (OA) outcomes across sex and race, which may relate to known sex and race disparities in clinical outcomes. DesignData were from the 2013-2015 visit of the Johnston County Osteoarthritis Project. Exposures were vibration perception threshold (VPT) measured at the bilateral medial femoral condyle (MFC) and first metatarsophalangeal joint (MTP), and pressure pain threshold (PPT) measured at the bilateral upper trapezius. Outcomes were knee pain severity and presence of knee symptoms, radiographic knee OA, and symptomatic knee OA in each knee. Cross-sectional associations of the exposures with the outcomes were examined using logistic regression models, overall and separately by sex and race. ResultsIn the VPT and PPT analyses, 851 and 862 participants (mean age 71 years, 68% female, 33% Black, body mass index 31 kg/m2) and 1585 and 1660 knees were included, respectively. Higher VPT (lower vibration sensitivity) at the MFC and first MTP joint was associated with all outcomes. Lower PPT (greater pressure pain sensitivity) was associated with greater knee pain severity. Associations of VPT and PPT with all outcomes were similar among females and males and Black and White individuals. ConclusionsDiminished vibration perception and greater pressure pain sensitivity were cross-sectionally associated with worse knee OA outcomes. Despite differences in VPT and PPT among females and males and Black and White adults, associations with knee OA outcomes did not differ by sex or race, suggesting neurophysiological differences do not relate to established disparities.

Diagnostic value of ultrasonography in knee osteoarthritis: A systematic review.

Knee osteoarthritis (KOA) is the most expected diagnosis for an arthropathy that causes discomfort and disability in older adults. Radiography is frequently used to assess patients with KOA and there have been few prior research evaluating the diagnostic efficacy of ultrasonography (US). The current study sought to assess the diagnostic efficacy of the US in identifying various characteristics of KOA in the scientific literature. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. A systematic search in PubMed, Web of Science, Scopus, and Embase databases was completed in March 2023. This study focused on the diagnostic value of US in KOA, including sensitivity, specificity, positive predictive value, and negative predictive value. The quality assessment was conducted using the Joanna Briggs Institute critical appraisal tools. Out of 552 records of database searches, finally, two studies met this systematic review's eligibility criteria and were included in the study. Both of the included studies were cross sectional studies. US demonstrated remarkable sensitivity with adequate specificity for the detection of radiographic knee OA; however, it was found not to be an appropriate method for the detection of early KOA. This study as the first systematic review aims to evaluate the diagnostic performance of US in detecting KOA. These findings shed light on the importance of investigating the different US features in the evaluation of KOA to reach appropriate sensitivity and specificity in the diagnosis.

Erosive hand osteoarthritis and sarcopenia: data from Osteoarthritis Initiative cohort

ObjectivesThere is no evidence linking specific osteoarthritis (OA) types, such as erosive hand OA (EHOA), with distant generalised changes in muscle composition (sarcopenia), which can potentially be modified. This study...

Effectiveness and safety of polyacrylamide hydrogel injection for knee osteoarthritis: results from a 12-month follow up of an open-label study

ObjectiveThere are few effective osteoarthritis (OA) therapies. A novel injectable polyacrylamide hydrogel (iPAAG) previously demonstrated efficacy and safety up to week 26 in an open-label study of knee OA. Here we report longer-term effectiveness and safety data.MethodsThis multi-centre, open-label study included patients with symptomatic and radiographic knee OA. Primary outcome was WOMAC pain (0–100 scale) at 13 weeks, and patients continued to 26 weeks before entering a further 26-week extension phase. Secondary efficacy outcomes included WOMAC stiffness and function subscales, Patient Global Assessment (PGA) and proportion of OMERACT-OARSI responders. Safety outcomes were adverse events (AEs).Results49 participants (31 women, mean age 70) received an ultrasound-guided, intra-articular injection of 6 ml iPAAG; 46 completed the extension phase to 52 weeks. There was a significant reduction in the WOMAC pain score from baseline to 52 weeks (− 17.7 points (95% CI − 23.1; − 12.4); p < 0.0001). Similar sustained improvements were observed for WOMAC stiffness (11.0 points; 95% CI − 17.0; − 4.9), physical function (18.0 points; 95% CI − 19.1; − 10.6), and PGA (16.3 points; 95% CI − 23.1; − 9.4). At 52 weeks 62.2% of patients were OMERACT-OARSI responders. From 26 to 52 weeks, 8 adverse effects (AE), including 1 serious AE (cerebrovascular accident) were reported in 5 subjects. None of the new adverse events were thought to be device related.ConclusionThis open-label study suggests persistent benefits and safety of iPAAG through 52 weeks after a single injection.Trial registration: Clinicaltrials.gov NCT04179552.

Weight-Bearing Physical Activity, Lower-Limb Muscle Mass, and Risk of Knee Osteoarthritis.

It has been demonstrated that total physical activity is not associated with risk of osteoarthritis. However, the association of different types of physical activity with incident knee osteoarthritis remains unclear. To determine whether weight-bearing recreational physical activities are associated with increased risk of incident knee osteoarthritis. This prospective cohort study used data from the Rotterdam Study (1996 to 2009), including participants with knee x-ray measurements at baseline and follow-up examinations. Participants with knee osteoarthritis at baseline were excluded. Residents aged 45 years and older of the Ommoord district in the city of Rotterdam in The Netherlands were invited to join the Rotterdam Study (78% response rate). Analysis was conducted in June 2023. Total, weight-bearing, and non-weight-bearing recreational physical activities collected by questionnaires at baseline. Incident radiographic knee osteoarthritis measured by knee x-ray was the primary outcome, and incident symptomatic knee osteoarthritis defined by x-ray and knee pain questionnaire was the secondary outcome. The association of different types of recreational physical activity with radiographic knee osteoarthritis was examined using logistic regression within generalized estimating equation framework after adjusting for potential confounders. A prespecified stratification analysis was planned on the basis of lower-limb muscle mass index (LMI) tertiles, measured by dual-energy x-ray absorptiometry. A total of 5003 individuals (2804 women [56.0%]; mean [SD] age, 64.5 [7.9] years) were included. The knee osteoarthritis incident rate was 8.4% (793 of 9483 knees) for a mean (SD) follow-up time of 6.33 (2.46) years. Higher weight-bearing activity was associated with increased odds of incident knee osteoarthritis (odds ratio [OR], 1.22; 95% CI, 1.10-1.35; P < .001), but non-weight-bearing activity was not (OR, 1.04; 95% CI, 0.95-1.15; P = .37). In the analysis stratified by LMI tertiles, the association of weight-bearing activity with incident osteoarthritis was found only among 431 patients in the lowest LMI tertile (OR, 1.53; 95% CI, 1.15-2.04; P = .003), but not among patients in the middle or high LMI tertile. The findings of this study suggest that weight-bearing activity is associated with incident knee osteoarthritis in people with low levels of lower-limb muscle mass, which might be a promising avenue for tailored advice for physical activity.

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

BackgroundTo 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.MethodsA 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.ResultsFall 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).ConclusionKnee 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.

Bicycling over a Lifetime Is Associated with Less Symptomatic Knee Osteoarthritis: Data from the Osteoarthritis Initiative.

This study aimed to evaluate the relationship between a history of bicycling and symptomatic and structural outcomes of knee osteoarthritis (OA), the most common form of arthritis. This was a retrospective, cross-sectional study within the Osteoarthritis Initiative (OAI), where we investigated OAI participants with complete data on bicycling, knee pain, and radiographic evidence of knee OA. We used a self-administered questionnaire at the 96-month OAI visit to identify participation in bicycling during four time periods throughout a participant's lifetime (ages 12-18, 19-34, 35-49, and >50 yr). Using logistic regression, we evaluated the influence of prior bicycling status (any history, history for each time period, number of periods cycling) on three outcomes at the 48-month OAI visit: frequent knee pain, radiographic OA (ROA), and symptomatic radiographic OA (SOA), adjusting for age and gender. A total of 2607 participants were included: 44.2% were male, mean age was 64.3 (SD, 9.0) yr, and body mass index was 28.5 (SD, 4.9) kg·m -2 . The adjusted risk ratios for the outcome of frequent knee pain, ROA, and SOA among those who reported any history of bicycling compared with non-bicyclers were 0.83 (0.73-0.92), 0.91 (0.85-0.98), and 0.79 (0.68-0.90), respectively. We observed a dose-response among those who participated in bicycling during more time periods. People who participated in bicycling had a lower prevalence of frequent knee pain, ROA, and SOA. The benefit appeared cumulative. This study indicates that bicycling may be favorable to knee health and should be encouraged.

The efficacy and safety of a fixed-dose combination of apocynin and paeonol, APPA, in symptomatic knee OA: A double-blind, randomized, placebo-controlled, clinical trial

ObjectiveApocynin (AP) and paeonol (PA) are low molecular weight phenolic compounds with a broad array of anti-inflammatory and immunoregulatory effects. This study assessed of a fixed-dose combination of APPA in people with symptomatic knee osteoarthritis (OA). MethodsA multi-center, randomized, placebo-controlled, double-blind phase 2a trial enrolled participants with radiographic knee OA (Kellgren-Lawrence, KL, grades 2-3) and pain ≥40/100 on WOMAC pain subscale, and evaluated the efficacy and safety of oral APPA over a 28-day period. APPA 800 mg or matching placebo was administered twice daily in a 1:1 ratio. Post-hoc analyses explored the response to APPA in sub-groups with more severe pain and structural severity. ResultsThe two groups were comparable at baseline; 152 subjects were enrolled and 148 completed the trial. There was no statistically significant difference between groups with respect to the primary outcome, WOMAC pain (mean difference between groups was -0.89, 95 % CI: -5.62, 3.84, p=0.71), nor WOMAC function or WOMAC total. However, predefined subgroup analyses of subjects with symptoms compatible with neuroplastic/neuropathic pain features showed a statistically significant effect of APPA compared to placebo. Adverse events (mainly gastrointestinal) were mild to moderate. ConclusionTreatment with APPA 800 mg twice daily for 28 days in subjects with symptomatic knee OA was not associated with significant symptom improvement compared to placebo. The treatment was well-tolerated and safe. While the study was not powered for such analysis, pre-planned subgroup analyses showed a significant effect of APPA in subjects with neuroplastic pain/severe OA, indicating that further research in the effects of APPA in appropriate patients is warranted.

Can gait patterns be explained by joint structure in people with and without radiographic knee osteoarthritis? Data from the IMI-APPROACH cohort

ObjectiveTo determine the association between joint structure and gait in patients with knee osteoarthritis (OA).MethodsIMI-APPROACH recruited 297 clinical knee OA patients. Gait data was collected (GaitSmart®) and OA-related joint measures determined from knee radiographs (KIDA) and MRIs (qMRI/MOAKS). Patients were divided into those with/without radiographic OA (ROA). Principal component analyses (PCA) were performed on gait parameters; linear regression models were used to evaluate whether image-based structural and demographic parameters were associated with gait principal components.ResultsTwo hundred seventy-one patients (age median 68.0, BMI 27.0, 77% female) could be analyzed; 149 (55%) had ROA. PCA identified two components: upper leg (primarily walking speed, stride duration, hip range of motion [ROM], thigh ROM) and lower leg (calf ROM, knee ROM in swing and stance phases). Increased age, BMI, and radiographic subchondral bone density (sclerosis), decreased radiographic varus angle deviation, and female sex were statistically significantly associated with worse lower leg gait (i.e. reduced ROM) in patients without ROA (R2 = 0.24); in ROA patients, increased BMI, radiographic osteophytes, MRI meniscal extrusion and female sex showed significantly worse lower leg gait (R2 = 0.18). Higher BMI was significantly associated with reduced upper leg function for non-ROA patients (R2 = 0.05); ROA patients with male sex, higher BMI and less MRI synovitis showed significantly worse upper leg gait (R2 = 0.12).ConclusionStructural OA pathology was significantly associated with gait in patients with clinical knee OA, though BMI may be more important. While associations were not strong, these results provide a significant association between OA symptoms (gait) and joint structure.

Predicting the onset of end-stage knee osteoarthritis over two- and five-years using machine learning

ObjectiveIdentifying participants who will progress to advanced stage in knee osteoarthritis (KOA) trials remains a significant challenge. Current tools, relying on total knee replacements (TKR), fall short in reliability due to the extraneous factors influencing TKR decisions. Acknowledging these limitations, our study identifies a critical need for a more robust metric to assess severe KOA. The end-stage KOA (esKOA) measure, which combines symptomatic and radiographic criteria, serves as a solid indicator. To enhance future trials that use esKOA as an endpoint, our study focuses on developing and validating a machine-learning tool to identify individuals likely to develop esKOA within 2 to 5 years. DesignUtilizing the Osteoarthritis Initiative (OAI) data, we trained models on 3,114 participants and validated them with 606 participants for the right knee, and similarly for the left knee, with external validation from the Multicentre Osteoarthritis Study (MOST) involving 1,602 participants. We aimed to predict esKOA onset at 2-to-2.5 years and 4-to-5 years, defining esKOA by severe radiographic KOA with moderate/severe symptoms or mild/moderate radiographic KOA with persistent/intense symptoms. Our analysis considered 51 candidate predictors, including demographics, clinical history, physical examination, and X-ray evaluations. An online tool predicting esKOA progression, based on models with ten and nine predictors for the right and left knees, respectively, was developed. ResultsExternal validation (MOST) for the right knee at 2.5 years yielded an Area Under Curve (AUC) of 0.847 (95 % CI 0.811 to 0.882), and at 5 years, 0.853 (95 % CI 0.823 to 0.881); for the left knee at 2.5 years, AUC was 0.824 (95 % CI 0.782 to 0.857), and at 5 years, 0.807 (95 % CI 0.768 to 0.843). Models with fewer predictors demonstrated comparable performance. The online tool is available at: https://eskoa.shinyapps.io/webapp/. ConclusionOur study unveils a robust, externally validated machine learning tool proficient in predicting the onset of esKOA over the next 2 to 5 years. Our tool can lead to more efficient KOA trials.

Performance of Radiological and Biochemical Biomarkers in Predicting Radio-Symptomatic Knee Osteoarthritis Progression.

Imaging biomarkers permit improved approaches to identify the most at-risk patients encountering knee osteoarthritis (KOA) progression. This study aimed to investigate the utility of trabecular bone texture (TBT) extracted from plain radiographs, associated with a set of clinical, biochemical, and radiographic data, as a predictor of long-term radiographic KOA progression. We used data from the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium dataset. The reference model made use of baseline TBT parameters adjusted for clinical covariates and radiological scores. Several models based on a combination of baseline and 24-month TBT variations (TBT∆TBT) were developed using logistic regression and compared to those based on baseline-only TBT parameters. All models were adjusted for baseline clinical covariates, radiological scores, and biochemical descriptors. The best overall performances for the prediction of radio-symptomatic, radiographic, and symptomatic progression were achieved using TBT∆TBT parameters solely, with area under the ROC curve values of 0.658 (95% CI: 0.612-0.705), 0.752 (95% CI: 0.700-0.804), and 0.698 (95% CI: 0.641-0.756), respectively. Adding biochemical markers did not significantly improve the performance of the TBT∆TBT-based model. Additionally, when TBT values were taken from the entire subchondral bone rather than just the medial, lateral, or central compartments, better results were obtained.

Baseline levels of circulating galectin-1 associated with radiographic hand but not radiographic knee osteoarthritis at a two-year follow-up

ObjectiveWe tested the potential of circulating galectin-1, interleukin (IL)-1 beta, IL-6, and tumour necrosis factor alpha (TNF alpha) levels at baseline in individuals with knee pain as biomarkers for development of radiographic knee and/or hand osteoarthritis (OA). DesignThis study comprised 212 individuals with knee pain from the Halland osteoarthritis cohort (HALLOA). Clinical characteristics and serum/plasma levels of galectin-1, IL-1 beta, IL-6, and TNF alpha were measured at baseline, and knee and hand radiographs were obtained at a two-year follow-up. The predictive value of circulating inflammatory markers and clinical variables at baseline was assessed using multinominal logistic regression for those who developed radiographic OA in knees only (n ​= ​25), in hands only (n ​= ​40), and in both knees and hands (n ​= ​43); the group who did not develop OA (n ​= ​104) was used as reference. Correlations were assessed using Spearman's correlation coefficients. ResultsAs expected, age was identified as a risk factor for having radiographic knee and/or hand OA at the two-year follow-up. Baseline circulating galectin-1 levels did not associate with developing radiographic knee OA but associated with developing radiographic hand OA (odds ratio (OR) for a 20% increased risk: 1.14, 95% confidence interval (CI) 1.01–1.29) and both radiographic knee and hand OA (OR for a 20% increased risk: 1.18, 95% CI 1.05–1.30). However, baseline IL-1 beta, IL-6, and TNF alpha did not associate with developing radiographic knee and/or hand OA. ConclusionNon-age adjusted circulating galectin-1 is superior to IL-6, IL-1 beta, and TNF alpha in predicting radiographic hand but not knee OA.

Development of radiographic knee osteoarthritis and the associations to radiographic changes and baseline variables in individuals with knee pain: a 2-year longitudinal study

ObjectivesThe aim was to study the development of radiographic knee osteoarthritis (RKOA) in individuals with knee pain over 2 years, and the associations between radiographic changes and baseline variables.DesignLongitudinal cohort...

Qualitative and Quantitative Measures in the Infrapatellar Fat Pad in Older Adults: Associations with Knee Pain, Radiographic Osteoarthritis, Kinematics, and Kinetics of the Knee

ObjectiveThe purpose of this study is to delineate cross-sectional associations between qualitative and quantitative measures of the infrapatellar fat pad (IPFP) and knee symptoms, structure, kinematics, and kinetics in older adults. MethodsNinety eligible subjects (90 knees, mean age 54.0 years, 68.9% female) were examined at our centre. We used T2-weighted fat-suppressed magnetic resonance imaging (MRI) to evaluate signal intensity alteration, maximum sagittal area, and depth of the IPFP. Symptomatic osteoarthritis (SOA) was a pain subscale score greater than 0 on the Western Ontario McMaster Osteoarthritis Index. A Kellgren-Lawrence grade ≥ 2 identified incident radiographic osteoarthritis (iROA). Three-dimensional gait data were employed to analyze knee joint kinematics and kinetics. Correlation and regression analyses assessed associations between IPFP measurements and SOA, iROA, kinematics, and kinetics. ResultsThere were strong and positive associations between IPFP signal intensity alteration and both SOA and iROA in multivariable regression analyses [OR (95% CI): 2.849 (1.440 to 5.636), 2.356 (1.236 to 4.492), respectively]. Conversely, a significant negative correlation was observed between IPFP maximum area and flexion angle [B (95%CI): -1.557 (-2.549 to -0.564)]. Moreover, adjusting for covariates did not reveal any significant correlation between IPFP parameters and other indicators (P > 0.05, respectively). ConclusionIPFP signal intensity alteration and area were associated with knee clinical symptoms, structural abnormalities, and flexion angle in adults over 40, respectively. These findings suggest that IPFP may be a crucial imaging biomarker in early and middle knee osteoarthritis.

Essential Fatty Acids and Osteoarthritis.

Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Although n-3 fatty acids reduce inflammation, different n-3 fatty acids have different effects on inflammation and clinical outcomes, with eicosapentaenoic acid (EPA) having the strongest effect. We examined whether specific essential fatty acid levels affected the development of OA. We studied participants from the Multicenter Osteoarthritis Study (MOST) at risk of developing knee OA. As part of MOST, participants were asked repeatedly about knee pain, and knee radiographs and magnetic resonance images (MRIs) were obtained. Using baseline fasting samples, we analyzed serum fatty acids with standard assays. After excluding participants with baseline OA, we defined two sets of cases based on their status through 60 months' follow-up: those developing incident radiographic OA and those developing incident symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage damage and synovitis and worsening knee pain and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of specific n-3 and n-6 fatty acids, adjusting for age, sex, body mass index, education, physical activity, race, baseline pain, smoking, statin use, and depressive symptoms. We studied 363 cases with incident symptomatic knee OA and 295 with incident radiographic knee OA. The mean age was 62 years (59% women). We found no associations of specific n-3 fatty acid levels, including EPA, or of n-6 fatty acid levels with incident OA (eg, for incident symptomatic knee OA, the odds ratio per SD increase in EPA was 1.0 [95% confidence interval 0.87-1.17]). Results for other OA outcomes also failed to suggest a protective effect of specific n-3 fatty acids with OA outcomes. We found no association of serum levels of EPA or of other specific n-3 fatty acids or n-6 fatty acids with risk of incident knee OA or other OA outcomes.

Evaluation of Dynamic Effects of Depressive Symptoms on Physical Function in Knee Osteoarthritis.

To assess how changes in depressive symptoms influence physical function over time among those with radiographic knee osteoarthritis (OA). Participants from the Osteoarthritis Initiative with radiographic knee OA (n=2,212) and complete data were identified at baseline. Depressive symptoms were assessed as a time-varying score at baseline and the first three annual follow-up visits using the Center for Epidemiological Studies Depression Scale (CES-D) Scale. Physical function was measured at the first four follow-up visits using 20-meter gait speed meters per second. The following two marginal structural models were fit: one assessing the main effect of depressive symptoms on gait speed and another assessing time-specific associations. Time-adjusted results indicated that higher CES-D scores were significantly associated with slower gait speed (-0.0048; 95% confidence interval -0.0082 to -0.0014), and time-specific associations of CES-D were largest during the first follow-up interval (-0.0082; 95% confidence interval -0.0128 to -0.0035). During subsequent follow-up time points, the influence of depressive symptoms on gait speed diminished. The negative effect of depressive symptoms on physical function may decrease over time as knee OA progresses.

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

PurposeAdvancing 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. MethodsWe analyzed data from the Multicenter Osteoarthritis Study (MOST) 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. ResultsTwenty 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, OR (95% CI)=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. ConclusionsEpigenetic 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.

Thigh muscle and fat volumes are associated with knee cartilage abnormalities and bone marrow edema-like lesions: data from the osteoarthritis initiative.

To investigate the associations of thigh muscle and fat volumes with structural abnormalities on MRI related to knee osteoarthritis. MRI studies of the thighs and knees from 100 individuals were randomly selected from the Osteoarthritis Initiative Cohort. Whole Organ MR Scoring (WORMS) and effusion-synovitis scoring were performed in all knee MRI. Thigh muscles, intermuscular fat, and subcutaneous fat were manually segmented in 15 consecutive MR thigh images. Radiographic Kellgren-Lawrence grades (KLG) were also obtained in all knee radiographs. Independent t-tests were used to investigate the associations between thigh muscle and fat volumes, and sex. Mixed-effects analyses were obtained to investigate the associations between thigh muscle and fat volumes, KLG, WOMAC pain score, cartilage and bone marrow WORMS, as well as effusion-synovitis scores. Women had higher subcutaneous fat volume than men (616.82 vs. 229.13 cm3, p < 0.01) and men had higher muscle volumes than women (p < 0.01). Quadriceps (coef = -2.15, p = 0.01) and vastus medialis (coef = -1.84, p = 0.03) volumes were negatively associated with the WORMS cartilage scores. Intermuscular fat volume (coef = 0.48, p = 0.01) was positively associated with WORMS bone marrow edema-like lesion (BMEL) scores. The quadriceps (coef = -0.99, p < 0.01) and hamstring (coef = -0.59, p = 0.01) volumes were negatively associated with WORMS BMEL scores. No evidence of an association was found between thigh muscle and fat volumes with KLG and effusion-synovitis grading (p > 0.05). Increased quadriceps and hamstring volumes were negatively associated with cartilage lesion and BMEL scores while no evidence of an association was found between thigh muscle and fat volumes, and radiographic knee osteoarthritis or effusion-synovitis grading.

Tick-Borne Disease Infections and Chronic Musculoskeletal Pain

Tick-borne diseases (TBDs) other than Lyme disease, such as spotted fever group rickettsiosis, ehrlichiosis, and galactose-α-1,3-galactose (α-gal) syndrome, are an emerging public health issue. Long-term sequelae secondary to Ehrlichia or Rickettsia infection are uncommon; however, musculoskeletal symptoms are often attributed to prior tick exposure. To evaluate the potential associations between prior exposure to TBDs and musculoskeletal symptoms, including radiographic osteoarthritis. This cross-sectional study analyzed serum samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing longitudinal, population-based study in Johnston County, North Carolina. Biospecimen testing and analysis were performed between May 2022 and November 2023. Participants in the JoCo OA project are noninstitutionalized White and Black Johnston County residents 45 years or older. The primary outcome was seropositivity with Ehrlichia IgG, Rickettsia IgG, and/or α-gal IgE and musculoskeletal symptoms. Secondary outcomes included risk factors associated with elevated α-gal IgE and weighted population point prevalence rates. Participants completed questionnaires, underwent physical assessments, and provided biospecimens for serological testing. Multivariable models were used to estimate associations of interest. Of the 605 participants who completed the fourth visit of the JoCo OA project, 488 (80.7%) had serum samples available for testing. The 488 participants had a median (IQR) age of 72 (68-78) years and included 336 females (68.9%) and 161 Black (33.0%) and 327 White (67.0%) individuals. The overall weighted point prevalence was 8.6% (95% CI, 5.9%-11.3%) for Ehrlichia IgG, 17.1% (95% CI, 12.6%-21.5%) for Rickettsia IgG, and 19.6% (95% CI, 15.3%-23.8%) for α-gal IgE level greater than 0.1 IU/mL. Only α-gal IgE was associated with knee pain, aching or stiffness (mean ratio, 1.30; 95% CI, 1.09-1.56). Antibodies to Rickettsia, Ehrlichia, and α-gal were not associated with symptomatic radiographic knee osteoarthritis. Male sex (odds ratio [OR], 2.63; 95% CI, 1.55-4.47), current smoker status (OR, 3.55; 95% CI, 1.38-9.18), and an attached tick bite in the past 5 years (OR, 3.99; 95% CI, 2.22-7.15) were all risk factors that were associated with α-gal IgE level greater than 0.1 IU/mL. Despite only 84 individuals (17.2%) recalling a tick bite in the past 5 years, 178 (36.5%) had evidence of prior tick-borne exposure, suggesting frequent human-tick interactions. Results of this cross-sectional study indicate no association between Ehrlichia or Rickettsia seropositivity and chronic musculoskeletal symptoms or osteoarthritis. Further investigation is needed into the pathogenesis of α-gal syndrome and interventions to reduce human-tick interactions.