Prevention Of Knee Osteoarthritis Research Articles

Gut microbiota metabolic pathways: Key players in knee osteoarthritis development

ObjectiveTo confirm the causality of gut microbiota pathway abundance and knee osteoarthritis (KOA). MethodsMicrobial metabolic pathways were taken as exposures, with data from the Dutch Microbiome Project (DMP). Data on KOA from the UK Biobank were utilized as endpoints. In addition, we extracted significant and independent single nucleotide polymorphisms as instrumental variables. Two-sample Mendelian randomization (MR) analysis was applied to explore the causal relationship between gut microbiota pathway abundance and KOA, and MR-Egger and weighted median were used as additional validation of the MR results. Meanwhile, Cochran Q, MR-Egger intercept, MR-PRESSO, and leave-one-out were used to perform sensitivity analyses on the MR results. ResultsMR results showed that enterobactin biosynthesis, diacylglycerol biosynthesis I, Clostridium acetobutylicum acidogenic fermentation, glyoxylate bypass and tricarboxylic acid cycle were the risk factors for KOA. (OR = 1.13,95%CI = 1.04–1.23;OR = 1.12,95%CI = 1.04–1.20;OR = 1.14,95%CI = 1.04–1.26; OR = 1.06,95%CI = 1.00–1.12) However, adenosylcobalamin salvage from cobinamide I, hexitol fermentation to lactate formate ethanol and acetate, purine nucleotides degradation II aerobic, L tryptophan biosynthesis and inosine 5 phosphate biosynthesis III pathway showed significant protection against KOA. (OR = 0.93,95%CI = 0.86–1.00;OR = 0.94,95%CI = 0.88–1.00;OR = 0.91,95%CI = 0.86–0.97;OR = 0.95,95%CI = 0.92–0.99; OR = 0.91, 95%CI = 0.85–0.98) Further multiplicity and sensitivity analyses demonstrated the robustness of the results. ConclusionOur study identified specific metabolic pathways in gut microbiota that promote or inhibit KOA, which provides the most substantial evidence-based medical evidence for the pathogenesis and prevention of KOA.

Causal link between metabolic related factors and osteoarthritis: a Mendelian randomization investigation.

Metabolic syndrome (MetS) is significantly associated with osteoarthritis (OA), especially in MetS patients with blood glucose abnormalities, such as elevated fasting blood glucose (FG), which may increase OA risk. Dietary modifications, especially the intake of polyunsaturated fatty acids (PUFAs), are regarded as a potential means of preventing MetS and its complications. However, regarding the effects of FG, Omega-3s, and Omega-6s on OA, the research conclusions are conflicting, which is attributed to the complexity of the pathogenesis of OA. Therefore, it is imperative to thoroughly evaluate multiple factors to fully understand their role in OA, which needs further exploration and clarification. Two-sample univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were employed to examine the causal effect of metabolic related factors on hip OA (HOA) or knee OA (KOA). The exposure and outcome datasets were obtained from Open GWAS IEU. All cases were independent European ancestry data. Three MR methods were performed to estimate the causal effect: inverse-variance weighting (IVW), weighted median method (WMM), and MR-Egger regression. Additionally, the intercept analysis in MR-Egger regression is used to estimate pleiotropy, and the IVW method and MR-Egger regression are used to test the heterogeneity. The UVMR analysis revealed a causal relationship between FG and HOA. By MVMR analysis, the study discovered a significant link between FG (OR = 0.79, 95%CI: 0.64∼0.99, p = 0.036) and KOA after accounting for body mass index (BMI), age, and sex hormone-binding globulin (SHBG). However, no causal effects of FG on HOA were seen. Omega-3s and Omega-6s did not have a causal influence on HOA or KOA. No significant evidence of pleiotropy was identified. The MR investigation showed a protective effect of FG on KOA development but no causal relationship between FG and HOA. No causal effect of Omega-3s and Omega-6s on HOA and KOA was observed. Shared genetic overlaps might also exist between BMI and age, SHBG and PUFAs for OA development. This finding offers a novel insight into the treatment and prevention of KOA from glucose metabolism perspective. The FG cutoff value should be explored in the future, and consideration should be given to demonstrating the study in populations other than Europeans.

Cyclic negative pressure promotes chondrocyte growth: Association of IGF-2 with EGR-1.

Knee osteoarthritis (KOA) is one of the most common degenerative joint diseases in the elderly worldwide. The primary lesion in patients with KOA is the degeneration of articular cartilage. This study aimed to observe the biological effects of cyclic negative pressure on C28/I2 chondrocytes and to elucidate the underlying molecular mechanisms. We designed a bi-directional intelligent micro-pressure control device for cyclic negative pressure intervention on C28/I2 chondrocytes. Chondrocyte vitality and proliferation were assessed using Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. The extracellular matrix was analyzed using real-time fluorescence quantitative polymerase chain reaction (PCR) and western blot, while the molecular mechanism of the chondrocyte response to cyclic negative pressure was explored through mRNA sequencing. Experimental data demonstrated that cyclic negative pressure promoted chondrocyte proliferation and upregulated the expression of chondrocyte-specific protein, namely the collagen type II alpha 1 chain (COL2A1) protein, and the transcription factor SRY-box transcription factor 9 (SOX9). Additionally, RNA sequencing analysis revealed that the gene levels of insulin-like growth factor 2 (IGF-2) and early growth response 1 (EGR-1) were significantly elevated in the cyclic negative pressure group. This study demonstrates that cyclic negative pressure stimulates the proliferation of C28/I2 chondrocytes by promoting the expression of EGR-1 and IGF-2. This new discovery may provide novel insights into cartilage health and KOA prevention.

Epidemiology of knee Osteoarthritis in the young adults

The prevalence of knee osteoarthritis (KOA) has been seen to grow due to the rising proportions of both the aging population and individuals affected by obesity, in comparison to previous decades. The disease is expected to result in a global rise in the disability population and escalated healthcare expenditures. Although the prevalence of KOA is predominantly associated with the elderly population, it is imperative to acknowledge that individuals under the age of 45 may also be susceptible to having this disorder. Recently, an estimated significant increase in the prevalence of KOA among younger age groups has been observed. This can have significant consequences for these young patients, including loss of employment, diminished quality of life, increased medical expenses, and melancholy. Nevertheless, there is a scarcity of epidemiological research pertaining to KOA among individuals below the age of 45. Therefore, based on the data of the Global Burden of Disease (GBD) study 2019, this paper analyses the incidence and prevalence of KOA among young and middle-aged adults (below 45 years of age). Additionally, it will present a concise summary of the risk factors associated with KOA and outline preventive measures. Young women, obese individuals, and those with a prior knee injury history have a higher chance of acquiring KOA. The education of patients is critical in the prevention of KOA.

1,25-Dihydroxyvitamin D Deficiency Accelerates Aging-related Osteoarthritis via Downregulation of Sirt1 in Mice.

Emerging observational data suggest that vitamin D deficiency is associated with the onset and progression of knee osteoarthritis (OA). However, the relationship between vitamin D level and OA and the role of vitamin D supplementation in the prevention of knee OA are controversial. To address these issues, we analyzed the articular cartilage phenotype of 6- and 12-month-old wild-type and 1α(OH)ase-/- mice and found that 1,25(OH)2D deficiency accelerated the development of age-related spontaneous knee OA, including cartilage surface destruction, cartilage erosion, proteoglycan loss and cytopenia, increased OARSI score, collagen X and Mmp13 positive chondrocytes, and increased chondrocyte senescence with senescence-associated secretory phenotype (SASP). 1,25(OH)2D3 supplementation rescued all knee OA phenotypes of 1α(OH)ase-/- mice in vivo, and 1,25(OH)2D3 rescued IL-1β-induced chondrocyte OA phenotypes in vitro, including decreased chondrocyte proliferation and cartilage matrix protein synthesis, and increased oxidative stress and cell senescence. We also demonstrated that VDR was expressed in mouse articular chondrocytes, and that VDR knockout mice exhibited knee OA phenotypes. Furthermore, we demonstrated that the down-regulation of Sirt1 in articular chondrocytes of 1α(OH)ase-/- mice was corrected by supplementing 1,25(OH)2D3 or overexpression of Sirt1 in mesenchymal stem cells (MSCs) and 1,25(OH)2D3 up-regulated Sirt1 through VDR mediated transcription. Finally, we demonstrated that overexpression of Sirt1 in MSCs rescued knee OA phenotypes in 1α(OH)ase-/- mice. Thus, we conclude that 1,25(OH)2D3, via VDR-mediated gene transcription, plays a key role in preventing the onset of aging-related knee OA in mouse models by up-regulating Sirt1, an aging-related gene that promotes articular chondrocyte proliferation and extracellular matrix protein synthesis, and inhibits senescence and SASP.

The KNee OsteoArthritis Prediction (KNOAP2020) challenge: An image analysis challenge to predict incident symptomatic radiographic knee osteoarthritis from MRI and X-ray images

The KNee OsteoArthritis Prediction (KNOAP2020) challenge was organized to objectively compare methods for the prediction of incident symptomatic radiographic knee osteoarthritis within 78 months on a test set with blinded ground truth. The challenge participants were free to use any available data sources to train their models. A test set of 423 knees from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study consisting of magnetic resonance imaging (MRI) and X-ray image data along with clinical risk factors at baseline was made available to all challenge participants. The ground truth outcomes, i.e., which knees developed incident symptomatic radiographic knee osteoarthritis (according to the combined ACR criteria) within 78 months, were not provided to the participants. To assess the performance of the submitted models, we used the area under the receiver operating characteristic curve (ROCAUC) and balanced accuracy (BACC). Seven teams submitted 23 entries in total. A majority of the algorithms were trained on data from the Osteoarthritis Initiative. The model with the highest ROCAUC (0.64 (95% confidence interval (CI): 0.57-0.70)) used deep learning to extract information from X-ray images combined with clinical variables. The model with the highest BACC (0.59 (95% CI: 0.52-0.65)) ensembled three different models that used automatically extracted X-ray and MRI features along with clinical variables. The KNOAP2020 challenge established a benchmark for predicting incident symptomatic radiographic knee osteoarthritis. Accurate prediction of incident symptomatic radiographic knee osteoarthritis is a complex and still unsolved problem requiring additional investigation.

Asymmetries and relationships between muscle strength, proprioception, biomechanics, and postural stability in patients with unilateral knee osteoarthritis.

Background: The pathological mechanism of knee osteoarthritis (KOA) is unknown. KOA degeneration may be associated with changes in muscle strength, proprioception, biomechanics, and postural stability. Objective: This study aimed to assess asymmetries in muscle strength, proprioception, biomechanics, and postural stability of bilateral lower limbs in patients with unilateral KOA and healthy controls and analyze correlations between KOA and these parameters. Methods: A total of 50 patients with unilateral KOA (age range: 50-70) and 50 healthy subjects were recruited as study participants (age range: 50-70). Muscle strength, proprioception, femorotibial angle (FTA), femoral condylar–tibial plateau angle (FCTP), average trajectory error (ATE), and center of pressure (COP) sways areas were accessed in study participants, and the correlation between these variables was investigated. Results: In patients with unilateral KOA, lower limb muscle strength was significantly lower on the symptomatic side than on the asymptomatic side (p < 0.01), while the proprioception (degree error), FTA, FCTP, and ATE were substantially higher compared to the asymptomatic side (p < 0.01). However, no significant difference was observed in the healthy controls (p > 0.05). Patients with unilateral KOA had lower muscle strength than healthy controls (p < 0.05), but their proprioception (degree error: the difference between the target and reproduction angles), ATE, and COP sway areas were higher (p < 0.05). Muscle strength was found to be negatively correlated with ATE and COP sways areas (p < 0.05), whereas proprioception (degree error) was positively correlated with ATE and COP sways areas (p < 0.05) in all study participants. However, no correlation was found between FTA, FCTP, and ATE, COP sways areas in patients with unilateral KOA (p > 0.05). Conclusion: In patients with unilateral KOA, muscle strength, proprioception, biomechanics, and postural stability of bilateral limbs are asymmetrical in unilateral KOA patients. Muscle strength, proprioception, and postural stability are significantly associated variables, and changes in these variables should be considered in KOA prevention and rehabilitation.

Risk Assessment for Hip and Knee Osteoarthritis Using Polygenic Risk Scores.

ObjectivePolygenic risk scores (PRS) allow risk stratification using common single‐nucleotide polymorphisms (SNPs), and clinical applications are currently explored for several diseases. This study was undertaken to assess the risk of hip and knee osteoarthritis (OA) using PRS.MethodsWe analyzed 12,732 individuals from a population‐based cohort from the Rotterdam Study (n = 11,496), a clinical cohort (Cohort Hip and Cohort Knee [CHECK] study; n = 908), and a high‐risk cohort of overweight women (Prevention of Knee OA in Overweight Females [PROOF] study; n = 328), for the association of the PRS with prevalence/incidence of radiographic OA, of clinical OA, and of total hip replacement (THR) or total knee replacement (TKR). The hip PRS and knee PRS contained 44 and 24 independent SNPs, respectively, and were derived from a recent genome‐wide association study meta‐analysis. Standardized PRS (with Z transformation) were used in all analyses.ResultsWe found a stronger association of the PRS for clinically defined OA compared to radiographic OA phenotypes, and we observed the highest PRS risk stratification for TKR/THR. The odds ratio (OR) per SD was 1.3 for incident THR (95% confidence interval [95% CI] 1.1–1.5) and 1.6 (95% CI 1.3–1.9) for incident TKR in the Rotterdam Study. The knee PRS was associated with incident clinical knee OA in the CHECK study (OR 1.3 [95% CI 1.1–1.5]), but not for the PROOF study (OR 1.2 [95% CI 0.8–1.7]). The OR for OA increased gradually across the PRS distribution, up to 2.1 (95% CI 1.4–3.2) for individuals with the 10% highest PRS compared to the middle 50% of the PRS distribution.ConclusionOur findings validated the association of PRS across OA definitions. Since OA is becoming frequent and primary prevention is not commonly applicable, PRS‐based risk assessment could play a role in OA prevention. However, the utility of PRS is dependent on the setting. Further studies are needed to test the integration of genetic risk assessment in diverse health care settings.

Are changes in meniscus volume and extrusion associated to knee osteoarthritis development? A structural equation model

To explore the interplay between (changes in) medial meniscus volume, meniscus extrusion and radiographic knee osteoarthritis (OA) development over 30 months follow-up (FU). Data from the PRevention of knee Osteoarthritis in Overweight Females study were used. This cohort included 407 middle-aged women with a body mass index ≥27kg/m2, who were free of knee OA at baseline. Demographics were collected by questionnaires at baseline. All menisci at both baseline and FU were automatically segmented from MRI scans to obtain the meniscus volume and the change over time (delta volume). Baseline and FU meniscus body extrusion was quantitatively measured on mid-coronal proton density MR images. A structural equation model was created to assess the interplay between both medial meniscus volume and central extrusion at baseline, delta volume, delta extrusion, and incident radiographic knee OA at FU. The structural equation modeling yielded a fair to good fit of the data. The direct effects of both medial meniscus volume and extrusion at baseline on incident OA were statistically significant (Estimate=0.124, p=0.029, and Estimate=0.194, p<0.001, respectively). Additional indirect effects on incident radiographic OA through delta meniscus volume or delta meniscus extrusion were not statistically significant. Baseline medial meniscus volume and extrusion were associated to incidence of radiographic knee OA at FU in middle-aged overweight and obese women, while their changes were not involved in these effects. To prevent knee OA, interventions might need to target the onset of meniscal pathologies rather than their progression.

Evolving Trends in Physical Therapy Management in the Prevention of Knee Osteoarthritis from Mild to Moderate Grade: A Systematic Review

Evolving Trends in Physical Therapy Management in the Prevention of Knee Osteoarthritis from Mild to Moderate Grade: A Systematic Review

Bidirectional Association Between Knee Osteoarthritis and Depressive Symptoms: A Nationwide Cohort Study

Both knee osteoarthritis (KOA) and depressive symptoms are common health issues affecting the quality of life of old adults. Although it is presumed that KOA has a bidirectional relationship with the depressive symptoms, no cohort study has proven it. This is the first study to determine the strength of association for the bidirectional relationship between KOA and depressive symptoms. Data were gathered from the nationally survey of China Health and Retirement Longitudinal Study in 2011-2015. The presence of depressive symptoms was defined by the 10-item Center for Epidemiologic Studies Depression Scale score of 10 or higher. The adjusted Cox proportional hazards regression model was conducted to estimate hazards ratios (HRs). Controlled covariates include gender, age, education, marital status, residence, number of chronic diseases, and disability. The analysis of KOA predicting the depressive symptoms onset consisted of 4,377 participants free from depressive symptoms at baseline. During 4 years follow-up, diagnosed KOA participants were more likely to have depressive symptoms than their peers without KOA (HR = 1.50, 95% CI: 1.23-1.83). The parallel analysis of depressive symptoms predicting KOA onset included 6,848 participants without KOA at baseline, those with depressive symptoms had a higher relative risk of developing KOA (HR = 1.64, 95% CI: 1.41-1.92). Our results provide compelling evidence that the KOA-depressive symptoms association is bidirectional, highlighting the importance of evaluating the relationship between physical and mental health among older people. Particularly, taking this association into consideration in the risk assessment and primary prevention of KOA and depression symptoms.

Association between meniscal volume and development of knee osteoarthritis.

:ObjectiveTo assess the association between meniscal volume, its change over time and the development of knee OA after 30 months in overweight/obese women.MethodsData from the PRevention of knee Osteoarthritis in Overweight Females study were used. This cohort included 407 women with a BMI ≥ 27 kg/m2, free of OA-related symptoms. The primary outcome measure was incident OA after 30 months, defined by one out of the following criteria: medial or lateral joint space narrowing (JSN) ≥ 1.0 mm, incident radiographic OA [Kellgren and Lawrence (K&L) ≥ 2], or incident clinical OA. The secondary outcomes were either of these items separately. Menisci at both baseline and follow-up were automatically segmented to obtain meniscal volume and delta-volumes. Generalized estimating equations were used to evaluate associations between the volume measures and the outcomes.ResultsMedial and lateral baseline and delta-volumes were not significantly associated to the primary outcome. Lateral meniscal baseline volume was significantly associated to lateral JSN [odds ratio (OR) = 0.87; 95% CI: 0.75, 0.99], while other measures were not. Medial and lateral baseline volume were positively associated to K&L incidence (OR = 1.32 and 1.22; 95% CI: 1.15, 1.50 and 1.03, 1.45, respectively), while medial and lateral delta-volume were negatively associated to K&L incidence (OR = 0.998 and 0.997; 95% CI: 0.997, 1.000 and 0.996, 0.999, respectively). None of the meniscal measures were significantly associated to incident clinical OA.ConclusionLarger baseline meniscal volume and the decrease of meniscal volume over time were associated to the development of structural OA after 30 months in overweight and obese women.

Knee muscle atrophy is a risk factor for development of knee osteoarthritis in a rat model

ObjectivesThe objective of this study was to investigate the effect of botulinum toxin type A (BTX-A)–induced quadriceps muscle atrophy on the cartilage and subchondral bone in an otherwise intact rat joint model. MethodsThe rat right quadriceps muscle atrophy was established by intramuscular injection of BTX-A. Twenty-four rats were divided randomly into 3 groups: The BTX-A–treated 4-week group; the BTX-A–treated 8-week group; and the control group injected with phosphate buffer saline were observed for 8 weeks. Muscle atrophy level was measured by weighing and histology examinations. Serum interleukin-1β level was tested by ELISA (enzyme linked immunosorbent assay); the subchondral bone was analysed by micro–computed tomography and the cartilage was measured by histology examinations (gross view, haematoxylin and eosin staining and Safranin-O/fast green staining) and immunohistochemistry test {collagen X [ColX]}. ResultsBTX-A intramuscular injection led to muscle atrophy. Characteristics of muscle atrophy appeared in two BTX-A–injected groups but not in the control group. Quadriceps atrophy did not affect interleukin-1β level in serum, but resulted in subchondral bone abnormal changes with reduced bone volume/total tissue volume ​and increased Structure Model Index. Furthermore, the more the severe cartilage damage, the higher the histologic damage scores, followed by the higher the percentage of collagen X–positive chondrocytes caused by muscle atrophy. ConclusionsQuadriceps muscle atrophy triggered the subchondral bone abnormal change and cartilage degeneration, which would be a risk factor for development of osteoarthritis. The translational potential of this articleOur results indicate that anti-quadriceps muscle atrophy can be a candidate therapeutic target in the prevention of knee osteoarthritis.

Predicting Knee Pain and Knee Osteoarthritis Among Overweight Women.

There is a need for prediction of knee osteoarthritis (KOA) in general practice to motivate subjects for preventive therapies and optimize preventive trials. To develop a prediction model, with questionnaire and physical examination variables, for incident frequent knee pain (FKP) and symptomatic KOA after 2.5 and/or 6.5 years among overweight and obese middle-aged women. Models were developed in the Prevention of Knee Osteoarthritis in Overweight Females study (age 50 to 60 years, body mass index [BMI] ≥ 27 kg/m2) (ISRCTN 42823086). FKP was defined as knee pain during most days in the past month. Symptomatic KOA was defined according to the combined (clinical and radiographic) American College of Rheumatology criteria. Multivariable analysis by backward stepwise deletion was performed for questionnaire and physical examination variables. The prediction model was externally validated in Rotterdam Study (RS)-III. Area under the curves (AUCs) of receiver operating characteristic were calculated. 32% of 237 women (mean age 55.7 ± 3.2 years; mean BMI, 31.9 ± 3.8 kg/m2) developed FKP and 30% developed symptomatic KOA. AUC of age and BMI was 0.63 (0.55 to 0.71) for incident FKP. The final model included age, BMI, mild knee symptoms, knee problems climbing stairs, morning stiffness, postmenopausal status, and heavy work. AUC was 0.71 (0.63 to 0.78). Results were similar for incident KOA. Applying external validation, similar results were observed in the RS-III. In this study, easy-obtainable variables modestly improved the prediction of FKP and symptomatic KOA above age and BMI. To improve the identification of high-risk individuals, development of valid tests for other known risk factors, like meniscal damage, that are applicable in primary care, are urgently needed.

Altered kinematics after anterior cruciate ligament reconstruction, and their role in the prevention of osteoarthritis

Background/Aims: Anterior cruciate ligament injury is common, and anterior cruciate ligament reconstruction has become the standard of care that aims to restore knee stability, return to activity, and prevent secondary injury. Methods: A literature review was carried out using PubMed and Science Direct databases from 1998 through 2017. Search terms included: anterior cruciate ligament reconstruction and knee osteoarthritis; kinematics after anterior cruciate ligament reconstruction; and prevention of knee osteoarthritis. A total of 356 studies matched the search terms. After removing duplicates and any studies that were not relevant, 73 studies remained. Findings: Individuals usually have impaired neuromuscular control after reconstruction, and abnormal biomechanical patterns may lead to loading of cartilage areas that are not commonly loaded and that, longitudinally, can lead to osteoarthritis. The knee adduction moment indicates loading of the knee joint and has been associated with the development of osteoarthritis and altered gait mechanics have also been implicated in the increased rate of osteoarthritis after anterior cruciate ligament reconstruction, including differences in tibial rotation during walking. Furthermore, altered ankle joint mechanics may be the result of deviations in ankle joint alignment secondary to the structural changes at the knee. It is clear that abnormal mechanical stimulation may cause dysfunction of articular chondrocytes and breakdown of cartilage extracellular matrix, leading to articular cartilage degradation and chondrocyte death. The affected joint will progress to post-traumatic osteoarthritis. Conclusions: The restoration of normal knee anatomy and mechanics, such as returning the joint to normal function, improving muscle strength, functional movement prevention programmes, restoring gait symmetry and weight management are recommended.

Effect of weight change on progression of knee OA structural features assessed by MRI in overweight and obese women

To evaluate the effects of weight change on progression of knee osteoarthritis (OA) structural features by magnetic resonance imaging (MRI) in overweight and obese women without clinical knee OA. 347 participants from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study were classified with latent class growth analysis into a subgroup with steady weight (n=260;+0.1±4.0kg,+0.2±4.4%), weight gain (n=43;+8.6±4.0kg,+9.8±4.1%) or weight loss (n=44;-9.0±7.2kg,-9.8±7.5%) over 2.5 years. Baseline and follow-up 1.5T MRIs were scored with MRI Osteoarthritis Knee Score (MOAKS) for progression of bone marrow lesions (BMLs), cartilage defects, osteophytes, meniscal abnormalities, meniscal extrusion and synovitis. Associations between subgroups and change in MRI features at knee-level were assessed using adjusted Generalized Estimating Equations. 687 knees from 347 women (median age 55.2 years, interquartile range (IQR) 5.5, median body mass index (BMI) 31.2kg/m2, IQR 5.3) were analyzed. Progression of synovitis was 18% in the weight gain vs 7% in the stable weight subgroup (OR 2.88; 95%CI 1.39-5.94). The odds for progression of patellofemoral (PF) BMLs and cartilage defects increased with 62% (OR 1.62; 95%CI 0.92-2.84) and 53% (OR 1.53; 95%CI 0.92-2.56) in the weight gain vs the stable weight subgroup. In overweight and obese women, progression of synovitis increased more than 2.5 times in a weight gain compared to a stable weight subgroup over 2.5 years. Large effect sizes were also found for the difference in progression of PF BMLs and PF cartilage defects between the weight gain and stable weight subgroup.

Bone matrix microdamage and vascular changes characterize bone marrow lesions in the subchondral bone of knee osteoarthritis.

Bone marrow lesions (BMLs) in the subchondral bone in osteoarthritis (OA) are suggested to be multifactorial, although the pathogenic mechanisms are unknown. Bone metabolism and cardiovascular risk factors associate with BML in epidemiologic studies. However, there are no studies at the tissue level investigating the relationship between these processes and BML. The aim of this study was to investigate the relationship between BMLs in the tibial plateau (TP) of knee OA and bone matrix microdamage, osteocyte density and vascular changes. TP were obtained from 73 patients at total knee replacement surgery and BMLs were identified ex vivo in TP tissue using MRI. Comparator 'No BML' tissue was from matched anatomical sites to the BMLs. Quantitative assessment was made of subchondral bone microdamage, bone resorption indices, osteocyte cellularity, and vascular features. Several key parameters were different between BML and No BML tissue. These included increased microcrack burden (p = .01, p = .0001), which associated positively with bone resorption and negatively with cartilage volume, and greater osteocyte numerical density (p = .02, p = .01), in the subchondral bone plate and subchondral trabeculae, respectively. The marrow tissue within BML zones contained increased arteriolar density (p = .04, p = .0006), and altered vascular characteristics, in particular increased wall thickness (p = .007) and wall:lumen ratio (wall thickness over internal lumen area) (p = .001), compared with No BML bone. Increased bone matrix microdamage and altered vasculature in the subchondral bone of BMLs is consistent with overloading and vascular contributions to the formation of these lesions. Given the important role of BMLs in knee OA, these contributing factors offer potential targets for the treatment and prevention of knee OA.

Relationships Between Tibiofemoral Contact Forces and Cartilage Morphology at 2 to 3 Years After Single-Bundle Hamstring Anterior Cruciate Ligament Reconstruction and in Healthy Knees.

Background:Prevention of knee osteoarthritis (OA) following anterior cruciate ligament (ACL) rupture and reconstruction is vital. Risk of postreconstruction knee OA is markedly increased by concurrent meniscal injury. It is unclear whether reconstruction results in normal relationships between tibiofemoral contact forces and cartilage morphology and whether meniscal injury modulates these relationships.Hypotheses:Since patients with isolated reconstructions (ie, without meniscal injury) are at lower risk for knee OA, we predicted that relationships between tibiofemoral contact forces and cartilage morphology would be similar to those of normal, healthy knees 2 to 3 years postreconstruction. In knees with meniscal injuries, these relationships would be similar to those reported in patients with knee OA, reflecting early degenerative changes.Study Design:Cross-sectional study; Level of evidence, 3.Methods:Three groups were examined: (1) 62 patients who received single-bundle hamstring reconstruction with an intact, uninjured meniscus (mean age, 29.8 ± 6.4 years; mean weight, 74.9 ± 13.3 kg); (2) 38 patients with similar reconstruction with additional meniscal injury (ie, tear, repair) or partial resection (mean age, 30.6 ± 6.6 years; mean weight, 83.3 ± 14.3 kg); and (3) 30 ligament-normal, healthy individuals (mean age, 28.3 ± 5.2 years; mean weight, 74.9 ± 14.9 kg) serving as controls. All patients underwent magnetic resonance imaging to measure the medial and lateral tibial articular cartilage morphology (volumes and thicknesses). An electromyography-driven neuromusculoskeletal model determined medial and lateral tibiofemoral contact forces during walking. General linear models were used to assess relationships between tibiofemoral contact forces and cartilage morphology.Results:In control knees, cartilage was thicker compared with that of isolated and meniscal-injured ACL-reconstructed knees, while greater contact forces were related to both greater tibial cartilage volumes (medial: R 2 = 0.43, β = 0.62, P = .000; lateral: R 2 = 0.19, β = 0.46, P = .03) and medial thicknesses (R 2 = 0.24, β = 0.48, P = .01). In the overall group of ACL-reconstructed knees, greater contact forces were related to greater lateral cartilage volumes (R 2 = 0.08, β = 0.28, P = .01). In ACL-reconstructed knees with lateral meniscal injury, greater lateral contact forces were related to greater lateral cartilage volumes (R 2 = 0.41, β = 0.64, P = .001) and thicknesses (R 2 = 0.20, β = 0.46, P = .04).Conclusion:At 2 to 3 years postsurgery, ACL-reconstructed knees had thinner cartilage compared with healthy knees, and there were no positive relationships between medial contact forces and cartilage morphology. In lateral meniscal-injured reconstructed knees, greater contact forces were related to greater lateral cartilage volumes and thicknesses, although it was unclear whether this was an adaptive response or associated with degeneration. Future clinical studies may seek to establish whether cartilage morphology can be modified through rehabilitation programs targeting contact forces directly in addition to the current rehabilitation foci of restoring passive and dynamic knee range of motion, knee strength, and functional performance.

Beneficial effects of a gait used while wearing a kimono to decrease the knee adduction moment in healthy adults.

The knee adduction moment (KAM) relates to medial knee osteoarthritis (OA). Several gait modifications to reduce the KAM for the prevention of knee OA have been studied. Most of the modifications, however, involve voluntary changes in leg alignment. Here we investigated the biomechanical effects for reducing the KAM of a walking style with a small trunk rotation and arm swing gait, which is a natural walking style used while wearing a kimono (Nanba walk) that shifts the ground reaction force toward the stance leg (reduced lever arm). Twenty-nine healthy adults (21.5 ± 0.6 years) participated in the present study. A three-dimensional analysis system with 10 cameras and 1 force plate was used to obtain the KAM and other biomechanical data. Surface electromyography (EMG) of the hip and trunk muscles (internal obliquus abdominal muscle: IO, external obliquus abdominal muscle: EO, multifidus muscle: MF, and gluteus medius muscle: Gmed) was also assessed, and integrated EMG (iEMG) of the four muscles was assessed in the first and second halves of the stance phase. The 1st and 2nd peak KAMs were significantly decreased during Nanba walking (0.40±0.09 and 0.37±0.13 Nm/kg) compared with normal walking (0.45±0.09 and 0.45±0.13 Nm/kg; P = 0.002, P<0.001, respectively). The lever arm lengths at the 1st and 2nd peak KAMs were also significantly decreased during Nanba walking compared with normal walking (p = 0.023 and p<0.001, respectively). The iEMGs of IO, EO and Gmed muscles during the first half, and the iEMGs of EO and GM during the second half of the stance phase were significantly increased during Nanba walking compared with normal walking. The Nanba gait modification could be a useful strategy for reducing the KAM with high activation of the trunk and hip joint muscles for the prevention and/or treatment of medial knee OA.

Long-term effects of a lifestyle intervention and oral glucosamine sulphate in primary care on incident knee OA in overweight women.

The present study was designed to evaluate the effect of a lifestyle intervention aimed to reduce body weight and of oral glucosamine sulphate on the incidence of knee osteoarthritis (OA) after 6-7 years in a population of middle-aged, overweight women, without knee OA at baseline. The Prevention of knee Osteoarthritis in Overweight Females study, ISRCTN42823086, was a randomized controlled trial with a 2 × 2 factorial design. Four hundred and seven women aged 50-60 years with a BMI of ⩾27 kg/m 2 and free of knee OA were randomized. Four hundred and seventy-seven knees from 245 participants were available after a mean follow-up time of 6.6 years. Nineteen per cent of all knees showed incident knee OA. Both interventions showed no significant preventive effect on incident knee OA. Despite the fact that per protocol analyses showed greater differences between both groups for the lifestyle intervention, significance was not reached. A significant effect of losing ⩾5 kg or ⩾ 5% of baseline weight in the first 12 months on the incidence of knee OA according to the primary outcome was found (odds ratio = 0.10; 95% CI: 0.02, 0.41). No significant preventive effect on incident knee OA of either the lifestyle intervention or the glucosamine intervention was found. As a proof of concept, the preventive effect of moderate weight loss in 1 year on the incidence of clinical knee OA is demonstrated. This trial provides important insights for future studies on the prevention of knee OA, which are currently lacking. ISRTCN registry, http://www.isrctn.com , ISRCTN42823086.