Association between Dietary Magnesium Intake and Radiographic Knee Osteoarthritis

ObjectiveTo examine the cross-sectional associations between dietary magnesium (Mg) intake and radiographic knee osteoarthritis (OA), joint space narrowing (JSN), and osteophytes (OST) respectively.MethodsA total of 1626 subjects were included in the study. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Radiographic knee OA was defined as Kellgren-Lawrence (K-L) Grade 2 in at least one leg. JSN and OST were assessed individually according to the Osteoarthritis Research Society International (OARSI) atlas. A multivariable logistic analysis model was applied to test the various associations after adjusting for potentially confounding factors.ResultsThe relative odds of radiographic knee OA were decreased by 0.53 times in the third quintile of Mg intake [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.28–1.01], 0.40 times in the fourth quintile (OR 0.40, 95% CI 0.17–0.94) and 0.34 times in the fifth quintile (OR 0.34, 95% CI 0.11–1.00) compared with those in the lowest quintile, while P for trend was 0.111. The relative odds of JSN were decreased by 0.49 times in the third quintile of Mg intake (OR 0.49, 95% CI 0.28–0.88) and 0.37 times in the fifth quintile (OR 0.37, 95% CI 0.14–0.98) compared with those in the lowest quintile, while P for trend was 0.088. There was no significant relationship between dietary Mg intake and the presence of OST.ConclusionsThe findings of this cross-sectional study indicate that Mg intake is inversely associated with radiographic knee OA and JSN. It supports potential role of Mg in the prevention of knee OA.

Level of Evidence

LevelIII, cross-sectional study.     

Delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) Shows No Change in Cartilage Structural Composition after Viscosupplementation in Patients with Early-Stage Knee Osteoarthritis

Introduction

Viscosupplementation with hyaluronic acid (HA) of osteoarthritic (OA) knee joints has a well-established positive effect on clinical symptoms. This effect, however, is only temporary and the working mechanism of HA injections is not clear. It was suggested that HA might have disease modifying properties because of its beneficial effect on cartilage sulphated glycosaminoglycan (sGAG) content. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a highly reproducible, non-invasive surrogate measure for sGAG content and hence composition of cartilage. The aim of this study was to assess whether improvement in cartilage structural composition is detected using dGEMRIC 14 weeks after 3 weekly injections with HA in patients with early-stage knee OA.

Methods

In 20 early-stage knee OA patients (KLG I-II), 3D dGEMRIC at 3T was acquired before and 14 weeks after 3 weekly injections with HA. To evaluate patient symptoms, the knee injury and osteoarthritis outcome score (KOOS) and a numeric rating scale (NRS) for pain were recorded. To evaluate cartilage composition, six cartilage regions in the knee were analyzed on dGEMRIC. Outcomes of dGEMRIC, KOOS and NRS before and after HA were compared using paired t-testing. Since we performed multiple t-tests, we applied a Bonferroni-Holm correction to determine statistical significance for these analyses.

Results

All KOOS subscales (‘pain’, ‘symptoms’, ‘daily activities’, ‘sports’ and ’quality of life’) and the NRS pain improved significantly 14 weeks after Viscosupplementation with HA. Outcomes of dGEMRIC did not change significantly after HA compared to baseline in any of the cartilage regions analyzed in the knee.

Conclusions

Our results confirm previous findings reported in the literature, showing persisting improvement in symptomatic outcome measures in early-stage knee OA patients 14 weeks after Viscosupplementation. Outcomes of dGEMRIC, however, did not change after Viscosupplementation, indicating no change in cartilage structural composition as an explanation for the improvement of clinical symptoms.     

Patients with Severe Radiographic Osteoarthritis Have a Better Prognosis in Physical Functioning after Hip and Knee Replacement: A Cohort-Study

Introduction

Although Total Hip and Knee Replacements (THR/TKR) improve Health-Related Quality of Life (HRQoL) at the group level, up to 30% of patients are dissatisfied after surgery due to unfulfilled expectations. We aimed to assess whether the pre-operative radiographic severity of osteoarthritis (OA) is related to the improvement in HRQoL after THR or TKR, both at the population and individual level.

Methods

In this multi-center observational cohort study, HRQoL of OA patients requiring THR or TKR was measured 2 weeks before surgery and at 2–5 years follow-up, using the Short-Form 36 (SF36). Additionally, we measured patient satisfaction on a 11-point Numeric Rating Scale (NRSS). The radiographic severity of OA was classified according to Kellgren and Lawrence (KL) by an independent experienced musculoskeletal radiologist, blinded for the outcome. We compared the mean improvement and probability of a relevant improvement (defined as a patients change score≥Minimal Clinically Important Difference) between patients with mild OA (KL Grade 0–2) and severe OA (KL Grade 3+4), whilst adjusting for confounders.

Results

Severe OA patients improved more and had a higher probability of a relevant improvement in physical functioning after both THR and TKR. For TKR patients with severe OA, larger improvements were found in General Health, Vitality and the Physical Component Summary Scale. The mean NRSS was also higher in severe OA TKR patients.

Discussion

Patients with severe OA have a better prognosis after THR and TKR than patients with mild OA. These findings might help to prevent dissatisfaction after THR and TKR by means of patient selection or expectation management.     

Genetic Polymorphisms of Interleukin-16 and Risk of Knee Osteoarthritis

BackgroundInterleukin-16 (IL-16), a pleiotropic cytokine, plays a fundamental role in inflammatory diseases. This study investigates the association between IL-16 polymorphisms and the risk of knee osteoarthritis (OA) in a Chinese population.MethodsThe IL-16 rs11556218, rs4072111, and rs4778889 polymorphisms were determined in 150 knee OA cases and 147 healthy controls through polymerase chain reaction-restriction fragment length polymorphism.ResultsThe results suggested that the variants in IL-16 gene rs11556218 site were associated with a decreased knee OA risk after adjusting for age, sex, BMI, and smoking and drinking status (TG vs. TT: OR, 0.69; 95% CI, 0.53–0.89; P = 0.006; GG vs. TT: OR, 0.64; 95% CI, 0.45–0.90; P = 0.042; dominant model: OR, 0.68; 95% CI, 0.29–0.87; P = 0.002; G vs. T allele: OR, 0.77; 95% CI, 0.66–0.90; P = 0.003). Similarly, subjects bearing the rs4072111 variant genotypes and alleles also had a lower susceptibility to knee OA compared with those bearing the wild-type (CT vs. CC: OR, 0.66; 95% CI, 0.53–0.83; P = 0.002; TT vs. CC: OR, 0.57; 95% CI, 0.40–0.82; P = 0.027; dominant model: OR, 0.65; 95%, CI 0.52–0.80; P <0.001; T vs. C allele: OR, 0.69; 95% CI, 0.58–0.81; P <0.001). Further, the C allele and the combined genotype (CC+CT) of rs4778889 were associated with a slightly decreased risk of knee OA. In addition, we found two high-risk haplotypes: TTT (OR, 3.70) and GCC (OR, 6.22). Finally, serum IL-16 levels of knee OA patients were significantly higher than those of controls (P = 0.001).ConclusionsDespite the small sample size, this is the first study suggesting IL-16 gene polymorphisms to be associated with the risk of knee OA.     

Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action

Although the predominant mechanism of intra-articular hyaluronan (hyaluronic acid) (HA) and hylans for the treatment of pain associated with knee osteoarthritis (OA) is unknown, in vivo, in vitro, and clinical studies demonstrate various physiological effects of exogenous HA. HA can reduce nerve impulses and nerve sensitivity associated with the pain of OA. In experimental OA, this glycosaminoglycan has protective effects on cartilage, which may be mediated by its molecular and cellular effects observed in vitro. Exogenous HA enhances chondrocyte HA and proteoglycan synthesis, reduces the production and activity of proinflammatory mediators and matrix metalloproteinases, and alters the behavior of immune cells. Many of the physiological effects of exogenous HA may be a function of its molecular weight. Several physiological effects probably contribute to the mechanisms by which HA and hylans exert their clinical effects in knee OA.     

Gait Biomechanics and Patient-Reported Function as Predictors of Response to a Hip Strengthening Exercise Intervention in Patients with Knee Osteoarthritis

ObjectiveMuscle strengthening exercises have been shown to improve pain and function in adults with mild-to-moderate knee osteoarthritis, but individual response rates can vary greatly. Predicting individuals who respond and those who do not is important in developing a more efficient and effective model of care for knee osteoarthritis (OA). Therefore, the purpose of this study was to use pre-intervention gait kinematics and patient-reported outcome measures to predict post-intervention response to a 6-week hip strengthening exercise intervention in patients with mild-to-moderate knee OA.MethodsThirty-nine patients with mild-to-moderate knee osteoarthritis completed a 6-week hip-strengthening program and were subgrouped as Non-Responders, Low-Responders, or High-Responders following the intervention based on their change in Knee injury Osteoarthritis Outcome Score (KOOS). Predictors of responder subgroups were retrospectively determined from baseline patient-reported outcome measures and kinematic gait parameters in a discriminant analysis of principal components. A 3–4 year follow-up on 16 of the patients with knee OA was also done to examine long-term changes in these parameters.ResultsA unique combination of patient-reported outcome measures and kinematic factors was able to successfully subgroup patients with knee osteoarthritis with a cross-validated classification accuracy of 85.4%. Lower patient-reported function in daily living (ADL) scores and hip frontal plane kinematics during the loading response were most important in classifying High-Responders from other sub-groups, while a combination of hip, knee, ankle kinematics were used to classify Non-Responders from Low-Responders.ConclusionPatient-reported outcome measures and objective biomechanical gait data can be an effective method of predicting individual treatment success to an exercise intervention. Measuring gait kinematics, along with patient-reported outcome measures in a clinical setting can be useful in helping make evidence-based decisions regarding optimal treatment for patients with knee OA.     

Intraarticular injection of hyaluronan prevents cartilage erosion,periarticular fibrosis and mechanical allodynia and normalizes stance time in murine knee osteoarthritis

Introduction  

Intraarticular hyaluronan (HA) is used clinically for symptomatic relief in patients with knee osteoarthritis (OA); however, the mechanism of action is unclear. In this study, we examined the effects of a single injection of HA on joint tissue pathology, mechanical allodynia and gait changes (measured by stride times) in a murine model of OA.     

Infrapatellar fat pad-derived mesenchymal stromal cell product for treatment of knee osteoarthritis: a first-in-human study with evaluation of the potency marker

Background aimsInfrapatellar fat pad-derived mesenchymal stromal cells (IFP-MSCs) have not yet been used in a human clinical trial. In this open-label phase 1 study, patients with knee osteoarthritis (OA) received a single intra-articular injection of autologous IFP-MSCs. Safety was assessed through physical examination of the knee joint, vital signs, laboratory tests and adverse events. Efficacy was evaluated with regard to pain and function using questionnaires, x-ray and magnetic resonance imaging (MRI). Indoleamine-2,3-dioxygenase (IDO) expression in IFP-MSCs primed with interferon gamma was used as an in vitro potency measurement in investigating the correlations of clinical outcomes.MethodsTwelve patients with symptomatic knee OA were recruited. IFP adipose tissue was harvested from each patient's knee through surgical excision for IFP-MSC manufacturing. Cryopreserved IFP-MSCs (5 × 10⁷ cells) were injected into the knee joint immediately after thawing.ResultsNo significant adverse events were observed. Patients who received IFP-MSCs exhibited clinically significant pain and functional improvement at 48-week follow-up. The MRI Osteoarthritis Knee Score average was also significantly reduced from 100.2 before injection to 85.0 at 48 weeks after injection. The IDO expression of the primed IFP-MSCs of the 12 patients was correlated with clinical outcomes after injection.ConclusionsA single intra-articular injection of IFP-MSCs appears to be a safe therapy for treating knee OA and may improve disease symptoms. IDO measurement of primed IFP-MSCs has potential as a potency marker of MSC products for immunomodulatory therapy.     

Association of vitamin D,BMD and knee osteoarthritis in postmenopausal women

Objectives:The aim of this study was to analyze the association of knee OA with bone mineral density (BMD) and vitamin D serum levels in postmenopausal women.Methods:A cross-sectional study including 240 postmenopausal women with knee OA was conducted. Demographic data were recorded along with balance and functionality scores. Knee OA severity was assessed by the radiological Kellgren & Lawrence scale. BMD and T-scores were calculated in hips and lumbar spine. Serum levels of vitamin D were also measured.Results:High BMI (p<0.005), high number of children (p=0.022) and family history of hip fracture (p=0.011) are significantly associated with knee OA severity. Lumbar spine OP is negatively associated with knee OA (p<0.005). A significant difference was detected between vitamin D deficiency and severe knee OA, adjusted for BMD [OR (95%CI); 3.1 (1.6-6.1), p=0.001]. BMD does not affect the relationship of vitamin D levels in relation to OA and vitamin D levels do not affect the relationship of BMD with OA.Conclusions:Low BMD has a protective role against knee OA while vitamin D deficiency contributes significantly to knee OA severity. However, the association between OA and OP is not affected by vitamin D deficiency and the association of OA and vitamin D serum levels is not affected by BMD.     

膝骨关节炎人群中血清锌与血脂紊乱的相关性研究

目的:探讨膝骨关节炎(Osteoarthritis,OA)人群中血清锌(Zinc,Zn)水平与血脂紊乱的相关性。方法:采用横断面研究,纳入在中南大学湘雅医院健康管理中心进行健康体检的935例膝OA患者作为研究对象。通过分光光度法检测纳入研究对象的血清Zn水平,并通过贝克曼库尔特AU 5800全自动生化分析仪检测血脂水平。根据血清Zn水平将研究人群进行五分类,采用Logistic回归模型探讨血清Zn水平与血脂紊乱的相关性。结果:Logistic回归模型结果显示,校正年龄和性别后,与第1分类(最低)血清Zn组相比,第2-5分类血清Zn组血脂紊乱患病率比值比和95%可信区间(95%confidence interval, 95%CI)分别为1.66 (95%CI:1.08, 2.56)、1.25 (95%CI:0.81, 1.93)、1.61 (95%CI:1.04, 2.49)和3.04 (95%CI:1.97, 4.68)(趋势检验P0.001)。多因素校正和性别亚组分析结果无明显变化。结论:膝OA人群血清Zn水平与血脂紊乱患病呈正相关,OA人群高血Zn可能为发生血脂紊乱的危险因素。     

Organisation of the motor cortex differs between people with and without knee osteoarthritis

IntroductionThe aim of this study was to investigate possible differences in the organisation of the motor cortex in people with knee osteoarthritis (OA) and whether there is an association between cortical organisation and accuracy of a motor task.MethodsfMRI data were collected while 11 participants with moderate/severe right knee OA (6 male, 69 ± 6 (mean ± SD) years) and seven asymptomatic controls (5 male, 64 ± 6 years) performed three visually guided, variable force, force matching motor tasks involving isolated isometric muscle contractions of: 1) quadriceps (knee), 2) tibialis anterior (ankle) and, 3) finger/thumb flexor (hand) muscles. fMRI data were used to map the loci of peak activation in the motor cortex during the three tasks and to assess whether there were differences in the organisation of the motor cortex between the groups for the three motor tasks. Root mean square of the difference between target and generated forces during muscle contraction quantified task accuracy.ResultsA 4.1 mm anterior shift in the representation of the knee (p = 0.03) and swap of the relative position of the knee and ankle representations in the motor cortex (p = 0.003) were found in people with knee OA. Poorer performance of the knee task was associated with more anterior placement of motor cortex loci in people with (p = 0.05) and without (p = 0.02) knee OA.ConclusionsDifferences in the organisation of the motor cortex in knee OA was demonstrated in relation to performance of knee and ankle motor tasks and was related to quality of performance of the knee motor task. These results highlight the possible mechanistic link between cortical changes and modified motor behavior in people with knee OA.     

Total knee replacement after high tibial osteotomy: time-to-event analysis and predictors

BACKGROUND:An important aim of high tibial osteotomy (HTO) is to prevent or delay the need for total knee replacement (TKR). We sought to estimate the frequency and timing of conversion from HTO to TKR and the factors associated with it.METHODS:We prospectively evaluated patients with osteoarthritis (OA) of the knee who underwent medial opening wedge HTO from 2002 to 2014 and analyzed the cumulative incidence of TKR in July 2019. The presence or absence of TKR on the HTO limb was identified from the orthopedic surgery reports and knee radiographs contained in the electronic medical records for each patient at London Health Sciences Centre. We used cumulative incidence curves to evaluate the primary outcome of time to TKR. We used multivariable Cox proportional hazards analysis to assess potential preoperative predictors including radiographic disease severity, malalignment, correction size, pain, sex, age, body mass index (BMI) and year of surgery.RESULTS:Among 556 patients who underwent 643 HTO procedures, the cumulative incidence of TKR was 5% (95% confidence interval [CI] 3%–7%) at 5 years and 21% (95% CI 17%–26%) at 10 years. With the Cox proportional hazards multivariable model, the following preoperative factors were significantly associated with an increased rate of conversion: radiographic OA severity (adjusted hazard ratio [HR] 1.96, 95% CI 1.12–3.45), pain (adjusted HR 0.85, 95% CI 0.75–0.96)], female sex (adjusted HR 1.67, 95% CI 1.08–2.58), age (adjusted HR 1.50 per 10 yr, 95% CI 1.17–1.93) and BMI (adjusted HR 1.31 per 5 kng/m², 95% CI 1.12–1.53).INTERPRETATION:We found that 79% of knees did not undergo TKR within 10 years after undergoing medial opening wedge HTO. The strongest predictor of conversion to TKR is greater radiographic disease at the time of HTO.

The burden of knee osteoarthritis (OA) on patients and health care systems is substantial and growing.¹ The current treatment strategy that relies largely on total knee replacement (TKR) for end-stage disease may not be sustainable.^2–5 Reduced quality of life and loss of productivity due to knee OA in middle-aged people in the workforce is particularly problematic.^5–8 The global prevalence of knee OA peaks at about 50 years of age.⁹ Worldwide, the estimated years lived with disability is 2.4 million for people younger than 50 years of age, the approximate age of peak prevalence for knee OA.^9,10 Accordingly, the number of middle-aged patients seeking treatment for knee OA, including TKR, is increasing. ¹¹ Joint replacement may not be the most appropriate treatment for these patients.¹² Earlier TKR is associated with prosthesis infection, ¹³ lower patient satisfaction¹⁴ and revision surgery;^15–18 about 25% of all TKRs are considered “likely inappropriate.”¹⁹ Clinicians have identified a clear treatment gap between exhausting nonoperative management and appropriateness for TKR, resulting in years of pain, decreased function, productivity losses and associated costs.^5–9,20,21 It is therefore imperative to identify additional effective treatments for the large group of patients with knee OA.Medial opening wedge high tibial osteotomy (HTO) is a limb realignment surgery intended for patients with medial compartment knee OA who are not suitable candidates for TKR because of less severe disease, younger age and greater physical demands. The purpose of HTO is to correct malalignment, thereby shifting load away from the more involved knee compartment and limit OA progression.^22,23 Substantial shifts in knee loading^24,25 have resulted in clinically important improvements in pain and function after HTO^26,27 and the procedure is cost-effective,^28,29 yet the surgery is uncommon in Canada.³⁰ Unlike the high and increasing rates of other knee surgical procedures including arthroscopy³¹ and TKR,³² rates of HTO remain low.^33,34High tibial osteotomy may help fill the treatment gap between nonsurgical treatments and definitive TKR. At the London Health Sciences Centre in London, Ontario, HTO is performed frequently with a goal of preventing or delaying the need for TKR. Thus, it is appropriate to investigate the duration of benefit of HTO, and the preoperative characteristics associated with it. When quantified as conversion from HTO to TKR, registries using administrative data enable large sample sizes (> 2500 patients) to estimate cumulative incidence of TKR.^30,35,36 However, there can be limitations in using only administrative data, including confirming the correct procedure, limb and diagnosis. Administrative data often lack detailed information assessed preoperatively, such as radiographic features (e.g., disease severity and lower limb alignment) and patient-reported outcome measures. Previously reported predictors of conversion to TKR such as female sex and greater age^30,35–39 may be influenced (perhaps confounded) by other clinical characteristics not typically included in administrative data. Therefore, our objective was to investigate the cumulative incidence of TKR after medial opening wedge HTO and potential predictors using data collected prospectively from a single Canadian centre that focuses on HTO. Specifically, we evaluated the time to conversion from HTO to TKR and investigated the association of HTO preoperative characteristics with subsequent TKR.     

Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis

Introduction

Mesenchymal stem cells (MSCs) can differentiate into various connective tissue cells. Several techniques have been used for the clinical application of MSCs in articular cartilage repair; however, there are many issues associated with the selection of the scaffold material, including its ability to support cell viability and differentiation and its retention and degradation in situ. The application of MSCs via a scaffold also requires a technically demanding surgical procedure. The aim of this study was to test the outcome of intra-articular transplantation of mesenchymal stem cells suspended in hyaluronic acid (HA) in the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis (OA).

Methods

Commercially available human MSCs were cultured, labeled with carboxyfluorescein diacetate succinimidyl ester (CFDA-SE), suspended in either PBS or HA, and injected into the knee joints of 7-month-old animals. The control animals were injected with either PBS or HA alone. The animals were sacrificed at 1, 3, and 5 weeks post transplantation, the knee joints harvested, and fluorescent microscopic analysis was performed. Histological and immunohistochemical analysis were performed at 5 weeks post transplantation.

Results

At 5 weeks post transplantation, partial cartilage repair was noted in the HA-MSC group but not in the other groups. Examination of CFDA-SE-labeled cells demonstrated migration, differentiation, and proliferation of MSC in the HA-MSC group. There was strong immunostaining for type II collagen around both residual chondrocytes and transplanted MSCs in the OA cartilage.

Conclusion

This scaffold-free and technically undemanding technique appears to result in the regeneration of articular cartilage in the spontaneous OA animal model. Although further examination of the long-term effects of transplantation is necessary, the findings suggest that intra-articular injection of HA-MSC mixture is potentially beneficial for OA.     

Beer and wine consumption and risk of knee or hip osteoarthritis: a case control study

IntroductionThe aim of this study was to investigate the association between alcoholic and non-alcoholic beverages and knee or hip osteoarthritis (OA).MethodsWe conducted a case–control study of Caucasian men and women aged 45 to 86 years of age from Nottingham, UK. Cases had clinically severe symptoms and radiographic knee or hip OA; controls had no symptoms and no radiographic knee or hip OA. Exposure information was sought using interview-based questionnaires and a semi-quantitative food frequency questionnaire to assess beverage consumption at ages 21 to 50 years. Odds ratios (ORs), adjusted ORs (aORs), 95% confidence intervals (CI) and P values were estimated using logistic regression models.ResultsA total of 1,001 knee OA, 993 hip OA and 933 control participants were included in the study. Increasing beer consumption was associated with an increasing risk of OA (P for trend ≤0.001). Compared to those who did not consume beer, aORs for people who consumed 20 or more servings of beer were 1.93 (95% CI 1.26 to 2.94) and 2.15 (95% CI 1.45 to 3.19) for knee OA and hip OA, respectively. In contrast, increasing levels of wine consumption were associated with decreased likelihood of knee OA (P for trend <0.001). Compared to those who did not consume wine, aOR for knee OA among those who consumed 4 to 6 glasses of wine per week and ≥7 glasses of wine per week was 0.55 (95% CI 0.34 to 0.87) and 0.48 (95% CI 0.29 to 0.80), respectively. No association was identified between non-alcoholic beverages and knee or hip OA.ConclusionsBeer consumption appears to be a risk factor for knee and hip OA whereas consumption of wine has a negative association with knee OA. The mechanism behind these findings is speculative but warrants further study.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0534-4) contains supplementary material, which is available to authorized users.     

Revisiting spatial distribution and biochemical composition of calcium-containing crystals in human osteoarthritic articular cartilage

Introduction

Calcium-containing (CaC) crystals, including basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP), are associated with destructive forms of osteoarthritis (OA). We assessed their distribution and biochemical and morphologic features in human knee OA cartilage.

Methods

We prospectively included 20 patients who underwent total knee replacement (TKR) for primary OA. CaC crystal characterization and identification involved Fourier-transform infra-red spectrometry and scanning electron microscopy of 8 to 10 cartilage zones of each knee, including medial and lateral femoral condyles and tibial plateaux and the intercondyle zone. Differential expression of genes involved in the mineralization process between cartilage with and without calcification was assessed in samples from 8 different patients by RT-PCR. Immunohistochemistry and histology studies were performed in 6 different patients.

Results

Mean (SEM) age and body mass index of patients at the time of TKR was 74.6 (1.7) years and 28.1 (1.6) kg/m², respectively. Preoperative X-rays showed joint calcifications (chondrocalcinosis) in 4 cases only. The medial femoro-tibial compartment was the most severely affected in all cases, and mean (SEM) Kellgren-Lawrence score was 3.8 (0.1). All 20 OA cartilages showed CaC crystals. The mineral content represented 7.7% (8.1%) of the cartilage weight. All patients showed BCP crystals, which were associated with CPP crystals for 8 joints. CaC crystals were present in all knee joint compartments and in a mean of 4.6 (1.7) of the 8 studied areas. Crystal content was similar between superficial and deep layers and between medial and femoral compartments. BCP samples showed spherical structures, typical of biological apatite, and CPP samples showed rod-shaped or cubic structures. The expression of several genes involved in mineralization, including human homolog of progressive ankylosis, plasma-cell-membrane glycoprotein 1 and tissue-nonspecific alkaline phosphatase, was upregulated in OA chondrocytes isolated from CaC crystal-containing cartilages.

Conclusions

CaC crystal deposition is a widespread phenomenon in human OA articular cartilage involving the entire knee cartilage including macroscopically normal and less weight-bearing zones. Cartilage calcification is associated with altered expression of genes involved in the mineralisation process.     

Changes in knee joint muscle activation patterns during walking associated with increased structural severity in knee osteoarthritis

PurposeTo determine whether alterations in knee joint muscle activation patterns during gait were related to structural severity determined by Kellgren–Lawrence (KL) radiographic grades, for those with a moderate knee OA classification.ScopeEighty-two individuals with knee OA, classified as moderate using a functional and clinical criterion were stratified on KL-grade (KL II, KL III and KL IV). Thirty-five asymptomatic individuals were matched for age and walking velocity. Lower limb motion and surface electromyograms from rectus femoris plus lateral and medial sites for the gastrocnemii, vastii and hamstring muscles were recorded during self-selected walking. Gait velocity and characteristics from sagittal plane knee angular displacement waveforms were calculated. Principal component analysis extracted amplitude and temporal features from electromyographic waveform. Analysis of variance models tested for main effects (group, muscle) and interactions (α = 0.05) for these features. No differences in anthropometrics, velocity, knee muscle strength and symptoms were found among the three OA groups (p > 0.05). Specific features from medial gastrocnemius, lateral hamstring and quadriceps amplitude and temporal patterns were significantly different among OA groups (p < 0.05).ConclusionsSystematic alterations in specific knee joint muscle activation patterns were associated with increasing structural severity based on KL-grades whereas other alterations were associated with the presence of OA.     

Prognostic factors for progression of clinical osteoarthritis of the knee: a systematic review of observational studies

IntroductionWe performed a systematic review of prognostic factors for the progression of symptomatic knee osteoarthritis (OA), defined as increase in pain, decline in physical function or total joint replacement.MethodWe searched for available observational studies up to January 2015 in Medline and Embase according to a specified search strategy. Studies that fulfilled our initial inclusion criteria were assessed for methodological quality. Data were extracted and the results were pooled, or if necessary summarized according to a best evidence synthesis.ResultsOf 1,392 articles identified, 30 met the inclusion criteria and 38 determinants were investigated. Pooling was not possible due to large heterogeneity between studies. The best evidence synthesis showed strong evidence that age, ethnicity, body mass index, co-morbidity count, magnetic resonance imaging (MRI)-detected infrapatellar synovitis, joint effusion and baseline OA severity (both radiographic and clinical) are associated with clinical knee OA progression. There was moderate evidence showing that education level, vitality, pain-coping subscale resting, MRI-detected medial femorotibial cartilage loss and general bone marrow lesions are associated with clinical knee OA progression. However, evidence for the majority of determinants was limited (including knee range of motion or markers) or conflicting (including age, gender and joint line tenderness).ConclusionStrong evidence was found for multiple prognostic factors for progression of clinical knee OA. A large variety in definitions of clinical knee OA (progression) remains, which makes it impossible to summarize the evidence through meta-analyses. More research on prognostic factors for knee OA is needed using symptom progression as an outcome measure. Remarkably, only few studies have been performed using pain progression as an outcome measure. The pathophysiology of radiographic factors and their relation with symptoms should be further explored.     

Association Between Single Nucleotide Polymorphisms of DOT1L Gene and Risk of Knee Osteoarthritis in a Chinese Han Population

To investigate associations between single nucleotide polymorphisms rs12982744 and rs12459350 in the DOT1L gene and knee osteoarthritis (OA) susceptibility in a Chinese Han population. DOT1L rs12982744 and rs12459350 polymorphisms were genotyped in patients with knee OA and age- and sex-matched OA-free controls from a Chinese Han population. A total of 605 patients with knee OA and 615 controls were enrolled in the study. GC and CC genotypes of rs12982744, and variant C, were associated with a significantly increased risk of knee OA. On stratification analysis, the association between the risk of OA and rs12982744 GC heterozygotes compared with GG homozygotes was stronger in females and those aged >65 years. In contrast, the GA and AA genotypes of rs12459350 were not significantly associated with the risk of knee OA, even after further stratification analysis according to age or sex. Our results showed that DOT1L rs12982744 G to C change and variant C genotype may contribute to knee OA risk in a Chinese Han population.     

Prevalence of Radiographic Osteoarthritis of the Knee and Its Relationship to Self-Reported Pain

Background and Aim

Osteoarthritis (OA) of the knee is one of the most common skeletal disorders, yet little data are available in Asian populations. We sought to assess the prevalence and pattern of radiographic OA of the knee, and its relationship to self-reported pain in a Vietnamese population.

Methods

The study was based on a sample of 170 men and 488 women aged ≥40 years who were randomly sampled from the Ho Chi Minh City (Vietnam). Radiographs of the knee were graded from 0 to 4 according to the Kellgren and Lawrence scale. Osteoarthritis was defined as being present in a knee if radiographic grades of 2 or higher were detected. Knee pain and symptoms were ascertained by direct interview using a structured questionnaire.

Results

The point prevalence of radiographic OA of the knee was 34.2%, with women having higher rate than men (35.3% vs 31.2%). The prevalence of knee OA increased with advancing age: 8% among those aged 40–49 years, 30% in those aged 50–59 years, and 61.1% in those aged ≥60 years. Greater BMI was associated with higher risk of knee OA. Self-reported knee pain was found in 35% of men and 62% of women. There was a statistically significant association between self-reported knee pain and knee OA (prevalence ratio 3.1; 95% CI 2.0 to 4.6).

Conclusions

These data indicate that approximately a third of Vietnamese men and women have radiographic OA in the knee, and that self-reported knee pain may be used as an indicator of knee osteoarthritis.     

Hyaluronan injection in murine osteoarthritis prevents TGFbeta 1-induced synovial neovascularization and fibrosis and maintains articular cartilage integrity by a CD44-dependent mechanism

Introduction

The mechanism by which intra-articular injection of hyaluronan (HA) ameliorates joint pathology is unknown. Animal studies have shown that HA can reduce synovial activation, periarticular fibrosis and cartilage erosion; however, its specific effects on the different cell types involved remain unclear. We have used the TTR (TGFbeta1 injection and Treadmill Running) model of murine osteoarthritis (OA), which exhibits many OA-like changes, including synovial activation, to examine in vivo tissue-specific effects of intra-articular HA.

Methods

The kinetics of clearance of fluorotagged HA from joints was examined with whole-body imaging. Naïve and treated knee joints were examined macroscopically for cartilage erosion, meniscal damage and fibrosis. Quantitative histopathology was done with Safranin O for cartilage and with Hematoxylin & Eosin for synovium. Gene expression in joint tissues for Acan, Col1a1, Col2a1, Col3a1, Col5a1, Col10a1, Adamts5 and Mmp13 was done by quantitative PCR. The abundance and distribution of aggrecan, collagen types I, II, III, V and X, ADAMTS5 and MMP13 were examined by immunohistochemistry.

Results

Injected HA showed a half-life of less than 2 h in the murine knee joint. At the tissue level, HA protected against neovascularization and fibrosis of the meniscus/synovium and maintained articular cartilage integrity in wild-type but not in Cd44 knockout mice. HA injection enhanced the expression of chondrogenic genes and proteins and blocked that of fibrogenic/degradative genes and proteins in cartilage/subchondral bone, whereas it blocked activation of both groups in meniscus/synovium. In all locations it reduced the expression/protein for Mmp13 and blocked Adamts5 expression but not its protein abundance in the synovial lining.

Conclusions

The injection of HA, 24 h after TGFbeta1 injection, inhibited the cascade of OA-like joint changes seen after treadmill use in the TTR model of OA. In terms of mechanism, tissue protection by HA injection was abrogated by Cd44 ablation, suggesting that interaction of the injected HA with CD44 is central to its protective effects on joint tissue remodeling and degeneration in OA progression.