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Large Scale Replication Study of the Association between HLA Class II/BTNL2 Variants and Osteoarthritis of the Knee in European-Descent Populations  [PDF]
Ana M. Valdes, Unnur Styrkarsdottir, Michael Doherty, David L. Morris, Massimo Mangino, Agu Tamm, Sally A. Doherty, Kalle Kisand, Irina Kerna, Ann Tamm, Margaret Wheeler, Rose A. Maciewicz, Weiya Zhang, Kenneth R. Muir, Elaine M. Dennison, Deborah J. Hart, Sarah Metrustry, Ingileif Jonsdottir, Gudbjorn F. Jonsson, Helgi Jonsson, Thorvaldur Ingvarsson, Cyrus Cooper, Timothy J. Vyse, Tim D. Spector, Kari Stefansson, Nigel K. Arden
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023371
Abstract: Osteoarthritis (OA) is the most common form of arthritis and a major cause of disability. This study evaluates the association in Caucasian populations of two single nucleotide polymorphisms (SNPs) mapping to the Human Leukocyte Antigen (HLA) region and deriving from a genome wide association scan (GWAS) of knee OA in Japanese populations. The frequencies for rs10947262 were compared in 36,408 controls and 5,749 knee OA cases from European-descent populations. rs7775228 was tested in 32,823 controls and 1,837 knee OA cases of European descent. The risk (major) allele at rs10947262 in Caucasian samples was not significantly associated with an odds ratio (OR) = 1.07 (95%CI 0.94 -1.21; p = 0.28). For rs7775228 the meta-analysis resulted in OR = 0.94 (95%CI 0.81-1.09; p = 0.42) for the allele associated with risk in the Japanese GWAS. In Japanese individuals these two SNPs are in strong linkage disequilibrium (LD) (r2 = 0.86) with the HLA class II haplotype DRB1*1502 DQA1*0103 DQB1*0601 (frequency 8%). In Caucasian and Chinese samples, using imputed data, these SNPs appear not to be in LD with that haplotype (r2<0.07). The rs10947262 and rs7775228 variants are not associated with risk of knee OA in European descent populations and they do not appear tag the same HLA class II haplotype as they do in Japanese individuals.
Knee Osteoarthritis  [cached]
Füsun Güler Uysal,Sibel Ba?aran
Türkiye Fiziksel Tip ve Rehabilitasyon Dergisi , 2009,
Abstract: Osteoarthritis (OA) is the most common form of arthritis and the prevalence of OA increases with age. It is the major contributor to functional impairment in older adults. Symptomatic knee OA prevalence is reported to be 13% among adults over 55 years old. OA process not only affects the articular cartilage, but involves the entire joint, including the subchondral bone, capsule, ligaments, synovial membrane, and periarticular muscles and represents the failure of an organ (the synovial joint). OA is initiated by a mechanical damage to the joint and it is a manifestation of attempts to heal the joint and ameliorate the abnormal biomechanics. The distinction between primary and secondary OA is not meaningful as OA is always secondary to another disease or condition. The diagnosis of OA in clinical practice should be made on the basis of history and physical examination. Radiography is needed to confirm clinical suspicion and rule out other conditions. Other inflammatory diseases, predisposing diseases to OA and local causes of knee pain are potential differential diagnoses. Treatment modalities for knee OA are non-pharmacological, pharmacological, intra-articular and surgical. The management of OA should be tailored for each patient and treatment guidelines should be taken into consideration. In this article the current treatment guidelines are reviewed in details. Turk J Phys Med Rehab 2009; 55 Suppl 1: 1-7.
Two Single-Nucleotide Polymorphisms in ADAM12 Gene Are Associated with Early and Late Radiographic Knee Osteoarthritis in Estonian Population  [PDF]
Irina Kerna,Kalle Kisand,Ann E. Tamm,Jaanika Kumm,Agu O. Tamm
Arthritis , 2013, DOI: 10.1155/2013/878126
Abstract: Objectives. To investigate associations of selected single-nucleotide polymorphisms (SNPs) in ADAM12 gene with radiographic knee osteoarthritis (rKOA) in Estonian population. Methods. The rs3740199, rs1871054, rs1278279, and rs1044122 SNPs in ADAM12 gene were genotyped in 438 subjects (303 women) from population-based cohort, aged 32 to 57 (mean 45.4). The rKOA features were evaluated in the tibiofemoral joint (TFJ) and patellofemoral joint. Results. The early rKOA was found in 51.4% of investigated subjects (72% women) and 12.3% of participants (63% women) had advanced stage of diseases. The A allele of synonymous SNP rs1044122 was associated with early rKOA in TFJ, predominantly with the presence of osteophytes in females (OR 1.57; 95% CI 1.08–2.29, ). The C allele of intron polymorphism rs1871054 carried risk for advanced rKOA, mostly to osteophyte formation in TFJ in males (OR 3.03; 95% CI 1.11–7.53, ). Also the CCAA haplotype of ADAM12 was associated with osteophytosis, again mostly in TFJ in males ( ). For rs3740199 and rs1278279, no statistically significant associations were observed. Conclusion.??ADAM12 gene variants are related to rKOA risk during the early and late stages of diseases. The genetic risk seems to be predominantly associated with the appearance of osteophytes—a marker of bone remodelling and neochondrogenesis. 1. Introduction Osteoarthritis (OA) is the most common joint disorder and represents a leading musculoskeletal health and socioeconomic burden [1]. The knee is one of the most affected sites [2]. Among recognized OA risk factors like age and overweight, the genetic background, as demonstrated in twins, is expected to play the significant role [3]. To date, several genomewide linkage analyses (GWAS) and numerous association studies of candidate genes have been performed to disclose genetic pattern of OA [4]. Despite promising evidence, only few genes like GDF5 and SMAD3 demonstrated proven susceptibility to OA [5] and these genes, in turn, interpret only a small part of the genetic contribution to the disease. Until now, promising but contradictory data are published for the association of a member of disintegrin and metalloproteinase family—ADAM12 with the pathogenesis of OA [6, 7]. ADAM12 is an active proteinase, which is highly expressed in remodelling and fast-growing tissues such as the placenta and malignant tumours [8]. One of the splice variant of ADAM12 was found to be overexpressed in human OA cartilage [9], and recently, we described the elevation of ADAM12 protein in serum of OA patients [10]. Additionally, one
Effectiveness of Iontophoresis Treatment on Knee Osteoarthritis
?zlem Alt?nda?,Neslihan Soran,Metin Er?in,Leman Ege
Romatizma , 2009,
Abstract: Objective: Osteoarthritis is the most common joint disease causing disability. The primary goals for osteoarthritis therapy are to relieve pain, maintain or improve functional status, and minimize deformity. Many treatment options, including non-pharmacological and pharmacological measures, have been recommended in the management of osteoarthritis. Among the non-pharmacological approaches is physiotherapy, which involves the use of physical modalities like heat therapy, exercise therapy, electrical stimulation, therapeutic ultrasound, iontophoresis, and phonophoresis. The aim of our study was to retrospectively evaluate the efficacy of iontophoresis in patients with knee osteoarthritis. Materials and Methods: The study group included 40 patients with knee osteoarthritis to whom ketoprofen gel iontophoresis was applied. Pre-treatment and post-treatment pain, functional status and physical limitation were evaluated by Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne Index, respectively. Results: There was significant difference between the pre- and post-treatment evaluation in all parameters (p<0.05). Conclusion: Iontophoresis may be considered as an alternative therapy in knee osteoarthritis that is inexpensive, simple and non-invasive.
Therapeutic ultrasound and effectiveness in knee osteoarthritis  [cached]
Emine Ganidagli,Rengin Guzel
Arsiv Kaynak Tarama Dergisi , 2013,
Abstract: In Turkey, ultrasound is one of the most commonly used methods for physical therapy of knee osteoarthritis. Therapeutic ultrasound affects the cells and tissues by thermal and nonthermal ways. As well as being used as an agent for deep heating, it has effects like stimulation of tissue regeneration, soft tissue repair, regulation of blood flow in chronic ischemic tissues, protein synthesis and bone repair.In this manuscript, detailed technical information on ultrasound is given and studies on knee osteoarthritis in recent years are reviewed. [Archives Medical Review Journal 2013; 22(2.000): 170-183]
Quantitative Cartilage Imaging in Knee Osteoarthritis  [PDF]
Felix Eckstein,Wolfgang Wirth
Arthritis , 2011, DOI: 10.1155/2011/475684
Abstract: Quantitative measures of cartilage morphology (i.e., thickness) represent potentially powerful surrogate endpoints in osteoarthritis (OA). These can be used to identify risk factors of structural disease progression and can facilitate the clinical efficacy testing of structure modifying drugs in OA. This paper focuses on quantitative imaging of articular cartilage morphology in the knee, and will specifically deal with different cartilage morphology outcome variables and regions of interest, the relative performance and relationship between cartilage morphology measures, reference values for MRI-based knee cartilage morphometry, imaging protocols for measurement of cartilage morphology (including those used in the Osteoarthritis Initiative), sensitivity to change observed in knee OA, spatial patterns of cartilage loss as derived by subregional analysis, comparison of MRI changes with radiographic changes, risk factors of MRI-based cartilage loss in knee OA, the correlation of MRI-based cartilage loss with clinical outcomes, treatment response in knee OA, and future directions of the field.
Current Surgical Treatment of Knee Osteoarthritis  [PDF]
Karolin R?nn,Nikolaus Reischl,Emanuel Gautier,Matthias Jacobi
Arthritis , 2011, DOI: 10.1155/2011/454873
Abstract: Osteoathritis (OA) of the knee is common, and the chances of suffering from OA increase with age. Its treatment should be initially nonoperative—and requires both pharmacological and nonpharmacological treatment modalities. If conservative therapy fails, surgery should be considered. Surgical treatments for knee OA include arthroscopy, cartilage repair, osteotomy, and knee arthroplasty. Determining which of these procedures is most appropriate depends on several factors, including the location, stage of OA, comorbidities on the one side and patients suffering on the other side. Arthroscopic lavage and débridement is often carried out, but does not alter disease progression. If OA is limited to one compartment, unicompartmental knee arthroplasty or unloading osteotomy can be considered. They are recommended in young and active patients in regard to the risks and limited durability of total knee replacement. Total arthroplasty of the knee is a common and safe method in the elderly patients with advanced knee OA. This paper summarizes current surgical treatment strategies for knee OA, with a focus on the latest developments, indications and level of evidence. 1. Introduction Osteoarthritis (OA) of the knee is the commonest joint disorder in the elderly, with a prevalence of about 30% in adults aged >60 years [1]. About half of these subjects will show symptoms such as joint pain, stiffness, effusion and limitation of joint function. With our aging population, the prevalence of OA in the “developed” world is expected to increase. It is anticipated that OA will become the fourth leading cause of disability in the coming decades [2]. The etiology of knee OA is multifactorial and includes generalized constitutional factors (e.g., aging, sex, obesity, heredity, and reproductive variables), local adverse mechanical factors (e.g., joint trauma, occupational and recreational abuse, alignment, and postmeniscectomy), and geographic factors. There is a significant genetic component to the prevalence of knee OA, with heritability estimates from twin studies of 0.39–0.65 independent of known environmental or demographic confounders [3]. Genetic variations lead to chondrocyte alterations resulting in osteoarthritis [4, 5]. Diagnostic criteria for OA of the knee include patient history, physical examination, and radiologic and laboratory findings [6]. However, the standard radiograph alone allows in most patients definitive diagnosis of knee OA. Other radiological modalities such as computer tomography, ultrasound imaging, MRI and bone scan can provide alternative or
The Relationship Between Knee Osteoarthritis and Osteoporosis  [cached]
Ilhan Sezer,Ozge G. Illeez,Serpil D. Tuna,Nilufer Balci
Eurasian Journal of Medicine , 2010,
Abstract: Objective: The aim of this study was to investigate the association between knee osteoarthritis (OA) and bone mineral density (BMD) in the femur and lumbar vertebrae. Materials and Methods: A total of 74 female patients (mean age 61.9 ±9.1 years, mean body mass index 27.09±4.24) diagnosed with knee OA were included in this study. To assess knee OA, bilateral weight-bearing antero-posterior knee radiographs were taken and graded from 0 to 4 according to Kellgren–Lawrence criteria. The BMD of the subjects was measured using dual-energy X-ray absorptiometry (DEXA). BMD measurements of those with OA were compared with those without OA. Results: While there was no correlation between BMD and the grade of knee OA, a significant negative correlation was found between age and femur BMD. Body mass index was positively correlated with OA and negatively correlated with OP. Conclusion: Further investigations are needed to demonstrate the association between knee OA and BMD.
Quantitative Cartilage Imaging in Knee Osteoarthritis  [PDF]
Felix Eckstein,Wolfgang Wirth
Arthritis , 2011, DOI: 10.1155/2011/475684
Abstract: Quantitative measures of cartilage morphology (i.e., thickness) represent potentially powerful surrogate endpoints in osteoarthritis (OA). These can be used to identify risk factors of structural disease progression and can facilitate the clinical efficacy testing of structure modifying drugs in OA. This paper focuses on quantitative imaging of articular cartilage morphology in the knee, and will specifically deal with different cartilage morphology outcome variables and regions of interest, the relative performance and relationship between cartilage morphology measures, reference values for MRI-based knee cartilage morphometry, imaging protocols for measurement of cartilage morphology (including those used in the Osteoarthritis Initiative), sensitivity to change observed in knee OA, spatial patterns of cartilage loss as derived by subregional analysis, comparison of MRI changes with radiographic changes, risk factors of MRI-based cartilage loss in knee OA, the correlation of MRI-based cartilage loss with clinical outcomes, treatment response in knee OA, and future directions of the field. 1. Introduction Magnetic resonance imaging (MRI) has revolutionized the field of clinical research in osteoarthritis (OA) because it can directly visualize all diarthrodial tissues, including cartilage, bone, menisci, ligaments, synovium, and others. As it has been recognized that OA is a disease of the entire joint, involving most (if not all) of the above tissues, MRI has substantial advantages over radiography, which can only delineate the bone. Owing to its three-dimensional coverage of anatomical structures [1, 2] (Figure 1), MRI additionally permits to obtain quantitative measures of relevant tissue structures (and their changes over time) in OA. Quantitative measures of cartilage morphology (i.e., thickness, volume, surface areas) represent potentially powerful surrogate endpoints in osteoarthritis (OA). These can be used to identify risk factors of structural disease progression and can facilitate the clinical efficacy testing of disease (or structure) modifying drugs in OA (DMOADs), which are not clinically available to date. Figure 1: 3D reconstruction of the knee cartilages after segmentation: (a) View from anteromedial with softtissues in grey (b) View from anterior-lateral, with the bone segmented and with the cartilage thickness distribution in the patella displayed in false colors (red: thick cartilage; blue: thin cartilage). The cartilage of the medial tibia (MT) is depicted dark blue, that of the lateral tibia (LT) green), that of the medial
Pharmacotherapeutic aspects of treating knee osteoarthritis with glucosamine sulfate  [PDF]
Steven Simoens, Gert Laekeman
Health (Health) , 2010, DOI: 10.4236/health.2010.27107
Abstract: Glucosamine sulfate is a natural constituent of cartilage and is used in the treatment of knee osteoarthritis. The aim of this study is to provide a short but comprehensive pharmacotherapeutic update on treating knee osteoarthritis with glucosamine sulfate. A literature search was conducted of PubMed, Centre for Reviews and Dissemination databases, Cochrane Reviews and EconLit up to January 2010. The literature review indicated that the mechanism of action of glucosamine sulfate is based on hypothesis, but its treatment effects in knee osteoarthritis are symptomatic. With steady-state peak concentrations at the 1,500 mg dosage in the range of 10 µM, it is estimated that only 2% of glucosamine is incorporated in the cartilage. A once-daily dosage of 1,500 mg of glucosamine sulfate is licensed for the treatment of symptomatic osteoarthritis and has been shown to reduce pain, improve function and exhibit similar safety to placebo. Glucosamine sulfate is likely to be a cost-effective treatment of knee osteoarthritis. In conclusion, a once-daily dosage of 1,500 mg of glucosamine sulfate is likely to be a safe, effective and cost-effective treatment of knee osteoarthritis as compared to placebo.
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