Etiology Of Osteoarthritis Research Articles

A bioarchaeological study of osteoarthritis among populations of northern China and Mongolia during the Bronze Age to Iron Age transition to nomadic pastoralism

This paper examines data on joint disease among archaeological populations of several sites within northern China and Mongolia to test hypotheses about cultural uniformity among pastoralists and potential changes in the levels and types of activities during the Bronze Age to early Iron Age transition from mixed economies to mounted pastoralism. Despite continuing debate on the etiology of osteoarthritis, there is general consensus that joint use is an important contributor to joint disease. The vertebrae and major limb joints (shoulder, elbow, wrist/hand, hip, knee, and ankle/foot) of adult samples from these two periods were analyzed for prevalence and patterns of joint disease with respect to sex, age, time period, and location. There were only two joint regions with a significant difference between males and females: at the elbow, where males had a higher prevalence, and at the hip, where it was higher among females. The findings indicated a positive relationship between age and osteoarthritis, and that the spine was one of the most affected areas, along with the elbow and knee. Between the two time periods, while not at the level of significance, there was a pattern of higher prevalence of osteoarthritis in the vertebrae and upper limb joints among the Iron Age sample, while the Bronze Age sample had higher rates within the lower limb joints. These findings suggest different mechanical stresses between the two periods, perhaps associated with changes from mobility by foot in the Bronze Age to increased mounted mobility during the Iron Age, including mounted warfare. However, when comparing the individual sites within the two periods and within geographic regions, there was no distinct pattern, as there was much variation within both the Bronze Age and the Iron Age sites, as well as within regions. These varied results among sites and regions suggest that were was no uniform pastoral way of life or movement that imprinted clear patterns of osteoarthritis among pastoral samples. Instead, these data suggest that varied activities, movements, and perhaps mixed economic practices and workload among the sexes may have been characteristic among the “pastoral” groups of the Inner Asian steppe.

A top-notch dilemma: The complex role of NOTCH signaling in osteoarthritis.

A study by Liu et al. in the current issue of Science Signaling explores the complex dual role of NOTCH in the etiology of osteoarthritis by comparing gain-of-function mouse models representing aberrant pathological signaling and transient physiological signaling.

CORR Insights(®): The 2015 Frank Stinchfield Award: Radiographic Abnormalities Common in Senior Athletes With Well-functioning Hips but Not Associated With Osteoarthritis.

T he current understanding of the etiology of hip osteoarthritis (OA) is that certain variations in hip anatomy predispose the joint to the development of OA [7]. Natural history studies have shown that hips with dysplasia and femoroacetabular impingement (FAI) are more likely to develop arthritis [1, 17]. When analyzing the etiology of idiopathic OA, up to 79% of hips can be attributed to underlying hip deformity, with dysplasia implicated in 39% to 49% and CAM deformity in 40% to 63% [4, 8, 16]. During the past 30 years, the innovation and adoption of surgical techniques such as periacetabular osteotomy (PAO) [6] and hip arthroscopy have allowed surgeons to alter the mechanical environment of the hip at risk forOAwith the goal of decreasing the likelihood that arthritis will develop. There is some evidence that these interventions can delay or even prevent OA [12, 15]. Consequently, the biggest challenge for surgeons is to identify the hip at mechanical risk for degeneration and to accurately correct the anatomical cause of the mechanical dysfunction. However, dysplastic and FAI anatomy are spectra of deformity that are modulated by many nonanatomical factors such as genetics, activity level, and age, making it difficult to predict which hips with dysplasia or FAI will eventually become symptomatic and develop OA. Previous estimates of radiographic prevalence in the general population range from 3% to 13% for dysplasia [9, 10] and 15% to 25% for FAI [8, 14] Although prior studies demonstrated that a large portion of arthritic hips had underlying dysplasia or FAI, it remains unknown how many hips with radiographic signs of dysplasia or FAI stay asymptomatic and continue to function into old age. In the current study, Anderson and colleagues reported the prevalence of hip dysplasia and FAI morphology in a group of highly functional senior athletes. Although other studies have This CORR Insights is a commentary on the article ‘‘The 2015 Frank Stinchfield Award: Radiographic Abnormalities Common in Senior Athletes With Well-functioning Hips but Not Associated With Osteoarthritis’’ by Anderson and colleagues available at: DOI: 10.1007/s11999-015-4379-6. The author certifies that he, or any member of his immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/ licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request. The opinions expressed are those of the writers, and do not reflect the opinion or policy of CORR or The Association of Bone and Joint Surgeons. This CORR Insights comment refers to the article available at DOI: 10.1007/s11999-0154379-6. S. Y. Pun MD (&) Department of Orthopaedic Surgery, Stanford University, 300 Pasteur Drive, Edwards R105, Stanford, CA 94305, USA e-mail: sypun@stanford.edu CORR Insights Published online: 16 July 2015 The Association of Bone and Joint Surgeons1 2015

The ClC-7 Chloride Channel Is Downregulated by Hypoosmotic Stress in Human Chondrocytes.

Articular chondrocytes in osteoarthritis (OA) patients are exposed to hypoosmotic stress because the osmolality of this synovial fluid is significantly decreased. Hypoosmotic stress can cause an efflux of Cl(-) and an associated decrease of cell volume. We have previously reported that a Cl(-) conductance contributes to the regulation of resting membrane potential and thus can alter intracellular Ca(2+) concentration ([Ca(2+)]i) in human chondrocytes. The molecular identity and pathologic function of these Cl(-) channels, however, remained to be determined. Here, we show that the ClC-7 Cl(-) channel is strongly expressed in a human chondrocyte cell line (OUMS-27) and that it is responsible for Cl(-) currents that are activated by extracellular acidification (pH 5.0). These acid-sensitive currents are inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS; IC50 = 13 μM) and are markedly reduced by small-interfering RNA-induced knockdown of ClC-7. DIDS hyperpolarized these chondrocytes, and this was followed by an increase in [Ca(2+)]i. ClC-7 knockdown caused a similar hyperpolarization of the membrane potential. Short-term culture (48 hours) in hypoosmotic medium (270 mOsm) reduced the expression of ClC-7 and decreased the acid-sensitive currents. Interestingly, these hypoosmotic culture conditions, or ClC-7 knockdown, resulted in enhanced cell death. Taken together, our results show that the significant hyperpolarization due to ClC-7 impairment in chondrocytes can significantly increase [Ca(2+)]i and cell death. Thus, downregulation of ClC-7 channels during the hypoosmotic stress that accompanies OA progression is one important concept of the complex etiology of OA. These findings suggest novel targets for therapeutic intervention(s) and drug development for OA.

A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand.

A number of studies have reported an association of GDF5 with osteoarthritis (OA) but have produced some divergent findings and their interpretation may not be straightforward. We investigated the association between GDF5 and OA using meta-analytic techniques, combining all published data up to Nov 2014. 16 independent samples from 11 research teams contributed data on SNP rs143383 (located in the 5'-UTR of GDF5) and knee, hip, and hand OA. The total number of cases and controls for this marker was 7,965 and 12,747 for knee OA, 6,363 and 9,727 for hip OA, and 4,335 and 5,991 for hand OA, respectively. The ORs for each OA phenotype were synthesized using random-effects models or fixed-effects models depending on the test of between-study heterogeneity. Using a random-effect model, a significant difference was identified between patients with knee OA and controls for the T-allele of rs143383 (Subtotal OR = 1.18, 95 % CI=1.10-1.27, P=1.84 × 10(-6)). For hand OA, a moderate association was also observed (Subtotal OR = 1.09, 95 % CI = 1.02-1.16, P = 0.01) for SNP rs143383 in the combined population. However, non-statistically significant summary OR of hip OA was found in both combined studies (Subtotal OR = 1.22, 95 % CI = 0.97-1.53, P = 0.09) and European studies (Subtotal OR = 1.16, 95 % CI = 0.91-1.48, P = 0.23). Our results demonstrate that SNP rs143383 of GDF5 is a compelling risk factor for both knee and hand OA, and provide further support for GDF5 in the etiology of OA. Further efforts to identify functional variants of GDF5 in in vitro and in vivo will be required.

Novel susceptability loci for osteoarthritis of the hand: Variants in coding EN GENE regulatory regions

Purpose: Osteoarthritis (OA) of the hand, is to a large extend, genetically determined. However, despite the large GWAS efforts into OA over the last years only one locus has been found to be associated to hand OA. We here aim to identify novel genes and pathways involved in the etiology of hand OA. Methods: We conducted a genome-wide association study of hand OA in a discovery set of 10,155 participants from the three Rotterdam Study cohorts (RS1, RS2 and RS3) using standardized age and gender adjustments. We have used a quantitative bilateral hand OA phenotype, summing all KL-scores of the hand joints for both hands (min score: 0, max score: 128). EasyQC was used to conduct quality control across cohorts. Results were combined in a jointed meta-analysis using inverse variance weighting. Genome-wide significant signals were analyzes for enrichment in genomic regulatory regions, using data from the ENCODE and Roadmap epigenetics project. Results: The discovery analysis yielded 16 loci with suggestive evidence for association (P<5*10-6 ) and another 3 loci with genome-wide significant association (p<5*10-8). These novel genome-wide significant loci include SNPs in or near the MGP, PTHLH and APBB2 genes. The risk alleles of MGP, PTHLH and APBB2 genes had a higher KL-sum score compared to the reference allele (delta KL-score was 7, 6, and 23 respectively) MGP codes for Matrix Gla Protein and is important for limiting calcification in tissues. Mutations in the MGP gene have been associated to Keutel Syndrome, which is characterized by abnormal mineralization of cartilage tissue. We here identified a SNP resulting in a protein-change to be associated with hand OA. The identified SNPs in the PTHLH-locus and the APBB2-locus co-localize with enhancer histone markers in osteoblast and chondrogenic cells from the Roadmap and ENCODE database, suggesting a potential gene regulatory function for these SNPs. Conclusions: We identified 3 loci to be associated to hand OA, a coding variant in the MPG gene and two intronic variants in APBB2 and CCDC91 located near gene regulatory marks specific for bone and/or cartilage. In addition, we have also found 16 loci suggestively associated to hand OA. Future analysis will consist of validation of our findings in other cohorts and further functional assessment and pathway analyses of the identified variants

Mitochondrial respiration and redox coupling in articular chondrocytes.

IntroductionChondrocytes rely primarily on glycolysis to meet cellular energy needs, but recent studies implicate impaired mitochondrial function in osteoarthritis (OA) pathogenesis. Our objectives were to investigate the ability of chondrocytes to upregulate mitochondrial respiration when challenged with a nutrient stress and determine the effect on mediators of chondrocyte oxidative homeostasis.MethodsPrimary bovine chondrocytes were isolated and cultured in alginate beads. Mitochondrial respiration was stimulated by culturing cells with galactose-supplemented media for a period of 1 or 5 days. Metabolic flexibility was assessed by measuring metabolite and enzymatic biomarkers of glycolytic and mitochondrial metabolism. Oxidative homeostasis was assessed by measuring (1) cellular glutathione content and redox homeostasis, (2) rates of nitric oxide and superoxide production, and (3) the abundance and activity of cellular anti-oxidant proteins, especially the mitochondrial isoform of superoxide dismutase (SOD2). The regulatory role of hypoxia-inducible factor 2α (HIF-2α) in mediating the metabolic and redox responses was evaluated by chemical stabilization with cobalt chloride (CoCl2).ResultsAfter 5 days of galactose culture, lactate production and lactate dehydrogenase activity were reduced by 92% (P <0.0001) and 28% (P = 0.051), respectively. Conversely, basal oxygen consumption increased 35% (P = 0.042) without increasing mitochondrial content. Glutathione redox homeostasis was unaffected by galactose culture. However, the production of nitric oxide and superoxide and the expression and activity of SOD2 were significantly reduced after 5 days in galactose culture. Nuclear protein expression and gene expression of HIF-2α, a transcription factor for SOD2, were significantly downregulated (more than twofold; P <0.05) with galactose culture. CoCl2-mediated stabilization of HIF-2α during the initial galactose response phase attenuated the reduction in SOD2 (P = 0.028) and increased cell death (P = 0.003).ConclusionsChondrocyte metabolic flexibility promotes cell survival during a nutrient stress by upregulating mitochondrial respiration and reducing the rate of reactive nitrogen and oxygen species production. These changes are coupled to a substantial reduction in the expression and activity of the mitochondrial anti-oxidant SOD2 and its pro-catabolic transcription factor HIF-2α, suggesting that an improved understanding of physiologic triggers of chondrocyte metabolic flexibility may provide new insight into the etiology of OA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0566-9) contains supplementary material, which is available to authorized users.

MicroRNA-146a Induced by Hypoxia Promotes Chondrocyte Autophagy through Bcl-2

Background/Aims: There have been many studies on the etiology of osteoarthritis (OA) with regard to the function of inflammatory cytokines, the process of cartilage degradation, the function of miR-146a, hypoxia stimulation and autophagy in OA chondrocytes, but there have been no reports on the relationship between miR-146a and autophagy in cartilage, especially under hypoxia. This study aimed to confirm the relationship of miR-146a and autophagy in cartilage under hypoxia. Methods: Chondrocytes were treated by hypoxia gradients, and the main factors including HIF-1α, HIF-2α, miR-146a and Bcl-2 and autophagy markers ULK-1, ATG-5 were detected by quantitative PCR (Q-PCR) and western blotting. The autophagy marker LC-3 was detected by immunofluorescence. The reciprocal effects between miR-146a and Bcl-2 were confirmed by several combinations of shRNAs and adenovirus-gene systems followed by Q-PCR and western blot detection. Results: Hypoxia maintained the chondrocytes phenotype and promoted autophagy and miR-146a expression via HIF-1α, but not HIF-2α, while miR-146a did not reversely affect HIF-1α. The autophagy induced by hypoxia through HIF-1α, miR-146a and Bcl-2. Simply, hypoxia induced HIF-1α, and HIF-1α increased miR-146a, but miR-146a suppressed Bcl-2, an autophagy inhibitor. While Bcl-2 affected neither HIF-1α nor miR-146a. The absence of both HIF-1α and miR-146a or Bcl-2 over-expression inhibited hypoxia-induced autophagy. Conclusion: HIF-1α, miR-146a and Bcl-2 play crucial roles during hypoxia-induced autophagy, Hypoxia, HIF-1α and miR-146a promote chondrocytes autophagy via depressing Bcl-2. We conclude that miR-146a may serve as a novel therapeutic target for protecting cartilage from degeneration in OA.

Prevalence of radiological femoroacetabular impingement in Japanese hip joints: detailed investigation with computed tomography

BackgroundFemoroacetabular impingement (FAI) has been highlighted as a new etiology for osteoarthritis of the hip, and its prevalence has been reported in the past decade. In the present study, we performed a detailed investigation of the anatomical parameters related to FAI and calculated the prevalence of FAI-related findings in asymptomatic Japanese hip joints using computed tomography. MethodsWe evaluated high-resolution reconstructed multislice computed tomography images in patients who had undergone computed tomography imaging in our institution for conditions unrelated to hip disorders. The examined parameters were as follows: center-edge (CE) angle; acetabular index; acetabular anteversion (five slices in the axial plane); and asphericity angle of the femoral head (AAFH) (six slices in multiple radial planes). The AAFH in the oblique axial slice through the center of the femoral neck is the so-called α-angle. We then examined the accurate prevalence of FAI-related findings in Japan. ResultsWe investigated a total of 103 hips. The mean age of the subjects was 59.4years. The mean CE angle was 31.1° and the mean acetabular index was 7.0°. The mean acetabular anteversion was 20.3° at the level of the hip center, and decreased as the slice level neared the superior margin of the femoral head. The mean AAFH ranged from 40.6° to 49.2° in the radial planes. The AAFH was largest at 60° rotated slice from the oblique axial slice through the center of the femoral neck. The prevalence of FAI-related findings in these Japanese hip joints was assessed as follows. An AAFH of >50° in any slice was detected in 51.5% of the hips, and acetabular anteversion was negative for all images in 16.5 % of the hips, meaning that a total of 56.3% of the images met the criteria for radiological FAI. ConclusionsWith consideration of our results, we emphasize that “anatomical or radiological FAI” is not uncommon in Japanese hips. Therefore, the diagnosis of FAI should be performed with the clinical findings taken into account.

TLR4 signalling in osteoarthritis--finding targets for candidate DMOADs.

Osteoarthritis (OA), the most common rheumatic disease, is characterized by joint-space narrowing due to progressive cartilage degradation and alterations in subchondral bone and the synovial membrane. These articular disturbances can have severe consequences, including pain, disability and loss of joint architectural integrity. Although the aetiology of OA is not understood, chondrocyte-mediated inflammatory responses triggered by the activation of innate immune receptors by damage-associated molecules are thought to be involved. In this Review, we examine the relationship between Toll-like receptor 4 (TLR4) and OA in cartilage as well as in other OA-affected tissues, such as subchondral bone and synovium. We also discuss the different TLR4 agonists associated with OA and their effects in joint tissues. Finally, we describe existing and novel strategies that might be used to develop TLR4-specific disease-modifying OA drugs (DMOADs).

Variations in the TNFα gene and their interactions with the IL4R and IL10 genes in relation to hand osteoarthritis.

BackgroundThe development of osteoarthritis (OA) involves inflammation, but the evidence for participation of genes propagating or inhibiting inflammation in the OA process is inconsistent. We investigated the associations of common variants in the TNFα gene, and their interactions with other cytokine genes, with hand OA among Finnish women.MethodsThis cross-sectional study was based on bilateral hand radiographs of 542 female dentists and teachers which were classified according to the presence of OA (radiographic K-L score ≥ 2 in ≥ 3 joints) using reference images. The genotypes were determined by PCR-based methods. The degree of pairwise linkage disequilibrium (LD) and haplotypes were constructed and analyzed by the SNPStats software. The associations between four TNFα SNPs and hand OA were tested using logistic regression adjusting for age, occupation, and BMI, and fitting a log-additive model of inheritance. Gene-gene interactions of TNFα SNPs with IL4R and IL10 SNPs were examined by stratified logistic regression analyses. Possible interactions of the TNFα SNPs with variants in the previously reported IL1β and IL6 genes in influencing hand OA were also explored.ResultsTwo TNFα polymorphisms (“-1031” and “-863”) were associated with hand OA (OR = 1.45, 95% CI 1.01-2.07 and 1.55, 1.06-2.25, respectively). These associations retained when adjusting further for IL1β “3954” and IL6 “174”. The TNFα G-A-G haplotype was associated with an increased risk of hand OA (1.61, 1.10-2.37, p = 0.01). Interactions were observed between TNFα “-1031” and IL4R Ser503Pro, TNFα “-1031” and IL10 “-1082”, and TNFα “-863” and IL10 “-1082” SNPs with regard to hand OA (p = 0.012, p = 0.0068, and p = 0.02, respectively). The carriage of the TNFα “-1031” minor allele doubled the risk (2.01, 1.26 - 3.22) only in women with the IL4R Ser/Ser genotype. Similarly, the TNFα “-1031” and “-863” minor alleles were associated with an increased risk of hand OA only in IL10 G/G or A/A homozygotes (2.54, 1.45-4.47 and 2.60, 1.46-4.62, respectively) but not in heterozygotes (G/A).ConclusionsOur results suggest that the TNF α gene variants play a role in the etiology of hand OA. In addition, the findings are suggestive of a gene-gene interaction of the TNF α with IL4R and IL10 genes.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-311) contains supplementary material, which is available to authorized users.

The nature of in vivo mechanical signals that influence cartilage health and progression to knee osteoarthritis.

Knee osteoarthritis is a disease that can be initiated along multiple pathways that ultimately leads to pain, loss of function and breakdown of the articular cartilage. While the various pathways have biological and structural elements, the mechanical pathways play a critical role in the development of the disease. The forces and motions occurring during ambulation provide mechanical signals sensed at the scale of the cell that are critical to healthy joint homeostasis. As such, ambulatory changes associated with aging, obesity, or joint injury that occur prior to the development of symptoms of OA can ultimately lead to clinical OA. Conversely, inter-scale signaling (e.g., pain) generated by biological changes in the early stages of OA can produce adaptive ambulatory changes that can modify the rate of OA progression. Thus, the nature of the physical and clinical response to the mechanical signals that occur during ambulation is critical to understanding the etiology of osteoarthritis.

Association of osteopontin with osteoarthritis.

The joint disease osteoarthritis (OA) is the most common form of arthritis, which mainly affects the older people. OA is becoming one of the major non-fatal health burdens of the world. The etiology of OA is mostly unclear, and it cannot be cured totally. Osteopontin (OPN) is a multifunctional phosphoprotein, of which overexpression and high level of presence in synovial fluid and articular cartilage were found to be associated with OA progression. Usually, in OA progression, OPN plays important role as an intrinsic regulator. Recent studies have taken attempt to use this protein as a diagnostic marker of OA and use OPN as a target for the drug development against OA. This review summarizes the role of OPN in OA, with focusing on the mechanism of action, and also discussing the diagnostic and therapeutic aspects of OA related to OPN.

A Brief History of USNCB: Motivation and Formation

A Brief History of USNCB: Motivation and Formation

Osteoarthritis pain: nociceptive or neuropathic?

In this article, we present the case for the existence of a subgroup of patients with osteoarthritis (OA) who experience pain with neuropathic features. Recognizing these patients as a distinct subgroup will allow clinicians to improve the management of their symptoms. We discuss the diagnostic criteria for pain to be classed as neuropathic, then systematically examine the applicability of these criteria to the symptoms, signs and pathology of OA. What are the implications for the preclinical development and clinical use of analgesics for OA? How should existing treatment options be reassessed? Differences in the aetiology of OA and the pharmacological sensitivity of patients with OA pain with neuropathic features, compared with other patients with OA, might explain the frequent negative findings of clinical trials of treatments for symptomatic OA. If the global prevalence of OA pain with neuropathic features is accurately represented by reports from small experimental groups of patients, then a substantial unmet need to tailor diagnosis and therapy for these individuals exists.

Dietary and caloric restriction and age‐related spinal osteoarthritis: a longitudinal study of primates (1025.7)

Dietary and/or caloric restriction have been shown to decrease the rate of senescence and increase maximum life span in several species, but how it impacts age‐related degenerative processes, such as osteoarthritis, is unclear. Like humans, Rhesus macaques develop spontaneous osteoarthritis with age and have been studied under dietary/caloric restriction protocols for almost two decades. We hypothesized that restricted macaques would develop less spinal osteoarthritis with age than monkeys fed a normal diet.We assessed osteoarthritis in the thoracolumbar spine of macaques from dietary/caloric restriction studies at the Wisconsin National Primate Research Center and the National Institute on Aging. We assessed osteophytosis (OST) and disc space narrowing (DSN) from annual radiographs of 68 macaques from the WNPRC (males, n=41 (20 restricted); females, n=27 (13 restricted)) and 104 macaques from NIA (males, n=52 (26 restricted); females, n=52 (22 restricted)) studies. A positive association between age and both OST (p&lt;0.001) and DSN (p&lt;0.001) was found in macaques from both sites, but no difference was found between normally fed and restricted animals (WNPRC: OST p=0.222, DSN p=0.574; NIA: OST p=0.238, DSN p=0.386) when adjusted for sex and body mass.Dietary/caloric restriction does not affect spinal osteoarthritis, which perhaps implicates loading as a contributor to the etiology of osteoarthritis.

Serum uric acid as a predisposing factor of clinico- radiological severity of osteoarthritis knee

Serum uric acid as a predisposing factor of clinico- radiological severity of osteoarthritis knee

Differential expression of seven mitochondrion enzymes in osteoarthritis cartilages and normal cartilages

Osteoarthritis (OA) is an aging-associated rheumatic disease characterized by reduced number of chondrocytes, loss of existing cartilage extracellular matrix, the production of matrix with abnormal composition and pathologic matrix calcification. Recent studies have reported mitochondrial dysfunction played an important role in human OA chondrocytes. Although several lines of evidence support the role for declines in enzyme activity in the etiology of OA, it remains unclear if the expressions of enzymes alter with OA. Here, we determined to quantify the expression of several enzymes in ETC and cytoplasm of mitochondrial in healthy and OA cartilage. These findings suggest that the decreased expression of enzymes in mitochondrial may contribute to OA.

Association of single nucleotide polymorphisms in estrogen receptor alpha gene with susceptibility to knee osteoarthritis: a case-control study in a Chinese Han population.

Osteoarthritis (OA) is the most prevalent form of arthritis and its multifactorial nature has been increasingly recognized. Genetic factors play an important role in OA etiology and estrogen receptor alpha (ESR1) gene polymorphisms may be involved. This study tried to explore whether the ESR1 gene single nucleotide polymorphisms (SNPs) were associated with primary knee OA in the Chinese Han population. Two SNPs, rs2234693 and rs9340799, were genotyped in 469 cases and 522 controls. Rs2234693 was associated with knee OA in the dominant genetic model (TT + TC versus CC) (P = 0.025) and a higher T allele frequency existed (P = 0.047) among females. The combined genotype (TT + TC) (P = 0.025) and T allele (P = 0.016) were related with mild knee OA only. For rs9340799, A allele was associated with knee OA in all subjects (P = 0.031) and females (P = 0.046). Statistical differences were detected in the dominant genetic model (AA + AG versus GG) among females (P = 0.030). The combined genotype (AA + AG) (P = 0.036) and A allele (P = 0.039) were merely correlated with mild knee OA. ESR1 gene is considerably associated with knee OA etiology in the Chinese Han population.

A Systematic Approach to Evaluating Knee Radiographs with a Focus on Osteoarthritis

Arthritis of the knee is commonly encountered in primary care and specialty settings. The initial work up and treatment of these patients requires a thorough evaluation and complete series of plain radiographs. Despite increased use of advanced imaging modalities, plain films remain the most instructive, available, and affordable diagnostic test. The evaluation of patients with arthritis can be challenging, by using a standardized approach one can perform a quick and adequately comprehensive evaluation. Here we outline an approach appropriate for the evaluation of these patients in any setting. Particularly, we advocate a complete history and physical exam augmented by a four view radiographic series: A weight bearing anterior-posterior (AP) of the knee, a 45 degree weight bearing posterior-anterior (PA) view of the knee, a standing lateral, and a Merchant view. Through our described systematic evaluation of these views, a great deal of information can be obtained often helping guide treatment plans created with the patient, and helping avoid a potential missed or delayed diagnosis. Background Osteoarthritis (OA) is the most common form of arthritis, and the knee is the principal large joint affected by this process [1]. In men and women over the age of fifty-five, an estimated ten percent develop disabling knee pain from OA; 25% of those affected are considered severely disabled [2]. The incidence of osteoarthritis of the knee increases with age, is strongly associated with obesity [3], and more commonly affects women [4]. OA is the single greatest contributor to disability [5,6], and in the elderly, its overall risk of disability is comparable to that of cardiovascular disease. The precise etiology, pathogenesis, and progression of OA are not yet completely understood. Taking a thorough history and performing a detailed physical examination is necessary when evaluating a patient with presumed osteoarthritis of the knee. The most common presenting symptom is pain, often associated with activity and relieved by rest. Additional symptoms include crepitus, swelling, limping, stiffness that typically improves after a brief period of activity [7], and progressive lower extremity deformity (e.g. bow-legged or knock-knee deformity). Patients should be asked about their occupation, history of trauma, and presence of previous knee pathology. Due to the fact that there is a 50% risk associated with genetic predisposition to OA, a careful family should be documented [8-10]. Physical exam may reveal genu valgum (knock-knee) or genu varum (bow-legged), an extensor mechanism lag, a leg-length discrepancy, or a flexion contracture. Arthritis is categorized as primary or secondary. Primary arthritis is an idiopathic condition that is thought to result from mechanical wear of the joint beyond the body’s reparative capabilities. In contrast, secondary arthritis is due to another condition or disease, such as trauma, autoimmune disorders, crystalline arthropathy, and congenital anomalies. The radiographic hallmarks of primary and secondary arthritis differ. Identifying these differences correctly can lead to significant adjustments in the approach to patient care and are one important aspect of radiographic evaluation of the patient with osteoarthritis. When evaluating both primary and secondary arthritis of the knee, weight-bearing radiographs from multiple views are essential to allow visualization of the functional joint space. The specific purpose of this review is to provide Internists, Physiatrists, Rheumatologists, and Orthopaedic Surgeons with a systematic method for evaluating radiographs to help guide appropriate treatment in the patient with osteoarthritis of the knee. Systematic Evaluation of the Arthritic Knee In the evaluation of the adult patient with degenerative joint