A method for Kashin-Beck disease auxiliary diagnosis based on the features in regions of the potential lesion.

BACKGROUND: Kashin-Beck disease (KBD) is a severe arthropathy that causes deformity. Patients with advanced stages of KBD often show symptoms, such as short stature. Early-stage diagnosis and treatment can effectively prevent the disease from worsening. Diagnosis of early-stage patients is usually made by X-ray examination. However, the time-consuming image recognition and the lack of professional doctors may delay the patient's condition. Therefore, a method that can efficiently complete the auxiliary diagnosis is necessary. PURPOSE: This study presents a KBD auxiliary diagnosis method based on radiographs, which uses deep learning to locate potential lesion regions and extract features for accurate diagnosis. METHODS: This work presents a method that relies on hand radiographs to locate eight regions of the potential lesion (RoPL) and finally make the KBD auxiliary diagnosis. The localization of RoPL is achieved through a two-step model, with the first step predicting a rough location and a deep convolutional neural network (DCNN) with attention mechanism used to generate precise center coordinates based on the previous step's results. Based on the localization result, regional features are extracted, which provides information about the joints and textures of RoPL from a finer granularity. Another DCNN is utilized to obtain general features from hand radiographs, which provide morphological and structural information about the entire hand bone These features offer a concatenated feature for categorization to raise accuracy. A doctor-like approach is adopted to diagnose based on regional features to enhance performance, and a final decision is made using a vote that considers diagnostic outcomes from all aspects. The dataset used in our study was collected by our research team in KBD-endemic areas of Tibet since 2017, containing 373 diseased and 764 normal images. RESULT: Our model guarantees that over 95% of the predicted coordinates are within five pixels of the real coordinates according to Euclidean distance. The accuracy of the diagnostic network achieved 91.3%, with precision and recall achieving 83% and 87%, respectively. Compared to the approach without exact localization of the illness region on the same test set, our method achieved a roughly 6% increase in accuracy and nearly 30% increase in recall rate. CONCLUSIONS: Based on hand radiographs, this study suggests a novel method for KBD diagnosis. The high-precision localization network guarantees precise extraction of lesion-prone regional features, and the multi-scale features and innovative classification method further enhance model performance compared to related approaches.

Identifying discriminative features for diagnosis of Kashin-Beck disease among adolescents.

INTRODUCTION: Diagnosing Kashin-Beck disease (KBD) involves damages to multiple joints and carries variable clinical symptoms, posing great challenge to the diagnosis of KBD for clinical practitioners. However, it is still unclear which clinical features of KBD are more informative for the diagnosis of Kashin-Beck disease among adolescent. METHODS: We first manually extracted 26 possible features including clinical manifestations, and pathological changes of X-ray images from 400 KBD and 400 non-KBD adolescents. With such features, we performed four classification methods, i.e., random forest algorithms (RFA), artificial neural networks (ANNs), support vector machines (SVMs) and linear regression (LR) with four feature selection methods, i.e., RFA, minimum redundancy maximum relevance (mRMR), support vector machine recursive feature elimination (SVM-RFE) and Relief. The performance of diagnosis of KBD with respect to different classification models were evaluated by sensitivity, specificity, accuracy, and the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: Our results demonstrated that the 10 out of 26 discriminative features were displayed more powerful performance, regardless of the chosen of classification models and feature selection methods. These ten discriminative features were distal end of phalanges alterations, metaphysis alterations and carpals alterations and clinical manifestations of ankle joint movement limitation, enlarged finger joints, flexion of the distal part of fingers, elbow joint movement limitation, squatting limitation, deformed finger joints, wrist joint movement limitation. CONCLUSIONS: The selected ten discriminative features could provide a fast, effective diagnostic standard for KBD adolescents.

Prevalence of pediatric Kashin-Beck disease in Tibet.

INTRODUCTION: To estimate the prevalence of Kashin-Beck disease (KBD) among children in 2017 in Changdu of Tibet. METHODS: We adopted a four-step recruitment to include children aged 7-12 years from seven identified historically endemic counties in Changdu. Posterior-anterior radiographs of right hand and wrist were taken and were graded at four sites (metaphysis, epiphysis, and bony end of phalanges and metacarpal and carpal bones). Two trained researchers independently read the films. Inter-rater reliability was assessed using weighted Kappa and percentage agreement. We fitted logistic regression model to examine the association of age, sex, and altitude of residential village with prevalence of KBD. We examined association between site involvement and severity of KBD using chi-square test. RESULTS: We recruited 13,573 children (mean age = 9.3 years, 48.40% girls) with a response rate of 95.81%. The overall prevalence of radiographic KBD was 0.26%. Luolong County had the highest prevalence (0.69%), followed by Bianba (0.26%), Basu (0.24%), Mangkang (0.14%), Zuogong (0.14%), Dingqing (0.07%), and Chaya (0.00%). A higher risk of radiographic KBD was associated with older age (P for trend <0.001) and girls (OR=1.86, 95% CI: 0.94, 3.70), but not the altitude of residential village (P for trend=0.957). Metaphysis was involved in all cases of KBD while lesions in epiphysis and bony end of phalanges and metacarpals were only observed in severe cases. CONCLUSIONS: The prevalence of radiographic KBD among children aged 7-12 years was low in Changdu compared with previous census data, suggesting the effectiveness of preventative measures. Key Points • In this study, 13,573 Tibetan children were taken X-ray films of their hands and wrists. • The prevalence of radiographic KBD among children aged 7-12 years was low in Changdu of Tibet. • The preventative measures against KBD launched by Chinese government were effective in decreasing new onsets of KBD among Tibetan children.

Kashin-Beck disease diagnosis based on deep learning from hand X-ray images.

BACKGROUND AND OBJECTIVE: Kashin-Beck Disease (KBD) is a serious endemic bone disease leading to short stature. The early radiological examinations are crucial for potential patients. However, many children in rural China cannot be diagnosed in time due to the shortage of professional orthopedists. In this paper, an algorithm is developed to automatically screening KBD based on hand X-ray images of subjects, which can help the government reducing human resources investment and assisting the poor precisely. METHODS: The KBD diagnosis method focuses on multi-feature fusion for classification. Two kinds of features presented in X-ray images are extracted by a deep convolutional neural network (DCNN). One is the global features that represent shapes and structures of the whole hand bone. The other is local features that represent edge and texture information from critical regions of the metaphysis. The global features tend to sketch the major informative parts, whereas other fine local features can provide supplementary information. Then both kinds of features are combined and fed into the KBD classifier of a fully connected neural network (FCNN) to obtain diagnostic results. RESULT: Our research team collected 960 samples in KBD endemic areas of Tibet from 2017 to 2018. The dataset contains 219 KBD positive images and 741 negative images. Experiments indicate that the method based on multi-feature achieves the best average accuracy and sensitivity rate of of 98.5% and 97.6% for diagnosis, which is 4.0% and 7.6% higher than the method with only the global features respectively. CONCLUSIONS: The KBD diagnosis method shows that our proposed multi-feature fusion helps to achieve higher diagnosis performance and stability compared with only using global features for detection. The automated KBD diagnosis algorithm provides substantial benefits to reduce large-scale screening costs and missed diagnosis rate.

Magnetic resonance imaging at 7.0 T for evaluation of early lesions of epiphyseal plate and epiphyseal end in a rat model of Kashin-Beck disease.

BACKGROUND: Kashin-Beck disease (KBD) is a disabling osteoarticular disease involving growth and joint cartilage. Early diagnosis can effectively prevent the progress of the disease. However, the early diagnosis of it is still very difficult. Our aim was to study the knee joint lesions of a rat KBD model using ultra-high field magnetic resonance imaging (MRI) and compare it with X-ray imaging to analyze the possible MRI manifestations of KBD, and to further explore ways to determine the pathological damage of KBD in the early stage. METHODS: A total of 96 Wistar rats were selected and randomly divided into 4 groups: normal diet (Group A), KBD-affected diet (Group B), normal diet+T-2 toxin (Group C), and KBD-affected diet+T-2 toxin (Group D). T-2 toxin was administered at a dose of 0.1 mg/kg/day. In the 4th week, 8th week, and 12th week, eight rats randomly selected in each group were sacrificed by cervical dislocation after undergoing X-ray and 7.0 T MRI imaging, and then knee joints were harvested, sliced, and subjected to hematoxylin-eosin (H&E) staining. RESULTS: Characteristic image changes including of continuity interruption and early closure and fusion of epiphyseal plates were observed on T1WI in rat model of KBD. The total necrosis rates in the H&E stain of group A to group D were 4.35, 52.38, 33.3, and 73.68%, respectively. The positive rate of image change under 7.0 T MRI was 0.833 VS. that under X-ray was 0.33 (P = 0.001). CONCLUSIONS: MRI at 7.0 T is highly sensitive to the early pathological changes of the epiphysis, epiphyseal plate, and metaphyseal end, which can improve imaging positive rate of KBD and decrease the rate of missed diagnosis. This imaging modality can be used for research on early joint lesions and for early diagnosis of KBD.

A preliminary analysis of microRNA profiles in the subchondral bone between Kashin-Beck disease and primary knee osteoarthritis.

INTRODUCTION: Kashin-Beck disease (KBD) is a chronic osteochondral disorder primarily associated with cartilage degeneration. The bone texture structure in KBD was also changed but it was not identical to primary knee osteoarthritis (OA). This study investigates the differences in microRNA (miRNA) profiles of subchondral bone collected from patients suffering from KBD in comparison with those with primary knee osteoarthritis (OA). METHODS: Subchondral bone tissues were taken from four patients with KBD and four patients with primary knee OA undergoing total knee replacement. The miRNA array profiling was performed using an Affymetrix miRNA 4.0 Array, and then the target gene predictions and function annotations of the predicted targets were performed. RESULTS: Our results showed that 124 miRNAs had lower expression levels in the subchondral bone sampled from KBD patients in comparison with OA patients. Gene ontology (GO) and KEGG pathway analyses of the predicted targets demonstrated numerous significantly enriched GO terms and signal pathways essential for bone development and integrity, such as metabolic processes, PI3K-Akt, and MAPK signaling pathways. CONCLUSIONS: Our study confirms that a large set of miRNAs are differentially expressed in the subchondral bone of patients with KBD and OA and contributes new insights into potential pathological changes in the subchondral bone of KBD patients.

The systematic review and meta-analysis of X-ray detective rate of Kashin-Beck disease from 1992 to 2016.

BACKGROUND: Kashin-Beck disease (KBD) is a serious human endemic chronic osteochondral disease. However, quantitative syntheses of X-ray detective rate studies for KBD are rare. We performed an initial systematic review and meta-analysis to assess the X-ray detective rate of KBD in China. METHODS: For this systematic review and meta-analysis, we searched five databases (PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), WanFang Data and the China Science and Technology Journal Database (VIP))using a comprehensive search strategy to identify studies of KBD X-ray detective rate in China that were published from database inception to January 13, 2018. The X-ray detective rate of KBD was determined via an analysis of published studies using a random effect meta-analysis with the proportions approach. Subgroup analysis and meta-regression were used to explore heterogeneity, and study quality was assessed using the risk of bias tool. RESULTS: A total of 53 studies involving 14,039 samples with X-ray detective rate in 163,340 observations in total were included in this meta-analysis. These studies were geographically diverse (3 endemic areas). The pooled overall X-ray detective rate for KBD was 11% (95%CI,8-15%;Z = 13.14; p < 0.001). The pooled X-ray detective rate estimates were 11% (95%CI, 6-17%; Z = 7.06; p < 0.001) for northeast endemic areas, 13% (95%CI, 7-20%; Z = 7.45; p < 0.001) for northwest endemic areas, and 8% (95%CI, 5-12%; Z = 7.90; p < 0.001) for southwest endemic areas. There was a significant relationship between the survey year and the X-ray detective rate of KBD. CONCLUSIONS: Our systematic review found that the summary estimate of the X-ray detective rate of KBD was 11% and, that KBD X-ray positive rate ranged from 8.00 to 15.00% depending on the study. Further research is required to identify effective strategies for preventing and treating KBD.

Comparison of bone texture between normal individuals and patients with Kashin-Beck disease from plain radiographs in knee.

To compare tibial bone texture between Kashin-Beck disease (KBD) patients and normal individuals from plain radiographs using an advanced image analysis. Plain knee radiographs were obtained from KBD patients (n = 49) and age-matched healthy controls (n = 98). KBD were graded with diagnostic criteria WS/T 207-2010. The textural values related to bone structure from medial and lateral tibial subchondral and trabecular bones were evaluated using entropy of Laplacian-based image (ELap), entropy of local binary patterns (ELBP), homogeneity indices (HI) of local angles (HIMean, HIPerp and HIParal), and fractal dimensions from horizontal (FDHor) and vertical (FDVer) structures. KBD patients were shorter in height and lighter in weight, and their tibial width was wider than controls. Anatomical angle of KBD patients showed more genu valgus. Total KBD patients and subgroups had higher ELap, HIMean, HIPerp and HIParal in detected tibial subchondral and trabecular bones than controls, except ELap in lateral subchondral bone. ELBP, FDHor and FDVer from the detected tibial bone in KBD patients and subgroups were lower than controls, except FDVer in lateral trabecular bone. Our results indicate that micro-scale in bone texture in KBD-affected knees can be quantitatively examined from plain radiographs using an advanced image analysis.

Serum levels of PIICP, PIIANP, and PIIBNP are decreased in patients with an endemic osteochondropathy, Kashin-Beck disease.

BACKGROUND: Kashin-Beck disease (KBD) is an endemic, chronic, degenerative osteoarthropathy. KBD is usually diagnosed by using X-ray image and clinical symptoms, lacking of serological biomarkers. The serum level of PIICP, PIIANP, and PIIBNP can specifically reflect the damage of the cartilage. So, in this study, the serum levels of PIICP, PIIANP, and PIIBNP were detected in order to determine whether they can be used as potential biomarkers for the diagnosis of KBD. METHOD: Using a status survey, the survey sites were selected in the KBD historical endemic areas and non-endemic areas in Jilin and Heilongjiang provinces. All local residents have undergone clinical examination, X-ray examination of the hands and knees, and questionnaire survey. A total of 554 people were surveyed, and 184 residents who are eligible for inclusion criteria were selected as our subjects. Fifty-six cases were diagnosed as KBD and 63 individuals were included as internal control and 65 subjects were included as external control. And blood samples of surveyed subjects were collected, and the serum was separated to detect the levels of PIICP, PIIANP, and PIIBNP by ELISA. Statistical analysis was performed using the SPSS software. RESULTS: There were no statistically significant differences in age and sex among the three groups. The Kruskal-Wallis H test showed that the serum levels of PIICP, PIIANP, and PIIBNP were significantly different among the three groups. Multiple comparisons using Dunnett's T3 test revealed that serum levels of PIICP, PIIANP, and PIIBNP were significantly lower in KBD patients than in internal and external control. However, there was no significant difference between the internal and external control. CONCLUSIONS: The results preliminarily indicated that the levels of PIICP, PIIANP, and PIIBNP in serum could reflect the abnormal synthesis of type II collagen in KBD patients and suggested that these indicators might be used as potential biomarkers for the diagnosis of KBD.

The characteristics of positive and confusing hand X-ray signs in diagnosing Kashin-Beck Disease in children in China.

When screening for Kashin-Beck disease (KBD) in children, hand X-ray examination is the most important measure. However, there is high rate of misdiagnosis because of confusing X-ray signs. We studied the characteristics of positive and confusing hand X-ray signs. Clinical and radiological examinations were conducted in all 7- to 12-year-olds in selected villages from some KBD and non-KBD areas. We analysed the radiological and epidemiological characteristics of the X-ray signs of KBD and the confusing signs. Images from 3,193 children were valid. No cases of KBD were found. Seventeen children (0.53%) had X-ray signs positive for KBD. The confusing X-ray signs included closure reaction of metaphysis-epiphysis (CRME, 14.28%), thumb variation (0.22%), little finger variation (8.89%), the second metacarpal-phalangeal variation (0.13%) and cystic change (3.85%). The onset of CRME in children occurred earlier in girls (9) than in boys (10). The onset occurred earlier in KBD areas (9) than in non-KBD areas (10). The onset occurred earlier in Han children (9) than in Tibetan children (11). In summary, KBD was effectively controlled in all investigated KBD endemic villages, and the age range should be adjusted to 7- to 11-year-olds in Han children to reduce the misdiagnosis rates in KBD surveillance.

Accidental or linked: separated odontoid process fused to the enlarged anterior arch of the atlas associated with atlantoaxial subluxation in a Kashin-Beck disease patient.

PURPOSE: KBD is an endemic disease affecting the epiphyseal growth plate and articular cartilage of multiple joints, resulting in extremities' deformation and skeletal dysplasia. More attention has been paid to the visible deformed extremities instead of inconspicuous spinal condition. There is a lack of reports concerning the spinal radiological features, especially for the atlantoaxial joint. The aim of this paper is to report a case of a Kashin-Beck disease (KBD) patient diagnosed with atlantoaxial subluxation, concomitant with separated odontoid process fused to the enlarged anterior arch of the atlas. METHODS: We report the case of a 60-year-old woman with 54 years' history of KBD complaining of occipitocervical pain, decreasing motor strength and sensory function of both upper and lower extremities. Subsequent radiological examinations of lateral plain radiography, computed tomography scans and magnetic resonance imaging were performed to reveal these rare characteristics of atlantoaxial joint in this patient. Then, we review the associated articles to postulate whether this anomaly is accidental or linked in a KBD patient. RESULTS: She had an extremely rare variant with three aspects of characteristics: atlantoaxial subluxation concurrent with severe spinal canal stenosis and spinal cord compression, odontoid process separating from the body of axis, and the enlarged anterior arch of the atlas fusion with odontoid process. Comparing with the congenital anomaly of atlantoaxial joint, we postulated that this aetiology of anomaly might be linked to the acquired form attributed to the histopathology of KBD, rather than an accidental event. CONCLUSIONS: The anomaly of atlantoaxial joint might occur in KBD patients. Larger numbers of KBD candidates with earlier symptoms are recommended for radiological examinations of atlantoaxial joint, especially for the adolescents. Spinal surgeons are suggested to involve the research of the spinal anatomy and variation for the prevention and earlier therapy for KBD patients.

Staged total knee arthroplasty for bilateral complex knee deformities from Kashin-Beck disease and skeletal dysplasia.

This study reported two cases of patients with Grade III Kashin-Beck disease (KBD) with skeletal dysplasia concomitant with complex knee deformity and functional limitation treated by staged total knee arthroplasty (TKA). Detailed pre-operative planning, bone resection, and soft tissue balancing in affected knees were performed in the surgeries in this report. The results demonstrated that TKA could correct lower limb alignment, alleviate knee pain, improve function, and provide good quality of life in people with KBD. Surgical efficacy is still lower compared with treatment for osteoarthritis; contributing factors include weak muscle strength, severe deformity and unequal length of the lower limb, weak extensor apparatus of the knee, and patient-specific factors.

Total hip replacement in adult patients with severe Kashin-Beck disease of the hip.

BACKGROUND: The treatment of elderly patients with Kashin-Beck disease (KBD) remains clinically challenging, and clinical data are very lacking. The aim of this study was to retrospectively evaluate pain and functional outcomes following total hip replacement in adult patients with severe KBD of the hip. METHODS: Twenty-two patients (32 hips) with KBD underwent primary hip replacement and were followed for at least 2 years. Radiographic and Clinical assessments were evaluated for each patient at 2 and 4 weeks and at 3, 6 and 12 months after the operation and annually thereafter. The efficacy index included the visual analogue scale (VAS) score, Harris hip score, functional score for adult Tibetans with Kashin-Beck Disease (FSAT-KBD) and radiographic outcomes. RESULTS: The patients underwent a follow-up, and the mean follow-up time was 3.8 years. VAS scores significantly decreased within the first 6 months postoperatively. This decrease continued until the final follow-up (p < 0.01). This result was supported by a significant increase in the Harris and FSAT-KBD scores after the surgery (p < 0.01). At the final follow-up, there was no change in prosthesis positioning or radiographic evidence of prosthesis loosening. One case received impacted allograft bone croutons and had worn polyethylene components replaced after 6 years because the patient suffered severe pelvic and femoral osteolytic lesions postoperatively. CONCLUSIONS: Hip replacement can relieve pain and improve joint function in treating severe KBD hip. Additional studies that are more extensive are needed to confirm the findings of our study.

Radiographic features of hand osteoarthritis in adult Kashin-Beck Disease (KBD): the Yongshou KBD study.

OBJECTIVE: Kashin-Beck Disease (KBD) is a rare and severe osteoarthropathy endemic to China. We evaluated the frequency and patterns of hand radiographic osteoarthritis (rOA) in adults with and without KBD. METHODS: Han Chinese (N = 438) from Yongshou County of central China underwent right hand radiography for determining case status. Presence of KBD was based on characteristic radiographic deformities of articular ends of bones including articular surface depression, carpal crowding, any subchondral bone deformities in the proximal end of phalanges or first metacarpal bone, or the distal ends of metacarpal bones 2-5, and any bony enlargement with deformity of the distal ends of phalanges. Hand rOA severity was determined by osteophyte (OST), joint space narrowing (JSN), and Kellgren and Lawrence (KL) grades. RESULTS: This study included 127 KBD and 311 non-KBD adults of similar mean age (39 years) and body mass index (BMI) (21 kg/m(2)). Inter- and intra-rater reliability for radiographic determination of case status and rOA features was high (kappa 0.72-0.96). Compared to non-KBD, KBD adults had significantly more severe hand rOA of the thumb, distal interphalangeal (DIP), proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints. Only KBD adults had end-stage carpometacapal (CMC) disease. In KBD, DIPs and PIPs were more affected than MCPs and the frequency of OSTs was significantly higher in PIPs than DIPs. CONCLUSIONS: Compared with age-matched adults from the same area and farming occupation, KBD hand rOA was more widespread and severe, particularly of PIPs and CMCs. The ability to differentiate adult KBD from non-KBD hand rOA will facilitate genetic analyses of the vast majority of affected individuals.

X-ray image characteristics and related measurements in the ankles of 118 adult patients with Kashin-Beck disease.

BACKGROUND: Kashin-Beck disease (KBD) is a chronic, degenerative osteoarthropathy that causes severe skeletal deformation. Although many researchers have proven that almost all KBD patients who showed an increaseing proximo-distal gradient had radiographic abnormalities of the ankle, few detailed description of radiographic changes in the ankles of patients with KBD has been reported, especially for variable measurements of ankle changes. The purpose of this study was to demonstrate the radiographic characteristics of the ankles of adult KBD patients. METHODS: One hundred and eighteen adult KBD patients from september to October 2010 in Rongtang county in China were examined with lateral radiographs of the right ankle. The morphological abnormalities in the talus, calcaneus, navicular bone, distal tibia, and joint space were analyzed, and the calcaneus length, height, length-height ratio, tuber angle, front angle, plantar angle, and distal tibia anteroposterior (AP) length were measured using Riepert's method. RESULTS: Eighty-one patients (68.6%) had abnormal ankle radiographs; 72 (88.9%) patients had talus changes, 69 (85.2%) patients had calcaneus changes, 28 (34.6%) patients had navicular bone changes, and 48 (59.2%) patients had distal tibia changes. For 118 KBD patients, the average calcaneus length was 7.4 cm, height was 4.3 cm, and the length-height ratio was 1.7. The calcaneus tuber angle was 28.2°, front angle was 38.0° and the plantar angle was 74.2°. The distal tibia anteroposterior length was 4.05 cm. Compared with 50 normal adults (control group), significant differences were found for the calcaneus length, the calcaneus length-height ratio, and the distal tibia AP length. CONCLUSIONS: Patients with KBD have characteristic abnormalities on ankle radiographs; talus depression and deformity, calcaneus shortening deformity, and distal tibia deformity with AP length widening were the most typical changes.

Gene expression analysis suggests bone development-related genes GDF5 and DIO2 are involved in the development of Kashin-Beck disease in children rather than adults.

OBJECTIVE: To investigate the differences in gene expression between children and adults with Kashin-Beck disease (KBD). METHODS: 12 children with KBD and 12 healthy children were selected and divided into 4 KBD vs. control pairs matched according to age and gender, with each pair having 3 KBD children and 3 healthy children. Additionally, 15 adults with KBD and 15 healthy adults were selected and divided into 5 KBD vs. control pairs matched according to age and gender, with each pair having 3 KBD adults and 3 healthy adults. Total RNA was isolated from peripheral blood mononuclear cells (PBMCs) respectively. A total of 367 target genes were selected based on previous genome-wide gene expression profile analysis. Expression levels of the 367 genes were evaluated by customized oligonucleotide microarray and the differentially expressed genes were identified. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was conducted to validate the microarray data. RESULTS: A total of 95 (25.9%) genes in KBD children and 158 (43.1%) genes in KBD adults were found to exhibit more than two-fold change in gene expression level relative to healthy controls. By comparing differentially expressed genes identified in KBD children to those of KBD adults, 42 genes were found to be differentially expressed only in KBD children. And 105 genes were found to be differentially expressed only in KBD adults. Further, 16 differentially expressed genes common to both KBD children and adults were found to be asynchronously expressed in KBD children compared to KBD adults. CONCLUSION: Significant differences in gene expression pattern were identified between KBD children and KBD adults, indicating different molecular mechanisms underlying cartilage lesions of KBD children and KBD adults. In addition, bone development-related genes GDF5 (expression ratio = 2.14±0.02) and DIO2 (expression ratio = 0.11±0.05) may contribute to the development of KBD in children rather than in adults.

Association of clinical features of bone and joint lesions between children and parents with Kashin-Beck disease in Northwest China.

We investigated the clinical features of bone and joint lesions in children with Kashin-Beck disease (KBD) and the association of these features with their parents to determine specific clinical features for diagnosing KBD. A total of 2,248 children (4 to 18 years old) and their parents were examined by stratified cluster sampling from 33 villages in six endemic counties and from six villages in a non-endemic county. We collected individual information, clinical symptoms, and radiological signs of the right hand. KBD in children and their parents was assessed using the "Diagnosis Criteria of Kashin-Beck disease in China (WS/T207-2010)." Univariate and multivariate analyses were used to examine the correlation of clinical features between parents and offspring with KBD. The rates of clinical features in children were correlated with those in parents (P < 0.01). The parents of child cases had higher rates of clinical features than the parents of child controls. The prevalence of radiographic alterations in the distal end of the phalanges in the parents of child cases was significantly higher than that in the parents of child controls (father, χ (2) = 14.83, P = 0.001; mother, χ (2) = 10.41, P = 0.001). The parents of child cases were more likely to be KBD cases than the parents of controls (adjusted odds ratio, 4.4-12.1). Recognizing significant correlations in clinical features between children and their parents with KBD is helpful for early clinical diagnosis and evaluation of disease severity. Some clinical features of KBD, such as radiographic alterations in the distal end of the phalanges, might be useful for diagnosing KBD.

Clinical features of Kashin-Beck disease in adults younger than 50 years of age during a low incidence period: severe elbow and knee lesions.

More than one million people are affected by Kashin-Beck disease (KBD) in a limited endemic area. However, few studies focused on the clinical features of adult KBD patients. The aim of this study was to investigate the clinical features of adult KBD patients who were younger than 50 years of age during a low incidence period. A special questionnaire was designed that surveyed general data, clinical symptoms, and signs and included the Visual Analogue Scale (VAS). Anthropometrics, the joint VAS, the range of joint motion (ROM), and joint function were measured. The VAS and joint dysfunction were compared among the different joints of extremities, and the relationship among the VAS, ROM, age, course of KBD, and number of enlarged knee and elbow joints elbow was analyzed. Two hundred forty-nine adult Tibetan KBD patients, matched with 249 healthy control subjects, have been surveyed. The VAS results show that the knee is the joint associated with the most pain, followed by the elbow. The elbow shows a higher percentage of limited ROM (47.0 %). The number of enlarged joints has a significant correlation with the VAS or elbow and knee ROM compared with the age or course of disease (P < 0.05). Severe elbow and knee lesions are important clinical features of KBD in adults younger than 50 years of age during a low incidence period. The number of enlarged joints can partially predict the VAS or ROM of elbow and knee and may be used for evaluating the patient's condition and function.

Sodium selenite for treatment of Kashin-Beck disease in children: a systematic review of randomised controlled trials.

OBJECTIVE: To assess the effectiveness and safety of sodium selenite in treatment of patients with Kashin-Beck disease (KBD). METHODS: We searched for all publications between January 1966 and October 2011 using seven electronic databases. All randomized controlled trials (RCTs) assessing the effects of sodium selenite on KBD vs no treatment or placebo were included. For dichotomous data, odds ratios (OR) and 95% confidence intervals (CI) were estimated according to the intention-to-treat principles. For continuous data, mean difference (MD) was used for outcomes pooled on the same scale. RESULTS: A total of 10 RCTs involving 2244 patients were included. The methodological quality of the included studies was low. When comparing the outcome of sodium selenite treatment group vs the control group, the OR of repairing rate of metaphyseal lesions was 5.63 (95% CI: 3.67-8.63) and repairing rate at the distal end of phalanges was 2.98 (95% CI: 1.32-6.70) based on X-ray assessment, which was statistically significant difference in favour of sodium selenite. In one RCT which reported data on clinical improvement, no statistically significant difference was observed in the treatment vs control group (OR 1.50, 95% CI: 0.43-5.30). Se content in hair was (MD 0.11, 95% CI: 0.09-0.13) which was statistically significant higher in selenium group. CONCLUSIONS: Current evidence suggests that sodium selenite is more effective than placebo or no treatment in patients with KBD. However, the evidence was limited by potential biases; thus, further high quality large-scale RCTs are still needed to evaluate the short term and long term effects of selenium.

Kashin-Beck disease in Sichuan, China: report of a pilot open therapeutic trial.

OBJECTIVE: The objective of the study was to identify adults with symptomatic Kashin-Beck disease (KBD) and observe the efficacy and safety of diclofenac sodium, naproxen, and glucosamine hydrochloride in these adult patients in Rang-tang (Sichuan Province), China. SUBJECTS AND METHODS: One hundred eighty-three adult patients with KBD were enrolled into this open study. Patients were randomized to receive diclofenac sodium 50 mg twice a day (BID), naproxen 300 mg BID, or glucosamine hydrochloride 750 mg BID for 6 weeks. The primary efficacy parameters evaluated were the visual analog pain scale, Western Ontario and McMaster Universities Osteoarthritis Index, and physical function subscores. Assessment of daily self-care activities and physician and patient global overall efficacy were also recorded. RESULTS: Diclofenac sodium, naproxen, and glucosamine hydrochloride all reduced the joint pain and improved physical function and daily self-care activities in adult patients with KBD. Visual analog pain scale scores, Western Ontario and McMaster Universities Osteoarthritis Index pain scores, physical function scores, and daily self-care activities subscore differences were statistically significant compared with baselines (P < 0.05). Comparison studies among the 3 agents showed no statistically significant difference in efficacy. The incidences of gastrointestinal adverse reactions were 18% and 14% in the diclofenac sodium group and the glucosamine hydrochloride group, respectively, which tended to be lower than the naproxen group (29%). However, the differences were not statistically significant. CONCLUSIONS: This report documents characteristic findings in these patients. Diclofenac sodium, naproxen, and glucosamine hydrochloride produced substantial improvements over baseline in pain relief, physical function, and daily self-care activities in these open observations of adult patients with KBD.