Outcomes of ankle arthrodesis in adult patients with ankle osteoarthritis in Kashin-Beck disease.

PURPOSE: We retrospectively evaluated the characteristics of these patients and the effectiveness of ankle arthrodesis in the treatment of ankle arthritis caused by Kashin-Beck disease (KBD). METHODS: A retrospective study of KBD patients with ankle osteoarthritis who underwent ankle arthrodesis between December 2012 and January 2022 was performed. A total of 46 patients were included. The general characteristics, clinical manifestations and imaging features of the patients were recorded and summarized. measured using the VAS score, and ankle function was assessed by the AOFAS ankle-hindfoot score. RESULTS: Multiple subchondral cystic changes were found in 42(91.3%) patients. The VAS scores for both resting and weight-bearing conditions were 6.28 ± 1.30 vs. 2.09 ± 1.12 (P < .001) and 6.87 ± 1.01 vs. 2.17 ± 0.98 (P < .001), respectively. The AOFAS scores were 59.17 ± 5.50 and 88.39 ± 1.42, respectively (P < .001). CONCLUSIONS: The subchondral multiple cystic transformation of the ankle KBD has a certain suggestive role.Arthrodesis is an effective method to reduce ankle pain and improve ankle function in KBD patients with ankle osteoarthritis.

A study on atypical Kashin-Beck disease: an endemic ankle arthritis.

BACKGROUND: To study the epidemiological characteristics of atypical Kashin-Beck disease cases without characteristic hand lesions such as interphalangeal joint enlargement and brachydactyly and the characteristics of ankle joint lesions. METHODS: We investigated Kashin-Beck in the endemic villages in Heilongjiang Province. The patients were judged according to the "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010). The severity of foot lesions was judged based on the changes of X-ray images. Residents of non-Kashin-Beck disease area were selected as normal controls in Jilin Province. RESULTS: A total of 119 residents over 40 years old were surveyed in a natural village in the non-endemic area. A total of 1190 residents over 40 years old were surveyed in 38 endemic areas of Kashin-Beck disease. A total of 710 patients with Kashin-Beck disease were detected, including 245 patients with grade I, 175 patients with grade II, 25 patients with grade III, and 265 atypical patients. Among all investigated patients, 92.0% (653/710) had ankle joint changes, and it was 80.0% (196/245) in grade I patients and 95.4% (167/175) in grade II. Varying degrees of ankle joint changes were found in both grade III and atypical patients. The grade of Kashin-Beck disease was correlated with the degree of ankle joint change (P < 0.001), and the correlation coefficient rs = 0.376. Atypical Kashin-Beck disease patients in mild and severe endemic area of Kashin-Beck disease were younger than those with typical Kashin-Beck disease. CONCLUSIONS: We found a correlation between the degree of ankle joint change and the grade of Kashin-Beck disease. The higher the grade of Kashin-Beck disease, the more serious the change of the ankle joint.

Growth surveillance indices and Kashin-Beck Disease in children.

Selenium, manganese, and calcium are necessary elements for maintaining normal growth and skeleton formation. Kashin-Beck disease mostly occurs in children, resulting in deformities, dwarfism, and disabilities. Selenium deficiency was considered a risk factor in China, while manganese was reportedly involved in it in Russia. Single-element regulation cannot be used in diagnosis because of unclear boundaries in patients compared to healthy individuals. In this study, new indices of elements were designed to predict the status of disease. MS (Mn/Se), CS (Ca'/Se), and MC (Mn/Ca') values were designed, and prediction formulas were generated by comparing healthy children with those with Kashin-Beck disease via multiple linear regression analysis and discriminant analysis. In the disease group, 42.86% of patients had positive MS, CS, and MC values, and 57.14% of patients had positive MS and CS values. In the treatment group, the patients presented improved indices. In the prediction group, subjects with negative clinical criteria features were predicted by new indices, and 26.67% of them presented with positive MS, CS, and MC values, whereas 40.00% had positive MS and CS values. The 3D model of MS, CS, and MC refers to the setup of elements. The MS, CS, and MC indices are helpful in disease prediction, diagnosis, prognosis, and surveillance. The distribution model of the indices could serve in the growth surveillance of children.

Polymorphism of MMP-3 gene and imbalance expression of MMP-3 / TIMP-1 in articular cartilage are associated with an endemic osteochondropathy, Kashin- Beck disease.

BACKGROUND: The etiology of Kashin-Beck disease (KBD), an endemic osteochondropathy, is largely unknown. Matrix metalloproteinase-3 (MMP-3) plays a central role in the initiation and progression of cartilage destruction, however, no study has reported on the relationship between KBD and MMP-3. The objective of this study was to explore the polymorphism of MMP-3 gene and expression of MMP-3 / TIMP-1(Tissue inhibitors of matrixmetalloproteinases-1) in the pathogenesis of KBD. METHODS: Single nucleotide polymorphism (SNP) genotyping was conducted in 274 KBD cases and 248 healthy controls for eight SNPs in MMP-3 using the Sequenom MassARRAY system. Additionally, the expression of MMP-3、TIMP-1 in different layers of the articular cartilage was analyzed by immunohistochemistry for 22 KBD patients, 15 osteoarthritis (OA) patients and 21 controls. RESULTS: The results showed that six SNPs (rs520540、rs591058、rs679620、rs602128、rs639752 and rs678815) in MMP-3 were associated with the increased risk of KBD, however, after Bonferroni correction, only the SNP rs679620 in the recessive model remained significant difference (OR = 2.31, 95%CI = 1.29-4.14, P = 0.0039), homozygous for "T" allele have a risk for KBD than "C" allele carriers. Moreover, the percentages of cells expressing MMP-3 in articular cartilage were significantly higher in the KBD and OA groups than in the controls (t = 5.37 and 4.19, P<0.01). While the KBD and OA groups had lower levels of TIMP-1 positive staining compared with the controls (t = 5.23and 5.06, P<0.01). And there was no significant different between KBD and OA for the levels of MMP-3 and TIMP-1 positive staining (t = 0.05and 0.28, P>0.05). CONCLUSIONS: MMP-3 is associated with the susceptibility of KBD, and the imbalance expression of MMPs / TIMPs leading to cartilage degradation may play an important role in cartilage degradation and osteoarthritis formation in OA and KBD.

Comparison of the major cell populations among osteoarthritis, Kashin-Beck disease and healthy chondrocytes by single-cell RNA-seq analysis.

Chondrocytes are the key target cells of the cartilage degeneration that occurs in Kashin-Beck disease (KBD) and osteoarthritis (OA). However, the heterogeneity of articular cartilage cell types present in KBD and OA patients and healthy controls is still unknown, which has prevented the study of the pathophysiology of the mechanisms underlying the roles of different populations of chondrocytes in the processes leading to KBD and OA. Here, we aimed to identify the transcriptional programmes and all major cell populations in patients with KBD, patients with OA and healthy controls to identify the markers that discriminate among chondrocytes in these three groups. Single-cell RNA sequencing was performed to identify chondrocyte populations and their gene signatures in KBD, OA and healthy cells to investigate their differences as related to the pathogenetic mechanisms of these two osteochondral diseases. We performed immunohistochemistry and quantitative reverse-transcription PCR (qRT-PCR) assays to validate the markers for chondrocyte population. Ten clusters were labelled by cell type according to the expression of previously described markers, and one novel population was identified according to the expression of a new set of markers. The homeostatic and mitochondrial chondrocyte populations, which were identified by the expression of the unknown markers MT1X and MT2A and MT-ND1 and MT-ATP6, were markedly expanded in KBD. The regulatory chondrocyte population, identified by the expression of CHI3L1, was markedly expanded in OA. Our study allows us to better understand the heterogeneity of chondrocytes in KBD and OA and provides new evidence of differences in the pathogenetic mechanisms between these two diseases.

The integrative analysis of DNA methylation and mRNA expression profiles confirmed the role of selenocompound metabolism pathway in Kashin-Beck disease.

Kashin-Beck disease (KBD) is an endemic chronic osteochondropathy. The etiology of KBD remains unknown. In this study, we conducted an integrative analysis of genome-wide DNA methylation and mRNA expression profiles between KBD and normal controls to identify novel candidate genes and pathways for KBD. Articular cartilage samples from 17 grade III KBD patients and 17 healthy controls were used in this study. DNA methylation profiling of knee cartilage and mRNA expression profile data were obtained from our previous studies. InCroMAP was performed to integrative analysis of genome-wide DNA methylation profiles and mRNA expression profiles. Gene ontology (GO) enrichment analysis was conducted by online DAVID 6.7. The quantitative real-time polymerase chain reaction (qPCR), Western blot, immunohistochemistry (IHC), and lentiviral vector transfection were used to validate one of the identified pathways. We identified 298 common genes (such as COL4A1, HOXA13, TNFAIP6 and TGFBI), 36 GO terms (including collagen function, skeletal system development, growth factor), and 32 KEGG pathways associated with KBD (including Selenocompound metabolism pathway, PI3K-Akt signaling pathway, and TGF-beta signaling pathway). Our results suggest the dysfunction of many genes and pathways implicated in the pathogenesis of KBD, most importantly, both the integrative analysis and in vitro study in KBD cartilage highlighted the importance of selenocompound metabolism pathway in the pathogenesis of KBD for the first time.

A comparative study of clinical effect of total knee arthroplasty in the treatment of primary osteoarthritis and osteoarthritis of Kashin-Beck disease.

OBJECTIVE: To evaluate the clinical efficacy of total knee arthroplasty (TKA) in the treatment of primary osteoarthritis (OA) and osteoarthritis of Kashin-Beck disease (KBD). METHODS: This study enrolled 77 KBD patients (77 knees, KBD-TKA) and 75 OA patients (75 knees, OA-TKA) who underwent TKA from September 2008 to June 2018. Clinical assessments for each patient were performed pre-operatively and last follow-up. The efficacy measures included the visual analogue scale (VAS) pain score, range of motion (ROM), Hospital for Special Surgery (HSS) score, and short form 36 Health Survey (SF-36) as well as related influencing factors between the two groups. RESULTS: All patients were followed up; the follow-up time of KBD-TKA was 14-132 months, with an average of 72.68 ± 37.55 months; OA-TKA was 15-120 months, with an average of 49.2 ± 28.91 months. There was no difference in pre-operative VAS score (7.29 vs. 7.24) and SF-36 (PCS) score (4.87 vs. 5.49) between KBD-TKA and OA-TKA (P > 0.05), while compared with OA, KBD-TKA had significantly worse pre-operative ROM (75.48° vs. 82.87°), HSS score (36.40 vs. 41.84), and SF-36 (MCS) score (26.28 vs. 28.73) (P < 0.05). At the final follow-up, there was no significant difference in VAS score (1.13 vs. 1.16), ROM (105.79 vs. 105.79), and HSS score (92.06 vs. 92.25) between KBD-TKA and OA-TKA (P > 0.05), while compared with OA, KBD-TKA had significantly worse SF-36 (PCS) score (36.90 vs. 42.00) and SF-36 (MCS) score (55.16 vs. 59.70) (P < 0.05). In a multivariate regression, controlling for multiple potential confounders, diagnosis of KBD was associated with poor quality of life after surgery, whereas pre-operative pain was specifically associated with post-operative pain. However, preoperative gender, age, BMI, and the angles of knee prosthesis (before and after surgery) were not associated with post-operative outcome. CONCLUSION: Patients with KBD undergoing primary TKA have excellent outcomes, comparable with OA at the final follow-up, in spite of worse pre-operative ROM, HSS score, and SF-36(MCS) score. However, KBD patients are worse than OA in terms of general health. Pre-operative age, gender, BMI, and the angles of knee prosthesis were not the factors influencing the clinical efficacy of TKA. The diagnosis of KBD was an independent risk factor for poor quality of life after TKA. Pre-operative pain was a clinically important predictor of outcome.

Comparison of the responsiveness of the WOMAC and the 12-item WHODAS 2.0 in patients with Kashin-Beck disease.

BACKGROUND: Several questionnaires have been used to assess the health status of patients with Kashin-Beck disease (KBD) in clinical trials, but the evidence regarding the responsiveness of these instruments in KBD patients is limited. Therefore, the aim of this study was to evaluate and compare the responsiveness of the Chinese version of the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) in KBD patients undergoing intra-articular injection of hyaluronic acid (HA). METHODS: A sample of 232 KBD patients treated with intra-articular injection of HA completed the WOMAC, 12-item WHODAS 2.0 and joint dysfunction index (JDI) both pre- and post-treatment. Responsiveness was assessed using correlation and receiver operating characteristic (ROC) curve analyses following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. RESULTS: Overall, there were significant improvements in the mean scores on the WOMAC and on the 12-item WHODAS 2.0, except for in the cognition domain. Correlation analysis showed that changes in the WOMAC and 12-item WHODAS 2.0 scores had moderate or weak positive associations with the changes in the JDI. However, acceptable areas under the ROC curve (value > 0.7) were found for all domains and for the total score on the WOMAC, but only for the mobility domain and the total score on the 12-item WHODAS 2.0. CONCLUSIONS: These results demonstrated that the WOMAC was more responsive than the 12-item WHODAS 2.0 in KBD patients treated with intra-articular injection of HA. Our findings support the continued use of the WOMAC as an outcome measure in assessing disability in KBD patients.

The urinary levels of CTX-II, C2C, PYD, and Helix-II increased among adults with KBD: a cross-sectional study.

BACKGROUND: Kashin-Beck disease (KBD) is an endemic osteoarthropathy, and its pathogenesis is still not entirely clear. Pathologically, many KBD changes are similar to those of osteoarthritis (OA). Therefore, this study aimed to identify changes in the levels of potential urinary biomarkers for OA, including C-telopeptide of type II collagen (uCTX-II), type II collagen cleavage neoepitope (uC2C), pyridinoline (uPYD), and uHelix-II, among adults with KBD. METHODS: Urinary samples of 83 external control (EC) subjects, 91 KBD patients, and 86 internal control (IC) subjects were tested by ELISA after the subjects completed a questionnaire and X-ray examination. RESULTS: The medians of the four markers in the KBD group were higher than those in the EC group and those in the IC group. The medians in the grade II KBD group were higher than those in the grade I group but were not statistically significant (P = 0.301, P = 0.408, P = 0.204, and P = 0.898 for uCTX-II, uC2C, uPYD, and uHelix-II, respectively). The area under the curve (AUC) of uCTX-II (0.775) was higher than that of the others (0.672, 0.639, and 0.628 for uC2C, uPYD, and uHelix-II, respectively). CONCLUSION: The levels of uCTX-II, uC2C, uPYD, and uHelix-II were elevated in adults with KBD and showed an increasing trend as the severity of KBD increased. The prediction accuracy of uCTX-II was more useful than that of the others for assisting in the diagnosis of KBD.

Conservative tibiotalocalcaneal fusion for partial talar avascular necrosis in conjunction with ankle and subtalar joint osteoarthritis in Kashin-Beck disease: A case report.

RATIONALE: Kashin-Beck disease (KBD) is known for some typical characters like finger joint enlargement, shortened fingers, and dwarfism. However, Avascular necrosis (AVN) of the talus in KBD has rarely been reported in the literature. Here, we reported on a KBD patient presented with partial AVN of the talus in conjunction with ankle and subtalar arthritis. PATIENT CONCERNS: A 50-year-old woman presented with severe pain and limited range of motion in her left ankle and subtalar joint while walking for 2 years. She had been walking with the aid of crutches for many years. Conservative treatment with rigid orthosis and activity restriction could not help reduce the pain in the left foot. DIAGNOSES: Radiographs demonstrated that partial AVN was developed in the body of the talus and arthritis was viewed in the left ankle and subtalar joint. Hence, we established the diagnosis of partial talar AVN in conjunction with ankle and subtalar arthritis. INTERVENTIONS: A conservative tibiotalocalcaneal fusion attempting to preserve as much viable talar body as possible was performed using a humeral locking plate and 2 cannulated compression screws. OUTCOMES: Bone union proved by CT scan and a good alignment of the left limb were achieved at 4-month follow-up postoperatively. LESSONS: Partial AVN of the talus along with ankle and subtalar arthritis in KBD patients has rarely been reported as it is not a common characteristic of KBD in clinical practice. Conservative tibiotalocalcaneal fusion could help preserving much more viable talar body, maintaining most structural integrity of the ankle joint, and achieving a stable and plantigrade foot postoperatively.

The levels of urine CTX-II, C2C, and PYD in children patients with Kashin-Beck disease in Qinghai Province of China.

BACKGROUND: Kashin-Beck disease (KBD) is an endemic and chronic osteoarthropathy. At present, the diagnosis of KBD mainly depends on the X-ray examination and which could not reflect early damage of cartilage sensitively. So, the aim of this study was to find effective and sensitive biomarkers for early diagnosis of pediatric KBD. METHODS: A total of 122 children aged 7-15 years old from 3 villages of Qinghai Province were eligible for the study. Thirty-one, 41, and 50 children were assigned in case, internal, and external control groups, respectively. The levels of CTX-II, C2C, and PYD in urine were measured by using ELISA and compared statistically. In addition, the receiver operating characteristic curve (ROC) analysis was used to assess the performance of diagnostic biomarkers. RESULTS: There were significant differences in levels of CTX-II, C2C, and PYD in urine of subjects among three groups. The levels of CTX-II and PYD in the case group were significantly higher than those in external and internal control groups. On the contrary, the level of C2C in the case group was lower than that in the external control group. Compared to the external control group, the area under the curve (AUC) of CTX-II, C2C, and PYD were 0.857, 0.837, and 0.79, and the AUC of CTX-II significantly higher than that of PYD. Compared to the internal control group, the AUC of CTX-II, C2C, and PYD were 0.911, 0.875, and 0.839, and there were no significant differences in the AUC among three indicators. CONCLUSION: Both CTX-II and PYD in urine could be used as biomarkers for early diagnosis of pediatric KBD, and the prediction accuracy of CTX-II was relatively superior.

Long-term efficacy of repeated sodium hyaluronate injections in adult patients with Kashin-Beck disease of the knee.

AIM: To prospectively evaluate the long-term efficacy and safety of repeated sodium hyaluronate injections for the treatment of knee pain due to Kashin-Beck disease (KBD). METHODS: A total of 85 patients with KBD-based knee pain were treated with two cycles of a 5-week course of sodium hyaluronate and received clinical assessments with a follow-up period of 24 months after the first cycle. The primary efficacy measure was the visual analogue scale (VAS) pain score. The second efficacy measure included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores; and the patients' and physicians' global assessments. Tolerability was evaluated based on adverse events (AEs). RESULTS: Seventy-one patients (83.5%) completed the final study. The VAS was significantly reduced from 65.06 ± 12.21 mm (mean ± standard deviation [SD]) at baseline to 30.17 ± 11.92 mm at 6 months and was maintained for 24 months (35.79 ± 7.92 mm, P < 0.01 vs baseline). This finding was supported by the secondary variables (the WOMAC A, B and C scores; the total WOMAC scores; and the global assessments of the patients and their physicians at months 6, 12, 18 and 24). The overall incidence of AEs during the first and second cycles was 8 (9.4%) and 7 patients (8.2%), respectively. No serious AEs were reported. CONCLUSIONS: Repeated once yearly cycles of intra-articular sodium hyaluronate injections may improve knee KBD symptoms during the inbetween cycle period as well as exert a significant carry-over effect for at least 1 year after the repeated cycle. Other randomized double-blind studies are needed to confirm the findings from our study.

RNA-seq analysis reveals different gene ontologies and pathways in rheumatoid arthritis and Kashin-Beck disease.

AIMS: To understand the pathogenesis of cartilage damage in Kashin-Beck disease (KBD) and rheumatoid arthritis (RA) which similar clinical symptoms. METHODS: RNA sequencing (RAN-seq) analysis was used to reveal the different pathogeneses between KBD and RA. The messenger RNA expression profiles of articular cartilage isolated from KBD patients (n = 3) and RA patients (n = 3) were compared using RNA-seq analysis. Differentially expressed genes (DEGs) were determined using the Benjamini-Hochberg approach. The Database for Annotation, Visualization and Integrated Discovery (DAVID 6.7) was employed to assess functional categories and Gene Ontology (GO). The Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology Based Annotation System (KOBAS 2.0) was used to identify significantly enriched KEGG pathways. RESULTS: In the individually sequenced dataset, we identified 1568 significant DEGs in KBD compared to RA (232 up-regulated genes and 1336 down-regulated genes). GO function analysis identified nine significant biological processes (BPs), eight molecular functions (MFs), and five cell components (CCs) in KBD, and also the top ten ranked significant BPs, MFs and CCs were found in RA. The KEGG pathway enrichment analysis identified biosynthesis of amino acids involved in KBD. The chemokine signaling pathway, nuclear factor-kappa B signaling pathway, B cell receptor signaling pathway, leukocyte transendothelial migration, and osteoclast differentiation were involved in RA. CONCLUSIONS: RNA-seq revealed that proteoglycan-mediated metabolic disorders contributed to the onset of KBD, whereas immune dysregulation was apparently involved in the pathogenesis of RA.

Integrating genome-wide DNA methylation and mRNA expression profiles identified different molecular features between Kashin-Beck disease and primary osteoarthritis.

BACKGROUND: Kashin-Beck disease (KBD) is an endemic osteochondropathy of unknown etiology. Osteoarthritis (OA) is a form of degenerative joint disease sharing similar clinical manifestations and pathological changes to articular cartilage with KBD. METHODS: A genome-wide DNA methylation profile of articular cartilage from five KBD patients and five OA patients was first performed using the Illumina Infinium HumanMethylation450 BeadChip. Together with a previous gene expression profiling dataset comparing KBD cartilage with OA cartilage, an integrative pathway enrichment analysis of the genome-wide DNA methylation and the mRNA expression profiles conducted in articular cartilage was performed by InCroMAP software. RESULTS: We identified 241 common genes altered in both the DNA methylation profile and the mRNA expression profile of articular cartilage of KBD versus OA, including CHST13 (NM_152889, fold-change = 0.5979, P methy = 0.0430), TGFBR1 (NM_004612, fold-change = 2.077, P methy = 0.0430), TGFBR2 (NM_001024847, fold-change = 1.543, P methy = 0.037), TGFBR3 (NM_001276, fold-change = 0.4515, P methy = 6.04 × 10-4), and ADAM12 (NM_021641, fold-change = 1.9768, P methy = 0.0178). Integrative pathway enrichment analysis identified 19 significant KEGG pathways, including mTOR signaling (P = 0.0301), glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate (P = 0.0391), glycosaminoglycan biosynthesis-keratan sulfate (P = 0.0278), and PI3K-Akt signaling (P = 0.0243). CONCLUSION: This study identified different molecular features between Kashin-Beck disease and primary osteoarthritis and provided novel clues for clarifying the pathogenetic differences between KBD and OA.

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.

Detection of the Urinary Biomarkers PYD, CTX-II, and DPD in Patients with Kashin-Beck Disease in the Qinghai Province of China.

Kashin-Beck disease (KBD) is an endemic degenerative osteoarthropathy of uncertain etiology. The aim of our study was to identify changes in C-telopeptide of type II collagen (CTX-II), pyridinoline (PYD), and deoxypyridinoline (DPD) among KBD patients. 54 KBD patients and 78 healthy controls were included this study. Urinary samples were collected and measured by ELISA. The median quantities of PYD, CTX-II, and DPD of KBD patients were 1107.73 ng/µmol.cre, 695.11 ng/µmol.cre, and 1342.34 pml/µmol.cre, while the median quantities of healthy controls were 805.59 ng/µmol.cre, 546.47 ng/µmol.cre, and 718.15 pml/µmol.cre, respectively. The differences between KBD patients and healthy controls were statistically significant (Z = 4.405, 3.653, and 3.724; P < 0.001). The higher levels of PYD, CTX-II, and DPD detected in KBD patients indicate that they could be used as biomarkers of KBD.

Reliability and validity of the 12-item WHODAS 2.0 in patients with Kashin-Beck disease.

The purpose of this study was to check the reliability and validity of the 12-item Chinese version of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) for the assessment of disability in patients with Kashin-Beck disease (KBD). We recruited 219 patients with KBD from the high-risk KBD area in the Shaanxi province, using stratified multistage random sampling. We assessed each patient using the Chinese version of the 12-item WHODAS 2.0 and the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC). Statistical evaluations of the instruments consisted of Cronbach's alpha, intraclass correlation coefficient (ICC), confirmatory factor analysis (CFA), and Pearson's correlation coefficient. Cronbach's alpha and ICC for the six domains ranged from 0.704 to 0.906 and 0.690 to 0.852, respectively. A six-factor structure fits the data well (CFI = 0.967, TLI = 0.944, RMSEA = 0.08). Regarding convergent validity, the four domains of the 12-item WHODAS 2.0 (getting around, self-care, life activity, and participation) showed moderate-to-strong correlation for all three domains of the WOMAC (0.428 < |r| < 0.804). Regarding divergent validity, the two domains of the 12-item WHODAS 2.0 (understanding and communication, and getting along with people) showed weak correlation for the three domains of WOMAC (0.182 < |r| < 0.295). The Chinese version of 12-item WHODAS 2.0 questionnaire is a reliable and valid instrument when administered to KBD patients.

Comparison of microRNA expression profiles of Kashin-Beck disease, osteoarthritis and rheumatoid arthritis.

Kashin-Beck disease (KBD) is a chronic osteochondropathy with unclear pathogeny. In this study, we compared the microRNA expression profiles of 16 KBD patients, 16 osteoarthritis (OA) patients and 16 rheumatoid arthritis (RA) patients and 16 healthy controls in their blood specimens. miRNAs expression profiling was performed using Exiqon miRCURY LNATM miRNAs Array. miRNAs target genes were predicted using miRror suite. Another independent mRNA expression profile dataset of 20 KBD patients and 15 healthy controls were integrated with the miRNA expression profiles of KBD. We identified 140 differently expressed miRNAs in KBD vs. CONTROLS: GO enrichment analysis found that hypoxia, Wnt receptor signaling pathway and vitamin B6 biosynthesis related GO terms were significantly overrepresented in the target genes of differently expressed miRNAs in KBD vs. CONTROL: 18 differently expressed common miRNAs were identified in KBD vs. Control, KBD vs. OA and KBD vs. RA. Integrating the lists of differently expressed miRNA target genes and mRNA differently expressed genes detected 6 common genes for KBD. Our results demonstrated the altered miRNAs expression profiles of KBD comparing to healthy controls, OA and RA, which provide novel clues for clarifying the mechanism of KBD.

Evaluation of the Sensitivity and Specificity of the New Clinical Diagnostic and Classification Criteria for Kashin-Beck Disease, an Endemic Osteoarthritis, in China.

This study aimed to evaluate the sensitivity and specificity of the new clinical diagnostic and classification criteria for Kashin-Beck disease (KBD) using six clinical markers: flexion of the distal part of fingers, deformed fingers, enlarged finger joints, shortened fingers, squat down, and dwarfism. One-third of the total population in Linyou County was sampled by stratified random sampling. The survey included baseline characteristics and clinical diagnoses, and the sensitivity and specificity of the new criteria was evaluated. We identified 3,459 KBD patients, of which 69 had early stage KBD, 1,952 had stage I, 1,132 had stage II, and 306 had stage III. A screening test classified enlarged finger joints as stage I KBD, with a sensitivity and specificity of 0.978 and 0.045, respectively. Shortened fingers were classified as stage II KBD, with a sensitivity and specificity of 0.969 and 0.844, respectively, and dwarfism was classified as stage III KBD with a sensitivity and specificity of 0.951 and 0.992, respectively. Serial screening test revealed that the new clinical classification of KBD classified stages I, II, and III KBD with sensitivities of 0.949, 0.945, and 0.925 and specificities of 0.967, 0.970, and 0.993, respectively. The screening tests revealed that enlarged finger joints, shortened fingers, and dwarfism were appropriate markers for the clinical diagnosis and classification of KBD with high sensitivity and specificity.

Reliability and validation of the joint dysfunction index as a new assessment instrument for therapeutic efficacy for Kashin-Beck disease.

The objective of this study was to evaluate the reliability and validity of the joint dysfunction index (JDI) for assessment of therapeutic efficacy for Kashin-Beck disease (KBD). In an initial survey, completed questionnaires were obtained from 276 of 281 patients (98.2 %). A follow-up survey was completed with 64 KBD patients among 276 cases. A third survey selected 60 KBD patients who underwent intra-articular injection of sodium hyaluronate in the knees ascertained from the findings of the second questionnaire. Reliability was assessed using test-retest, "split-half" reliability and Cronbach's alpha coefficient. Factor analysis and item-to-domain correlation were used to analyze validity. The coefficient of variation (CV) was used to measure the sensitivity of scale. Feasibility assessment included consideration of completion time, rate of recovery, and time of completion. Reliability analysis comprised a test-retest correlation coefficient of 0.404-0.546 and a kappa test of 0.404-0.546. Internal consistency analysis comprised a Cronbach alpha coefficient of 0.689 and a split-half coefficient of 0.677. Principal component factor analysis for validity testing extracted a common factor with a cumulative variance contribution of 45.44 %. The JDI score from 276 KBD cases revealed no significant difference associated with age, gender, education, or the body mass index. Sensitivity analysis showed that there was no significant difference between pre-treatment and post-treatment values, with a CV of 96.55-172.06 %. In conclusion, the JDI can be used to evaluate the efficacy of agents used to treat KBD.