Plasma metabolites and inflammatory proteins profiling predict outcome of Fufang Duzhong Jiangu granules treating Kashin-Beck disease.

To investigate predictive biomarkers that could be used to identify patients' response to treatment, plasma metabolomics and proteomics analyses were performed in Kashin-Beck disease (KBD) patients treated with Fufang Duzhong Jiangu Granules (FDJG). Plasma was collected from 12 KBD patients before treatment and 1 month after FDJG treatment. LC-MS and olink proteomics were employed for obtaining plasma metabolomics profiling and inflammatory protein profiles. Patients were classified into responders and non-responders based on drug efficacy. Enrichment analyses of differential metabolites and proteins of the responders at baseline and after treatment were conducted to study the mechanism of drug action. Differential metabolites and proteins between the two groups were screened as biomarkers to predict the drug efficacy. The receiver operating characteristic curve was used to evaluate the prediction accuracy of biomarkers. The changes in metabolites and inflammatory proteins in responders after treatment reflected the mechanism of FDJG treatment for KBD, which may act on glycerophospholipid metabolism, d-glutamine and d-glutamate metabolism, nitrogen metabolism and NF-kappa B signaling pathway. Three metabolites were identified as potential predictors: N-undecanoylglycine, ß-aminopropionitrile and PC [18:3(6Z,9Z,12Z)/20:4(8Z,11Z,14Z,17Z)]. For inflammatory protein, interleukin-8 was identified as a predictive biomarker to detect responders. Combined use of these four biomarkers had high predictive ability (area under the curve = 0.972).

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.

Roles of glycoprotein glycosylation in the pathogenesis of an endemic osteoarthritis, Kashin­Beck disease, and effectiveness evaluation of sodium hyaluronate treatment

Background/aim: We aimed to explore the roles of glycoprotein glycosylation in the pathogenesis of Kashin­Beck disease (KBD), and evaluated the effectiveness of sodium hyaluronate treatment. Materials and methods: Blood and saliva were collected from KBD patients before and after the injection of sodium hyaluronate. Normal healthy subjects were included as controls. Saliva and serum lectin microarrays and saliva and serum microarray verifications were used to screen and confirm the differences in lectin levels among the three groups. Results: In saliva lectin microarray, bindings to Sophora japonica agglutinin (SJA), Griffonia (Bandeiraea) simplicifolia lectin I (GSL-I), Euonymus europaeus lectin (EEL), Maackia amurensis lectin II (MAL-II), Sambucus nigra lectin (SNA), Hippeastrum hybrid lectin (HHL), and Aleuria aurantia lectin (AAL) were higher in the untreated KBD patients than in the control group. Increased levels of HHL, MAL-II, and GSL-I in the untreated KBD patients discriminated them in particular from the treated ones. Jacalin was lower in the untreated KBD patients compared to the treated KBD and control groups. In serum lectin microarray, HHL and peanut agglutinin (PNA) were increased in the untreated KBD group in comparison to the control one. AAL, Phaseolus vulgaris agglutinin (E+L) (PHA-E+L), and Psophocarpus tetragonolobus lectin I (PTL-I) were lower in the untreated KBD patients compared to the treated KBD and control groups. Hyaluronate treatment appeared to normalize SNA, AAL, and MAL-II levels in saliva, and HHL, PNA, AAL, PTL-I, and PHA-E+L levels in serum. Saliva reversed microarray verification confirmed significant differences between the groups in SNA and Jacalin, in particular for GSL-I levels, while serum reversed microarray verification indicated that HHL, PNA, and AAL levels returned to normal levels after the hyaluronate treatment. Lectin blot confirmed significant differences in HHL, AAL, and Jacalin in saliva, and HHL, PNA, PHA-E+L, and AAL in serum. Conclusion: HHL in saliva and serum may be a valuable diagnostic biomarker of KBD, and it may be used as follow-up for the hyaluronate treatment.

Serious Selenium Deficiency in the Serum of Patients with Kashin-Beck Disease and the Effect of Nano-Selenium on Their Chondrocytes.

To investigate selenium (Se) concentrations in serum of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and Kashin-Beck disease (KBD), together with the effect of Se supplement (chondroitin sulfate [CS] nano-Se [SeCS]) on CS structure-modifying sulfotransferases in KBD chondrocyte. Fifty serum samples from each group with aged-matched (40-60 years), normal control (N), RA, OA, and KBD (25 males and females, respectively) were collected to determine Se concentrations. Furthermore, the KBD chondrocytes were divided into two groups following the intervention for 24 h: (a) non-treated KBD group and (b) SeCS-treated KBD group (100 ng/mL SeCS). The ultrastructural changes in chondrocytes were observed by transmission electron microscopy (TEM). Live/dead staining was used to observe cell viability. The expression of CS-modifying sulfotransferases including carbohydrate sulfotransferase 12, 13, and 15 (CHST-12, CHST-13, and CHST-15, respectively), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction and western blotting analysis after SeCS intervention. The Se concentrations in serum of KBD, OA, and RA patients were lower than those in control. In OA, RA, and control, Se concentrations were higher in male than in female, while it is opposite in KBD. In the cell experiment, cell survival rate and mitochondrial density were increased in SeCS-treated KBD groups. Expressions of CHST-15, or CHST-12, and CHST-15 on the mRNA or protein level were significantly increased. Expression of UST slightly increased on the mRNA level, but no change was visible on the protein level. Se deficiency in serum of RA, OA, and KBD was observed. SeCS supplemented in KBD chondrocytes improved their survival rate, ameliorated their ultrastructure, and increased the expression of CS structure-modifying sulfotransferases.

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.

Effects of five types of selenium supplementation for treatment of Kashin-Beck disease in children: a systematic review and network meta-analysis.

OBJECTIVE: To compare the effectiveness of five kinds of selenium supplementation for the treatment of patients with Kashin-Beck disease, and rank these selenium supplementations based on their performance. DESIGN: We searched for all publications between 1 January 1966 and 31 March 2017 using seven electronic databases. GRADE system to network meta-analyses (NMAs) was applied to rate the quality of the evidence. We conducted a random effects model NMA in STATA 12.1 to determine comparative effectiveness of each intervention. Rankings were obtained by using the surface under the cumulative ranking curve (SUCRA) values and mean ranks. RESULTS: A total of 15 randomised controlled trials involving 2931 patients were included. After assessment of the overall quality of the evidence, we downgraded our primary outcomes from high to low or very low quality. NMAs showed that all five kinds of selenium supplementation had higher metaphysis X-ray improvement which were superior to placebo. Ranking on efficacy indicated that selenium salt was ranked the highest, followed by sodium selenite + vitamin E, selenium enriched yeast, sodium selenite and then sodium selenite + vitamin C. CONCLUSIONS: Based on the results of NMA, all five types of selenium supplements are more effective than placebo and so that selenium supplementation is of help in repairing metaphyseal lesions. Since the overall quality of the evidence was low or very low, the SUCRA values may be misleading and should be considered jointly with the The Grading of Recommendations Assessment, Development and Evaluation (GRADE) confidence in the estimates for each comparison. The quality of the evidence is insufficient to draw a conclusion about what method of selenium supplementation is most effective. PROSPERO REGISTRATION NUMBER: CRD42016051874.

Zinc: the Other Suspected Environmental Factor in Kashin-Beck Disease in Addition to Selenium.

Kashin-Beck disease (KBD) is an endemic chronic osteochondral disease characterized by high prevalence, disability, and morbidity and is distributed from the northeast to the southwest in China, in some regions of Eastern Siberia in Russia, and in North Korea. Although the selenium deficiency etiological hypothesis for KBD has been proposed by scientists for decades, the idea that selenium deficiency is one of the most important environmental factors but not the primary and sole pathogenic factor for KBD has been widely accepted. Zn2+, which is closely involved in the synthesis of enzymes, nucleic acids, and proteins, is an essential microelement in vivo. A conundrum still exists in research on the relationship between Zn2+ and KBD due to inconsistent results, but it has been confirmed that Zn2+ can help repair metaphyseal lesions in patients with KBD, indicating that Zn2+ might play a key role in the pathogenesis of KBD, although the mechanism is unknown. The zinc-ZIP8-MTF1 axis in chondrocytes forms a catabolic cascade that promotes upregulation of the crucial effector matrix-degrading enzymes MMP3, MMP13, and ADAMTS5, thereby leading to osteoarthritis (OA) cartilage destruction. Zinc finger protein-related genes, the ZNT family, and the ZIP family of Zn2+ transporter genes have been found to be differentially expressed in KBD by high-throughput screening. Therefore, Zn2+ could play a key role in the pathogenesis of KBD.

Effect of calcium and vitamin D on growth, rickets and Kashin-Beck disease in 0- to 5-year-old children in a rural area of central Tibet.

OBJECTIVE: To evaluate the effect of calcium (15 mmol/day) and vitamin D (625 µg/month), as single supplement or in combination, vs. no supplement on growth, clinical signs of rickets and Kashin-Beck disease (KBD) and dental health. METHODS: Prospective controlled trial involving children aged 0-5 years living in four groups of villages in a KBD-endemic rural area of central Tibet who received either calcium and/or vitamin D or no supplement. The cohort was followed over 3 years. Primary outcome was the impact of the different supplementation regimes on KBD, rickets and growth; secondary outcomes were impact on urinary levels of calcium and phosphorus, biomarkers of bone and cartilage turnover, and dental health. RESULTS: No difference was observed between the four groups with regard to anthropometric data, rickets, KBD, urinary levels of CrossLaps(®) and CartiLaps(®) . Weight for height or age, mid-upper arm circumference and skinfold thickness decreased in the four groups. Height for age increased and the prevalence of KBD fell in the four groups. Dental health was better in the group receiving calcium and vitamin D. Urinary calcium levels increased after 3 years of follow-up in all groups; the group receiving vitamin D had a higher increase (P-value: 0.044). The same global increase was observed for urinary phosphorus levels; the group receiving calcium had a higher increase (P-value: 0.01). CONCLUSIONS: Calcium and vitamin D failed to improve growth and bone metabolism of children living in a KBD-endemic rural area. Calcium and vitamin D supplementation improved dental health.

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.

The roles of selenium, insulin-like growth factor binding protein 2 and suppressor of cytokine signaling 3 in the pathogenesis of Kashin-Beck disease.

We aimed to verify the levels of IGFBP2 and SOCS3 in cartilage and chondrocytes of Kashin-Beck disease (KBD) patients and the effects of different selenium concentrations on the protein expression levels. Chondrocytes were cultured with sodium selenite in vitro. Immunohistochemistry and western blotting were used to verify the protein expressions. IGFBP2 and SOCS3 were up-regulated in KBD chondrocytes and decreased with increasing selenium concentrations. IGFBP2 expressed highest in the middle zone of KBD cartilage, SOCS3 expressed higher in the middle and deep zone. IGFBP2 and SOCS3 may be the biomarkers for KBD diagnosis and evaluating the effect of selenium supplement.

Hyaluronic acid and glucosamine sulfate for adult Kashin-Beck disease: a cluster-randomized, placebo-controlled study.

To evaluate the efficacy and safety of hyaluronic acid (HA) and glucosamine sulfate (GS) in alleviating symptoms and improving function of Kashin-Beck disease (KBD). A cluster-randomized, placebo-controlled trial was conducted in 150 patients with KBD. Participants were randomly allocated to receive intra-articular injection hyaluronic acid (IAHA) for 4 weeks, oral GS for 12 weeks, or oral placebo for 12 weeks. The primary outcome measures were 20 % and 50 % reductions in pain from baseline measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index. Secondary outcome measures included WOMAC index parameters of pain, stiffness, and physical function. The third outcome measure was mean change in Lequence score. HA and GS were effective in reducing WOMAC pain by 20 % (differences of 43.5 % and 25.4 %) and 50 % (differences of 43.4 % and 26.9 %). Both HA and GS significantly reduced WOMAC pain, WOMAC stiffness, and WOMAC normalized score compared with placebo group (all P < 0.05). IAHA was significantly more effective than oral GS in improving WOMAC normalized score (P = 0.034), pain (P = 0.002), stiffness (P = 0.018), and function (P = 0.044). The results indicate that HA and GS were more effective than placebo in treating KBD and HA was more effective than GS.

Role of inflammation in the process of clinical Kashin-Beck disease: latest findings and interpretations.

Kashin-Beck disease (KBD), a particular type of osteoarthritis (OA), and an endemic disease with articular cartilage damage and chondrocytes apoptosis, can affect many joints, and the most commonly affected joints are the knee, ankle, and hand. KBD has traditionally been classified as a non-inflammatory OA. However, recent studies have shown that inflammation has played an important role in the development of KBD. Nowadays, clinical KBD is not only an endemic disease, but also a combined result of many other non-endemic factors, which contains age, altered biomechanics, joint trauma and secondary OA. The characteristics of the developmental joint failure of advanced KBD, because of the biochemical and mechanical processes, are tightly linked with the interaction of joint damage and its immune response, as well as the subsequent state of chronic inflammation leading to KBD progression. In this review, we focus on the epidemiology, pathology, imaging, cytokines and transduction pathways investigating the association of inflammation with KBD; meanwhile, a wide range of data will be discussed to elicit our current hypotheses considering the role of inflammation and immune activation in KBD development.

The long-term efficacy and tolerability of hyaluronic acid in adult patients with Kashin-Beck disease of the knee.

The aim of this study was to prospectively evaluate the long-term efficacy and tolerability of hyaluronic acid (HA) for the treatment of knee pain due to Kashin-Beck disease (KBD). A total of 113 patients with KBD-based knee pain were treated with a 3-week course of HA. Clinical assessments were performed for each patient at 0 (baseline), 1, 2, 4, 8, 12, 24, and 52 weeks. The primary efficacy measure was the visual analog scale (VAS) pain score. The secondary efficacy measures included the WOMAC A (pain), B (stiffness), and C (function) scores; the total WOMAC score; and the global assessments by patients and physicians. Tolerability was evaluated based on adverse events (AEs) and physician reporting. The VAS was significantly reduced within the first 4 weeks of treatment, and the reduction was maintained over 52 weeks (p < 0.001 at each endpoint). These data were supported by the secondary variables WOMAC A (all p < 0.001), WOMAC B (p = 0.002, 0.003, and 0.019, respectively), WOMAC C (all p < 0.001), total WOMAC (all p < 0.001), and the global assessments by patients and physicians at weeks 12, 24, and 52. No serious AEs were reported, and the overall incidence of AEs was 10.6 %. This study suggests that the intra-articular injection of HA is effective and well tolerated for the treatment of knee pain due to KBD as HA therapy resulted in an improvement of symptoms for at least 52 weeks. Additional randomized double-blind studies are needed to confirm our findings.

Effects of the consumption of rice from non-KBD areas and selenium supplementation on the prevention and treatment of paediatric Kaschin-Beck disease: an epidemiological intervention trial in the Qinghai Province.

OBJECTIVE: Based on the aetiological hypothesis of Kaschin-Beck disease (KBD), different interventions were adopted, and the preventive and therapeutic effects of interventions was observed and evaluated in this trial. DESIGN: A total of 358 children from seven villages of Qinghai Province in China were examined, and 280 children aged 6-11 years old were eligible for the trial. The children were divided into three groups that received either no intervention (n = 64), 150 kg/person of rice from non-KBD areas (n = 103) or 7 kg/family of selenium-iodine salt (n = 113) for 12 months. Data were collected and used to calculate the proportion of patients with X-ray lesions, the proportion of new patients and the metaphyseal repair rate. All indicators were analysed with Pearson chi-square or Fisher's exact tests. The registration number of this trial is ChiCTR-PNRC-12002309 (http://www.chictr.org). RESULTS: After interventions, the proportion of patients with X-ray lesions increased dramatically in the control group and decreased significantly in two intervention groups; significant differences were seen between the control group and two intervention groups (P < 0.05). Moreover, significant differences were observed in the proportions of new patients and the metaphyseal repair rates between the control group and two intervention groups (P < 0.05). Additionally, the proportion of new patients was lowest and the metaphyseal repair rate was highest in group B. CONCLUSIONS: The effects of eating rice from non-KBD areas and selenium supplementation on the prevention and treatment of paediatric KBD were notable, the consumption of rice might be the most effective and safest intervention and should be encouraged.

Evaluation of the therapeutic effect of treatment with intra-articular hyaluronic acid in knees for Kashin-Beck disease: a meta-analysis.

OBJECTIVE: To assess the efficacy and safety of intra-articular hyaluronic acid (IAHA) injection in knee joints of patients with Kashin-Beck disease (KBD). METHODS: We searched nine electronic databases as well as unpublished data from inception until November 30th 2013 using a combination of search terms for KBD and hyaluronic acid (HA). For dichotomous data, odds ratios (OR) and 95% confidence intervals (CI) were estimated. For continuous data, standard mean difference (SMD) was used for outcomes pooled on the difference scale using a "random-effects" or "fixed-effects" model. We also compared the mean and standard deviation of cytokine levels in post-treatment. RESULTS: The seven eligible trials included 954 IAHA and 495 control patients. The methodological quality of included trials was low. The overall effectiveness of the IAHA group and control group were 93.7% and 62.9%, respectively. IAHA group resulted in very large treatment effects compared to pre-treatment values in 12 months, with SMD values ranging from 1.19-2.64 (all P < 0.05). Compared to controls, SMDs in IAHA group ranged from 0.19-0.64 at 1 week to 1 month (all P > 0.05) and 0.68-1.47 at 2 months to 12 months (all P < 0.05). There was significant improved of HA, cluster of differentiation44 (CD44), keratan sulfate (KS), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and nitric oxide (NO) contents in serum compared with that in the post-treatment and healthy control in non-KBD area (all P < 0.05). CONCLUSION: IAHA for the treatment of KBD was safe and efficacious at 12 months with low and transient adverse reactions. However, more high-quality randomized controlled trials (RCTs) are needed to confirm its therapeutic effect.

Chondroitin sulfate and/or glucosamine hydrochloride for Kashin-Beck disease: a cluster-randomized, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of chondroitin sulfate and/or glucosamine hydrochloride in alleviating symptoms and improving the dysfunction of Kashin-Beck disease (KBD) patients. METHODS: We undertook a cluster-randomized, placebo-controlled trial in 251 patients with KBD. Participants were randomly allocated to comparing (1) chondroitin sulfate, (2) glucosamine hydrochloride, (3) a combination of chondroitin sulfate and glucosamine hydrochloride, or (4) placebo, for 6 months duration. The primary outcome measures of interest were 20% and 50% reductions in pain from baseline, measured by pain subscale in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index. Secondary outcome measures included parameters in the WOMAC Index such as pain, stiffness, and physical function, as well as patients' quality of life by the 12-item Short-Form General Health Survey. The trial registration number is ChiCTR-TRC-11001480 (http://www.chictr.org/). RESULTS: A combination therapy of chondroitin sulfate and glucosamine hydrochloride was effective in reducing WOMAC pain by 20% (differences of 23.4%, P=0.006) and 50% (differences of 15.7%, P=0.016), WOMAC pain (P=0.032), WOMAC stiffness (P=0.043), and WOMAC total score (P=0.035). Chondroitin sulfate used alone was also found to be effective in reducing WOMAC total score and stiffness score (P=0.038 and P=0.023, respectively). No significant positive effects in improving WOMAC Index scores were observed with glucosamine hydrochloride alone. CONCLUSION: The findings of this study indicate that a combination of chondroitin sulfate and glucosamine hydrochloride was more effective than placebo in treating KBD.

A randomized, single-blind comparison of the efficacy and tolerability of hyaluronate acid and meloxicam in adult patients with Kashin-Beck disease of the knee.

The aim of this study was to prospectively evaluate the efficacy and tolerability of hyaluronic acid (HA) and meloxicam for the treatment of knee pain due to Kashin-Beck disease (KBD). A total of 162 patients with KBD-based knee pain were randomly assigned to treatment with a 3-week course of HA (n = 80) and a 12-week course of meloxicam (n = 82). Clinical assessments for each patient were made at 0 (baseline), 1, 2, 4, 8, and 12 weeks. The primary efficacy measure was visual analog scale (VAS) pain score. Second efficacy measures comprised the Western Ontario and McMaster Universities (WOMAC) A (pain), B (stiffness), and C (function) scores as well as patients' and physicians' global assessments. Tolerability was evaluated based on adverse events (AEs) and physician reporting. The VAS rapidly decreased in both groups over 12 weeks. The VAS improvement observed in HA group was lower at week 1 (p = 0.001) but better at weeks 8 and 12 (p < 0.001) than the meloxicam group, which were supported by the secondary variables of WOMAC A (p = 0.001) and WOMAC C (p < 0.001) scores and the global assessments of the patients and their physicians (p = 0.020 and 0.003, respectively). No serious AEs were reported, and the overall incidence of AEs among patients treated with meloxicam was higher than in patients treated with HA (p = 0.012). This study suggests that intra-articular injection of HA and administration of oral meloxicam should be efficacious and well tolerated in the treatment of knee pain due to KBD; the onset of action of meloxicam was faster than that of HA, whereas HA therapy resulted in a more prolonged increasing improvement of symptoms than meloxicam. In addition, HA treatment was likely superior to meloxicam with respect to tolerability. Other randomized double-blind studies are needed to confirm the findings of our open-label study.

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.

Synthesis and characterization of selenium-chondroitin sulfate nanoparticles.

A novel selenium-chondroitin sulfate (SeCS) was synthesized by ultrasonic and dialysis method. With characterization by FTIR, XRD and TEM, the SeCS was found to form nanoparticles in distilled water through a self-aggregation progress. The SeCS nanoparticles had sizes between 30 and 200 nm with selenium entrapment efficiency of about 10.1%. The anti-toxin capacity of SeCS nanoparticles was demonstrated through MTT and apoptosis assays in vitro. Results indicated that the SeCS was less cytotoxic to chondrocytes than sodium selenite. In particular, the SeCS could obviously alleviate chondrocyte apoptosis induced by T-2 toxin compared to chondroitin sulfate. These results thus represent an advanced understanding of the properties of SeCS nanoparticles and demonstrate their exciting potential applications in therapy of Kashin-Beck disease (KBD) and osteoarthritis.

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.