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The effectiveness of treatments for Kashin–Beck disease: a systematic review and network meta-analysis

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Abstract

Objectives

This study aims to evaluate the efficacy of treatments for Kashin–Beck disease (KBD).

Method

We searched PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, SinoMed, Chinese National Knowledge Infrastructure, reference lists and published systematic reviews and registries of ongoing trials through May 2015 for randomised controlled trials (RCTs) of treatments for KBD. Outcomes of interest were pain, function, stiffness, overall clinical improvement, radiographic improvement (X-ray) and adverse events. Frequentist network meta-analyses were conducted using random-effects consistency model to assess the efficacy of treatments for KBD.

Results

Forty-four RCTs with 9815 participants were included in the review. In children or adolescents, selenium (risk ratio 1.88, 95% confidence interval (CI) 1.51–2.33), vitamin C (2.03, 1.40–2.95) and aspirin (2.14, 1.12–4.08) were effective for radiographic structure improvement. In adults, chondroitin plus glucosamine was the best for pain (standardised mean difference 1.46, 95% CI 1.07–1.85), followed by intra-articular injection of hyaluronic acid (IAH) (1.09, 0.70–1.48), chondroitin (0.84, 0.47–1.21), diclofenac (0.63, 1.18–1.08), naproxen (0.55, 0.12–0.98), meloxicam (0.52, 0.03–1.01) and glucosamine (0.40, 0.13–0.67) compared to placebo, with similar results for other clinical outcomes in adults. However, the strength of most evidence was limited by the small number of trials with low to moderate quality.

Conclusions

Selenium supplement has demonstrated some benefits for structural improvement of the disease in children. Chondroitin, glucosamine, IAH and nonsteroid anti-inflammatory drugs are effective for symptom improvements of KBD in adults. Evidence of surgical and complementary treatments for symptoms and aspirin and vitamin C for structure has yet to be established.

Key Points

• There were 23 nutraceuticals, pharmaceuticals and surgical and complementary treatments assessed for Kashin–Beck disease (KBD) in randomised trials.

• Among the 23 treatments, chondroitin, glucosamine, IAH and non-steroid anti-inflammatory drugs are more effective than placebo to relieve symptoms for adults with KBD.

• Selenium supplement is more effective than placebo for radiographic improvement in children or adolescents.

• The efficacy of surgeries, aspirin, vitamin C and complementary treatments for KBD has not been established yet.

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References

  1. Allander E (1994) Kashin-Beck disease. An analysis of research and public health activities based on a bibliography 1849-1992. Scand J Rheumatol Suppl 99:1–36

    Article  CAS  PubMed  Google Scholar 

  2. Moreno-Reyes R, Suetens C, Mathieu F, Begaux F, Zhu D, Rivera MT, Boelaert M, Neve J, Perlmutter N, Vanderpas J (1998) Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine status. N Engl J Med 339(16):1112–1120. https://doi.org/10.1056/NEJM199810153391604

    Article  CAS  PubMed  Google Scholar 

  3. Utiger RD (1998) Kashin-Beck disease—expanding the spectrum of iodine-deficiency disorders. N Engl J Med 339(16):1156–1158. https://doi.org/10.1056/NEJM199810153391611

    Article  CAS  PubMed  Google Scholar 

  4. Li D, Han J, Guo X, Qu C, Yu F, Wu X (2016) The effects of T-2 toxin on the prevalence and development of Kashin-Beck disease in China: a meta-analysis and systematic review. Toxicol Res 5(3):731–751. https://doi.org/10.1039/C5TX00377F

    Article  CAS  Google Scholar 

  5. Yang L, Zhao GH, Yu FF, Zhang RQ, Guo X (2016) Selenium and iodine levels in subjects with Kashin-Beck disease: a meta-analysis. Biol Trace Elem Res 170(1):43–54. https://doi.org/10.1007/s12011-015-0463-8

    Article  CAS  PubMed  Google Scholar 

  6. Chasseur C, Suetens C, Nolard N, Begaux F, Haubruge E (1997) Fungal contamination in barley and Kashin-Beck disease in Tibet. Lancet 350(9084):1074. https://doi.org/10.1016/S0140-6736(05)70453-0

    Article  CAS  PubMed  Google Scholar 

  7. Suetens C, Moreno-Reyes R, Chasseur C, Mathieu F, Begaux F, Haubruge E, Durand MC, Neve J, Vanderpas J (2001) Epidemiological support for a multifactorial aetiology of Kashin-Beck disease in Tibet. Int Orthop 25(3):180–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Li L, Wang Q, Tian JH, Yang KH, Tian HL, Shi CH, Jiang J,  Wu TX, Liao YJ (2013) The relationship between the exposure and metabolism of iodine and Kaschin-Beck disease:a systematic review. Chinese Journal of Evidence-Based Pediatrics: 176–180 [In Chinese]. https://www.cjebp.net/CN/abstract/abstract9054.html

  9. Yao Y, Pei F, Kang P (2011) Selenium, iodine, and the relation with Kashin-Beck disease. Nutrition 27(11-12):1095–1100. https://doi.org/10.1016/j.nut.2011.03.002

    Article  CAS  PubMed  Google Scholar 

  10. Wang Y, Yang Z, Gilula LA, Zhu C (1996) Kashin-Beck disease: radiographic appearance in the hands and wrists. Radiology 201(1):265–270. https://doi.org/10.1148/radiology.201.1.8816556

    Article  CAS  PubMed  Google Scholar 

  11. Mathieu F, Begaux F, Lan ZY, Suetens C, Hinsenkamp M (1997) Clinical manifestations of Kashin-Beck disease in Nyemo Valley, Tibet. Int Orthop 21(3):151–156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang FQ, Wang ZW, Ping ZG, Guo X (2005) Epidemiological investigation of the declined prevalence of Kashin-Beck disease in Linyou County, Shaanxi Province, China. Chin J Endemiol 06:637–638 [in Chinese]

    Google Scholar 

  13. Li FZ, Deng JY, Yang RM, Li DW, Ma GJ, Liao P, Hou CH, Zheng YT, Zhang L, Wu G (2006) Investigating report on prevalence rate of Kaschin-Beck disease in adults in Sichuan Province in 2005. Endemic Dis Bull 01:23–25 [in Chinese]

    Google Scholar 

  14. Sun L-Y, Yuan L-J, Fu Y, Deng J-Y, Wang L-H (2012) Prevalence of Kaschin-Beck disease among Tibetan children in Aba Tibetan and Qiang Autonomous Prefecture: a 3-year epidemiological survey. World J Pediatr 8(2):140–144. https://doi.org/10.1007/s12519-012-0351-7

    Article  PubMed  Google Scholar 

  15. Tomlinson R (1999) Beijing conference reviews Kashin-Beck disease. BMJ 318(7182):485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jirong Y, Huiyun P, Zhongzhe Y, Birong D, Weimin L, Ming Y, Yi S (2012) Sodium selenite for treatment of Kashin-Beck disease in children: a systematic review of randomised controlled trials. Osteoarthr Cartil 20(7):605–613. https://doi.org/10.1016/j.joca.2012.02.012

    Article  CAS  Google Scholar 

  17. Yu FF, Xia CT, Fang H, Han J, Younus MI, Guo X (2014) Evaluation of the therapeutic effect of treatment with intra-articular hyaluronic acid in knees for Kashin-Beck disease: a meta-analysis. Osteoarthr Cartil 22(6):718–725. https://doi.org/10.1016/j.joca.2014.04.012

    Article  CAS  Google Scholar 

  18. Mills EJ, Thorlund K, Ioannidis JP (2013) Demystifying trial networks and network meta-analysis. BMJ 346:f2914. https://doi.org/10.1136/bmj.f2914

    Article  PubMed  Google Scholar 

  19. General office of endemic disease control, People’s Republic of China (1983) X-ray criteria of treatment effect on Kashin-beck disease (trial)

  20. Ministry of Health, People’s Republic of China (1996) The judging of treatment effect on Kashin-beck disease (WS/T 79-1996)

  21. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, Norris S, Falck-Ytter Y, Glasziou P, DeBeer H, Jaeschke R, Rind D, Meerpohl J, Dahm P, Schunemann HJ (2011) GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 64(4):383–394. https://doi.org/10.1016/j.jclinepi.2010.04.026

    Article  PubMed  Google Scholar 

  22. Puhan MA, Schunemann HJ, Murad MH, Li T, Brignardello-Petersen R, Singh JA, Kessels AG, Guyatt GH, Group GW (2014) A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis. BMJ 349:g5630. https://doi.org/10.1136/bmj.g5630

    Article  PubMed  Google Scholar 

  23. Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G (2013) Graphical tools for network meta-analysis in STATA. PLoS One 8(10):e76654. https://doi.org/10.1371/journal.pone.0076654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. White IR (2015) Network meta-analysis. Stata J 15(4):951–985

    Article  Google Scholar 

  25. Bucher HC, Guyatt GH, Griffith LE, Walter SD (1997) The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 50(6):683–691

    Article  CAS  PubMed  Google Scholar 

  26. Dias S, Welton NJ, Caldwell DM, Ades AE (2010) Checking consistency in mixed treatment comparison meta-analysis. Stat Med 29(7-8):932–944. https://doi.org/10.1002/sim.3767

    Article  CAS  PubMed  Google Scholar 

  27. Higgins JPT, Green S (editors) (2011) Cochrane handbook for systematic reviews of interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available from http://www.cochrane-handbook.org/.

  28. da Costa BR, Reichenbach S, Keller N, Nartey L, Wandel S, Juni P, Trelle S (2016) Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet 387(10033):2093–2105. https://doi.org/10.1016/S0140-6736(16)30002-2

    Article  CAS  PubMed  Google Scholar 

  29. Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P (2010) OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthr Cartil 18(4):476–499. https://doi.org/10.1016/j.joca.2010.01.013

    Article  CAS  Google Scholar 

  30. Vane JR, Botting RM (1998) Mechanism of action of nonsteroidal anti-inflammatory drugs. Am J Med 104(3A):2S–8S discussion 21S-22S

    Article  CAS  PubMed  Google Scholar 

  31. Monfort J, Pelletier JP, Garcia-Giralt N, Martel-Pelletier J (2008) Biochemical basis of the effect of chondroitin sulphate on osteoarthritis articular tissues. Ann Rheum Dis 67(6):735–740. https://doi.org/10.1136/ard.2006.068882

    Article  CAS  PubMed  Google Scholar 

  32. Henrotin Y, Mobasheri A, Marty M (2012) Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis? Arthritis Res Ther 14(1):201. https://doi.org/10.1186/ar3657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Singh JA, Noorbaloochi S, MacDonald R, Maxwell LJ (2015) Chondroitin for osteoarthritis. Cochrane Database Syst Rev 1:CD005614. https://doi.org/10.1002/14651858.CD005614.pub2

    Article  PubMed  Google Scholar 

  34. Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, Hochberg MC, Wells G (2005) Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev (2):CD002946. https://doi.org/10.1002/14651858.CD002946.pub2

  35. Zou K, Wong J, Abdullah N, Chen X, Smith T, Doherty M, Zhang W (2016) Examination of overall treatment effect and the proportion attributable to contextual effect in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis 75(11):1964–1970. https://doi.org/10.1136/annrheumdis-2015-208387

    Article  PubMed  Google Scholar 

  36. Trigkilidas D, Anand A (2013) The effectiveness of hyaluronic acid intra-articular injections in managing osteoarthritic knee pain. Ann R Coll Surg Engl 95(8):545–551. https://doi.org/10.1308/003588413X1362996004943210.1308/rcsann.2013.95.8.545

  37. Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G (2006) Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev (2):CD005321. https://doi.org/10.1002/14651858.CD005321.pub2

  38. Xie DM, Wang RH, Liao YL, Xu L, Yue JR, Deng CY (2016) Selenium supplement for Kashin-Beck disease: a network meta-analysis. Chin J Evid Based Med 16(11):1284–1290 [in Chinese]. https://doi.org/10.7507/1672-2531.20160195

    Article  Google Scholar 

  39. Zou K, Liu G, Wu T, Du L (2009) Selenium for preventing Kashin-Beck osteoarthropathy in children: a meta-analysis. Osteoarthr Cartil 17(2):144–151. https://doi.org/10.1016/j.joca.2008.06.011

    Article  CAS  Google Scholar 

  40. Quan W, Xiu-xia L, Lun L, Jin-hui T, Ke-hu Y, Tai-xiang W, Yong-jian L (2013) Correlation between selenium and Kaschin-Beck disease. Chin J Evid Based Med 13(12):1421–1430

    Google Scholar 

  41. Han J, Wang W, Qu C, Liu R, Li W, Gao Z, Guo X (2015) Role of inflammation in the process of clinical Kashin-Beck disease: latest findings and interpretations. Inflamm Res 64(11):853–860. https://doi.org/10.1007/s00011-015-0861-6

    Article  CAS  PubMed  Google Scholar 

  42. Roach JE, Tomblin W, Eyring EJ (1975) Comparison of the effects of steroid, aspirin and sodium salicylate on articular cartilage. Clin Orthop Relat Res 106:350–356

    Article  Google Scholar 

  43. Wluka AE, Ding C, Wang Y, Jones G, Urquhart DM, Cicuttini FM (2015) Aspirin is associated with reduced cartilage loss in knee osteoarthritis: data from a cohort study. Maturitas 81(3):394–397. https://doi.org/10.1016/j.maturitas.2015.04.015

    Article  CAS  PubMed  Google Scholar 

  44. Manicourt DH, Druetz-Van Egeren A, Haazen L, Nagant de Deuxchaisnes C (1994) Effects of tenoxicam and aspirin on the metabolism of proteoglycans and hyaluronan in normal and osteoarthritic human articular cartilage. Br J Pharmacol 113(4):1113–1120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Canter PH, Wider B, Ernst E (2007) The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: a systematic review of randomized clinical trials. Rheumatology 46(8):1223–1233. https://doi.org/10.1093/rheumatology/kem116

    Article  CAS  PubMed  Google Scholar 

  46. Rosenbaum CC, O’Mathuna DP, Chavez M, Shields K (2010) Antioxidants and antiinflammatory dietary supplements for osteoarthritis and rheumatoid arthritis. Altern Ther Health Med 16(2):32–40

    PubMed  Google Scholar 

  47. Nuesch E, Trelle S, Reichenbach S, Rutjes AW, Tschannen B, Altman DG, Egger M, Juni P (2010) Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study. BMJ 341:c3515. https://doi.org/10.1136/bmj.c3515

    Article  PubMed  PubMed Central  Google Scholar 

  48. Chen ZL, Ma JM (1979) “Aspirin for Kashin-Beck disease: A preliminary observation on the efficacy.” Medical Journal of Chinese People’s Liberation Army(02):128. [in Chinese]

  49. Niu GH, Zhang BZ, Hou SF (1990) The effect of half dose of selenium supplementation on prevention and treatment of Kaschin Beck disease Chinese Journal of Endemic Diseases 9(2):99–100 [in Chinese]

  50. Moreno-Reyes R, Mathieu F, Boelaert M, Begaux F, Suetens C, Rivera MT, Nève J, Perlmutter N, Vanderpas J (2003) Selenium and iodine supplementation of rural Tibetan children affected by Kashin-Beck osteoarthropathy. Am J Clin Nutr 78(1):137–144

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Contributors

KZ conceptualised and designed the study. KZ and JLH screened the literature and selected the study. KZ extracted data and accessed the quality of trials, conducted the analysis and wrote the draft of the manuscript. QZ wrote part of the discussion. WZ and BD advised on the analysis and the representation of the results. All authors contributed to the intellectual interpretation of the findings and approved the final manuscript.

Funding

QZ was supported by the Innovation Research Grant from the University of Electronic Science and Technology, Chengdu, China.

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Correspondence to Weiya Zhang.

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Zou, K., Hu, J., Zhou, Q. et al. The effectiveness of treatments for Kashin–Beck disease: a systematic review and network meta-analysis. Clin Rheumatol 38, 3595–3607 (2019). https://doi.org/10.1007/s10067-019-04704-0

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