Open Access Research BMJ Open: first published as 10.1136/bmjopen-2017-017883 on 6 March 2018. Downloaded from Effects of five types of selenium supplementation for treatment of Kashin-Beck disease in children: a systematic review and network meta- analysis Dongmei Xie,1,2 Yulin Liao,2 Jirong Yue,1,2 Chao Zhang,3 Yanyan Wang,2 Chuanyao Deng,2 Ling Chen2 To cite: Xie D, Liao Y, Yue J, ABSTRACT Strengths and limitations of this study et al. Effects of five types of Objective To compare the effectiveness of five kinds of selenium supplementation selenium supplementation for the treatment of patients ► The present network meta-analysis (NMA) integrated for treatment of Kashin- with Kashin-Beck disease, and rank these selenium Beck disease in children: a evidence from direct and indirect comparisons. supplementations based on their performance. systematic review and network We applied GRADE system to NMA-based GRADE Design We searched for all publications between 1 meta-analysis. BMJ Open working group to rate the quality of the evidence. January 1966 and 31 March 2017 using seven electronic 2018;8:e017883. doi:10.1136/ ► We comprehensively summarised all randomised- databases. GRADE system to network meta-analyses bmjopen-2017-017883 controlled trials (RCTs) of selenium supplements for (NMAs) was applied to rate the quality of the evidence. We Kashin-Beck disease. ► Prepublication history and conducted a random effects model NMA in STATA 12.1 to additional material for this ► Despite our exhaustive search, only 15 RCTs determine comparative effectiveness of each intervention. paper are available online. To conducted in China were included in this review. Rankings were obtained by using the surface under the view these files, please visit Some trials may have been published in local cumulative ranking curve (SUCRA) values and mean ranks. the journal online (http:// dx. doi. journals that were missed in our search. org/ 10. 1136/ bmjopen- 2017- Results A total of 15 randomised controlled trials ► The overall quality of the evidence was low or very involving 2931 patients were included. After assessment 017883). low. The surface under the cumulative ranking curve of the overall quality of the evidence, we downgraded http://bmjopen.bmj.com/ values may be misleading and should be considered Received 22 May 2017 our primary outcomes from high to low or very low jointly with the GRADE confidence in the estimates Revised 16 January 2018 quality. NMAs showed that all five kinds of selenium for each comparison. Accepted 22 January 2018 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 north Korea and China.3 KBD is prevalent in enriched yeast, sodium selenite and then sodium selenite 377 counties of 14 provinces in China, with + vitamin C. 4 0.64 million cases. KBD occurs in childhood on September 25, 2021 by guest. Protected copyright. Conclusions Based on the results of NMA, all five and includes alterations in the epiphysial types of selenium supplements are more effective than placebo and so that selenium supplementation is of help plate and metaphysis. This leads to a variety of in repairing metaphyseal lesions. Since the overall quality complications, such as bony deformity, joints of the evidence was low or very low, the SUCRA values enlargement, growth retardation and func- may be misleading and should be considered jointly tional impairment in multiple joints, which is with the The Grading of Recommendations Assessment, a significant human and social economically 1National Clinical Research Development and Evaluation (GRADE) confidence in the problem for all individuals involved. More- Center for Geriatrics, West China estimates for each comparison. The quality of the evidence over, KBD can also cause disruptive cartilage Hospital, Sichuan University is insufficient to draw a conclusion about what method of metabolism lipid peroxidation, and disturb the 2 Department of Geriatrics, selenium supplementation is most effective. metabolism of selenium and sulfur.5 6 Because West China Hospital, Sichuan PROSPERO registration number CRD42016051874. University, Chengdu, China of the incomplete ability of the cartilage to 3Center for Evidence-based repair itself, only few therapies are available to Medicine and Clinical Research, treat KBD. For example, non-steroidal anti-in- Taihe Hospital, Hubei University INTRODUCTIOn flammatory drugs,7 sodium hyaluronate,8 phys- of Medicine, Shiyan, China Kashin-Beck disease (KBD) is an endemic, ical therapy9 and chondroitin sulfate combined 10 Correspondence to chronic, disabling degenerative disorder of with glucosamine are an option. Moreover, 1 2 Dr Jirong Yue; peripheral joints and spine. It is present orthopaedists have demonstrated that surgery yuejirong11@ hotmail. com primarily among people in southeast Siberia, to repair joint defects is beneficial.11 12 Xie D, et al. BMJ Open 2018;8:e017883. doi:10.1136/bmjopen-2017-017883 1 Open Access BMJ Open: first published as 10.1136/bmjopen-2017-017883 on 6 March 2018. Downloaded from Although the aetiology of KBD is multifactorial, one by the National Health and Family Planning Commis- of the major environmental risk factors is selenium defi- sion of China.16 We excluded the following studies: (1) ciency.13 Since the 1970s, selenium was administered in studies with small sample sizes (numbers of patients <20 several severely endemic regions. A meta-analysis study in each treatment group); (2) preventive studies; (3) consisting of 5 randomised-controlled trials (RCTs) studies without available information of interest. The as well as 10 non-RCTs demonstrated benefits of sele- studies in which individuals with and without KBD were nium administration in preventing KBD in children.14 enrolled only if the therapeutic effect data could be Another systematic review suggested that sodium sele- extracted. Outcome of interest to this review was the nite (Se) was effective for the treatment of patients rate of repair of metaphyseal lesions using X-ray film. already affected with KBD.15 Besides Se tablet, there Typically, repair was defined as being cured basically or are other selenium supplements used for treating KBD, improved significantly of metaphyseal lesions according including selenium salts (Se salt), selenium enriched to the latest judgement standard of X-ray for treatment yeast (Se yeast), combining sodium selenite and vitamin effect of KBD.17 E (Se+VE) and combining sodium selenite and vitamin C (Se+VC). At the time of our review, there were few Data extraction and quality evaluation head-to-head comparisons of different types of sele- Two authors (YL and DX) independently screened all cita- nium supplement for treatment of KBD. In light of tions identified by the searches. Full-text articles of poten- the need for government policy-makers and clinical tial studies were obtained and assessed according to the care workers to know the effects of a set of alternative aforementioned inclusion criteria. The data extraction options, a systematic review and network meta-analysis form included publication (first author, year of publica- (NMA) was performed. This study aimed at comparing tion), demographics (sample size and age), interventions the effectiveness of administration of selenium in (dose, administration route and length of therapy), the treating patients with KBD, and rank these selenium follow-up period and outcomes. To determine the overall supplementations based on their performance. OR, data were extracted to the closest 12 months because this time point was reported in all included RCTs. Two reviewers independently evaluated the methodological METHOD quality of individual study according to the Cochrane 18 In this study, a protocol was devised according to PRISMA risk-of-bias tool. In our review, we applied the GRADE 19 (Preferred Reporting Items for Systematic Reviews and system to our NMA based on the GRADE working group. Meta-Analyses) guidelines. The protocol was registered The methods of rating the quality of direct comparison on International prospective register of systematic reviews are the same for GRADE in traditional meta-analysis. (PROSPERO), and the trial registration number was Evidence was downgraded by one level from ‘high quality’ http://bmjopen.bmj.com/ CRD42016051874. for significant (or by two levels for very significant), study limitations (risk of bias), indirect of evidence, inconsis- Search strategy tency, imprecision of effects or potential bias in publica- We searched all the literature from 1 January 1966 to tion. The rating of quality of indirect estimates was based 31 March 2017. In our study, we used electronic data- on the ratings of the two pairwise estimates that contrib- bases, including EMBASE, MEDLINE, The Cochrane utes to the indirect estimate of the comparison of interest. Database of Systematic Reviews, The Cochrane Central The lower rating score of direct comparisons comprises Register of Controlled Trials, The Chinese Biomedical the confidence score of indirect comparisons. When on September 25, 2021 by guest. Protected copyright. Database, Chinese National Knowledge Infrastructure, direct and indirect evidences were available, the highest Chinese Science and Technique Journals Database, and score was used as a quality score for NMA assessment.19 In the Wan Fang database. Keywords used in our search addition, we needed to consider the